Virus World

SARS-CoV-2 mortality has been extensively studied in relationship to a patient’s predisposition to the disease. However, how sequence variations in the SARS-CoV-2 genome affect mortality is not understood. To address this issue, we used a whole-genome sequencing (WGS) association study to directly link death of SARS-CoV-2 patients with sequence variation in the viral genome. Specifically, we analyzed 3,626 single stranded RNA-genomes of SARS-CoV-2 patients in the GISAID database (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) with reported patient’s health status from COVID-19, i.e. deceased versus non-deceased. In total, evaluating 28,492 loci of the viral genome for association with patient/host mortality, two loci, 12,053bp and 25,088bp, achieved genome-wide significance (p-values of 1.24e-12, and 1.24e-26, respectively).

Mutations at 25,088bp occur in the S2 subunit of the SARS-CoV-2 spike protein, which plays a key role in viral entry of target host cells. Additionally, mutations at 12,053bp are within the ORF1ab gene, in a region encoding for the protein nsp7, which is necessary to form the RNA polymerase complex responsible for viral replication and transcription. Both mutations altered amino acid coding sequences, potentially imposing structural changes that could enhance viral infectivity and symptom severity, and may be important to consider as targets for therapeutic development.

Preprint available at bioRxiv (Nov. 24, 2020):

https://doi.org/10.1101/2020.11.17.386714

A novel experimental vaccine against respiratory syncytial virus (RSV), a leading cause of severe respiratory illness in the very young and the old, has shown early promise in a Phase 1 clinical trial. The candidate, DS-Cav1, was engineered and developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, who were guided by their atomic-level understanding of the shape of an RSV protein. An interim analysis of study data showed that one dose of the investigational vaccine prompted large increases in RSV-neutralizing antibodies that were sustained for several months. 

First described in 1956 as a cause of infant pneumonia, the health burden of RSV has long been underappreciated. In fact, the virus is an important contributor to serious illness worldwide and causes as many as 118,000 deaths annually among young children. In the United States each year, RSV infections account for approximately 57,000 hospitalizations and 2 million outpatient clinic visits among children younger than five years old, according to the Centers for Disease Control and Prevention. 

“A vaccine to prevent RSV is a long-sought goal that has eluded us for decades,” said NIAID Director Anthony S. Fauci, M.D. “The early results of this trial suggest that this structure-based strategy for developing an RSV vaccine may bring that goal within reach.”  After four weeks, levels of RSV-neutralizing antibodies in those who received 50 µg of vaccine (with or without alum) had increased sevenfold over the levels present prior to vaccination. A single dose of 150 µg without alum boosted neutralizing antibody levels 12-fold, while alum-adjuvanted vaccine at that dose prompted a 15-fold surge in neutralizing antibodies. The vaccine-induced antibody levels greatly exceed those seen following natural RSV infection in human challenge trials (where healthy volunteers are exposed to pathogens under carefully controlled conditions in order to observe the course of infection), when neutralizing antibody levels merely triple over those present before infection.

Original findings were published in Science on 02 August 2019:

https://doi.org/10.1126/science.aav9033