• Long COVID: major findings, mechanisms and recommendations – “Long COVID is a multisystemic illness encompassing ME/CFS, dysautonomia, impacts on multiple organ systems, and vascular and clotting abnormalities. It has already debilitated millions of individuals worldwide, and that number is continuing to grow. On the basis of more than 2 years of research on long COVID and decades of research on conditions such as ME/CFS, a significant proportion of individuals with long COVID may have lifelong disabilities if no action is taken. Diagnostic and treatment options are currently insufficient, and many clinical trials are urgently needed to rigorously test treatments that address hypothesized underlying biological mechanisms, including viral persistence, neuroinflammation, excessive blood clotting and autoimmunity.” 
  • Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19 – “Here, we analyzed a cohort of patients who seemingly recovered from SARS-CoV-2 infection, as concluded from multiple negative PCR tests on both nasopharyngeal swabs and bronchoalveolar lavage protracting for up to 300 days, but who still clinically deteriorated and eventually died. In most of these cases, pneumonia was the primary or co-primary cause of death, a finding that was confirmed by pathology examination of the lungs. Our work shows that these patients, despite the apparent molecular negativity, still harbored virus-infected cells in their lungs, particularly in the para-bronchial glands and in the bronchial cartilage. This is consistent with the conclusion that these patients had never cleared the infection. The absence of SARS-CoV-2 infection in the respiratory epithelium possibly explains the apparent negativity of these patients to PCR tests performed on bronchoalveolar lavage. These results highlight the relevance of post-mortem pathology examination as a crucial diagnostic tool.”
  • Understanding Post-Acute Sequelae of SARS-CoV-2 Infection through Data-Driven Analysis with Longitudinal Electronic Health Records: Findings from the RECOVER Initiative – “In this study, we developed a data-driven approach to identify a broad spectrum of clinical abnormalities (incident diagnoses and medication use) experienced by SARS-CoV-2 infected patients who survived beyond the first 30 days of the infection.”
  • Symptoms and risk factors for long COVID in non-hospitalized adults – “Individuals with confirmed SARS-CoV-2 infection were at increased risk of reporting a wide range of symptoms at ≥12 weeks after infection, compared to propensity score-matched patients with no record of suspected or confirmed SARS-CoV-2 infection, after accounting for both sociodemographic and clinical characteristics and the reporting of symptoms before infection. The symptoms most associated with SARS-CoV-2 infection included some that are already recognized in previous studies, such as anosmia, shortness of breath, chest pain and fever, but also included a range of other symptoms that have previously not been widely reported such as hair loss and sexual dysfunction. Previous SARS-CoV-2 infection was independently associated with the reporting to primary care of 20 of the 33 symptoms included in the WHO case definition and an additional 42 symptoms, beyond 12 weeks from infection. SARS-CoV-2 infection was associated with a 26% relative increase in risk of reporting at least one of the symptoms included in the WHO case definition for long COVID.”
  • Biomarkers in long COVID-19: A systematic review – “Long COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.”
  • One-Year Adverse Outcomes Among US Adults With Post–COVID-19 Condition vs Those Without COVID-19 in a Large Commercial Insurance Database – “This case-control study leveraged a large commercial insurance database and found increased rates of adverse outcomes over a 1-year period for a PCC cohort surviving the acute phase of illness. The results indicate a need for continued monitoring for at-risk individuals, particularly in the area of cardiovascular and pulmonary management.”
  • Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 30 March 2023 – “An estimated 1.9 million people living in private households in the UK (2.9% of the population) were experiencing self-reported long COVID (symptoms continuing for more than four weeks after the first confirmed or suspected coronavirus (COVID-19) infection that were not explained by something else) as of 5 March 2023.”
  • One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry – “At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death.”
  • Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) – “T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.”
  • ACE2-independent infection of T lymphocytes by SARS-CoV-2 – “It has been shown that SARS-CoV-2-infected human monocytes, monocyte-derived macrophages, and dendritic cells in vitro, which potentially plays a major role in COVID-19 pathogenesis.16,17 However, whether SARS-CoV-2 infects lymphocytes, which do not express ACE2, to result in lymphopenia is still unknown. This knowledge gap also brings difficulty for our understanding of how lymphocytes lost the ability to control viral infection. Here, we provided evidence that activated T lymphocytes could be infected by SARS-CoV-2 in an ACE2-independent manner. The infection leads to pronounced T-cell apoptosis in vitro or in patients with COVID-19. Our findings shed light on the understanding of SARS-CoV-2 infection-induced lymphopenia.”
  • The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: a systematic review and meta-analysis – “Our work shows that 45% of COVID-19 survivors, regardless of hospitalization status, were experiencing a range of unresolved symptoms at ∼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies.”
  • Acute and postacute sequelae associated with SARS-CoV-2 reinfection – “In sum, in this study of 5,819,264 individuals, we provide evidence that reinfection contributes to additional health risks beyond those incurred in the first infection including all-cause mortality, hospitalization and sequelae in a broad array of organ systems. The risks were evident in the acute and postacute phases of reinfection. The evidence suggests that for people who already had a first infection, prevention of a second infection may protect from additional health risks. Prevention of infection and reinfection with SARS-CoV-2 should continue to be the goal of public health policy.”
  • Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection – “In summary, POTS-related diagnoses appear to be acquired with increased frequency after, compared to before, COVID-19 vaccination, particularly when compared to more commonly diagnosed conditions, but at a rate that is approximately five times lower than after SARS-CoV-2 infection. Additional research regarding the relation between COVID-19 vaccination and POTS is needed. By further developing the evidence base and augmenting understanding around emerging vaccine side effects, clinical researchers may work to enhance medical trust and improve quality of care as well as communications around vaccines, with the ultimate goal of optimizing vaccine uptake.”
  • Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics – “Neurological manifestations of long COVID exist as a major complication of COVID-19 post-infection, affecting up to one third of patients with COVID symptoms lasting longer than four weeks. Although SARS-CoV-2 neurotropism, viral-induced coagulopathy, endothelial disruption, systemic inflammation, cytokine overactivation and neuroglial dysfunction have been hypothesized as mechanisms associated with pathogenesis of long COVID condition, further clinical, neuropathological, and experimental models are needed to address many of the unknown questions about pathogenesis. Similarly, current and potential therapeutics to target these hypothesized pathogenic mechanisms using anti-inflammatory, anti-viral, and neuro-regenerative agents are potentially able to reverse neurological sequelae but still require well designed clinical trials studies to prove their efficacy.”
  • The SARS-CoV-2 main protease induces neurotoxic TDP-43 cleavage and aggregates – “SARS-CoV-2 infection results in multilineage neural cell dysregulation, decreased new neuron generation, and a reduction in overall brain size in patients, even those with mild respiratory COVID-19.2 The infectivity of SARS-CoV-2 in neural cells has been confirmed in human neural progenitor cells, brain organoids and nonhuman primates.3,9,10 Overall, there is a critical need to determine which viral factors contribute to central nervous system (CNS) disorders. Hence, our identification of Nsp5 as cytotoxic towards neuroblasts and glial cells demonstrates a direct killing effect of SARS-CoV-2 infection on neuronal cells through TDP-43 cleavage, which may lead to further CNS dysfunction, including neuroinflammation. Nevertheless, the effects of TDP-43 cleavage by the viral protease Nsp5 on host neural damage still need to be further confirmed in organoids, animal models, and infected patients.”
  • Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics – “Neurological manifestations of long COVID exist as a major complication of COVID-19 post-infection, affecting up to one third of patients with COVID symptoms lasting longer than four weeks. Although SARS-CoV-2 neurotropism, viral-induced coagulopathy, endothelial disruption, systemic inflammation, cytokine overactivation and neuroglial dysfunction have been hypothesized as mechanisms associated with pathogenesis of long COVID condition, further clinical, neuropathological, and experimental models are needed to address many of the unknown questions about pathogenesis. Similarly, current and potential therapeutics to target these hypothesized pathogenic mechanisms using anti-inflammatory, anti-viral, and neuro-regenerative agents are potentially able to reverse neurological sequelae but still require well designed clinical trials studies to prove their efficacy.”
  • SARS-CoV-2 restructures host chromatin architecture – “Here we found that SARS-CoV-2 infection notably restructures 3D host chromatin, featuring widespread compartment A weakening and A–B mixing, and global reduction in intra-TAD chromatin contacts (Fig. 6e). The epigenome is also altered, including a global reduction in active chromatin mark H3K27ac and a specific increase in H3K4me3 at pro-inflammatory gene promoters. Interestingly, these changes were quite unique to SARS-CoV-2 compared with infection by common-cold coronavirus or immune stimuli. What we characterized here represents a direct cell-autonomous effect elicited by SARS-CoV-2 on the host chromatin. Consistent with our results, some compartmental changes after infection have also been reported 34. In parallel, SARS-CoV-2 also imposes non-cell-autonomous effects on the 3D genome35. An important unanswered question is exactly how SARS-COV-2 infection restructures host chromatin and whether viral regulators are involved. In this light, ORF8 was recently found to disrupt the host epigenome7, suggesting that specific viral factors could confer the chromatin restructuring we discovered in this work.”
  • MRI Reveals Significant Brain Abnormalities Post-COVID – “MRI results showed that patients who recovered from COVID-19 had significantly higher susceptibility values in the frontal lobe and brain stem compared to healthy controls. The clusters obtained in the frontal lobe primarily show differences in the white matter.”
  • Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection – “Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.”
  • Mast cell activation symptoms are prevalent in Long-COVID – “MCA symptoms were increased in LC and mimicked the symptoms and severity reported by patients who have MCAS. Increased activation of aberrant mast cells induced by SARS-CoV-2 infection by various mechanisms may underlie part of the pathophysiology of LC, possibly suggesting routes to effective therapy.”
  • Long COVID after breakthrough SARS-CoV-2 infection – “In sum, our findings provide evidence of increased risk of death and post-acute sequelae in people with BTI compared to controls with no evidence of SARS-CoV-2 infection; the risks were reduced in comparative analyses involving BTI versus SARS-CoV-2 infection without prior vaccination. Our results show that SARS-CoV-2 vaccination before infection only partially reduced the risk of death and post-acute sequelae. Measures for the prevention of breakthrough infections are needed to most optimally reduce the risk of the long-term health consequences of SARS-CoV-2 infection.”
  • Long-COVID in children and adolescents: a systematic review and meta-analyses – :Protective measures are essential to prevent long-COVID in children. We need to understand the long-COVID pathophysiology and symptomatology to support clinical management systems, establish rehabilitation programs, and design guidelines and therapeutic research. Long-COVID represents a significant public health concern, and there are no guidelines to address its diagnosis and management. Our meta-analyses further support the importance of continuously monitoring the impact of long-COVID in children and adolescents and the need to include all variables and appropriate control cohorts in studies to better understand the real burden of pediatric long-COVID.:
  • Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes – Our results suggest that the identified subphenotypes are highly consistent across the two cohorts with distinct patient populations and geographical characteristics. These four subphenotypes also covered the major PASC conditions that have been reported from existing independent studies, such as cardiovascular, respiratory, neurological and gastrointestinal conditions. Our study verified the co-existence of these dominate subphenotypes and can inform focused disease areas of treatment development for PASC.
  • Multi-organ impairment and long COVID: a 1-year prospective, longitudinal cohort study – “Organ impairment persisted in 59% of 331 individuals followed up at 1 year post COVID-19, with implications for symptoms, quality of life and longer-term health, signaling the need for prevention and integrated care of long COVID.”
  • Cognitive deficits in people who have recovered from COVID-19 – “People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalized (N = 192), but also for non-hospitalized cases who had biological confirmation of COVID-19 infection (N = 326). Analyzing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.”
  • AGA Institute Rapid Review of the Gastrointestinal and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19 – “GI symptoms are associated with COVID-19 in <10% of patients. In studies outside of China, estimates are higher. Further studies are needed with standardized GI symptoms questionnaires and liver function test checks on admission to better quantify and qualify the association of these symptoms with COVID-19. Based on findings from our meta-analysis, we provide several Best Practice Statements for the consultative management of COVID-19.”
  • Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features – “Post-COVID-19 syndrome shows high prevalence and multisystem involvement among survivors. The syndrome overlaps with ME/CFS and previous post-SARS syndromes. Nonetheless, a lack of consensus on the characterization of PCS needs to be addressed. The syndrome is likely to involve many immunological processes. Manifestations of PCS may be partially explained by a neuroinflammatory process involving the activation of astrocytes and microglia. The hypothalamus and its network are implicated in the ongoing neuroinflammation and might be a major cause of some of the persistent symptoms. As vaccine rollout increases and the world is looking into a post-COVID era, developing accurate laboratory and clinical guidelines for PCS is crucial to define and identify PCS. Long-term specialized brain imaging and glial marker studies are urgently needed to determine whether PCS exhibits a specific imprint in the CNS. There are several clinical trials on various anti-inflammatory agents—such as corticosteroids—currently being performed, and these studies may help to improve our understanding—especially if they are aided by extensive measurements of the relevant biomarkers.”
  • Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19 – The initial inflammatory response mounted upon SARS-CoV-2 infection could potentially drive the changes in monocyte functionality, as inflammation is well known to activate the coagulation system57,58,59. Moreover, while our results are focused on the functionality of monocytes, previous data have shown that platelets from patients with COVID-19 are activated ex vivo during the acute phase of disease and have increased capacity to form monocyte-platelet aggregates48, which supports the notion of inflammation driving the initial activation and functional switch of these cell types, promoting the initiation of hemostasis issues and potentially the diminished innate immune functions upon secondary stimulation.
  • Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation – “An understanding of the immunopathology leading to severe manifestations of COVID-19, in both adults and children, is of critical importance for effective management and treatment of the disease. MIS-C shows remarkable similarity to pediatric TSS (5–9). Using in silico modeling and analysis, we found that SARS-CoV-2 encodes a superantigen motif near its S1/S2 cleavage site. This region is highly similar in sequence and structure to the SEB SAg motif that interacts with both the TCR and CD28 (21) and mediates TSS. SEB enables large-scale T cell activation and proliferation (12), resulting in massive production of proinflammatory cytokines including IFNγ, TNFα, and IL-2 from T cells, as well as IL-1 and TNFα from antigen-presenting cells (12). This cytokine storm leads to multiorgan tissue damage like what is now observed in MIS-C. Our results suggest that the hyperinflammatory syndrome originates from superantigenic activity by SARS-CoV-2 S glycoprotein. Furthermore, these findings also raise the possibility that the hyperinflammation observed in severe cases of COVID-19 in adults may also be driven by the SAg-like activity of the S protein. Indeed, SAgs induce an inflammatory cytokine signature similar to that which predicts severity and death in COVID-19, including IL-6, TNFα, IL-8, and IL-1β (12, 29). Moreover, our analysis of the T cell immune response in COVID-19 patients shows that those with more severe and hyperinflammatory clinical courses exhibit TCRVβ skewing consistent with SAg activity.”
  • SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming – “Using primary nasal epithelial organoid cultures, we found that the virus attaches to motile cilia via the ACE2 receptor. SARS-CoV-2 traverses the mucus layer, using motile cilia as tracks to access the cell body. Depleting cilia blocks infection for SARS-CoV-2 and other respiratory viruses. SARS-CoV-2 progeny attach to airway microvilli 24 h post-infection and trigger formation of apically extended and highly branched microvilli that organize viral egress from the microvilli back into the mucus layer, supporting a model of virus dispersion throughout airway tissue via mucociliary transport. Phosphoproteomics and kinase inhibition reveal that microvillar remodeling is regulated by p21-activated kinases (PAK). Importantly, Omicron variants bind with higher affinity to motile cilia and show accelerated viral entry. Our work suggests that motile cilia, microvilli, and mucociliary-dependent mucus flow are critical for efficient virus replication in nasal epithelia.”
  • Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants – “The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.”
  • Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection – “Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection.”
  • Impaired function and delayed regeneration of dendritic cells in COVID-19 – “In summary, we provide evidence that the depletion, enhanced turnover and phenotypic alterations of circulating DCs observed in COVID-19 patients extend beyond the acute phase of the disease. The persistent phenotypic alteration and dysfunctionality of circulating DCs and monocytes was especially apparent in more severe disease and associated with the prolonged inflammatory response. The consequences of depletion and dysfunctionality of blood APCs are not known. While these changes may reflect a regulatory mechanism to reduce overactivation of the immune response in COVID-19, the described alterations together with the profound lymphopenia could make patients more vulnerable to secondary infections, which were shown to be more prevalent in COVID-19 patients [60,61]. This needs to be taken into account in the clinical management of COVID-19.”
  • Six-month sequelae of post-vaccination SARS-CoV-2 infection: A retrospective cohort study of 10,024 breakthrough infections – “In summary, the present data show that prior vaccination against COVID-19, especially after two doses, is associated with significantly less risk of many but not all outcomes of COVID-19, in younger but not older individuals. These findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the urgent need to identify or develop additional preventive and curative interventions for sequelae of COVID-19.”
  • Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients – “This study reports volumetric differences in the whole brainstem and four subregions in ME/CFS, long COVID, and HC. We showed that pons, SCP, and whole brainstem volumes were significantly larger in long COVID patients compared with HC. Similarly, pons and whole brainstem volumes were significantly larger in ME/CFS patients compared with HC. Interestingly, no brainstem subregion volumes were significantly different between ME/CFS and long COVID patients between ME/CFS and long COVID patients. To the authors’ knowledge this is the first investigation to demonstrate the overlap between ME/CFS and long COVID metrics using MRI. We also demonstrated that “pain” and “breathing difficulty” are strongly associated with brainstem volumes in ME/CFS and long COVID.”
  • Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors – “Vaccines and drugs have helped reduce disease severity and blunt the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, ongoing virus transmission, continuous evolution, and increasing selective pressures have the potential to yield viral variants capable of resisting these interventions. Here, we investigate the susceptibility of natural variants of the main protease [Mpro; 3C-like protease (3CLpro)] of SARS-CoV-2 to protease inhibitors. Multiple single amino acid changes in Mpro confer resistance to nirmatrelvir (the active component of Paxlovid). An additional clinical-stage inhibitor, ensitrelvir (Xocova), shows a different resistance mutation profile. Importantly, phylogenetic analyses indicate that several of these resistant variants have pre-existed the introduction of these drugs into the human population and are capable of spreading. These results encourage the monitoring of resistance variants and the development of additional protease inhibitors and other antiviral drugs with different mechanisms of action and resistance profiles for combinatorial therapy.”
  • Severely ill patients with COVID-19 display impaired exhaustion features in SARS-CoV-2–reactive CD8+ T cells – “Recent studies in patients with COVID-19 have verified the presence of CD8+ T cells that are reactive to SARS-CoV-2 (5, 7, 8). However, the nature and types of CD8+ T cell subsets that respond to SARS-CoV-2 and whether they play an essential role in driving protective or pathogenic immune responses remain elusive. Here, we report on single-cell transcriptome and TCR sequence analyses of >87,000 in vitro activated, virus-reactive CD8+ T cells and >20,000 CD8+ T cells expressing activation markers ex vivo, from a total of 39 patients with COVID-19 and 10 healthy, prepandemic donors. To compare the molecular properties of antigen-specific SARS-CoV-2–reactive CD8+ T cells to other common respiratory virus–reactive CD8+ T cells, we also isolated virus-reactive CD8+ memory T cells from healthy control participants and analyzed their single-cell transcriptomes.”
  • Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals – “Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage.”
  • SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes – “SARS-CoV-2 infected T helper cells express higher amounts of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID-19 patients.”
  • Long-Term Effect of COVID-19 on Lung Imaging and Function, Cardiorespiratory Symptoms, Fatigue, Exercise Capacity, and Functional Capacity in Children and Adolescents: A Systematic Review and Meta-Analysis – “The results indicate that, similar to adults, children and adolescents suffering from long COVID may experience persistent abnormalities in lung imaging and function, cardiorespiratory symptoms, fatigue, decreased exercise capacity and decreased functional capacity between 3 to 12 months after the infection. Fatigue and dyspnea were among the most commonly reported symptoms associated with long COVID.”
  • Long-term gastrointestinal outcomes of COVID-19 – “In sum, in this study of 154,068 people who survived the acute phase of COVID-19, we show increased risk and burden of post-acute gastrointestinal sequelae spanning several disease categories including acid disorders, functional intestinal disorders, pancreatic disorders, hepatic and biliary disease. The risks were evident even among those whose acute COVID-19 did not necessitate hospitalization. Our findings suggest that post-acute COVID-19 care strategies should include attention to gastrointestinal health and disease.”
  • SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism – “We found that SARS-CoV-2 infection causes immunodeficiency in recovered patients”
  • Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals – “COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes.”
  • Post‐COVID‐19 fatigue and anhedonia: A cross‐sectional study and their correlation to post‐recovery period – “The study revealed high scores of different subtypes of self‐assessment anhedonia scale (including total intensity, total frequency, and total changes scores) in the studied group, also high score of fatigue assessment scale in those patients. Positive statistically significant correlation between anhedonia and fatigue in post‐COVID‐19 group, also negative statistically significant correlation between duration after recovery and the other 2 variables(anhedonia and fatigue) in the examined patients.”
  • AIDS and COVID-19 are two diseases separated by a common lymphocytopenia – “We observe a comparable reduction in B cells in both diseases and a more severe reduction in the total amount of T cells in COVID-19 as compared to AIDS patients”
  • SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein – “Builds on a growing body of research that Covid directly interacts with microglia and triggers inflammatory response in the brain.”
  • SARS-CoV-2 is associated with changes in brain structure in UK Biobank – “UK-based study by researchers using MRI scans and controls for pre-existing conditions.”
  • COVID-19 related stroke in young individuals – “Data supporting an association between COVID-19 and stroke in young populations without typical vascular risk factors, at times with only mild respiratory symptoms, are increasing.”
  • Acute Ischemic Stroke During the Convalescent Phase of Asymptomatic COVID-2019 Infection in Men – “Acute ischemic stroke could be part of the next wave of complications of COVID-19, and stroke units should be on alert and use serological testing, especially in younger patients or in the absence of traditional risk factors.”
  • Excess risk for acute myocardial infarction mortality during the COVID-19 pandemic – “The trend of mortality suggests that age and sex disparities have persisted even through the recent Omicron surge, with excess AMI-associated mortality being most pronounced in younger-aged adults.”
  • Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study – “Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding.”
  • SARS-CoV-2 promotes microglial synapse elimination in human brain organoids – “Neuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection initiate neuronal cell death and cause a loss of post-synaptic termini.”
  • Is the Frontal Lobe the Primary Target of SARS-CoV-2? – “There is some evidence that SARS-CoV-2 could preferentially and directly target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET imaging.”
  • Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study – “Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms.”
  • Defective antifungal immunity in patients with COVID-19 – “During COVID-19 infection immune dysregulation increasing the risk of secondary IFD is likely a combination of clinical intervention/immunosuppression, host factors (existing underlying conditions and/or host predisposition) and the pathophysiology of COVID-19 infection. A three-phase breakdown in the innate antifungal immunity has been proposed, where, initially, severe disruption to the respiratory epithelium resulting from an excessive pro-inflammatory response to COVID-19 infection and limited mucociliary clearance provides ample opportunity for fungal tissue invasion.”
  • Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study – “In conclusion, 6–18 months following symptomatic SARS-CoV-2 infection, adults were at greater risk of a diverse group of symptoms, poorer quality of life and wide-ranging impairment of their daily activities, which could not be explained by confounding. Sequelae were more likely following severe infection and were not observed following asymptomatic infection and pre-infection vaccination may be protective.”
  • The long‐term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status – “This 2‐year study of a selected population of SARS survivors, showed significant impairment of DLCO, exercise capacity and health status persisted, with a more marked adverse impact among HCW.”
  • COVID-19-associated candidiasis and the emerging concern of Candida auris infections – “CAC has been recognized during the COVID-19 pandemic, and the therapeutic strategies recommended for CAC due to Candida species, such as C. albicans, C. tropicalis, and C. glabrata, are similar to those before the era of COVID-19. Close surveillance for the incidence of multidrug-resistant C. auris infections among patients with COVID-19 is essential, since the treatment options are limited and inappropriate treatment may jeopardize the clinical outcome of affected individuals.”
  • More than 50 long-term effects of COVID-19: a systematic review and meta-analysis – “This systematic review and meta-analysis shows that 80% (95% CI 65–92) of individuals with a confirmed COVID-19 diagnosis continue to have at least one overall effect beyond 2 weeks following acute infection. In total, 55 effects, including symptoms, signs, and laboratory parameters, were identified, with fatigue, anosmia, lung dysfunction, abnormal chest X-ray/CT, and neurological disorders being the most common.”
  • Longitudinal evaluation of neurologic-post acute sequelae SARS-CoV-2 infection symptoms – “Early in the neuro-PASC syndrome, fatigue and headache are the most commonly reported symptoms. At 6 months, memory impairment and decreased concentration were most prominent. Only one-third of participants had completed resolution of neuro-PASC at 6 months, although persistent symptoms trended toward improvement at follow-up.”
  • Mental Morbidities and Chronic Fatigue in Severe Acute Respiratory Syndrome Survivors – “Psychiatric morbidities and chronic fatigue persisted and continued to be clinically significant among the survivors at the 4-year follow-up. Optimization of the treatment of mental health morbidities by a multidisciplinary approach with a view for long-term rehabilitation, especially targeting psychiatric and fatigue problems and functional and occupational rehabilitation, would be needed.”
  • Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium – “These findings indicate that T cell–mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post–COVID-19 smell loss.”
  • Akt-Fas to Quell Aberrant T Cell Differentiation and Apoptosis in Covid-19 – “The role of an Akt-mediated CD95 signal as a causal factor rather than a marker in this aberrancy warrants exploration since CD95 could be implicated in the exuberant effector differentiation and death of T cells in severe Covid-19 (21). Given the dual function of CD95, CD95-mediated differentiation and death may be advancing T cells to greater effector acquisition, fewer numbers, and immune dysregulation (Table 1). This may be a pathological state yielding tissue damage due to superantigenic stimulation of T cells not specific to SARS-Cov-2. Whether CD95-mediated death and/or differentiation is pathogenic can be tested in murine models of severe/lethal Covid-19, like the K18 hACE2 model (55).”
  • Understanding the Effects of Age and T-Cell Differentiation on COVID-19 Severity: Implicating a Fas/FasL-mediated Feed-Forward Controller of T-Cell Differentiation – “T-cell differentiation and acquisition of effector function is accomplished via Feed-forward control. In Covid-19, there is nonspecific and possibly bystander cytotoxic CD8+ T-cell activation which may be a double-edged sword, exerting damage to tissues and vital organs like the lung and pancreas (14, 30–32, 52, 53, 60). The FFL proposed here gives a mechanism for both the exuberant T-cell response observed in severe cases and the protective effect of Tn (12, 23, 32, 37). It also anticipates the consequences of a diminishing pool of Tn if we are to consider the documented reduction of the naive T cell repertoire in SARS Cov-2 convalescence (34, 52), which may be induced by the superantigenic nature of infection and the bystander activation of T cells (30, 32). If this dynamic is correct and appreciable, COVID-19 reinfections may manifest more severe disease as T cell repertoires age and Tn reduce in frequency, manifesting in an individual and demographic level”
  • Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses – “Consistent with this interpretation, RNA sequencing (RNA-seq) analysis of infected A549-ACE2 cells treated with CBD for 24 hours shows a notable suppression of SARS-CoV-2–induced changes in gene expression. CBD effectively eradicated viral RNA expression in the host cells, including RNA coding for spike, membrane, envelope, and nucleocapsid proteins (Fig. 4, A and B). Both SARS-CoV-2 and CBD each induced significant changes in cellular gene expression (figs. S5 and S6). Principal components analysis (PCA) of host cell RNA shows almost complete reversal of viral changes, but rather than returning to a normal cell state, the CBD + virus-infected cells resemble those treated with CBD alone (Fig. 4C). Clustering analysis using Metascape reveals some interesting patterns and associated themes (Fig. 4D and figs. S7 and S8). For example, viral induction of genes associated with chromatin modification and transcription (cluster 1) is reversed by CBD, although CBD alone has no effect. Similarly, viral inhibition of genes associated with ribosomes and neutrophils (cluster 3) is largely reversed by CBD, but the drug alone has no effect. This contrasts with clusters 5 and 6 where CBD alone induces strong activation of genes associated with the host stress response. Together, these results suggest that CBD acts to prevent viral protein translation and associated cellular changes.”
  • Distinguishing features of Long COVID identified through immune profiling – “Persistent sequelae are a prominent and debilitating consequence of infection with SARS-CoV-21,3,29. Our exploratory analyses identified key significant immunological differences relative to demographically matched control populations at >400 days post infection. A number of significant changes in circulating leukocytes, including increases in non-classical monocytes, activated B cells, double-negative B cells, exhausted T cells, and IL-4/IL-6 secreting CD4 T cells, and decreases in conventional DC1 and central memory CD4 T cells were identified. In addition, antibodies to SARS-CoV-2 antigens and herpesvirus lytic antigens were elevated in participants with Long COVID. I”
  • Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany – “We observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection.”
  • Neurological complications of COVID-19 in children and the associated immunological responses – “Neonates and children infected with SARS-CoV-2 or COVID-19 infection are thought to be at higher risk of inflammatory responses leading to injury and critical illness. Examination of the peripheral blood may be important for identifying seriously ill patients or patients with severe COVID-19 disease as well as patients with MIS-C. This peripheral blood examination is important as it can allow the investigators to understand the values of neutrophil toxic granulations, burr cells, and schistocytes, and cytokines. Several children have indicated COVID-19 mediated complications including stroke, and encephalopathy, suggesting that COVID-19 can impose a severe impact on children. This severe COVID-19 disease in children is associated with an inflammatory response mediated by the immune system, associated with MIS-C. Considering all these aspects, cytokine storms should be given primary importance while developing the treatment and preventive options against COVID-19 in children.”
  • Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae – “In conclusion, the presence of circulating spike in PASC patients up to 12 months after diagnosis suggests that SARS-CoV-2 viral reservoirs may persist in the body. There are likely many overlapping immunological and inflammatory phenomena contributing to PASC and the detection of spike cannot alone confirm the presence of active viral reservoirs. However, if our finding can be validated in a larger cohort, it would provide strong support for the use of spike as a biomarker for PASC, making it easier to identify patients and assess treatment strategies.”
  • Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States – “Due to the impact of mitigations such as social distancing and our comparison of a single disease (Covid-19) to groups of causes such as deaths from pneumonia and influenza, these rankings are likely conservative lower bounds.”
  • Hospitalizations of Children and Adolescents with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, July 2021–January 2022 – “Coinciding with emerging predominance of the Omicron variant, rates of COVID-19–associated hospitalization among children and adolescents increased rapidly during the last 2 weeks of December 2021, especially among those aged 0–4 years. Moreover, among adolescents, hospitalization rates were higher among those who were unvaccinated.”
  • Diabetes risk rises after COVID, massive study finds – “Even mild SARS-CoV-2 infections can amplify a person’s chance of developing diabetes, especially for those already susceptible to the disease.”
  • Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19 – “Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.”
  • Characterizing long COVID in an international cohort: 7 months of symptoms and their impact – “Patients with Long COVID report prolonged, multisystem involvement and significant disability. By seven months, many patients have not yet recovered (mainly from systemic and neurological/cognitive symptoms), have not returned to previous levels of work, and continue to experience significant symptom burden.”
  • Multiple early factors anticipate post-acute COVID-19 sequelae – “Our analyses provided a framework to understand the heterogeneity of “long COVID” and a rich resource for investigating the biological factors that contribute to PASC, which can potentially be utilized to monitor and guide interventional trials to treat and prevent post-acute COVID-19 symptoms.”
  • Risks and burdens of incident diabetes in long COVID: a cohort study – “In the post-acute phase, we report increased risks and 12-month burdens of incident diabetes and antihyperglycaemic use in people with COVID-19 compared with a contemporary control group of people who were enrolled during the same period and had not contracted SARS-CoV-2, and a historical control group from a pre-pandemic era. Post-acute COVID-19 care should involve identification and management of diabetes.”
  • Acute encephalitis in pediatric multisystem inflammatory syndrome associated with COVID-19 – “Patients with MIS-C may present acute encephalitis characterized by rapid-onset encephalopathy and EEG abnormalities (slow wave activity and/or epileptic abnormalities), in some cases associated with focal neurological signs that disappear with immunomodulatory therapy. The detection through neurological evaluation of sentinel neurological signs and distinctive EEG patterns documentable at disease onset will allow timely diagnosis and treatment of these cases.”
  • Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants – “The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.”
  • 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study – “At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.”
  • Dysautonomia in Long Haul Covid-19 Infection Impairs Activities of Daily Living and Mental Health: The Patient Perspective (P9-9.004) – “Dysautonomia in long haul COVID-19 patients has a devastating impact on daily living and mental health. It is imperative to recognize these effects and understand them from the patient perspective in order to develop compassionate, validating, and efficacious neurological, psychological, and social interventions for this population.”
  • Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children – “In conclusion, this study suggests that CoV infection of the CNS is common and multiple cytokine expression profiles are involved in the initial host’s immune response to the infection, which could induce immune impairment in the brain. Therefore, this study highlights the importance of the neurotropic ability of CoV and its involvement in the CNS, especially in children who need more attention to control this serious viral infection.”
  • COVID-19 Heart Lesions in Children: Clinical, Diagnostic and Immunological Changes – “Outcome of COVID-19 pandemic still requires investigation. Currently, analysis of long-term consequences of SARS-CoV-2’s impact on the body of children and adults is ongoing. Approximately 20–55% of patients in young and middle age with COVID-19 were hospitalized, and up to 18.5% of them had a severe course of the disease [132], wherein patients with cordial and vessels pathology, especially children, including children with congenital pathology, take special place [43,132]. Thus, extensive evidence suggests that the heart damage in COVID-19 is triggered by systemic hyperinflammation caused by viral infection.”
  • Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C – “In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.”
  • Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated With COVID-19 in the United States – “Unlike classic KD, coronary arteries may be spared in early MIS-C; however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms.”
  • Asymptomatic SARS-COV-2 infection in children’s tonsils – “At least for the initial variants, children were supposedly less exposed to the virus, predominantly presenting mild or asymptomatic infection. In the present study, we describe how SARS-CoV-2 can silently infect palatine tonsils and adenoids from asymptomatic children. We studied 48 children who underwent adenotonsillectomy between October 2020 and September 2021. None of them had experienced signs or symptoms of acute upper airway infection in the month prior to surgery.”
  • Comparison of Persistent Symptoms Following SARS-CoV-2 Infection by Antibody Status in Nonhospitalized Children and Adolescents – “Findings here show that nonhospitalized youth may also experience persistent COVID symptoms that last for at least several months. Risk factors include having severe symptoms with initial infection, not being vaccinated and having obesity. These findings have important implications to inform post-pandemic recovery as we learn more about those who are reporting chronic impacts of initial infections. In the case of the pediatric population, resources in both clinical and community/school settings can be developed to support this important subgroup of those infected with SARS-CoV-2, especially given the findings here that children who are experiencing persistent COVID symptoms may not have been hospitalized or experienced severe symptoms upon initial infection.”
  • Multisystem inflammatory syndrome in children (MIS-C) showing disseminated aspergillosis, cytomegalovirus reactivation and persistent SARS-COV-2: Case report with autopsy review – “Although MIS-C is generally considered to be a post-infectious hyperimmune reaction, persistence of SARS-COV-2 is a feature in all autopsies of MIS-C patients reported to date, suggesting a possible role in the pathogenesis, at least in fatal cases.”
  • Neurological involvement associated with COVID-19 infection in children – “In these MIS-C cases, 46% and 92% of children were reported positive COVID-19 reverse transcription polymerase chain reaction (RT-PCR) and serum antibody (IgG and/or IgM), respectively. This evidence suggests that while MIS-C occurred, most children might not have an active COVID-19 infection”
  • Neurological Manifestations of COVID-19 in Children: Time to Be More Vigilant – “Several neurological presentations have been documented in children and adults with COVID-19 infections. Parainfectious complications include autoimmune encephalitis, autoimmune epilepsy, central nervous system demyelination, Guillain-Barre syndrome, and acute necrotizing encephalopathy.4 With inflammation playing a major role, these conditions probably share a final common pathway; this also explains the benefit of immunotherapy in these conditions. Because these parainfectious neurological syndromes have an infectious trigger (herpes, dengue, etc.), COVID-19 testing may be appropriate in patients with these disorders.3”
  • Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations – “The presence of elevated sC5b9 even in children with minimal symptoms of COVID-19 disease is particularly striking. This finding implies that SARS-CoV-2 clinical syndromes are associated with robust complement activation, even when symptoms are minimal. We also found higher levels of complement activation in patients with more severe manifestations of COVID-19 than in those with minimal COVID-19, implying that some degree of complement activation may be necessary to combat the virus, but excessive complement activation may lead to an overly robust immune response. Notably, patients with MIS-C, who have generally cleared SARS-CoV-2 infection at the time of presentation, also had high levels of complement activation. We would therefore expect that the particle which incites complement activation is no longer present. This implies that prolonged and excessive activation in the host may be what leads to pathology.”
  • Investigation of the effect of COVID-19 on sperm count, motility, and morphology – “The sperm concentration of the COVID-19 negative group was significantly higher than those in the COVID-19 positive group. No statistically significant difference was detected between the groups for sperm motility and morphology. It was observed that men with COVID-19 had decreased sperm concentrations suggesting that COVID-19 may have a negative effect on male fertility.”
  • Tip of the iceberg: erectile dysfunction and COVID-19 – In summary, COVID-19 infection could affect male sexual function through endothelial damage in erectile tissue, testicular damage, and psychological alterations. Long-term and well-designed studies are needed to clarify the role of COVID-19 on ED.
  • Evaluation of science advice during the COVID-19 pandemic in Sweden – “The Swedish response to this pandemic was unique and characterized by a morally, ethically, and scientifically questionable laissez-faire approach, a consequence of structural problems in the society. There was more emphasis on the protection of the “Swedish image” than on saving and protecting lives or on an evidence-based approach. A strategy was never discussed among all relevant parties, and never implemented nor communicated to the public. In addition, there was an unwillingness and incapacity to admit any failures at all governmental levels; or to take any responsibility for the clearly detrimental outcomes for Swedish society. There were even attempts to revise history by changing, or deleting official documents, communication, and websites, and gaslighting the public. The Swedish authorities involved were not self-critical and did not engage in any official and open dialogue and misled the public by withholding correct information and even spreading misleading information. A small group of so-called experts with a narrow disciplinary focus received a disproportionate and unquestioned amount of power in the discussion, nationally and internationally. There was no intellectual/scientific discussion between stakeholders (including independent experts from different disciplines), and the international advice of WHO, ECDC and the scientific community was ignored and/or discredited.”
  • The effect of SARS-CoV-2 variant on respiratory features and mortality – “This retrospective study examined the frequency of respiratory features across four major variants since the outset of the COVID-19 pandemic. Additionally, patients were categorized based on vaccination status and mortality risk was assessed. This study found that there were significant reductions in the risks of mortality for patients who were vaccinated during the Delta period. Additionally, there are substantially fewer lower respiratory features associated with later variants, such as Omicron. Meanwhile, as the frequency of lower respiratory features has decreased, there is a substantial uptick in the frequency of upper respiratory features. This study also showed substantial favorable benefits in patients who are fully vaccinated compared with the unvaccinated or only partially vaccinated, the fully vaccinated population experienced significantly fewer features involving the upper and lower respiratory tract. This study indicates that because of numerous factors, including viral evolution, enhanced immunity, and likely improved treatment modalities, respiratory features involving the lower respiratory tract are reported with less frequency compared with earlier stages of the pandemic.”
  • Risk of death following COVID-19 vaccination or positive SARS-CoV-2 test in young people in England – “Whilst COVID-19 vaccination has been linked to an increased risk of myocarditis and other cardiac events in young people, we found no evidence of substantially increased mortality risk, either due to cardiac events or overall, from mRNA vaccines, which suggest that cases of myocarditis or myopericarditis due to mRNA COVID-19 vaccines are unlikely to be fatal. We do, however, find evidence of an increased risk of cardiac death after a first dose of a non mRNA vaccine among females. It should also be noted that non mRNA vaccines are no longer used in the UK vaccination programme28. This provides reassurance that mRNA vaccines pose minimal risk of increased mortality in the first twelve weeks post-vaccination in young individuals.”
  • Internal Tremors and Vibration Symptoms Among People with Post-Acute Sequelae of SARSCoV-2: A narrative review of patient reports – “These findings suggest that a group of people who report experiencing PASC exhibit a prolonged and debilitating symptom complex that prominently involves vibrations and tremors. While symptom experiences were heterogenous—in symptom timing, medical history, and initial infection, for instance—there were also common themes in how people described these symptoms and their effects. People also reported how testing and medical care have not yet identified possible mechanisms or successful treatment for these symptoms.”
  • Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis – “COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises.”
  • Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors – “The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality).”
  • Shorter telomere lengths in patients with severe COVID-19 disease – “Critically short telomeres impair the regenerative capacity of tissues and trigger loss of tissue homeostasis and disease.”
  • Accelerated biological aging in COVID-19 patients – “We also find the increasing acceleration of epigenetic aging and telomere attrition in the sequential blood samples from healthy individuals and infected patients developing non-severe and severe COVID-19”
  • 18F-FDG brain PET hypometabolism in patients with long COVID – “This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients’ symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.”
  • Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome – “We investigated thrombogenicity in a cohort of 21 patients with PCS with a median time following symptoms onset of 23 months using a dynamic microfluidic assay. Our data show a significant increase in platelet binding on both collagen and anti-VWF A3 in patients with PCS compared with that in controls, which positively correlated with VWF antigen (Ag) levels, the VWF(Ag):ADAMTS13 ratio (on anti-VWF A3), and inversely correlated with ADAMTS13 activity (on collagen). Thrombi forming on collagen presented different geometries in patients with PCS vs controls, with significantly increased thrombi area mainly attributable to thrombi length in the patient group. Thrombi length positively correlated with VWF(Ag):ADAMTS13 ratio and thrombin generation assay results, which were increased in 55.5% of patients. α(2)-Antiplasmin levels were normal in 89.5% of patients.”
  • Diabetes risk rises after COVID, massive study finds – “People who get COVID-19 have a greater risk of developing diabetes up to a year later, even after a mild SARS-CoV-2 infection, compared with those who never had the disease, a massive study1 of almost 200,000 people shows.”
  • High-dimensional characterization of post-acute sequelae of COVID-19 – “We show that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems.”
  • Assessment of Sequelae of COVID-19 Nearly 1 Year After Diagnosis – “At the nearly 1-year follow-up, COVID-19 survivors still had multi-system issues, including those in the respiratory functioning, radiography, quality of life, and anxiety and depression. Moreover, non-severe cases also showed some sequelae and the proportion of IgG negative cases in the non-severe patients was higher than that in severe cases. Therefore, conducting follow-ups and preventing the reinfection of SARS-CoV-2 in this group is necessary.”
  • Association of COVID-19 with short- and long-term risk of cardiovascular disease and mortality: a prospective cohort in UK Biobank – “COVID-19 infection, including long-COVID, is associated with increased short- and long-term risks of CVD and mortality. Ongoing monitoring of signs and symptoms of developing these cardiovascular complications post diagnosis and up till at least a year post recovery may benefit infected patients, especially those with severe disease.”
  • Cardiac Arrhythmias in Post-COVID Syndrome: Prevalence, Pathology, Diagnosis, and Treatment – “The spectrum of possible cardiac arrhythmias is broad, ranging from benign ventricular extrasystoles to atrial fibrillation and sudden cardiac death from ventricular arrhythmias. Thereby, the frequency of occurrence clearly correlates with cardiovascular comorbidities. However, cardiac arrhythmias can also affect previously healthy individuals or athletes. Together with other symptoms of the post-COVID condition, cardiac arrhythmias cause a further reduction in the quality of life.”
  • Cardiac impairment in Long Covid 1-year post SARS-CoV-2 infection – “Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.”
  • Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers” – “The results demonstrate a statistically significant depletion of CGM volume in 24 COVID-19 infected patients. Reduced CGM volume likely influences their long term neurological sequelae and may impair post COVID-19 patient’s quality of life and productivity.” – “This study contributes to understanding effects of COVID-19 infection on patient’s neurocognitive and neurological function, with potential for producing serious long term personal and economic consequences, and ongoing challenges to public health systems.”
  • Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome – “In conclusion, the present study shows that advanced age, the presence of comorbidities and elevated serum IL-6 levels are associated with the severity of COVID-19 and represent good markers to differentiate severe COVID-19 from mild clinical forms. Furthermore, high serum levels of IL-17 and IL-2, as well as low levels of IL-4 and IL-10, appear to constitute a long COVID-19 cytokine profile (molecular signature), and identification of these markers as a potential target may establish more adequate treatment and prevention strategies for specific groups.”
  • Elevated vascular transformation blood biomarkers in Long-COVID indicate angiogenesis as a key pathophysiological mechanism – “Long-COVID patients suffer prolonged, diffuse symptoms and poorer health. Vascular transformation blood biomarkers were significantly elevated in Long-COVID, with angiogenesis markers (ANG-1/P-SEL) providing classification accuracy of 96%. Vascular transformation blood biomarkers hold potential for diagnostics, and modulators of angiogenesis may have therapeutic efficacy.”
  • Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches – “To date, the pathogenesis of COVID-19 mostly remains unclear. The knowledge of the mechanisms of endothelial activation and dysfunction can be used to understand the pathogenesis of COVID-19. Uncontrolled inflammation is the common feature of severe COVID-19. Meanwhile, more attention should be paid to non-traditional forms of inflammation, as therapeutic tools will likely be extremely different for these pathways. For instance, endothelial inflammation has been rarely reported in the pathogenesis of many infectious diseases, but may be much more significant than we know.”
  • Endothelial dysfunction in acute and long standing COVID−19: A prospective cohort study – “COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.”
  • Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis – “A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.”
  • Frequency and phenotype of headache in covid-19: a study of 2194 patients – “In this study, headache occurred in one of every four confirmed COVID-19 cases. Headache is a common symptom in systemic viral infections. In addition, in our sample, we estimated that headache was the first symptom of COVID-19 in 6% of patients, with an early onset in most of the cases. The phenotype of headache attributed to acute SARS-CoV-2 infection shows a bilateral headache predominantly affecting the forehead, with pressing quality, with severe intensity, and frequently accompanied by typical migraine symptoms, in line with previously published studies.”
  • Headache as a Symptom of COVID-19: Narrative Review of 1-Year Research – “Headache is a common symptom of COVID-19, resulting from mechanisms involving individual factors and SARS-CoV-2 characteristics such as its neuro-invasive potential and ability to produce inflammation. Although several questions still need to be answered, studies on COVID-19 have helped to regain interest in 9.2.2 headache attributed to systemic viral infection. However, COVID-19 headache research represents a unique opportunity to better understand COVID-19 in general and advance in the knowledge of both secondary and primary headaches.”
  • Autoimmunity is a hallmark of post-COVID syndrome – “Although several reports, including ours, have shown the relevance of autoantibodies on mortality in acute COVID-19, little is known about the factors associated with their emergence. Herein we confirmed that most autoantibodies are correlated with anti-SARS-CoV-2 antibodies, as shown by Liu et al.. In patients with PCS, a proinflammatory state is evident, suggesting that bystander activation contributes to the emergence of autoimmunity. In addition, despite the increased risk of death in patients with acute COVID-19 influenced by age, sex, and BMI, we demonstrate that these factors do not influence the autoimmune response in PCS. It should be further characterized whether these features are implicated in new-onset overt autoimmunity.”
  • Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease – “The progressive resolution of radiological abnormalities in the majority of post-COVID-19 patients has been described (Han et al., 2021), and in our study even the three patients with persistent respiratory abnormalities showed improved CT and reduced airway immune cell infiltration. This fits with the hypothesis that SARS-CoV-2 infection can result in organizing pneumonia, with subsequent changes reflecting ongoing epithelial damage and healing parenchyma rather than established fibrosis (Kory and Kanne, 2020). Moreover, the involvement of the immune response in different aspects of ongoing respiratory disease post-COVID-19 suggests that this recovery could be accelerated using immunomodulatory treatments.”
  • Common skin signs of COVID-19 in adults: An update – “Cutaneous findings can be clues to diagnosis and infection severity in viral illnesses, including COVID-19. The authors provide an update on the diagnostic and prognostic value of the 5 most common cutaneous abnormalities associated with COVID-19 in adult patients: morbilliform rash, urticaria, vesicles, pseudo-chilblains, and vaso-occlusive lesions.”
  • Dermatologic manifestations and complications of COVID-19 – “It is important to be aware of the dermatologic manifestations and complications of COVID-19. Knowledge of the components is important to help identify potential COVID-19 patients and properly treat complications.”
  • COVID-19 – A vascular disease – “Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to multi-system dysfunction with emerging evidence suggesting that SARS-CoV-2-mediated endothelial injury is an important effector of the virus. Potential therapies that address vascular system dysfunction and its sequelae may have an important role in treating SARS-CoV-2 infection and its long-lasting effects.”
  • Risk of autoimmune diseases in patients with COVID-19: a retrospective cohort study – “In conclusion, our preliminary data suggest that COVID-19 is associated with a significantly different risk of various autoimmune diseases. It is crucial for physicians to have relevant notions and to recognize these autoimmune manifestations in order to respond appropriately in the ongoing pandemic and long-term post-pandemic phase. The impact of vaccination on the development of autoimmune diseases should also be studied in the future.”
  • Limited recovery from post-acute sequelae of SARS-CoV-2 at 8 months in a prospective cohort – “In summary, a considerable proportion of patients experience persistent symptoms after SARS-CoV-2 infection and a fifth of patients met our definition for Long COVID at 8 months. Persistent symptoms impact HRQoL and there appears to be little change between 4 and 8 months. A significant proportion of patients experience abnormal functional recovery at 8 months. The long-term significance of these findings is unknown.”
  • Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study – “There is increasing evidence regarding the link between endothelial dysfunction and persistent long COVID-19 symptoms. Risk stratification of long COVID-19 patients may be important to their management. The evaluation of endothelium quality by FTM to non-invasively detect endothelial dysfunction needs to be studied further to improve the management of long COVID-19 patients.”
  • Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study – “[18F]FDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased [18F]FDG uptake in several “target” and “non-target” tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body [18F]FDG PET in disclosing the pathophysiology of long COVID.”
  • Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection – “This study demonstrates the presence of long-term neuropsychological sequelae following SARS-CoV-2 infection, regardless of the severity of the respiratory disease in the acute phase. Some of the cognitive deficits could be explained by psychiatric variables, emphasizing the importance of considering a broad range of psychiatric symptoms. However, not all neuropsychological sequelae could be explained by these variables. The presence of correlations between olfaction, emotion recognition, and episodic memory, which share common functional and anatomical substrates, reinforces the hypothesis that the virus targets the CNS (notably the limbic system). Finally, the data support the notion of different clinical phenotypes, paving the way for clinical guidelines and recommendations for the management of long-term neurological impairment following SARS-CoV-2 infection.”
  • Long COVID Syndrome and Cardiovascular Manifestations: A Systematic Review and Meta-Analysis – “With ever-increasing COVID-19 cases, evidence of the association between COVID-19 pathology and cardiovascular manifestations is paramount. Considering this, our meta-analysis delineates that long COVID syndrome is associated with an increased burden of cardiovascular manifestations. Further this study emphasizes to conduct large-scale, multicenter researches to address the heterogeneity of post-COVID cardiovascular sequelae in different age groups and genders, as well as a pinpointing of the exact pathomechanism that can provide valuable evidence and aid in the identification of novel therapeutic targets to prevent the development of cardiovascular disease in COVID-19 patients.”
  • Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus – “Long COVID is emerging as a major public health issue. Our current understanding of pathophysiological mechanisms and treatment options remains limited; however, there is great optimism as several national and international research initiatives promise to disentangle the complexities of this disease. The high burden of cardiopulmonary symptoms along with other organ manifestations underscores the need for multispecialty input,274,275 a model that is likely to also profit other chronic diseases. Proactive screening and investigation, where appropriate, could allay fears and anxiety among patients. Considerable efforts to find the right balance between cost-effective investigations and benefit to patients are needed to ensure sustainable service provision in these challenging economic times. Finally, the vast inequalities43,276 in healthcare provision exposed by COVID-19 will continue to be magnified by long COVID, a problem that calls for global humanitarian efforts to promote and fund equitable access to healthcare, social and welfare support, and vaccines across the world.”
  • Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration – “In long-haul COVID-19 patients with orthostatic intolerance complaints, the hemodynamic abnormalities change over time after the onset of symptoms. Patients studied early after the onset of the disease mainly exhibited POTS during the tilt test, but patients studied later in the time course of the disease showed OH or had a normal heart rate and blood pressure response during the tilt. This suggests that the hemodynamic abnormalities in individual patients may change over time. If confirmed in serial follow-up tilt test studies in these patients, patient management may need to be changed over time. In addition, the objective abnormalities of the orthostatic intolerance, cerebral blood flow measurements, show a reduction in the degree of abnormalities. However, the improvement is modest, and patients still have orthostatic intolerance. Whether this pattern of further improvement is sustained, and results in reduction of orthostatic intolerance complaints, needs to be studied in the future.”
  • Long-Term Brain Disorders in Post Covid-19 Neurological Syndrome (PCNS) Patient – “The alterations of the cerebral parenchyma found and documented in our patient, with the recent study of MRI, are findings completely similar to those that are recognized in about 40–45% of patients suffering from migraine to system immune disorders, as well as inflammation of the connective tissue. These conditions, which have as their common denominator a vascular microsuffering caused by vasoconstriction, generate microthrombosis with consequent microvascular alterations, leading to neuronal degeneration and subsequent gliosis. These areas evolve in minute focal areas of altered signal intensity recognizable in neuroimaging with Magnetic Resonance as signal hyperintensity in long TR images, especially in FLAIR, expression of gliosis reactive to neuronal damage. These additional aspects of COVID-19 infection can further evidence the harmful action of COVID-19 in the central nervous system.”
  • Long-term cardiac pathology in individuals with mild initial COVID-19 illness – “In summary, in the present cohort of individuals with mild initial COVID-19 illness, cardiac symptoms were related to subclinical inflammatory cardiac involvement, which may, at least in part, explain the pathophysiological background of persistent cardiac symptoms. Notably, profound myocardial injury or structural heart disease is not prerequisite for the presence of symptoms defying the classical definitions of viral myocarditis. Subclinical cardiovascular inflammation is increasingly recognized as a risk factor in chronic autoimmune systemic conditions, necessitating further research to establish long-term outcome in the context of post-COVID.”
  • Long-term cardiovascular outcomes of COVID-19 – “In summary, using a national cohort of people with COVID-19, we show that risk and 12-month burden of incident cardiovascular disease are substantial and span several cardiovascular disease categories (ischemic and non-ischemic heart disease, dysrhythmias and others). The risks and burdens of cardiovascular disease were evident even among those whose acute COVID-19 did not necessitate hospitalization. Care pathways of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease.”
  • Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study – “COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.”
  • Long-term neurologic outcomes of COVID-19 – “In conclusion, our report provides a comprehensive analysis of neurologic outcomes at 12 months. We show increased risk of an array of neurologic disorders spanning several neurologic disease categories including stroke (both ischemic and hemorrhagic), cognition and memory disorders, peripheral nervous system disorders, episodic disorders, extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, and other disorders including Guillain–Barré syndrome, and encephalitis or encephalopathy. The risks were evident in all examined subgroups and were evident even in people who were not hospitalized during the acute phase of the disease. Altogether, the findings call for attention to the long-term neurologic consequences of SARS-CoV-2 infection. Both healthcare system planning, and more broadly, public policy making, should take into account the long-term neurologic (and other) consequences of infection with SARS-CoV-2.”
  • Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis – “Findings: In a meta-analysis of 18 studies encompassing 10,530 patients (hospitalised and non-hospitalised), overall prevalence for neurological symptoms three months after COVID-19 onset was: fatigue (37%), brain fog (32%), memory issues (28%), attention disorder (22%), myalgia (17%), anosmia (12%), dysgeusia (10%), and headache (15%). The prevalence of neuropsychiatric symptoms was sleep disturbances (31%), anxiety (23%), and depression (17%).”
  • Molecular Imaging Findings on Acute and Long-Term Effects of COVID-19 on the Brain: A Systematic Review – “Molecular imaging techniques such as PET and SPECT have been used to shed light on how coronavirus disease 2019 (COVID-19) affects the human brain. We provide a systematic review that summarizes the current literature according to 5 predominant topics”
  • Neurobiology of COVID-19 – “Patients with COVID-19 can present with a wide range of neurological manifestations that can be due to the injury to central and peripheral nervous system via a cytokine storm, blood clots, direct damage by SARS-Cov2, and/or molecular mimicry. This review, while presenting what is currently known about this virus and the related clinical neurology, represents only the base of what will eventually become a separate active field of research.”
  • Neuropsychologic Profiles and Cerebral Glucose Metabolism in Neurocognitive Long COVID Syndrome – “The present study reports a prospective assessment of 31 patients self-presenting to our outpatient clinic because of neurocognitive symptoms more than 6 mo after a SARS-CoV-2 infection with long COVID syndrome. Although 39% of patients report a relevant disability at work and everyday life due to these symptoms, an exhaustive assessment including a detailed cognitive battery showed only mild impairment in individual patients, and cerebral 18F-FDG PET failed to reveal a distinct pathologic signature.”
  • Neurovascular injury with complement activation and inflammation in COVID-19 – “Injury to the microvasculature by immune complexes with complement activation is the key central event that results in breakdown of the blood–brain barrier, microthromboses, perivascular inflammation and neuronal injury. We postulate that these events are central to the development of the neurological manifestations seen in acute COVID-19 and possibly in long-COVID. Importantly, these studies suggest that therapeutic approaches targeted against the development of immune complexes should be considered.”
  • Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect? – “Orthostatic intolerance observed in patients following infection with the COVID-19 virus and the development of Long COVID syndrome is induced by a pathologic response of the vasa vasorum of the capacitance vessels, leading to impaired vessel function. Dysfunction of the vasa vasorum includes endothelial dysfunction, microthrombus formation and disturbance of the rheological parameters of the blood cells. If the assumption holds true that the primary etiology of OI is a consequence of this microcirculatory dysfunction in contrast to the autonomic dysfunction, this would lead, in turn, to more specific treatment options and a potentially improved therapy outcome for the patient.”
  • Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients – “The complaints of long-haul COVID patients, the severity of the complaints, the orthostatic intolerance complaints in daily life, the orthostatic intolerance complaints during the tilt table test and the objective abnormalities of the orthostatic intolerance (the abnormal cerebral blood flow decrease and the abnormal cardiac index decrease) are very similar to those of the ME/CFS patients. This makes it very likely that long-haul COVID is the same in terms of disease as ME/CFS, where the trigger for its onset has been an infection with the SARS-CoV-2 virus. The treatment of long-haul COVID should therefore be similar to that of ME/CFS.”
  • Persistent capillary rarefication in long COVID syndrome – “Our current data strongly suggest that COVID-19 leaves a persistent capillary rarefication even 18 months after infection. Whether, to what extent, and when the observed damage might be reversible remains unclear.”
  • Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin – “Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.”
  • Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 “long haulers” – “Non-hospitalized Covid-19 “long haulers” experience prominent and persistent “brain fog” and fatigue that affect their cognition and quality of life.”
  • Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study – “Neurocognitive long-COVID symptoms can persist ≥1 year after COVID-19 symptom onset and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titer elevations. This may indicate autoimmunity as a cofactor in etiology of long COVID.”
  • Plasma Biomarkers of Neuropathogenesis in Hospitalized Patients With COVID-19 and Those With Postacute Sequelae of SARS-CoV-2 Infection – “We enrolled a total of 64 study participants, including 9 hospitalized patients with COVID-19 encephalopathy (CE), 9 posthospitalization neuro-PASC (PNP) patients, 38 nonhospitalized neuro-PASC (NNP) patients, and 8 HC subjects. Patients with CE were older, had higher pNfL and pGFAP concentrations, and more frequent pN Ag detection than all neuro-PASC groups. PNP and NNP patients exhibited similar PASC symptoms, decreased quality-of-life measures, and cognitive dysfunction, and 1 of the 38 (2.6%) NNP patients had pN Ag detectable 3 weeks postsymptoms onset. Patients with neuro-PASC presenting with anxiety/depression had higher neuroglial scores, which were correlated with increased anxiety on quality-of-life measures.”
  • Post‐acute COVID‐19 syndrome (PCS) and health‐related quality of life (HRQoL)—A systematic review and meta‐analysis – “Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.”
  • Postural tachycardia syndrome and long COVID: an update – “There is a growing concern that, in addition to long COVID, we may now also be facing an epidemic of PoTS.12 There has never been a greater need to invest in NHS services to serve the unmet needs of this population. Perhaps we can learn from the rapid development of multidisciplinary teams in long COVID clinics and utilise these new skills and resources in the long term to also provide long overdue equitable access to therapeutic pathways for all patients with PoTS.”
  • Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) – “Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest that our platelet and clotting grading system provides a simple and cost-effective diagnostic method for early detection of Long COVID/PASC as a major determinant of effective treatment, including those focusing on reducing clot burden and platelet hyperactivation.”
  • Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study – “Our findings suggest that COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke. This indicates that acute myocardial infarction and ischaemic stroke represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19.”
  • SARS-CoV-2 infection and persistence in the human body and brain at autopsy – “Our study has several important limitations. First, our cohort largely represents older unvaccinated individuals with pre-existing medical conditions who died from severe COVID-19, limiting our ability to extrapolate findings to younger, healthier or vaccinated individuals. Second, our cases occurred during the first year of the pandemic, before widespread circulation of variants of concern, and thus findings might not be generalizable to current and future SARS-CoV-2 variants. Finally, although it is tempting to attribute clinical findings observed in post-acute sequelae of SARS-CoV-2 to viral persistence, our study was not designed to address this question. Despite these limitations, our findings fundamentally improve the understanding of SARS-CoV-2 cellular distribution and persistence in the human body and brain and provide a strong rationale for pursuing future similar studies to define mechanisms of SARS-CoV-2 persistence and contribution to post-acute sequelae of SARS-CoV-2.”
  • Symptom Persistence Despite Improvement in Cardiopulmonary Health – Insights from longitudinal CMR, CPET and lung function testing post-COVID-19 – “In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health.”
  • The neurobiology of long COVID – “Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 and represent a major component of the post-acute COVID-19 syndrome, also known as long COVID. Here, we review what is understood about the pathobiology of post-acute COVID-19 impact on the CNS and discuss possible neurobiological underpinnings of the cognitive symptoms affecting COVID-19 survivors. We propose the chief mechanisms that may contribute to this emerging neurological health crisis.”
  • Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients – “In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.”
  • Understanding COVID-19 in children: immune determinants and post-infection conditions – “A remarkable feature of the COVID-19 pandemic is the wide range of outcomes following SARS-CoV-2 infection and the different outcomes in children and adults. While a large proportion of the population has an asymptomatic and mild illness, others suffer severe or fatal disease and post-infectious complications including post-COVID-19 sequalae and multisystem inflammatory syndromes. Answers to the key questions posed by the widely differing responses to SARS-CoV-2 infection need to be searched in the uniqueness of children’s immune system. Future studies based on the comparison of the host response to SARS-CoV-2 in children and adults of increasing age through system biology approach could provide an important opportunity to understand how the “successful immune response” differs from the “unsuccessful or disease enhancing response” seen in the elderly as well as in pediatric post-infection conditions.”
  • Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study – “In conclusion, in patients with lethal COVID-19, organs are mainly affected by an inflammatory response. Extensive inflammatory changes in the brain, especially in the olfactory bulbs and medulla oblongata, might cause anosmia and dampening of the respiratory system. Virally infected cells are sporadically present up to 6 weeks after the start of symptoms, and neutrophils and NETs are present for weeks after onset of symptoms. The formation of NET–platelet aggregates might have a role in COVID-19-associated coagulopathy. The disproportionate presence of aggregated neutrophils and NETs in comparison with the sporadic presence of virus suggests an autonomous maladaptive immune response.”
  • Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 – “In conclusion, CoVs are zoonotic pathogens and infect humans via inter-species transmission. SARS-CoV and MERS-CoV are two notorious examples of CoVs crossing the species barrier and resulting in human infection.”
  • SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation – “Our results described above demonstrate that NSP12, the central component of coronaviral replication and transcription machinery of SARS-CoV-2, is a multi-functional protein that is not only directly involved in the replication of viral RNA as known previously, but can also promote the activation of RIPK1 which may in turn promote inflammation and the expression of host viral receptor ACE2 and additional factors such as EGFR which can enhance viral survival and propagation. The role of RIPK1 in driving inflammatory response in human diseases has been well established.14 We conclude that SARS-CoV-2 is able to hijack the host inflammatory response mediated by RIPK1 to its own advantage to enhance viral survival and replication in host cells. Since inhibition of RIPK1 can reduce the replication of both 323P and 323L SARS-CoV-2 in human lung organoids, our results suggest that RIPK1 kinase inhibitors may provide an effective therapy for severe COVID-19 as well as reducing the spread of SARS-CoV-2 variants.”
  • Amyloidogenesis of SARS-CoV-2 Spike Protein – “In conclusion, we herein proposed a simple molecular mechanism for how SARS-CoV-2 S-protein endoproteolyzed by NE can form amyloidogenic S-peptides, such as segment 194–203, and lead to exposure of multiple amyloidogenic segments in proteolytically nicked S-protein.”
  • Analysis of cardiopulmonary findings in COVID-19 fatalities: High incidence of pulmonary artery thrombi and acute suppurative bronchopneumonia – “Our study shows that secondary acute bronchopneumonia can be found in a substantial number of patients with COVID-19 and may be the major cause of death. Furthermore, a high incidence of thrombotic/thromboembolic events is seen in COVID-19 decedents. We classified 5 types of thrombotic/thromboembolic vascular occlusions in lung specimens from COVID-19 decedents: microthrombi; non-organized thrombi in mid-sized pulmonary arteries with incomplete occlusion of the vessel lumen, likely representing pulmonary thromboemboli; partially organized thrombi in mid-sized pulmonary arteries completely occluding the vessel lumen; bone marrow emboli, likely shock-related; and septic pulmonary thromboemboli. Our findings support the concept that COVID-19 is a systemic disease, with major involvement of the lungs, that increases the risk of thrombotic/thromboembolic events and cardiac complications, contributing to fatal outcomes in SARS-CoV-2 infected individuals.”
  • Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis – “Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.”
  • Assessing Brain Capillaries in Coronavirus Disease 2019 – “Multiple lines of evidence indicate endothelial dysfunction may contribute to severe COVID-19 illness. Lung examination demonstrates megakaryocytes,5 and the cells have now been reported in other organs.6 One possibility is that altered endothelial or other signaling is recruiting megakaryocytes into the circulation and somehow permitting them to pass through the lungs. Although this initial study does not investigate mechanism, it is notable that we found megakaryocytes in cortical capillaries in 33% of cases examined. Because the standard brain autopsy sections taken sampled at random only a minute portion of the cortical volume, finding these cells suggests the total burden could be considerable. By occluding flow through individual capillaries, these large cells could cause ischemic alteration in a distinct pattern, potentially resulting in an atypical form of neurologic impairment.”
  • Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases – “Overt fulminant myocarditis has been reported in isolated patients with SARS-CoV-2 infection. However, the current data indicate that the presence of SARS-CoV-2 in cardiac tissue does not necessarily cause an inflammatory reaction consistent with clinical myocarditis. The long-term consequences of this cardiac infection requires further investigation.”
  • Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales – “Substantial increases in the relative incidence of arterial thromboses and VTEs 1 to 2 weeks after diagnosis of COVID-19 decline with time since diagnosis, although doubling of the incidence of VTEs persisted for up to 49 weeks after diagnosis. These results support continued policies to prevent severe COVID-19 with effective COVID-19 vaccines, early review and management of vascular risks in patients with COVID-19, and use of secondary preventive agents in patients at high risk of vascular diseases. New simple treatment strategies to reduce infection-associated VTE and arterial thromboses are needed.”
  • Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome – “The post-acute sequelae of COVID-19 present major problems for many patients, their physicians and the health-care system. They are unrelated to the severity of the initial infection, are often highly symptomatic and can occur after vaccination. Many sequelae involve cardiovascular autonomic dysfunction, with postural orthostatic tachycardia syndrome in 30% of individuals. Prognosis is unknown, and treatment is still unsatisfactory.”
  • Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases – “Acute tissue injuries and microglial activation were the most common abnormalities in COVID-19 brains. Focal evidence of encephalitis-like changes was noted despite the lack of detectable virus. The majority of older subjects showed age-related brain pathologies even in the absence of known neurologic disease. Findings of this study suggest that acute brain injury superimposed on common pre-existing brain disease may put older subjects at higher risk of post-COVID neurologic sequelae.”
  • Cardiac inflammation in COVID-19: Lessons from heart failure – “While the underlying disease mechanisms are not completely understood, preliminary data suggest that both local and systemic inflammation play a critical role in evoking and potentiating existing or new cardiac functional abnormalities. While myocardial infiltration of immune cells and cardiomyocyte necrosis are short term complications of COVID-19, the long-term effects remain to be seen. These could easily include cardiac hypertrophy, cardiac fibrosis and decreased cardiac output, leading to potentiated cardiac dysfunction. Therefore, patients who recover from severe COVID-19 could be at increased risk of developing HF, and there is a reason and need to continue monitoring these patients for cardiac health issues in the long run. Given the worldwide prevalence of this disease and the strong association with CVDs, additional studies are needed to gain a better understanding of the molecular mechanisms that drive COVID-19 related cardiac remodeling and to develop effective screening and therapeutic interventions against COVID-19-associated HF in the future.”
  • Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis – “In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia.”
  • Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging – “Cardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.”
  • Cardiac involvement in the long-term implications of COVID-19 – “More than 18 months have passed since the WHO announced the pandemic nature of COVID-19. In that time, we have learned that cardiac injury is common during acute COVID-19 and that it is associated with worse short-term outcomes, that the aetiology of cardiac injury is multifactorial and that imaging abnormalities are common irrespective of the severity of the acute illness. However, much remains to be learned about the natural history and clinical importance of these findings in survivors of acute COVID-19, especially those with post-acute COVID-19 syndrome.”
  • Cardiac pathology in COVID-19: a single center autopsy experience – “Cardiovascular comorbidities were prevalent, and pathologic changes associated with hypertensive and atherosclerotic cardiovascular disease were the most common findings. Despite markedly elevated inflammatory markers and cardiac enzymes, few patients exhibited inflammatory infiltrates or necrosis within cardiac myocytes. A unifying pathophysiologic mechanism behind myocardial injury in COVID-19 remains elusive, and additional autopsy studies are needed.”
  • Cardiac SARS-CoV-2 infection is associated with pro-inflammatory transcriptomic alterations within the heart – “This study reveals that cardiac infection induced transcriptomic alterations mainly linked to immune response and destruction of cardiomyocytes. While endothelial cells are primarily targeted by the virus, we suggest cardiomyocyte destruction by paracrine effects. Increased pro-inflammatory gene expression was detected in SARS-CoV-2-infected cardiac tissue but no increased SARS-CoV-2 associated immune cell infiltration was observed.”
  • Rapid flow cytometric analysis of fibrin amyloid microclots in Long COVID – “Long COVID has become a major global health and economic burden. A major contributor to the exponential rise in numbers is arguably the absence of a clear suite of diagnostic tools to identify patients that may benefit from specific treatments. The causes of the persistent symptoms of Long COVID include immune dysregulation, autoantibodies, immune dysregulation, reactivation of latent viruses, viral persistence, organ damage, and hypercoagulability.”
  • Cardiovascular complications of severe acute respiratory syndrome – “In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn”
  • A systematic review and meta-analysis of incidence, prognosis, and laboratory indicators of venous thromboembolism in hospitalized patients with coronavirus disease 2019 – “The occurrence of VTE, DVT, and pulmonary embolism has been substantial among hospitalized patients with COVID-19, especially among those with severe COVID-19. Patients with severe COVID-19 and VTE had significantly greater mortality compared with similar patients without VTE. An increased D-dimer level might be an indicator of the occurrence of VTE in patients with COVID-19.”
  • Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia – “The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.”
  • Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe – “Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the Covid-19 pandemic. The majority of children have significantly raised levels of N-terminal pro B-type natriuretic peptide, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. In comparison with adults with COVID-19, mortality in children with multisystem inflammatory syndrome associated with COVID-19 is uncommon despite multisystem involvement, very elevated inflammatory markers, and the need for intensive care support.”
  • Acute Ischemic Stroke During the Convalescent Phase of Asymptomatic COVID-2019 Infection in Men – “This case series suggests that the risk for AIS is higher in adults 50 years or younger during the convalescent period of a COVID-19 infection without respiratory symptoms. Acute ischemic stroke could be part of the next wave of complications of COVID-19, and stroke units should be on alert and use serological testing, especially in younger patients or in the absence of traditional risk factors.”
  • Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis – “Acute myocardial injury is common in patients with COVID-19 and is associated with adverse prognosis.”
  • Acute Pulmonary Embolism and COVID-19 – “In our study, we found a significant difference in C-reactive protein level and D-dimer value between PE-positive and PE-negative groups, which may suggest that patients with a positive COVID-19 test with higher levels of inflammation and D-dimer values are more susceptible to developing PE. In addition, we found that nonintubated patients who developed PE required more oxygen prior to pulmonary CT angiography evaluation than did their non-PE counterparts. We did not find a significant difference in ICU admissions, requirement for intubation, or duration of intubation between patients who developed PE and those who did not. In fact, 72% (52 of 72) of PEs were diagnosed in patients who did not require ICU-level care. This is in sharp contrast to a recently published study (5) highlighting PE to be associated with ICU admission and mechanical ventilation. Our results suggest that even patients who do not have severe enough illness to qualify for ICU care can develop acute PE.”
  • An interesting finding: What is the relation between aortic enlargement and COVID-19? – “This study shows that the mean aortic diameter of COVID-19 patients is larger than non–COVID-19 patients with similar comorbidities referred to a pandemic hospital. COVID-19, age, and coronary artery disease are the most influential factors that affect the aortic diameter, and the COVID-19 was the leading factor.”
  • Impact of COVID-19 on liver – “The main cause of mortality in COVID-19 infection respiratory failure caused by infection of the upper and lower respiratory tract. The liver is one of the most affected organs other than the respiratory system. Evaluation of patients suspected of having COVID-19 infection, should pay careful attention to symptoms and signs of digestive manifestations in addition to the main pulmonary presentations. If liver dysfunction is ruled in, then liver enzyme levels, monocyte count, and prothrombin time should be checked. Abdominal ultrasound and CT of the chest and abdomen should be depending on different case conditions. The concomitant liver disease, (e.g., viral hepatitis, fatty liver, liver cirrhosis, or hepatoma), needs to be confirmed. As for management, medications known to insult the liver must be used carefully and LFTs should be monitored at regular intervals.”
  •  Assessing Brain Capillaries in Coronavirus Disease 2019 – “Multiple lines of evidence indicate endothelial dysfunction may contribute to severe COVID-19 illness. Lung examination demonstrates megakaryocytes, and the cells have now been reported in other organs. One possibility is that altered endothelial or other signaling is recruiting megakaryocytes into the circulation and somehow permitting them to pass through the lungs. Although this initial study does not investigate mechanism, it is notable that we found megakaryocytes in cortical capillaries in 33% of cases examined. Because the standard brain autopsy sections taken sampled at random only a minute portion of the cortical volume, finding these cells suggests the total burden could be considerable. By occluding flow through individual capillaries, these large cells could cause ischemic alteration in a distinct pattern, potentially resulting in an atypical form of neurologic impairment.”
  • Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19 – “clinically significant, these have the potential to become a public health problem. Lung perfusion imaging offers a simple triage tool, within the broader panel of investigations, to improve understanding of the natural history of thromboembolic phenomena in COVID-19 and contribute, alongside tests of exercise physiology and function, towards separating haemodynamic sequelae from deconditioning and dysfunctional breathing-related functional limitations.”
  • Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank – “Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.”
  • Cardiovascular Injury Due to SARS-CoV-2 – “Data are emerging that highlight the extent of cardiovascular involvement in COVID-19 patients, including evidence that SARS-CoV-2 causes myocarditis and increases cardiac risk. The incidence of cardiac injury is much greater in patients with severe disease presentation and those in intensive care.”
  • Cardiovascular Magnetic Resonance for Patients With COVID-19 – “Public health guidelines and vaccine development are expected to result in fewer incident cases of COVID-19. However, the clinical spectrum of recovery after acute COVID-19 with regard to cardiovascular disease is unresolved. Reports to date have raised the potential of sustained cardiac injury in patients who have recovered from COVID-19. CMR is a key noninvasive clinical and research tool because of its comprehensive evaluation of myocardial function, structure, and tissue composition.”
  • Cardiovascular manifestations and treatment considerations in COVID-19 – “COVID-19 is similar to SARS and MERS with regard to host vulnerability, specifically in those with substantial cardiovascular comorbidities. Greater transmissibility of COVID-19 has resulted in a worldwide pandemic, a record number of infected individuals and an excess mortality that far exceeded previous coronavirus-related outbreaks. Myocardial injury is common in COVID-19 and portends a worse prognosis. Differentiating between the various causes of myocardial injury is crucial to determining the treatment course. The cardiovascular considerations for treatment, including anticoagulation, ACEI or ARB use, anti-arrhythmic management, immunosuppression/modulation, and haemodynamic support, are important and continue to evolve.”
  • Chronic biopsy proven post-COVID myoendocarditis with SARS-Cov-2 persistence and high level of antiheart antibodies – “COVID-19 can lead to long-term severe post-COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post-COVID myoendocarditis.”
  • Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study – “In summary, our study highlights an urgent need for health-care services to support this large and rapidly increasing patient population in whom a substantial burden of symptoms exists, including reduced exercise capacity and large decrements in health-related quality of life 1 year after hospital discharge. Without effective treatments, long COVID could become a highly prevalent new long-term condition. Our study also provides a rationale for investigating treatment strategies for long COVID with a precision-medicine approach to target treatments to the relevant phenotype to restore health-related quality of life.”
  • Clinical presentation and management strategies of cardiovascular autonomic dysfunction following a COVID-19 infection – A systematic review – “There is evidence from the scientific literature about different types of cardiovascular autonomic dysfunction developing during and after COVID-19. More data about the prevalence of autonomic disorders associated with a SARS-CoV-2 infection are needed to quantify its impact on human health.”
  • Coronavirus Disease 2019–Associated Coagulopathy – “It is now clear that the outcome of COVID-19 depends on the severity of both pulmonary and circulatory involvement, thus encompassing alveolar damage and local (ie, lung) and systemic thrombosis. The current evidence supports the development of a thrombotic process in COVID-19, which can be defined as immuno-thrombo-inflammation. This is likely the consequence of derangement of multiple biological pathways, including endothelial injury, macrophage/monocyte and neutrophil activation, exacerbated by prolonged immobilization, and development of antiphospholipid antibodies.”
  • COVID-19 and Hypercoagulability: A Review – “The presence of a hypercoagulable state and evidence for the development of thrombotic complications in patients with COVID-19 is expanding. Although mechanisms regarding development of these complications are not entirely clear, it is unnervingly apparent that this thrombotic state is in part responsible for the high mortality of the disease. Several mechanisms involving vascular endothelial injury, proinflammatory cytokines, complement, serum procoagulants, and shutdown of anti-coagulation pathways have been discussed, all of which may be vital in developing more specific treatments as this disease evolves. However, data is limited and further investigation is needed.”
  • COVID-19 and stroke: A review – “COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Severe COVID-19 infection renders patients bedridden, and in certain cases requiring instrumental support. Collectively, it predisposes patients to cerebrovascular events. Due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised from initial encounter, treatment, to rehabilitation. The understanding of the underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.”
  • The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings – “The widespread effects of COVID-19 include neurological disorders but there have been, to date, no detailed clinical reports of their nature (Guan et al., 2020; Helms et al., 2020; Mao et al., 2020; Varatharaj et al., 2020). Our London and regional cohort describes a range of neurological syndromes including encephalopathies, para- and post-infectious CNS syndromes including encephalitis, ADEM with haemorrhage and necrotic change, transverse myelitis, ischaemic stroke and GBS.”
  • Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies – “Several months on from the declaration of the COVID-19 pandemic, new symptom patterns and syndromes such as ‘long COVID’ are emerging. These patterns may be explained by autonomic instability and may result from deconditioning, hypovolaemia or immune- or virus-mediated neuropathy. We anticipate that these syndromes will represent a large proportion of primary and secondary care consultations in coming months. Clinicians must be aware that prompt and correct diagnosis with careful management are essential for recovery.”
  • Pathophysiology of SARS-CoV-2: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience – “We report a comprehensive autopsy series of 67 COVID-19 positive patients revealing that this disease, so far conceptualized as a primarily respiratory viral illness, also causes endothelial dysfunction, a hypercoagulable state, and an imbalance of both the innate and adaptive immune responses. Novel findings reported here include an endothelial phenotype of ACE2 in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy, addressing the prominent coagulopathy and neuropsychiatric symptoms. Another original observation is that of macrophage activation syndrome, with hemophagocytosis and a hemophagocytic lymphohistiocytosis-like disorder, underlying the microangiopathy and excessive cytokine release. We discuss the involvement of critical regulatory pathways.”
  • Effectiveness of HEPA Filters at Removing Infectious SARS-CoV-2 from the Air – “Air filtration simulation experiments quantitatively showed that an air cleaner equipped with a HEPA filter can continuously remove SARS-CoV-2 from the air. The capture ratios for SARS-CoV-2 in the air when the air cleaner was equipped with an antiviral-agent-coated HEPA filter were comparable to those with the conventional HEPA filter, and there was little effect on SARS-CoV-2 in the air that passed through the antiviral-reagent-coated HEPA filter.”
  • Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged <18 Years — United States, March 1, 2020–June 28, 2021 – “These data suggest an increased risk for diabetes among persons aged <18 years with COVID-19, which is supported by independent studies in adults (4–7). These findings underscore the importance of COVID-19 prevention among all age groups, including vaccination for all eligible children and adolescents, and chronic disease prevention and treatment.”
  • Pathophysiology of COVID-19-associated acute kidney injury – “Acute tubular injury seems to be a common occurrence in patients with COVID-19 AKI, but is often mild, despite severely altered kidney function. Endothelial injury, microvascular thrombi, local inflammation and immune cell infiltration have been repeatedly observed in patients with COVID-19 AKI; however, differences and similarities in the pathophysiology of COVID-19 AKI and non-COVID sepsis-associated AKI remain to be established. A high incidence of thrombi and intravascular coagulation might be one striking difference.”
  • Incidence of Hearing Loss in COVID-19 Patients: A COVID Hospital-based Study in the Eastern Part of India – “Hearing loss in COVID-19 has not received much attention by the medical professionals.COVID-19 infection could have deleterious effects on the inner ear specifically on the hair cells of the cochlea despite patients are asymptomatic. The proper understanding of the mechanisms behind hearing loss in COVID-19 infections needs further research.”
  • COVID-19 and Sudden Sensorineural Hearing Loss: A Systematic Review – “SARS-CoV-2 has the potential to cause damage to the audio-vestibular system, resulting in SSNHL. However, the exact mechanisms of SARS-CoV-2 on the audio-vestibular system remain fully understood. Although numerous investigations have been conducted on COVID-19-related SSNHL, they are fragmented and unsystematic. The true prevalence of SSNHL in COVID-19 patients around the world is unknown. Glucocorticoids are the preferred medication to treat COVID-19-related SSNHL. Hearing testing is recommended when HL is suspected in COVID-19 individuals, and if SSNHL is identified, prompt and vigorous treatment is critical.”
  • Hearing Loss, Tinnitus, and Dizziness in COVID-19: A Systematic Review and Meta-Analysis – “COVID-19 can cause hearing loss, tinnitus, and dizziness. These findings, however, should be interpreted with caution given insufficient evidence and heterogeneity among studies. Well-designed studies and follow-up assessments on otologic symptoms of SARS-CoV-2 using standard objective tests are recommended.”
  • Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia – “Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.”
  • COVID-19 disease and immune dysregulation – “While COVID-19 was originally characterized as hyperinflammatory in its pathophysiology, emerging evidence demonstrates the possibility of a strongly immunosuppressive phenotype in more critical disease states. While immune activation from neutrophils and complement may contribute to inflammatory damage in the lungs, decreased antiviral responses, dysregulated macrophages and dendritic cells, and severe lymphopenia contribute to a suppressed state in which viral replication and secondary infections are prone. IL-6/STAT3 signaling may be an important contributor to this immune dysregulation and deserves further investigation. Ultimately, when considering the future of immune therapy in COVID-19, it will be essential to understand each patient’s immune profile and adjust treatments accordingly.”
  • Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases – “Our results indicate that SARS-CoV-2 antigen persistence in infected tissues serves as a basis for postacute COVID-19. The concept that viral antigen persistence instigates immune perturbation and postacute COVID-19 requires validation in controlled clinical trials.”
  • Younger and Rural Children are More Likely to be Hospitalized for SARS-CoV-2 Infections – “We identified cases of SARS CoV2 positive patients seen in the Arkansas Childrens Hospital (ACH) ED or hospitalized between May 27, 2020, and April 28, 2022 using ICD10 codes within the Pediatric Hospital Information System (PHIS) Database. We compared infection waves for differences in patient characteristics, and used logistic regressions to examine which characteristics led to a higher chance of hospitalization. Findings: We included 681 preDelta cases, 673 Delta cases, and 970 Omicron cases. Almost 17% of patients were admitted to the hospital. Compared to Omicron infected children, preDelta and Delta infected children were twice as likely to be hospitalized (OR=2.2 and 2.0, respectively; p<0.0001). Infants less than 1 year of age were >3 times as likely to be hospitalized than children ages 5 to 14 years regardless of wave (OR=3.42; 95%CI=2.36 to 4.94). Rural children were almost 3 times as likely than urban children to be hospitalized across all waves (OR=2.73; 95%CI=1.97 to 3.78). Finally, those with a complex condition had nearly a 15 fold increase in odds of admission (OR=14.6; 95%CI=10.6 to 20.0). Conclusions: Children diagnosed during the preDelta or Delta waves were more likely to be hospitalized than those diagnosed during the Omicron wave. Younger and rural patients were more likely to be hospitalized regardless of wave. We suspect lower vaccination rates and larger distances from medical care influenced higher hospitalization rates.”
  • Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health – “We demonstrate myeloid recovery but persistent T cell abnormalities in convalescent COVID-19 patients more than three months after initial infection. These changes are more marked with age and are independent of ongoing subjective ill-health, fatigue and reduced exercise tolerance.”
  • Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19 – “Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. A novel population of naïve interferon-activated T cells is expanded in acute COVID-19 and is recruited into the memory compartment during convalescence in adults but not children. This was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.”
  • Large-Vessel Giant Cell Arteritis following COVID-19—What Can HLA Typing Reveal? – “LV-GCA may be considered an autoimmune disease triggered by SARS-CoV-2 infection, one of the broad spectra of manifestations within post-COVID-19 syndrome. However, many overlapping features of GCA and COVID-19 may lead to the delayed recognition of LV-GCA, indicating the need to highlight the potential link between SARS-CoV2 and the development of LV-GCA. The prompt initiation of therapy is necessary in order to avoid severe vascular complications. Future studies will better define the pathogenetic roles of specific HLA alleles in patients who developed GCA following SARS CoV-2 infection.”
  • SARS-CoV ORF-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome – “Our observations indicate the SARS-CoV ORF-9b provides a receptive intracellular environment for viral replication by targeting the mitochondrial MAVS signalosome. ORF-9b localizes to mitochondria where it promotes mitochondrial elongation by enhancing DRP1 degradation. In the presence of ORF-9b, MAVS becomes concentrated into small puncta and subject to PCBP2 and AIP4 ubiquitination. The degradation of MAVS is accompanied by a loss of TRAF3 and TRAF6, two key signaling intermediaries in anti-viral defenses. In addition, acute ORF-9b expression results in ATG5-dependent autophagosome formation.”
  • Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection – “This study identifies human cardiac pericytes as a novel target of SARS-CoV-2. We demonstrate that pericyte infection leads to innate inflammatory response, NF-kB-dependent pericyte cell death, and production of soluble factors that activate endothelial cells. These findings position mural cell infection as a new mechanism contributing to the cardiovascular manifestations of COVID-19.”
  • Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction – “This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.”