Persistent Immunological Dysfunction: A Key Feature of Post-Acute Sequelae of SARS-CoV-2 Infection


Several millions of individuals who have recovered from SARS-CoV-2 infection continue to experience debilitating symptoms and health issues for months, a condition known as post-acute sequelae of SARS-CoV-2 (PASC).

In this article, we delve into a study that sheds light on the immune response in individuals with PASC, comparing it to convalescent asymptomatic and uninfected participants six months after their COVID-19 diagnosis. The findings provide crucial insights into the persistent immunological dysfunction associated with PASC, highlighting the potential role of viral persistence and mucosal involvement in the etiology of this condition.

Persistent Alterations in Immune Parameters

The study reveals that both convalescent asymptomatic and PASC cases display higher percentages of CD8+ T cells, a type of immune cell involved in targeting virus-infected cells. However, there is a notable difference in the proportion of CD8+ T cells expressing the mucosal homing receptor β7 in PASC patients, suggesting a potential disruption in the mucosal immune response. Additionally, CD8+ T cells in PASC patients show increased expression of PD-1, perforin, and granzyme B, indicating persistent immune activation.

Elevated Levels of Interferons and IgA

Furthermore, the study highlights elevated plasma levels of type I and type III interferons, which play critical roles in antiviral defense and mucosal immunity, respectively. These findings align with the hypothesis of continuous viral replication and suggest the potential involvement of the mucosa in the pathogenesis of PASC. Notably, PASC patients also exhibit higher levels of IgA antibodies targeting the S and N viral proteins, particularly in those who experienced severe acute disease. The presence of sustained high levels of viral-specific IgA at six months post-infection supports the notion of ongoing viral stimulation and the maintenance of plasmablast cells.

Correlations and Implications

The study identifies a strong positive correlation between interferon-λ and IgA levels in PASC individuals. This correlation, along with the observed alterations in immune parameters, suggests that monitoring IgA levels could serve as a simple and effective method for assessing chronic COVID-19-infected patients. The findings also highlight the importance of accurately monitoring immune parameters associated with SARS-CoV-2 infection, as even patients without major symptoms at six months post-infection continue to exhibit immune dysregulation.

Clinical Relevance of the Study

The study’s cohort, comprising a significant percentage of symptomatic patients, aligns with previous research, which indicates that around 30% to 50% of individuals experience post-COVID conditions six to twelve months after acute infection. Fatigue remains the most commonly reported symptom, followed by dyspnea and various neurological or psychiatric symptoms. These findings emphasize the need for comprehensive monitoring of individuals recovering from COVID-19, considering both symptomatic and asymptomatic cases, to better understand the long-term effects of the disease and provide appropriate care and support.


The study presents compelling evidence of persisting immunological dysfunction in individuals with PASC, even six months after SARS-CoV-2 infection. The alterations in mucosal immune parameters, the presence of viral-specific IgA antibodies, and the correlation with interferon levels suggest ongoing viral replication and mucosal involvement in the etiology of PASC. The findings underscore the importance of closely monitoring immune parameters and investigating the potential long-term consequences of COVID-19, both for symptomatic and asymptomatic individuals, to better manage and treat PASC.

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