Prof Salim Abdool Karim Weekly COVID-19 UPDATES

23 January 2023
After a 5-month hiatus, my weekly emails on Covid-19 are re-starting today. Thanks to GIZ for their interim funding that has enabled us to get up and running to produce Covid-19 epidemic intelligence for South Africa over the next 6 months while we try to secure longer-term support.
Well, let’s start with the global situation (Slide 2). Yesterday, there were about 280,000 confirmed cases and 2,275 deaths across the world. Given the declines in testing, these numbers are likely to be a substantial under count. Regardless, with more than a quarter million cases a day, it is a stark reminder that we are still living in the midst of a pandemic. South Africa remains in low transmission at present.
The concern globally is the potential for new waves due to the variant XBB.1.5, which has now been found in South Africa as well. So, what is XBB.1.5?  XBB.1.5 is a descendant of the omicron XBB subvariant of BA.2.  XBB, which was circulating in the UK in September last year, emanates from a cross between two earlier BA.2 strains: BA.2.75 and BA.2.10.1. Both strains are likely to have infected the same person leading to the creation of this cross – strain that has elements of both. This variant has the 2 key characteristics of new variants of concern – higher transmission and immune escape. 
Faster transmission – higher Ro – is critical for a new variant to outpace past variants to become dominant. Each new variant of concern has had a substantial transmission advantage that has enabled it to lead to new waves of infection (slide 3). Yunlong Cao from China had shown a short while back in the pre-print in Slide 4 (now published in Nature) how the mutations in the sub-lineages of omicron were influenced by immunity and that they were getting progressively more efficient in transmission. He anticipated that the XBB lineage would be one to watch. The XBB.1 sub-lineage has more immune escape than all its predecessors, as shown by David Ho’s team (Slide 5), who even used the word “alarming” in the title of their article to describe antibody evasion by XBB.
These studies provide empiric evidence of higher transmissibility and immune escape, the key requirements to become dominant.  So, will we likely see XBB.1.5 become globally dominant?
The XBB.1.5 sub-lineage of XBB spread rapidly causing a wave in Singapore in November last year (Slide 6). Looking at the USA also provides some clues. XBB.1.5 has been spreading rapidly in the US over the last few weeks and has now become dominant (>50%) – look at the purple component of each week’s bar to see how it has been spreading there (Slide 7).  But the global trends are not showing an expected upward trend if XBB.1.5 is spreading rapidly in many countries as we saw with omicron BA.1 (Slide 8). However, the trends in slide 8 need to be treated with caution as testing rates have declined in most countries and so the lack of an upward trend may be due to under-testing. Even with under testing, a major wave of new infections would likely produce an upward trend. So, it does not look like XBB.1.5 is behaving in the same way as omicron BA.1 that spread across the globe like wildfire creating waves in country after country in rapid succession. But it could still create spikes, or even waves, in several countries – the one thing that is certain in Covid-19, it is that the future remains uncertain.
Omicron BA.1, BA.2 and BA.5 variants spread widely infecting a high proportion of the population across the globe creating high prevalence of natural immunity. Since omicron spread at a time when vaccination rates were high is many countries, it created widespread hybrid immunity, which is associated with very higher antibody levels than vaccination alone or natural infection alone. Further, while new variants have been able to escape some antibodies, new variants have not had similar abilities to escape from T-cell immunity as seen in this Cell paper (Slide 9). These likely mitigate against the prospects of XBB.1.5 causing similar waves to those we saw with omicron or delta, especially with regard to severe illness or hospitalisations. 
So, what should you do?  Three things.
  1. Be fully vaccinated with a booster within the last 6-9 months. A recent study in the NEJM found somewhat better neutralisation in those who had 2 boosters compared to those who had one booster (Slide 10).
  2. Do as many things as you can outdoors. Since the risk of infection is much lower outdoors, do things like eating at restaurants outdoors, weather permitting.
  3. When you have to go into a poorly ventilated indoor space, wear a mask. 
These 3 actions are part of the vaccination+ strategy and are a light enough set of measures so that they are not too disruptive while offering substantial mitigation of risk.
Salim S. Abdool Karim, FRS
Director: CAPRISA
CAPRISA Professor of Global Health: Columbia University