COVID‐19 immunopathology: From acute diseases to chronic sequelae

Abstract

The clinical manifestation of coronavirus disease 2019 (COVID‐19) mainly targets the lung as a primary affected organ, which is also a critical site of immune cell activation by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, recent reports also suggest the involvement of extrapulmonary tissues in COVID‐19 pathology. The interplay of both innate and adaptive immune responses is key to COVID‐19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long‐term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS‐CoV‐2, in acute and post‐acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID‐19.

Cellular and molecular heterogeneities and signatures, and pathological trajectories of fatal COVID-19 lungs defined by spatial single-cell transcriptome analysis

“…1E, 1F, and Table S3). In particular, there were increased inflammatory cells including MMs from 9.4% to 17.51-21.37% and NK cells from 1.00% to 2.32-9.19%, and adaptive immune cells including T cells from 2.40% to 4.34-6.81% and B cells from 1.91% to 2.70-10.51%, which were consistent with the reported inflammatory and cellular immune response following SARS-CoV-2 infection [12].…”

Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with post‐acute sequelae of COVID‐19

“…Recent data suggest that clinical and biological markers decline in most COVID‐19 survivors over time, although with different kinetics. 10 , 14 , 35 , 36 To address this question in our cohort, we asked if individuals with PASC showed slower normalization of the strong perturbations in monocyte/macrophage‐related factors than individuals without PASC. Since no repetitive sampling was performed in the DigiHero cohort, this analysis was restricted to interpatient group comparisons (Figure 1B ).…”

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID

“…It is also quite fascinating since the wide community of scientists suggests that Tregs during the SARS-CoV-2 infection get activated, suggesting their immunoregulatory or immunosuppressive activities to prevent immune cells of both innate and adaptive immune response from damaging self-tissues mainly by limiting the excessive release of pro-inflammatory cytokines and chemokines [ 20 , 82 ]. However, it is also possible that in the early stages of infection, a greater proportion of activated Tregs might weaken the immune system’s ability to fight off viruses such as SARS-CoV-2 [ 9 , 20 ]. The excessive production of pro-inflammatory cytokines that causes ARDS, however, may be caused by a decrease in the number of Tregs with compromised functions in severe instances or later stages of the illness [ 21 ].…”

“…Strong T-cell responses have been associated with less severe outcomes in numerous infections. Hyperactivation, however, can potentially have negative effects as the infection spreads [ 1 , 9 ]. Furthermore, in this context, several studies have linked increased levels of effector molecules produced by CD8+ T cells with better clinical outcomes in acute COVID-19 [ 10 , 11 ].…”