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Nkosazana Dlamini Zuma, chairperson of the National Coronavirus Command Council. Picture: SIYABULELA DUDA
Nkosazana Dlamini Zuma, chairperson of the National Coronavirus Command Council. Picture: SIYABULELA DUDA

The global waning of the most recent resurgence of Covid-19, dominated by the Omicron variant, has largely mirrored the experience of SA, where Omicron was initially identified.

Early reports from SA on the decoupling of infections and progression to severe disease and death due to the Omicron variant were met with doubt and scepticism by many governments and scientists in high-income countries. Cultural imperialism? Perhaps. Nevertheless, the same decoupling has now been observed globally in settings with high levels of population immunity induced by vaccines and/or past Sars-CoV-2 infection.

The attenuation of the clinical course of infection by the Omicron variant compared with the wild type and preceding variants of concern, has materialised despite the heightened transmissibility and infectiousness of the Omicron variant relative to the wild type virus and earlier variants that dominated during previous waves.

Natural infection and vaccine-induced immunity were associated with substantial decline in effectiveness (vaccine conferring about 30% protection) against infections and mild Covid-19 due to Omicron compared with the preceding Delta variant (70%-80% protection). This decline in effectiveness was due to mutations in the Omicron variant rendering it evasive to antibody neutralising activity (the mediator of protection against infection by preventing the virus from attaching to and infecting the human cells).

Nevertheless, immunity derived from past infections and vaccines still conferred high levels of protection against severe Covid-19 and death, largely attributed to the “T-cell” immune responses. The “T-cell” responses, particularly those referred to as natural killer (NK) cells act by identifying and killing off human cells infected by the virus, preventing further replication of the virus and infection of other cells and consequently protecting against severe Covid-19.

In contrast to the relative resistance of Omicron to antibody activity induced by vaccines designed against the ancestry virus, or by infections from anteceding variants due to extensive mutations, these mutations had substantially less effect on the multidimensional repertoire of T-cell immunity induced by either vaccines or past infections. Consequently, the experience of vaccines (or preceding infections) having diminished ability to protect against infection, while maintaining high levels of protection against severe Covid-19 even due to Omicron, is analogous to earlier experience with the Beta variant wave. However, notably, Omicron arose when the level of population immunity is greater than twofold compared to when the Beta variant dominated in SA.

The evolution of the Sars-CoV-2 virus indicates that further resurgences and new variants are likely, as is already occurring with an offshoot (the BA2 lineage) of the parent Omicron variant (BA1), which could be even more transmissible. Nevertheless, it is unlikely that the virus will accumulate a multitude of mutations enabling it to broadly evade the multidimensional “T-cell” immunity induced by vaccines, and even less so the greater breadth of T-cell responses that follow natural infection.

Notably, the most robust antibody responses that are able to mitigate much of the antibody-evasiveness of even Omicron, are evident in individuals who developed immunity from a combination of vaccination and natural infection (in either sequence), with such hybrid immunity also conferring a greater depth of T-cell responses.

Before the Omicron wave testing for Sars-CoV-2 antibodies — a reasonable proxy for the presence of underlying memory T-cells at a population level — indicated that 70% of unvaccinated adults older than 18 had been infected during the first three waves of Covid-19 in Gauteng. This high level of seropositivity is also prevalent elsewhere in SA, as high as 85% in more densely populated settings. Following on the Omicron wave, during which an estimated 30%-40% of South Africans were probably infected, in all likelihood more than 80% of the population has now been infected at least once since the start of the pandemic.

The high force of infection by Sars-CoV-2 in SA has come at the huge cost of 290,000 lives lost to Covid-19, with an attributable fatality rate of 490 per 100,000. The high attributable death rate in SA ranks it among the top 10 countries by death rate as at mid-January 2022, twofold higher than the UK (at 220 per 100,000). 

That the department of health requires a medical certificate to determine eligibility for a third dose is ludicrous.

Inadvertently, this high force of infection in SA resulted in natural infection being the dominant pathway to developing a high level of population immunity against Covid-19, in SA as elsewhere in Africa. The high death rate in SA also puts to rest the misguided narrative that Covid-19 causes no more deaths than would occur during a severe seasonal influenza season.

In SA, using the same approach to impute infections through seroprevalence studies and deaths using excess mortality attributable deaths, the imputed infection fatality risk for Covid-19 before the Omicron wave was 0.642%. This compares with seasonal influenza, which infects one-third of the population annually and results in 10,000-11,000 deaths (an infection fatality risk of 0.055%). In people older than 50, who have accounted for more than 80% of all Covid-19 deaths in SA, the Covid-19 infection fatality risk is in excess of 5%.

With the passing of the Omicron wave, and with more than 60% of those older than 50 having received at least a single dose of Covid-19 vaccine, the vast majority of this highly susceptible group (often due to underlying comorbidities) now have reasonable protection against severe Covid-19. Nevertheless, people older than 50, particularly those with underlying immune-suppressive medical conditions, still have substantial residual risk of severe Covid-19, which can be reduced by providing third doses of vaccines in the vaccinated and intensifying efforts to reach the unvaccinated.

That the department of health requires a medical certificate to determine eligibility for a third dose, which increases protection against Covid-19 hospitalisation from 70% to 90% for the Pfizer/BioNTech vaccine, is ludicrous when more than 15-million doses of Covid-19 vaccines are lying in depots across SA. Increasing vaccine coverage across all age groups remains important, since hybrid immunity is superior to vaccine-only or infection-only induced immunity, and would enhance protection against infection and severe Covid-19.

In addition, vaccinated individuals have about 50% lower risk of suffering from the debilitating effects of prolonged illness (long Covid) compared with unvaccinated individuals, which is important to age groups that are not at high risk of severe Covid-19. Nevertheless, optimal vaccination of groups at highest risk needs to be addressed as a national priority and would achieve much more than bean counting of the number of random doses of vaccine being administered.  

The high seropositivity in unvaccinated individuals in SA even before the Omicron wave also attests to the limited value of the restrictions imposed by the government for limiting infections. At best the restrictions spread out infections over a one- to two-week longer period, which partially assisted health-care facilities in weathering the storms of Covid-19 cases during earlier waves.

SA is now in a dramatically different phase of the pandemic due to the extensive underpinning immunity against severe Covid-19. The continued management of Covid-19 as a national crisis to justify the continued enactment of the State of Disaster Act, which enables the national coronavirus command council to decide on regulations that are often no longer fit for purpose, is unjustifiable.

The recent rescinding of some regulations on contact tracing, which unsurprisingly was a dismal failure and waste of resources in a country such as SA, as well as the lifting and/or easing of the need for isolation in individuals known to be infected with the virus, indicate a shift away from any pretence that we have the ability to prevent the spread of the virus. This approach very much accepts that Covid-19 is here to stay, and any notion of “herd immunity” is misguided with the current tools at our disposal. Also, the target of 70% vaccine coverage to reach “herd immunity” is outdated, since SA has already surpassed that target for immunity through natural infection alone, and very likely the rest of Africa too.

Adopting a wait-and-see attitude before deciding on transitioning to the management of Covid-19 as another disease in our midst is unwarranted.

The remaining restrictions, such as limiting the size of outdoor gatherings and not allowing full attendance at sporting events, have zero value in managing the pandemic at this stage in SA. Instead, they pose a continued impediment to the recovery of the economy, and remain detrimental to the livelihoods of our people. Getting back to normality is also critical to the mental wellbeing of South Africans, the education of children and allowing students to develop to their fullest capabilities on campuses.

Despite uncertainties about what to expect from the Sars-CoV-2 virus, which has not ceased to surprise, it is extremely unlikely that the virus will develop mutations enabling it to substantially evade T-cell immunity induced by infection or hybrid immunity. Consequently, adopting a wait-and-see attitude before deciding on transitioning to the management of Covid-19 as another disease in our midst, which we need to improve vaccines and treatment options, is unwarranted.

Should variants arise that are completely immune evasive, that would be the start of a pandemic within a pandemic. Rather than pretending we need to be under “code red” before making what amounts to a pragmatic decision informed by the current best scientific evidence, it is critical that an independent body be commissioned to review and reflect on the successes and failures over the past 23 months of SA’s response to the pandemic.

SA had a false start in leading the initiative to get back to normality when it announced that it would abandon contact tracing and quarantine in mid-December 2021 only to retract it a few days later as contravening regulations under the state of disaster. But it should now join countries such as Denmark and the UK, which are getting back to normal, comfortable in the knowledge of extensive immunity against severe Covid-19.

Adopting such an approach is not being dismissive of the future suffering and death Covid-19 will cause in SA, but the magnitude thereof is unlikely to rival the 58,000 deaths to come from tuberculosis in SA in 2022. The reopening of society and the ending of Covid-19 theatre — like wearing masks to enter restaurants but removing them as soon as we are seated, or wearing masks made of material — requires the termination of the state of disaster and disbandment of the national coronavirus command council.

• Madhi is dean of the faculty of health sciences and professor of vaccinology at the University of the Witwatersrand; director: vaccines and infectious diseases at the Wits Analytics Research Unit; and co-director: African Leadership in Vaccinology Expertise.

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