Convalescent COVID-19 Patients Without Comorbidities Display Similar Immunophenotypes Over Time Despite Divergent Disease Severities

Abstract

COVID-19, the disease caused by SARS-CoV-2 infection, can assume a highly variable disease course, ranging from asymptomatic infection, which constitutes the majority of cases, to severe respiratory failure. This implies a diverse host immune response to SARS-CoV-2. However, the immunological underpinnings underlying these divergent disease courses remain elusive. We therefore set out to longitudinally characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity. Our unique convalescent COVID-19 cohort consists of 74 patients not confounded by comorbidities. This is the first study of which we are aware that excludes immune abrogations associated with non-SARS-CoV-2 related risk factors of disease severity. Patients were followed up and analyzed longitudinally (2, 4 and 6 weeks after infection) by high-dimensional flow cytometric profiling of peripheral blood mononuclear cells (PBMCs), in-depth serum analytics, and transcriptomics. Immune phenotypes were correlated to disease severity. Convalescence was overall associated with uniform immune signatures, but distinct immune signatures for mildly versus severely affected patients were detectable within a 2-week time window after infection.

Reduced Monocyte Proportions and Responsiveness in Convalescent COVID-19 Patients

“…2c). These findings are consistent with prior studies demonstrating a decrease in circulating monocytes during convalescent COVID-19 infection 25, 26 .…”

“…In addition, these studies showed that monocytes in convalescent individuals display increased levels of inflammatory genes [21][22][23][24] , antigen presentation molecules, including HLA-DQA and HLA-DPA 20 , and the activation marker CD169 21 . However, other studies have demonstrated a decrease in monocyte percentages in convalescent individuals including those who had severe disease 25,26 . While a growing body of research has shed light on monocyte behavior during the convalescent phase, contrasting findings underscore the need for more detailed studies to unravel these complexities.…”

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic

“…In this module, we also identified several hub-high traffic genes that were crucial in regulating the host immune response during COVID-19. These hub-high traffic genes included CDKN2A (308,309), OASL (282,310), CCL5 (311)(312)(313)(314)(315)(316), KIF2C (4), and CD8A (317). Among them, the CCL5 hub-high traffic gene has the most important role in regulating the inflammatory response and the host immune system; however, its excessive expression can amplify inflammatory responses toward immunopathology (e.g., cytokine storm) (311,314).…”

Body composition and cardiorespiratory fitness of overweight COVID-19 survivors in different severity degrees: a cohort study

“…The convalescent period after infection is susceptible to different complications, especially with distinct immunological signatures that open an "immunological window," allowing the development of complications such as acute myocardial infarction and myocarditis, among other clinical manifestations 27 , 28 . Therefore, the morphophysiological parameters were collected after recovery from the acute sequelae recorded within the subdivision of symptoms (mild, moderate, and severe/critical).…”