A recently published South African study set out to determine sero-positivity against SARS-CoV-2 before the fourth wave of COVID-19, in which the omicron variant was dominant. Sero-positivity measures the presence of antibodies against the virus; it indicates past infection. The study focused on Gauteng, the country’s economic hub. Ozayr Patel asked Shabir Madhi to unpack the results and explain why the findings suggest that South Africa has reached a turning point in the pandemic.
What we found
The results show the levels of sero-positivity – in other words what percentage of people have antibodies to the virus – among just over 7,000 people from whom samples were taken. From these results the following rates were calculated:
In those under 12 years of age, none of who received a COVID-19 vaccine, 56% showed presence of antibodies to SARS-CoV-2
In those over 50 it was 80%, including 70% if unvaccinated and 93% if vaccinated
In high density inner city areas the sero-positivity prevalence was 85%
Using the seroprevalence data, together with COVID-19 attributable deaths using excess mortality data from the South African Medical Research Council, the study was also able to impute the risk of dying following infection by SARS-CoV-2 prior to the Omicron wave in South Africa. This infection fatality risk for COVID-19 was 0.57% pre-omicron in Gauteng. This is substantially higher than 0.019% imputed for seasonal flu, which infected one-third of the population each year pre-COVID, calculated using similar methods.
Vaccination coverage: We discovered high levels of hybrid immunity: that is immunity gained from a combination of previous infections plus vaccinations.
At the time of the onset of the omicron wave, 36% of people in Gauteng had at least one dose of the vaccine. This was higher – 61% – in those over the age of 50. (This cohort was responsible for more than 80% of deaths pre-omicron.)
Based on sero-survey, 70% of vaccinated people were also infected pre-omicron. Hence they would have had substantial hybrid immunity, which has been shown to induce a broader repertoire of immune responses against the virus. Such hybrid immunity in South Africa has, however, come at the cost of loss of 300,000 lives based on South African Medical Research Council excess mortality estimates. These are three-fold higher than the official recorded number of deaths.
Based on another study, the hybrid immunity is expected to confer greater protection against infection and mild COVID-19 compared with immunity only from vaccine or natural infection.
Hospitalisations and death rates: Our study also analysed the temporal trends in COVID-19 cases, hospitalisations and deaths (recorded and COVID attributable from excess mortality) from the start of the pandemic up until the tail end of the Omicron wave. The study found a massive decoupling between the number of people becoming infected with the virus relative to COVID hospitalisation and death rates during the course of omicron compared with earlier waves. This was true across all adult age groups.
The omicron wave was associated with 10% of all hospitalisations since the start of the pandemic, whereas 44% of hospitalisations had transpired during the course of the Delta variant wave. More impressively, only 3% of COVID deaths since the start of the pandemic occurred during the omicron wave, compared with 50% during the delta dominant wave.
The findings of decoupling of infections and severe or fatal COVID-19 were similar in the 50-59 year age group. In this group the omicron wave contributed to 15% of recorded COVID hospitalisations and 2% of deaths since the start of pandemic. This compares with 46% of hospitalisations and 53% of deaths occurring in the third wave, dominated by delta. The data for people over 60 years old was similar.
The survey also found that 58% of children under 12 years of age (all unvaccinated) were sero-positive. They were not more heavily affected during the Omicron wave.
The delta dominant wave which was the most severe in South Africa, coincided with South Africa’s belated COVID vaccine rollout. The high death rate during that wave is an indictment of the missed opportunities that could have prevented a large percentage of the deaths which transpired. In particular, the delayed procurement and roll out of COVID-19 vaccines in South Africa, as well as the ill-informed decision to against the WHO recommendation on the continued use of the AstraZeneca vaccine which was available to in South Africa when the Beta variant was circulating in South Africa.
In summary, the omicron wave contributed to less than 5% of all COVID-19 deaths in Gauteng. Since the start of the pandemic, the delta variant wave contributed to 50% of all of the deaths. The balance is split roughly equally between the first and second waves caused by ancestry and the beta variant.
Our findings also show that natural infection has been high and is playing a major role in how the pandemic has unfolded especially in countries with low to moderate COVID-19 rollout. These high levels of infections have, however, resulted in a massive loss of lives; which to date is likely under-estimated in low and middle income countries as shown from the South African data.
What the findings tell us
The findings indicate that South Africa is moving into the convalescent phase of the COVID pandemic – the recovery phase. This is likely to be the same in other countries with low or modest vaccine uptake, but high force of past infections. As such, South Africa needs to recaliberate its approach to the pandemic and to start managing it as we would do for other respiratory infections which too cause large number of hospitalisations and deaths.
There are still a few unknowns. Another resurgence is likely, and there might well be another variant. But it would be very surprising if further variants are able to evade the T-cell arm of the immune system which is stimulated by vaccines and natural infection. The T-cell (cell mediated immunity) arm of the immune system, appears to be the main mediator of protecting against severe COVID-19, even when there are breakthrough infections in vaccinated people or reinfections.
So why do I believe that we are at the tail end of this pandemic? It depends what metric you use. If it’s about infections, we’re not at the tail end. If it’s about the number of deaths that will transpire from COVID-19 during 2022, relative to the number of deaths that will transpire from other preventable causes of death in countries such as South Africa, then I believe the country has pretty much arrived towards the end of this pandemic.
In South Africa about 10,000 to 11,000 people die of seasonal influenza every year. In 2019 tuberculosis killed 58 000 in 2019. But we are not declaring an emergency in South Africa to deal with flu or tuberculosis. Deaths from HIV, and complications from HIV, are about 70,000. But South Africa isn’t shutting down the country to prevent deaths and infections from these diseases.
Only 12% of people across the continent have received one dose of vaccination. The implications of our findings are that:
- Vaccine coverage must be enhanced by ensuring that adequate booster doses are given to those who require it. We might need to continue boosting. This might need to be on an annual basis for the next two to three years, especially for high risk individuals. The time line for this is until we have more experience on the durability of protection of vaccines, particularly in settings with a high prevalence of hybrid immunity (where protection may be even longer lasting. )
Campaigns should be focused primarily on high risk groups, including getting over 90% of people over 50 years of age vaccinated before the next resurgence anticipated. This should be the focus rather than the current arbitrary target of vaccinating 40%-70% of the population.
It’s still beneficial to expand vaccinations in settings with high sero-positivity. Studies on hybrid immunity show this delivers more robust and broader repertoire immune responses that could heighten protection against infection, and reduce the magnitude of future resurgences.
It’s also important that key non-pharmacuetical interventions are kept in place. This includes wearing masks in crowded poorly ventilated indoor places, and particularly high risk individuals when there is an increase in virus transmission activity.
Our findings support the optimism expressed at the beginning of 2022 in South Africa that a turning point had been reached in the pandemic. Many in high income countries dismissed this view as not applicable to their settings despite high vaccine coverage. But their experience has since generally aligned with South Africa’s.
Lastly, better COVID vaccines are required. But the world is no longer at “code red”. And it’s time to rebuild livelihoods, economies and all other facets of life that were affected over the past two years. This is particularly true in fragile low and middle income countries.
Shabir A. Madhi, Dean Faculty of Health Sciences and Professor of Vaccinology at University of the Witwatersrand; and Director of the SAMRC Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand