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Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity


Senior Member
SARS-CoV-2 infection and the antigenic challenge induced by vaccinations against this pathogen elicit a diverse immunological response in humans. A variable immune response is expected during infection, but the ability of SARS-CoV-2 to evade host immunity and induce a deleterious effect on immune-regulating cells, such as macrophages, lymphocytes and natural killer cells make it a complex viral infection to be challenged. Consequently, variable outcomes of infection have been observed. In a small percentage of individuals, such outcomes include the manifestation of lymphocytopenia and autoimmunity. Vaccinations against COVID-19 have also been shown to evoke variance in the immune response in a fraction of vaccinated individuals. Here, we debate such occurrences of immune variance and discuss the underlying pathogenesis of immune deficits and contradictory cases of autoimmune states induced by COVID-19 which have puzzled the scientific community.

Observations of lymphopenia in COVID-19 patients with ominously decreased absolute T-cell counts and elevated levels of proinflammatory cytokines, for example, IFN-γ, IL-6 and IL-8 [1], have puzzled scientists worldwide. Persistently positive antinuclear antibodies 12 months post-COVID in individuals with long-COVID have been reported to be associated with persisting symptoms and inflammation (TNF-α) in a subset of COVID-19 survivors [2]. Though a considerable amount of data has been published on the typical immune response to SARS-CoV-2 infection and COVID-19 vaccination; very little is known about why deviations are observed in an increasing fraction of cases where the immune system is weakened to a remarkable extent. As the Spike (S) protein is known to be the pivotal antigen that incites the production of antibodies and T-killer cells after SARS-CoV-2 infection or vaccination by mRNA vaccines, a variation in the quantitative or qualitative immune response against the S protein and other antigenic components is expected to determine the clinical severity and pattern of COVID-19. Cases where a reduced lymphocyte count occurs and the disease is carried into a chronic symptomatic phase called long-COVID or post-COVID sequelae are puzzling, however. Inadequate viral clearance or persistence of the immune-evading virus can be the underlying cause of long-COVID, but a qualitative immune deficiency in the presence of a normal lymphocyte count in some cases warrants further investigation.

Understanding the complex immune outcomes in COVID-19 would clarify how SARS-CoV-2 interacts with the immune system and makes regulatory cells too weak to target the viral antigen. Manifestations of lymphocytopenia are alarming, and observations of the production of autoimmune antibodies further complicate our understanding of the molecular mechanisms at play in COVID-19 [3]. The spectrum of immune manifestations might be due to the different HLA genotypes which determine the immune response in humans, and differences in disease presentation and hospitalization may be due to some pre-existing susceptibility as a result of unique genetic and clinical profiles. Such lymphotropic effects, as are observed with lymphocytopenia, have resulted in the manifestation of certain opportunistic infections in patients with post-COVID infection states. The EBV, HSV and certain strains of other viruses have been detected in patients with COVID-19 and long-COVID with lymphocytopenia [4]. Reports of extensive fungal infections following COVID-19 and in long-COVID further describe the possible consequences of lymphopenia as a result of SARS-CoV-2 infection and its persistence in patients. While the emergence of TB cases in patients with reduced lymphocyte counts following or during SARS-CoV-2 infection has not been described, the reactivation of TB during COVID-19 remains a real possibility in countries where TB is common, such as in South East Asia [5].

continue reading (long paper): https://www.futuremedicine.com/doi/10.2217/fvl-2022-0218