Science and the Coronavirus: Remdesivir for COVID-19 and targets of T cell responses to SARS-CoV-2 coronavirus in humans
Positive data about the use of remdesivir has emerged in a randomised controlled clinical trials of over 1000 patients. Meanwhile, a paper from La Jolla Institute of Immunology suggests there is a possibility that a significant population may have pre-existing immunity to SARS-CoV2 due to previous exposure to similar coronaviruses.
Remdesivir for the Treatment of COVID-19
The coronavirus continues to rampage across the world. Although several therapies have been utilised to slow and destroy the virus, nothing has been effective so far.
The authors of this paper conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with COVID-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results based on findings from an analysis that showed a shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days as compared with 15 days in those who received placebo.
In conclusion, it was found that remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. Read the entire study here.
Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals
• Measuring immunity to SARS-CoV-2 is key for understanding COVID19 and vaccine development
• Epitope pools detect CD4+ and CD8+ T cells in 100 and 70% of convalescent COVID patients
• T cell responses are focused not only on spike but also on M, N and other ORFs
• T cell reactivity to SARS-CoV-2 epitopes is also detected in non-exposed individuals
Understanding the adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting COVID-19 pathogenesis, and the calibration of pandemic control measures.
In this study, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively, using HLA class I and II predicted peptide ‘megapools’. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.