Prof Salim Abdool Karim Weekly COVID-19 UPDATES

19 June 2022
This week's missive will be covering 5 issues:
1.  Masks work! It never ceases to amaze me at how so many innovative studies are continuing to generate valuable new scientific findings in this pandemic. You may recall that a few weeks ago, I shared the views of a South African scientist that masks do not work or if they work, they may work elsewhere but not in South Africa. This week, PNAS published an analysis that provides compelling evidence that masks work and work in many different settings across all 6 continents. The authors summarise their study as, “We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior (n = 20 million).” By using a Bayesian approach, they estimated, “the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R.” If there are any doubters out there that masks don’t work in community settings, this is a useful evidence-based approach to help you carve out your arguments in response. In summary, masks have reduced the transmission of SARS-CoV-2 by 19% overall. Not anywhere near as good as vaccines but the protective benefits of masks are still meaningfully slowing viral transmission.  
2. Paxlovid effective only in those at high risk of severe disease: While the Covid-19 response was dominated by public health measures in year 1 (2020), it was dominated by vaccination in year 2 (2021). I anticipate that it will be dominated by treatment by the end of year 3 (2022), especially if/when Pi (the next variant of concern) emerges. For the next variant of concern to get to a point that it will be named Pi, it will have to be able to transmit faster and it will have to be able to escape immunity. If and when such a variant emerges, vaccines may be able to reduce severe disease but the speed of transmission, may mean that even a small proportion of severe cases may translate into many people with severe disease within a narrow interval. Treatment will become important as the mainstay of our response in such an eventuality. Fortunately, several generic manufacturers from India are already making Paxlovid, many have pledged to make it available in poor countries in the same way they made ARVs available. So, who should be prioritised for Paxlovid, which is a 5-day course (twice daily) that needs to be initiated within 3 days of testing positive for SARS-CoV-2? This week, Pfizer (makers of Paxlovid) released a Press Statement saying that Paxlovid has no clinical benefit in those at low risk of severe disease. This makes it a lot simpler to ration scarce supplies of this treatment – focusing its allocation to the elderly, immunocompromised and those with co-morbidities. Please note that real world effectiveness estimates are still being awaited before we can be confident in Paxlovid’s benefits.
3. South Africa’s 5th wave: The 5th wave is over and cases have continued to decline (slide 2) in South Africa. The differences in the waves are quite marked (slide 4). While the first 3 waves followed a similar pattern but with growing magnitude, wave 5 (BA.4/5 wave) mimicked wave 4 (BA.1 wave) but with a markedly diminished magnitude. This was expected due to the presence of some antibody cross-reactivity against BA.4 from immunity to the initial omicron sub-variants. In South Africa’s 5th wave, hospitalisations have dropped substantially and deaths, which increased only minimally (slides 8 and 9) are just following the expected trend though persistently at a slightly higher level. In short, South Africa is now in the 3 month period of low transmission when cases can be expected to remain low until the next variant or sub-variant emerges. This is a good time to ease most of the public health measures but strengthen the rules on minimising indoor transmission with vaccination in anticipation of the next wave. This can be done through implementing a requirement that public indoor spaces and public transport should be restricted to those who are vaccinated or have a recent negative test result. Why do this? The risk of onward secondary transmission of SARS-CoV-2 is about 68-72% lower from vaccinated people, ie. if vaccinated people do become infected, they have a substantially lower chance of spreading the virus to others, especially in poorly ventilated high-risk settings.  
4. Global pandemic: Globally, cases have reached trough levels – a level that we have not seen very often in the last 2.5 years. The overall downward trend is turning slowly (slide 13), driven by cases mainly from high income countries (slides 14 & 15). One of the high income countries where cases are rising, even though it is early days, is the UK.
5. UK epidemic trends: Jeremy Farrar sent me the latest trends in the UK epidemic. Cases have been rising from a low base – driven by an increasing proportion of BA.4 viruses. In slides 17 and 18 we have, using figures from Our World in Data, put both South Africa and the UK on the same scale (though with different Y-axis peaks). In slide 19, Marothi has extrapolated (no mathematical modelling) what the next UK wave could look like if it followed a similar trend to South Africa’s BA.4 5th wave. Note there are there too many caveats to list here to this approach – I provide it just to give a glimpse of what a future wave could look like if it roughly followed the trend of same variant in other settings. Of course, it is impossible to predict the future as there are so many unknowns; slide 19 is just one possible scenario. 
Salim S. Abdool Karim, FRS
Director: CAPRISA
CAPRISA Professor of Global Health: Columbia University