Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome

Abstract

Background The immunopathological pathways enabling post-COVID syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition. Methods Thirty-three patients were included for longitudinal clinical and autoantibody analyses of whom 12 patients were assessed for cytokines and lymphocyte populations. Patients were followed during 7-11 months after acute COVID-19. Autoimmune profile and immunological status were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry. Results Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by upregulated IFN-α, TNF-α, G-CSF, IL-17A, IL-6, IL-1β, and IL-13, whereas IP-10 was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of IgG S1-SARS-CoV-2 antibodies remained elevated over time. Discussion The clinical manifestations of PCS are associated with the persistence of a proinflammatory, and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

Autoimmunity is a hallmark of post-COVID syndrome

“…The specific processes behind its emergence and the impact of biological changes on clinical phenotypes remain poorly understood. Patients with PCS may exhibit persistence of inflammation and predominance of an immune effector phenotype after recovery [ 1 ].…”

“…In addition, anti-IFN antibodies are implicated in mortality and correlate with age [ 4 ]. Autoantibodies may persist after COVID-19, and latent PolyA increases over time in PCS [ 1 ]. In a recent study by Liu et al [ 5 ], the authors observed that SARS-CoV-2 infection, even in the absence of severe clinical disease, can cause a broad autoantibody response exhibiting sex-specific patterns of prevalence and antigen specificity.…”

“…[ 5 ]. In patients with PCS, a proinflammatory state is evident [ 1 ], suggesting that bystander activation contributes to the emergence of autoimmunity [ 10 ]. In addition, despite the increased risk of death in patients with acute COVID-19 influenced by age, sex, and BMI [ 11 , 12 ], we demonstrate that these factors do not influence the autoimmune response in PCS.…”

Fermented Carica papaya and Morinda citrifolia as Perspective Food Supplements for the Treatment of Post-COVID Symptoms: Randomized Placebo-Controlled Clinical Laboratory Study

“…The causes and mechanisms underlying post-COVID syndrome are still to be investigated. Several current hypotheses include chronic self-maintaining inflammation, immune system and redox imbalance, an autoimmune phenomenon, and a hormonal component [ 67 , 68 ]. In the present clinical study we attempted to evaluate the effects of FFS on some of these mechanisms: functions of circulating phagocytes PMN crucial for the defence from secondary infections and a source of self-maintaining inflammation.…”

“…Protection against oxidative stress in COVID-19 and post-COVID patients is essential because imbalance of normal redox status to the oxidative millie seems to be one of the major causes of post-COVID syndrome [ 5 , 67 , 68 ]. According to our data, overproduction of highly oxidising agents nitrites/nitrates and their presence in plasma is a characteristic feature of post-severe-COVID period ( Figure 4 ).…”