Prof Salim Abdool Karim Weekly COVID-19 UPDATES

10 February 2022

This week I will cover 2 important developments, one is the outbreak of BA.2 in South African schools and the other is a finding from the Veteran’s Administration study in the USA that is very concerning.

But first, it is good to see that the omicron wave is continuing its rapid decline globally (slide 9). You may be interested in noting that despite this overall trend, Hong Kong is experiencing record high levels of omicron cases this week – they reached a new record high of 1,325 cases on Friday. Hong Kong previously experienced a small outbreak of Delta cases through animal-to-human transmission (slide 10). Phylogenetic studies showed that some hamsters in a pet shop had spread the Delta variant among the other hamsters and these pet hamsters then spread the Delta variant to their human owners. Animal-to-human transmission has been well documented – you may recall that in 2020, farmworkers in Denmark spread the virus to the minks – the virus developed some mutations in minks, which the minks then spread to other farmworkers. This Hong Kong anecdote is just a reminder of animal-to-human spread which is too small a fraction of all transmissions to be too concerned about at this time but it should not be forgotten. People-to-people spread is so dominant in Covid-19 that we tend to forget about other sources of the virus.

You may recall that I mentioned last week that cases were rising in South Africa when we were expecting the cases to go down. I thought that the decline was most likely due to school opening in light of the temporal association. This week, I can confirm that the data supports this. South Africa experienced a short-term reversal in its epidemic decline (slide 2). So, what caused the rise in cases (or the aborted decline in cases)?

The age-specific trends in case numbers show that the increases are restricted to those below 20 years, mostly in the teen years, ie. children in school. It is quite striking (slide 4) that cases have continued to decline in every other age group except those below 20 years. Schools are a congregate setting, which includes gatherings without masks during the meal breaks. In this particular case, the schools served as an opportunity for BA.2 to spread in South Africa (slide 4).

Lesley Scott, who works with Wendy Stevens, puts out a regular bulletin providing information on the tests being done by the NHLS and I was surprised to see this week’s graph of S-gene target failure. Omicron (like Alpha) has a genetic deletion at positions 69-70 which makes it negative on the S-gene in PCR tests but it remains positive on the other genes and so still produces a positive PCR test with S-gene target failure. On slide 5, we see that S-gene negative (BA.1) omicron is now only 40% of the circulating viruses. Omicron that is S-gene positive (BA.2) is now dominant in South Africa. Phylogenetic data confirms this.

In short, BA.2 is now the predominant version of omicron in South Africa and it caused outbreaks in several schools when they reopened in January. Since most infections in children are asymptomatic or mild, most were not detected and so it did not lead to a substantial new rise in cases.

For those not familiar with BA.2, it can most simply be described as a version of omicron. Omicron is not a single virus but many viruses that have minor variations in their genetic code. BA.2 is a bit different in that it has over 20 genetic differences from BA.1 – so many that it could have been independently created. But, even with so many genetic differences, the actual virus (phenotype) is sufficiently similar to BA.1.  Usually the differences are small enough that all these versions of omicron are neutralised by the same antibody response and so effectively, it does not really matter which version of omicron a person got infected with as their omicron immune response is similar and will protect them from re-infection with omicron. This explains why BA.2 did not spread much beyond the schools where those spared omicron infection before school reopened now created a critical mass for omicron to spread in schools. And because BA.2 is more transmissible than BA.1, this version of omicron spreads faster and outcompetes BA.1, making it now more common. Will we see a new wave with BA.2?  Not likely because BA.1 antibodies have cross-neutralisation with BA.2. So, BA.2 does not pose a threat because BA.1 has already spread across the country generating immunity to BA.1, BA.2 and the other versions of omicron. For example, there were over 100 versions of Delta variant but we were not concerned about the individual versions as any version gave a person a Delta-variant immune response.

Just on the reopening of schools, there are several studies that have looked at school closures and reopenings, even with some restrictions like masks, that show how difficult it is to prevent school outbreaks and why schools are important in trying to slow viral transmission. In slides 6 and 7, I have provided 2 of the most authoritative studies (published in Science and Nature) on what restrictions are most impactful to slowing viral transmission – both show that closing schools has an impact on viral transmission. But we have to balance this with the impact of closing schools on learning and childhood development. It turns out that the decision to proceed with reopening schools in South Africa did lead to an outbreak of omicron (version BA.2) but its effects were not substantial and it was short-lived, such that schools are now experiencing minimal clinically-apparent infections and so learning can proceed with minimal disruption.

Finally, I was taken aback to see the findings in the study in slide 18. This paper came out in Nature Medicine this week. It is deeply concerning!  In short, a study of over 150,000 people who had Covid-19 infection found that they had a substantially higher risk of cardiovascular events – stroke, heart attacks, myocarditis, etc – than a historical control group AND a concurrent group of people who did not get Covid-19. These raised risks (which starts 30 days after infection and last for more than a year) were present in those with mild infection and those with severe infection (although even higher in those with severe infection). If these findings are confirmed, it means that we will dealing with a long-term legacy of cardiovascular illness of Covid-19 for years to come!

Salim S. Abdool Karim, FRS
Director: CAPRISA
CAPRISA Professor of Global Health: Columbia University