Prof Salim Abdool Karim Weekly COVID -19 UPDATES

23 May 2022

Today’s missive covers 3 issues:

The global situation looks good, despite the challenges in some countries such as China. Overall, the number of cases has reached the trough level (Slide 15) of about 5 cases per million population. This is within the range of the global trough level after each of the previous waves. But, this is merely the lull before the next wave, if past trends persist. The possible beginnings of the next wave are already evident in North America (Slide 16), which has a worrying trend in escalating numbers of cases. Given that the nascent wave that is taking off in North America is being driven by omicron sub-variants and not an entirely new variant, it is quite likely to follow a similar trend to that seen in South Africa’s 5th wave, namely a “half-hearted” wave that does not reach new highs in daily cases for a range of reasons, including hybrid immunity (natural infection + vaccination, which generates up to 100-fold higher antibody levels of vaccination on its own).

South Africa:
Good news! The 5th wave in South Africa has reached its peak (a relatively low peak) and case numbers are now declining.  This wave is largely due to BA.4 and to a lesser extent, BA.5. I have not seen an official announcement of the start of the 5th wave by the Department of Health, but the 5th wave is already declining (Slide 2). This post-peak decline trend is now present in most provinces (Slides 20 and 21). There has been an increase in hospitalisations (Slide 2), but the increase has been quite modest compared to the past waves. 

Why should waves be publicly announced? Why not just let it pass, hoping that only a few will notice the increase in cases? The main reason why the start and end of waves need to be reported to the public is so that the public is aware of the increased risk when the wave starts and can “live smartly with the virus” by adjusting risk-taking behaviour when cases are high and/or rising in a wave. If the start and end of a wave is not announced, then the lay public will need to individually follow the case trends to decide if a wave is present so that they can appropriately adjust risk-taking.

Why a wave now? Amy Maxmen sent me an interesting question on the succession of omicron sub-variants. In South Africa, the omicron sub-variants have changed at a much faster rate than we have seen with previous variants of concern – this may be due to the large number of mutations in omicron, which creates many more opportunities for sub-variants. Based on data from the NGS consortium from the NICD website (Slide 11), I can summarise the successive changes in omicron sub-variants:

BA.1 was the predominant lineage in January at 55%, but BA.2 dominated in February (86%) and March (78%).  BA.4 and BA.5 were 16% of lineages in March, but were dominant in April (64%).  BA.4 and BA.5 make up 96% of May sequences.  Note that BA.3 continues to be detected at low levels. Only a few sequences from May are available at this time but are showing BA.4 / BA.5 dominance. If this trend continues, we can expect a new sub-variant by mid-June as each sub-variant has not dominated for more than 6-10 weeks….

So, while Omicron sequences (of its sub-variants) have been predominant since December 2021, the sub-variants have been replacing each other in rapid succession (Bold = dominance = >50% of sequences), as follows:
December 2021: BA.1
January 2022: BA.1 / BA.2
February 2022: BA.1/ BA.2 / BA.3 
March 2022:  BA.2 / BA.3 / BA.4 / BA.5
April 2022: BA.4 / BA.5

Finally, I want to share one of my major concerns – the poor immune responses following vaccination in immunocompromised individuals. Slide 12 provides some data that show the substantially lower antibody concentrations following vaccination in immunosuppressed individuals.

While it is not known for sure where variants emerge from, a potentially important source of new variants is the multiple mutations that occur during persistent infection in immunocompromised people. If this is true, then it is important to note that large numbers of immunocompromised individuals have been vaccinated or have had natural infection or both and that they may have only low antibody concentrations – not enough to clear the virus but enough to drive the replicating virus to escape the antibodies. Hence, poor vaccine immune responses in immunocompromised individuals may drive the creation of new variants – variants are being created in the midst of high levels of both natural infection (including reinfection) and vaccination. 

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