Virus World

BACKGROUND

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1–2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.

METHODS

In this phase 2a–b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)–negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection.

RESULTS

Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, −0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups.

CONCLUSIONS

The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. 

Published in NEJM (May 5, 2021):

https://doi.org/10.1056/NEJMoa2103055 

In just weeks, covid-19 deaths have snowballed from a few isolated cases to thousands across the country each day. 

The U.S. surgeon general had warned that last week would be like Pearl Harbor as he attempted to create context for the threat — but it turned out that more than five times as many Americans died from covid-19 last week than were killed in the World War II raid. You can grasp the scale when you compare a single week’s pandemic deaths with how many people die of major causes in a typical week.

In early and mid-March, when America began widespread closures, quarantines and social distancing, covid-19 caused many fewer deaths than other common causes — fewer in a week than chronic liver disease or high blood pressure, and far fewer than suicide or the common flu. By the end of March, the toll was closer to the average weekly deaths from diabetes and Alzheimer’s disease. Into April, weekly covid-19 deaths climbed past those from accidents and chronic lower respiratory disease. And last week, covid-19 killed more people than normally die of cancer in this country in a week. Only heart disease was likely to kill more people that week. 

Some experts had predicted that the deaths could peak last week, but there is no decline this week, with new high tolls Tuesday (2,369) and Wednesday (2,441) and another 2,206 on Thursday. That means covid-19 is on pace to be the largest single killer of Americans this week.

Viruses enter cells and initiate infection by binding to their cognate cell surface receptors. The expression and distribution of viral entry receptors therefore regulates their tropism, determining the tissues that are infected and thus disease pathogenesis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus known to co-opt the peptidase angiotensin-converting enzyme 2 (ACE2) for cell entry.

The interaction between SARS-CoV-2 and ACE2 is critical to determining both tissue tropism and progression from early SARS-CoV-2 infection to severe coronavirus disease 2019 (COVID-19). Understanding the cellular basis of SARS-CoV-2 infection could reveal treatments that prevent the development of severe disease, and thus reduce mortality....

Published in Science (July 31, 2020):

https://doi.org/10.1126/science.abc6156