Thread by @rvenkayya

THREAD
As scientists race to understand the new COVID variants, we have a valuable tool at hand: multiple ongoing Phase 3 vaccine trials. These can provide valuable insights into vaccine protection as well as the natural epidemiology of the variants via the placebo arms. 1/

https://twitter.com/kakape/status/1342063459350020097

The first indication of whether vaccine protection is affected will come from the lab: neutralization studies assessing whether vaccine-induced antibodies are as effective at neutralizing the new variant as earlier strains of SARS-CoV-2. Similar activity will be reassuring. 2/

But neutralization assays only assess the antibody contribution to protection, and they won’t measure transmissibility of the new variant. Animal models can provide some information, but definitive answers will only come from clinical and epi studies. 3/

https://twitter.com/rvenkayya/status/1343570297400811532?s=20

This is where ongoing Phase 3 trials come in. The trials weren’t designed or powered to assess vaccine protection against a new variant but could be amended to conduct key descriptive analyses and provide useful insights. 4/

The first step would be to sequence viruses from COVID cases (not necessarily planned) to follow the emergence of the variant in the study population. The variants are almost certainly present in the Phase 3 trials in the UK and S Africa and will appear elsewhere over time. 5/

Several descriptive analyses can then be conducted:
🔹vaccine efficacy against the new variant, including against severe disease
🔹clinical profile of disease caused by the variant
🔹natural epidemiology of the variant as compared to earlier strains in the placebo arm 6/

We can also look at parameters that correlate with transmission. In trials where prevention of infection is being assessed (eg, weekly nasal swabs in AZ trial), we could look for differences in VE against infection caused by the variant vs earlier strains. 7/

Virus titers in the nose may correlate with transmission. In all trials, we can compare nasal Ct values between cases caused by the variant vs others, elucidating both natural epidemiology (placebo arm) and impact of vaccination. 8/ @dkenned11 journals.plos.org/plosbiology/ar…

Amendments to the Ph3 protocols are likely to be necessary to conduct these analyses, but there are standard procedures for this. Sequencing of all virus strains may not have been planned but could be done on stored samples; 9/

Many of these analyses require contemporary (not historical) comparisons between the vaccine and well-matched placebo arms, reinforcing the value of maintaining placebo groups as long as possible. 10/ @sciencecohen
sciencemag.org/news/2020/12/m…

In most cases, these would be post-hoc or descriptive analyses, which can be confounded and need to be interpreted with appropriate caveats and caution. Nevertheless, they could provide valuable information for future decision making and vaccine development. 11/