Nevashan Govender

Mpox is an emerging viral infection and has since May 2022 been reported in a multi-country outbreak involving predominantly previously non-endemic countries. In addition, the number of cases of mpox is also rising in some endemic countries in Western and Central Africa. The disease is a notifiable medical condition in South Africa, with no cases reported before 2022. However, in 2022, coinciding with the peak of a multi-country mpox outbreak, five mpox cases were diagnosed in the country. Genomic sequencing and analysis revealed the presence of a monkeypox virus variant, which was circulating during the multi-country outbreak, namely Clade IIb sub-lineage B.1.7 (hMPXV). After the fifth case was reported in 2022, there were no cases detected for the following 20 months. In May 2024, mpox cases were again detected in South Africa leading to concerns that the virus may have been silently transmitting in the country since 2022. Whole genome sequencing and analysis for 22 mpox cases reported during May to September 2024, were compared with sequences obtained from mpox cases reported in South Africa in 2022, and cases that have been reported globally. It was found that the sequences of the 2024 cases analysed in this study, clustered with Clade IIb hMPXV and sub-lineage B.1.20 and B.1.6 sequences. The results indicate that the detection of mpox cases in South Africa was an extension of the ongoing multi-country outbreak. Detection of different sub-lineages of hMPXV indicates reintroductions of the virus in the country since 2022, with local transmission of Clade IIb B1.20 hMPXV.

Introduction The Omicron BA.1/BA.2 wave in South Africa had lower hospitalisation and mortality than previous SARS-CoV-2 variants and was followed by an Omicron BA.4/BA.5 wave. This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves. Methods Data from South Africa’s national hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100,000 people. Mortality rates in the Delta, Omicron BA.1/BA.2 and Omicron BA.4/BA.5 wave periods were compared by post-imputation random effect multivariable logistic regression models. Results In-hospital deaths declined 6-fold from 37,537 in the Delta wave to 6,074 in the Omicron BA.1/BA.2 wave and a further 7-fold to 837 in the Omicron BA.4/BA.5 wave. The case fatality ratio (CFR) was 25.9% (N=144,798), 10.9% (N=55,966) and 7.1% (N=11,860) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves respectively. After adjusting for age, sex, race, comorbidities, health sector and province, compared to the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.32-1.56) and Delta (aOR 3.22; 95% CI 2.98-3.49) wave. Being partially vaccinated (aOR 0.89, CI 0.86-0.93), fully vaccinated (aOR 0.63, CI 0.60-0.66) and boosted (aOR 0.31, CI 0.24-0.41); and prior laboratory-confirmed infection (aOR 0.38, CI 0.35-0.42) were associated with reduced risks of mortality. Conclusion Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa’s first three waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.

We provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa’s severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic to date. Although we found no evidence of increased reinfection risk associated with circulation of the Beta (B.1.351) or Delta (B.1.617.2) variants, we did find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 1 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021.

Background Clinical severity of patients hospitalised with SARS-CoV-2 infection during the Omicron (fourth) wave was assessed and compared to trends in the D614G (first), Beta (second), and Delta (third) waves in South Africa. Methods Weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases/100,000 population defined the start and end of each wave. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. Disease severity was compared across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of acute respiratory distress, supplemental oxygen, mechanical ventilation, intensive-care admission or death. Results 335,219 laboratory-confirmed SARS-CoV-2 admissions were analysed, constituting 10.4% of 3,216,179 cases recorded during the 4 waves. In the Omicron wave, 8.3% of cases were admitted to hospital (52,038/629,617) compared to 12.9% (71,411/553,530) in the D614G, 12.6% (91,843/726,772) in the Beta and 10.0% (131,083/1,306,260) in the Delta waves (pConclusion The trend of increasing cases and admissions across South Africa’s first three waves shifted in Omicron fourth wave, with a higher and quicker peak but fewer admitted patients, who experienced less clinically severe illness and had a lower case-fatality ratio. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and prior infection levels.

A new SARS-CoV-2 variant of concern, Omicron (B.1.1.529), has been identified based on genomic sequencing and epidemiological data in South Africa. Presumptive Omicron cases in South Africa have grown extremely rapidly, despite high prior exposure and moderate vaccination coverage. The available evidence suggests that Omicron spread is at least in part due to evasion of this immune protection, though Omicron may also exhibit higher intrinsic transmissibility. Using detailed laboratory and epidemiological data from South Africa, we estimate the constraints on these two characteristics of the new variant and their relationship. Our estimates and associated uncertainties provide essential information to inform projection and scenario modeling analyses, which are crucial planning tools for governments around the world. One Sentence Summary We report a region of plausibility for the relative transmissibility and immune escape characteristics of the SARS-CoV-2 Omicron variant estimated by integrating laboratory and epidemiological data from South Africa.