Dataset Information

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection.

ABSTRACT: SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared with those of healthy and convalescent individuals, with the exception of an increase in B lymphocytes. Our findings show increased frequencies of T cell activation markers (CD69, OX40, HLA-DR, and CD154) in hospitalized patients, with other T cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization followed by an increase in PD1 frequencies in nonhospitalized individuals. Interestingly, many of these changes were found to increase over time in nonhospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation after SARS-CoV-2 infection. Changes in T cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation after SARS-CoV-2 infection, highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

SUBMITTER: Files JK

PROVIDER: S-EPMC7773371 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection.

Files Jacob K JK Boppana Sushma S Perez Mildred D MD Sarkar Sanghita S Lowman Kelsey E KE Qin Kai K Sterrett Sarah S Carlin Eric E Bansal Anju A Sabbaj Steffanie S Long Dustin M DM Kutsch Olaf O Kobie James J Goepfert Paul A PA Erdmann Nathan N

The Journal of clinical investigation 20210101 1

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared with those of healthy and convalescent individuals, with the exception of an increase ...[more]

PMID: 33119547

Similar Datasets

Project description:Introduction: Neutralizing antibodies have been shown to develop rapidly following SARS-CoV-2 infection, specifically against spike (S) protein, where cytokine release and production is understood to drive the humoral immune response during acute infection. Thus, we evaluated the quantity and function of antibodies across disease severities and analyzed the associated inflammatory and coagulation pathways to identify acute markers that correlate with antibody response following infection. Methods: Blood samples were collected from patients at time of diagnostic SARS-CoV-2 PCR testing between March 2020-November 2020. Plasma samples were analyzed using the MesoScale Discovery (MSD) Platform using the COVID-19 Serology Kit and U-Plex 8 analyte multiplex plate to measure anti-alpha and beta coronavirus antibody concentration and ACE2 blocking function, as well as plasma cytokines. Results: A total of 230 (181 unique patients) samples were analyzed across the 5 COVID-19 disease severities. We found that antibody quantity directly correlated with functional ability to block virus binding to membrane-bound ACE2, where a lower SARS-CoV-2 anti-spike/anti-RBD response corresponded with a lower antibody blocking potential compared to higher antibody response (anti-S1 r = 0.884, P < 0.001; anti-RBD r = 0.75, P < 0.001). Across all the soluble proinflammatory markers we examined, ICAM, IL-1β, IL-4, IL-6, TNFα, and Syndecan showed a statistically significant positive correlation between cytokine or epithelial marker and antibody quantity regardless of COVID-19 disease severity. Analysis of autoantibodies against type 1 interferon was not shown to be statistically significant between disease severity groups. Conclusion: Previous studies have shown that proinflammatory markers, including IL-6, IL-8, IL-1β, and TNFα, are significant predictors of COVID-19 disease severity, regardless of demographics or comorbidities. Our study demonstrated that not only are these proinflammatory markers, as well as IL-4, ICAM, and Syndecan, correlative of disease severity, they are also correlative of antibody quantity and quality following SARS-CoV-2 exposure.

Project description:BackgroundCOVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population.MethodsWe collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients' sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays.ResultsWe found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10-11 months) and one and a half years (17-18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age.ConclusionsWe concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.

Dataset Information

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection.

Publications

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets