- Lagging vaccination rates and waning immunity from natural infections in South Africa may lead to a fourth wave from December.
- Heterogenous seropositive rates within provinces makes it hard it forecast which regions would be most affected.
- Deploying single doses in teens of the two-dose Comirnaty vaccine less optimal for efficacy, despite being a South Africa health policy decision.
- South Africa healthcare worker participants in the Johnson & Johnson Phase III Sisonke trial to receive a booster from next month.
South Africa is at risk of entering a fourth wave of Covid-19 infections from December or in January, owing to a significant chunk of the population yet to be vaccinated, and protection from a prior infection likely to have waned at five to six months, Covid-19 vaccine investigator Shabir Madhi says. South Africa is on the tail end of its third wave, which peaked on 8 July.
South Africa is one of the epicentres for Covid-19 vaccine development, particularly as the Beta variant of concern was first identified in the country, which has been found to have a negative impact on vaccine efficacy. Also, due to South Africa having as much as 20% of people living with HIV, side effect concerns raising this infection risk with Covid-19 vaccines is top of mind among local investigators. Madhi is the local lead investigator in AstraZeneca’s and Novavax’s respective Covid-19 vaccine clinical trials.
Madhi notes that while there might be an increase in infections in the months to come, the rate of hospitalisations might not be as severe as previous waves. People recovering from a previous infection could still be protected against severe disease, he explains. Based on current experience, there could be some residual protection in the general population, which may have contributed to lower infection and severe disease events in some provinces, he adds.
While the most recent wave saw a higher rate of death events than the first wave, this is due to the more transmissible Delta variant, Madhi explains. In the first wave, the daily new confirmed Covid-19 deaths peaked at 292, which rose to 577 in the second wave. In the third wave, it peaked at 420 deaths, according to Our World in Data.
Lockdowns should be regional
Once signs of a fourth wave start, lockdowns should only be enforced for specific, relevant provinces, Madhi says. A national approach, which the country has taken so far during the pandemic, is not logical as each province will be affected differently, he adds. For instance, there is no rationale for having the same level of lockdown in provinces in inland, eastern provinces, when the rising infection rates are in coastal regions.
“We need a more nuanced approach – restrictions haven’t assisted in preventing infections,” Madhi says, adding harsh lockdowns are designed to reach zero community infections, which is not the endgame for South Africa’s health policy authorities. The only basis for going to higher levels of restrictions is if there is a threat that health facilities will be overwhelmed, rather than to prevent infections, he argues.
But trying to pinpoint which provinces might bear the brunt of the next wave is challenging to forecast because of SARS-CoV-2 seropositivity heterogeneity between provinces, Madhi says. In fact, seropositivity can vary between 5–43% in the same province prior to the peak of the second wave, he adds.
People who live in more affluent neighbourhoods may be less likely to be seropositive as they likely had the luxury of social distancing and working from home, Madhi notes. And so, if they are still unvaccinated, they are more likely to be hospitalised in future waves. But from a public health perspective, these small pockets are unlikely to overwhelm the health system, he says.
Single dose in teens less than optimal
Earlier this month, South Africa started to vaccinate teens aged 12–17 years old with a single dose of Pfizer/BioNTech’s Comirnaty vaccine, which is broadly used as a two-dose vaccine. “I have reservations – it may have limited value,” Madhi says.
The rationale behind this public health strategy is that heart inflammation issues with mRNA vaccines are usually associated with the second dose, Madhi added. Yet, if this were the case, then the two dose-schedule should have remained with the female vaccine recipients, as myocarditis and pericarditis are predominantly seen with males, he explained.
The lower than anticipated uptake of vaccine in adults may have contributed to the expansion of a sub-optimal dosing in teens, Madhi says, adding: “It’s likely because the vaccines are expiring at the end of the year.” Comirnaty’s estimated vaccine effectiveness against symptomatic disease with the Delta variant is around 36% with a single dose, and 88% with the two-jab schedule, according to a study published on the New England Journal of Medicine on 21 July.
These Comirnaty doses should have been used as a third dose in older adults, especially in people who have underlying conditions.
These Comirnaty doses should have been used as a third dose in older adults, especially in people who have underlying conditions, Madhi says. Alternatively, the doses could have been used in people who have received a single dose of Johnson & Johnson’s (J&J) Covid-19 vaccine, he adds.
That said, South Africa is unlikely to deploy boosters in the public anytime soon, Madhi says. Boosters may be deployed but only within the context of clinical trials. In fact, healthcare worker participants in the single-dose J&J Sisonke trial (NCT04838795) are likely to receive their boosters from early next month, he notes.
In the US, on 20 October, the FDA expanded the authorisation of the J&J vaccine to allow a booster shot at least two months after receiving an earlier dose. Current experience, particularly with regards to the aggressive Delta variant and waning antibodies, demonstrates that a single dose of J&J is not optimal, Madhi adds.
Vaccine rollout obstacles persist
There have been many obstacles in delivering vaccines in adults in South Africa, even in older people who need them the most. South Africa is at the point of the pandemic where there is supply security, but the challenge remains with deploying them, Madhi says. Comirnaty and J&J’s JNJ-78436735 are the two authorised Covid-19 vaccines in the country.
The initial issue for vaccine deployment was that a central management approach was used, Madhi says. People needed to register, and have their details plugged into an electronic data system, after which the person would be directed to a vaccination centre. This was abandoned as it made vaccines less accessible.
Today there are walk-in vaccination sites which opens access, Madhi says. In the province of Limpopo, one of the country’s poorer regions, there is a high vaccination rate due to pop-up sites, he said. Yet these walk-in facilities are still not as abundant as they should be, though there is increasing interest in the potential of this approach, he adds. As with other parts of the world, misinformation is also fuelling vaccine hesitancy across all age groups.
As for other vaccines yet to receive authorization in the country, Sinovac’s Coronavac has a pending regulatory review owing to South African authorities seeking more information on how the vaccine would perform in a country with a high HIV-positive rate.
Russia-developed Sputnik V was to be the third vaccine authorised but makers were asked to provide evidence on its safety, particularly around its potential increased risk of HIV infection due to use of an adenovirus 5 (Ad5) as a vector. Sputnik V is a two-dose vaccine that uses the Ad26 and Ad5 vectors. This concern is based on evidence from HIV trials showing the adenovirus-5 vector increased susceptibility to HIV infection, he adds.
As for Novavax, with the company staging a Phase II trial (NCT04533399) in the country, manufacturing issues have stalled its progress, Madhi said. “We keep hoping to hear more updates each month, then it’s not realised.”
Graphs by GlobalData data journalist Andrew Hillman