Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

The study titled “Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection” focuses on the immune dysregulation in individuals recovering from COVID-19.

Here’s a detailed summary:

Study Overview: The study undertook an integrated analysis of immune responses in 69 individuals at various stages of recovery (12, 16, and 24 weeks post-infection) from mild, moderate, severe, or critical COVID-19. It aimed to understand the persistence of symptoms associated with long COVID by examining changes at the transcriptional, cellular, and serological levels.

Key Findings:

  1. Stable Immune Responses: Anti-Spike and anti-RBD IgG responses remained largely stable up to 24 weeks post-infection and correlated with the severity of the disease.
  2. Altered Immune Cell Populations: Significant differences were observed in both innate (like NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (including T helper, T follicular helper, and regulatory T cells) when compared to healthy controls. These differences were most pronounced at 12 and 16 weeks post-infection.
  3. RNA Sequencing Insights: RNA sequencing of blood samples indicated significant changes in gene expression for up to 24 weeks post-infection, even in individuals who had mild disease without hospitalization. Over 950 genes were differentially expressed at 12 weeks post-infection compared to healthy controls, with a notable increase in genes related to immune response and metabolism.
  4. Persistent Transcriptional Changes: The study found persistent alterations in gene expression in convalescents, suggesting ongoing immune and metabolic dysregulation months after infection. This could potentially explain the long-lasting symptoms seen in some individuals recovering from COVID-19.
  5. Blood Transcriptional Modules (BTMs): Using Gene Set Variation Analysis, the study identified 80 BTMs that were differentially active in convalescents. These BTMs, related to transcription, translation, cell cycle, and immune cell populations, highlighted that some convalescents still had persistent transcriptional dysregulation at 24 weeks post-infection.
  6. Systems-Level Integration: The study integrated BTM activity scores with anti-Spike and anti-RBD antibody data and flow cytometry data. This revealed a complex interplay of relationships between circulating immune cell populations, transcriptional dysregulation, and humoral immune responses in COVID-19 convalescent patients.
  7. Recovery and Persistent Symptoms: The data suggest ongoing immune dysregulation in convalescents, which has been supported by other studies. Despite the anticipated decay in IgA and IgM, a large percentage of convalescents remained seropositive for both RBD- and Spike-specific Ig (all isotypes) for the duration of the study, with this decay less pronounced at 24 weeks post-infection in the severe COVID-19 convalescents compared to the mild cohort.

Conclusions: The study concludes that SARS-CoV-2 infection leads to persistent changes to the peripheral immune system long after the infection is cleared. These changes have important implications for understanding the symptoms associated with long COVID and for future research in this area. The findings underscore the need for continued monitoring and research into the long-term effects of COVID-19, particularly in relation to the immune system’s response and recovery.

Read More: https://www.medrxiv.org/content/10.1101/2021.07.30.21261234v1.full

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