Prof Madhi Addresses Omicron Subvariant Concerns
In an interview about new Omicron subvariants, leading vaccinologist Prof Shabir Madhi said that “we don’t need to be concerned” about any current threat they may pose to South Africa. However, he stressed that it can still be lethal, particularly in those without underlying T cell immunity. He also noted that boosters are also important for high-risk populations, while some sort of seasonality needs to be observed for COVID for it to make boosters worthwhile for those at low risk due to the way vaccination protection wanes.
The XBB 1.5 SARS-CoV-2 subvariant, nicknamed ‘Kraken’ by researchers, is now accounting for more than half of cases in the United States, and appears much more transmissible and antibody-evasive than the original Omicron variant which evolved in Southern Africa. Prof Pravin Manga, editor of the Wits Journal of Clicnical Medicine interviewed Prof Madhi and asked him what the emergence of Omicron subvariants meant for South Africa.
Prof Madhi, who is the Dean of the Faculty of Health Sciences at Wits University, noted that before this new XBB.1.5 variant, there were BA4 and BA5, which created a “mini surge” in the middle of last year when they arrived in SA. There were concerns that these strains seemed more antibody-resistant than previous ones, stoking fears that they would result in increased hospitalisations and deaths.
In light of the current situation, he says that “the short answer is that we don’t need to be concerned.”
One important aspect of immunity which was becoming apparent was that, although neutralising antibodies were important in protecting against contracting and transmitting the virus, “what seems to be playing a greater role in protecting against severe disease is the T cell immunity, the Natural Killer cell immunity.” This immunity is much more diverse than that from antibodies, instead of merely targeting the Spike protein is rather “multi-epitopic”, targeting the N-protein as well.
“Now this T cell immunity appears to be holding strong. It appears to be less affected by all these mutations. In fact, close to 75 to 80% of vaccine-induced T cell immunity is conserved despite the multiple mutations have arisen in Omicron and its subvariants.”
Differing impacts across countries
With regard to the impact of the virus, Prof Madhi noted that China had pursued its ‘zero COVID’ policy, along with “suboptimal” coverage of vaccines (especially among ages 60+) that were “probably not the best”, meaning that large portions of the population were essentially naïve to the virus.
SA meanwhile, had 90% of the population infected at least once with COVID, and coupled with vaccination, meant that many will have highly robust immunity, which appears to last for 9–12 months compared to vaccine-only immunity where protection starts wanes after 4–6 months.
“What is unlikely to materialise in a country such as South Africa is large numbers of hospitalisations,” he says.
Protecting at-risk populations and the need for new vaccines
At present, he says there is not a strong case for boosters, but people at greater risk, such as those over 60, people with underlying medical conditions, and compromised immune systems, hybrid immunity is likely not enough protection. In these cases probably at least four doses of vaccination. From a public health standpoint, the population under 45 without underlying conditions would require a huge effort for only a nominal benefit as they are no longer at high risk of severe disease.
Timing is also important, due to the waning of vaccine protection, as the best time to get a booster is “probably around two or three weeks before the start of the next resurgence.” Otherwise, it’s useless to get a booster now if the next resurgence is in six months and antibodies will have waned – an obvious logistical challenge for little benefit. Therefore, in order for boosters to be useful, the virus will have to settle into some sort of predictable seasonality such as with influenza.
As for people who are at risk, at least four doses are probably required, though the case for a fifth is thin. Annual boosters are a likely option, and there is a need for a second generation of vaccines. These vaccines would need to be resilient against further mutations that may arise.
Novavax, monoclonal antibodies and Paxlovid
Regarding Novavax, Prof Madhi said that it had been licensed for use in South Africa, but their bivalent vaccine was not yet available. It would not be procured by government but rather by a private company – a situation which needs to change in terms of who is allowed to bring in vaccines. Another issue is whether the no fault compensation used by the government for public sector vaccinations would be used in the private sector as well.
Prof Manga also asked about whether there had been any success with monoclonal antibody treatment, to which Prof Madhi answered that there had been some limited use in the country but overall, monoclonal antibodies were “spectacularly unsuccessful” as they were highly specific and generally unable to keep up with mutations.
In general, antivirals hold much better promise, particularly Paxlovid which is unfortunately not available in South Africa. It was disappointing that it was not available in the country,
Benefits to both pregnant mothers and babies
Regarding pregnant women and children, Prof Madhi said that their own study shows that a substantial amount of transmission takes place between mothers and children. Infants with COVID under six months are often hospitalised, especially in the first month of life. Vaccination reduces the risk of hospitalisation and protects the baby as well, with research showing that babies born to vaccinated mothers were 80% less likely to develop COVID, “which is really a huge benefit,” he noted. This is likely a little reduced with Omicron because the only thing that babies get from the mother is antibodies, not T cell immunity.
Vaccination also reduces the risk of adverse pregnancy outcomes such as stillbirth, and safety “is simply not an issue” as supported by the data. He says there is case for vaccinating pregnant women, even under 45, in the second trimester of the pregnancy so that more antibodies are transferred to the foetus.
