ABSTRACT
CD4+ T cells are central to long-term immunity against viruses through the functions of T helper 1 (TH1) and T follicular helper (TFH) cell subsets. To better understand the role of these subsets in coronavirus disease 2019 (COVID-19) immunity, we conducted a longitudinal study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ T cell and antibody responses in convalescent individuals who seroconverted during the first wave of the pandemic in Boston, MA, USA, across a range of COVID-19 disease severities. Analyses of spike (S) and nucleocapsid (N) epitope-specific CD4+ T cells using peptide and major histocompatibility complex class II (pMHCII) tetramers demonstrated expanded populations of T cells recognizing the different SARS-CoV-2 epitopes in most individuals compared with prepandemic controls. Individuals who experienced a milder disease course not requiring hospitalization had a greater percentage of circulating TFH (cTFH) and TH1 cells among SARS-CoV-2-specific cells. Analysis of SARS-CoV-2-specific CD4+ T cells responses in a subset of individuals with sustained anti-S antibody responses after viral clearance also revealed an increased proportion of memory cTFH cells. Our findings indicate that efficient early disease control also predicts favorable long-term adaptive immunity.
Subject(s)
COVID-19 , SARS-CoV-2 , CD4-Positive T-Lymphocytes , Epitopes , Humans , Longitudinal Studies , Memory T Cells , Severity of Illness IndexSubject(s)
Biological Products/adverse effects , Coronavirus Infections/immunology , Interleukin-23 Subunit p19/antagonists & inhibitors , Pneumonia, Viral/immunology , Psoriasis/drug therapy , Respiratory Tract Infections/epidemiology , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Betacoronavirus/immunology , Biological Products/administration & dosage , COVID-19 , Clinical Decision-Making , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Humans , Interleukin-23 Subunit p19/metabolism , Odds Ratio , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Psoriasis/immunology , Respiratory Tract Infections/chemically induced , Respiratory Tract Infections/immunology , Respiratory Tract Infections/prevention & control , Risk Assessment , SARS-CoV-2 , Signal Transduction/drug effects , Signal Transduction/immunologySubject(s)
COVID-19/epidemiology , Clinical Decision-Making/methods , Immunosuppressive Agents/adverse effects , Psoriasis/drug therapy , Tumor Necrosis Factor Inhibitors/adverse effects , COVID-19/immunology , COVID-19/virology , Clinical Trials, Phase III as Topic , Humans , Pandemics , Psoriasis/immunology , Risk Assessment/statistics & numerical data , SARS-CoV-2/immunologyABSTRACT
BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).