Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

The study titled “Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms” delves into the complexities and potential mechanisms underlying the long-term health consequences of COVID-19, also known as Long COVID or Post-acute sequelae of COVID-19 (PASC).

Here’s a detailed summary:

Introduction to PASC:

PASC refers to a range of persistent symptoms experienced by a subset of patients following acute SARS-CoV-2 infection, lasting for many months. The symptoms vary widely among individuals, suggesting the involvement of different underlying biological factors which are not mutually exclusive. The paper explores various mechanisms, comparing them with other virus-initiated chronic syndromes like post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), to understand the potential pathways for PASC symptom development​​.

Acute COVID-19 Overview:

Acute COVID-19 manifestations range from asymptomatic to severe cases requiring hospitalization. On average, an acute COVID-19 case lasts between 1 and 4 weeks, but a subset of patients develop persistent symptoms for many months. These long-term symptoms can occur in patients with severe acute cases and in those who experienced mild or asymptomatic infections​​.

Connection with Other Chronic Syndromes:

The phenomenon of long-term symptoms post-infection is not unique to COVID-19. Many viruses and bacteria have been associated with the development of chronic symptoms in some patients. PASC shares similarities with conditions like ME/CFS, where most cases begin with a viral infection. Viruses such as neurotrophic herpesviruses and enteroviruses are commonly implicated in ME/CFS development, suggesting a link between viral infections and chronic symptomatology​​.

Pathways to Chronic Symptoms:

  1. Organ or Tissue Injury: Some PASC symptoms may stem from organ or tissue damage during acute COVID-19, such as lung parenchymal and small airway disease, pulmonary fibrosis, or acute kidney injury.
  2. Virus Persistence: In some patients, SARS-CoV-2 may persist in body sites or tissue reservoirs after acute infection, with studies showing prolonged detection of viral RNA or proteins in certain cases.
  3. Immune Response Dysregulation: SARS-CoV-2 might dysregulate the host immune response, allowing previously dormant pathogens to reactivate and cause new chronic symptoms. Humans accumulate persistent viruses over time, which can reactivate under stress or immunosuppression.
  4. Impact on Microbiome and Virome: The virus may interact with the host microbiome and virome, influencing the activity of bacteria, fungi, and parasites, which in turn could contribute to chronic symptoms.
  5. Functional Redundancy in Pathogen-Driven Processes: Different persistent pathogens might modify human gene expression, immunity, and metabolism via similar mechanisms, contributing to the development of chronic symptoms​​.


The paper underscores the complex and multifaceted nature of PASC, involving organ or tissue damage, virus persistence, immune response dysregulation, and interactions with other pathogens. The individualized nature of PASC symptoms suggests that personalized therapeutic approaches may be required for effective management. Understanding the underlying mechanisms of PASC is crucial for developing targeted treatments and improving the quality of life for those affected by Long COVID.

Read More: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260991/

Leave a comment