Gene

2019-20 coronavirus outbreak

Biology

Odds

Virology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Outbreak

Coronavirus disease 2019 (COVID-19)

Genetics

Pediatrics

Genotyping

Genotype

Infectious disease (medical specialty)

Internal medicine

Odds ratio

Medicine

Pandemic

Disease

Logistic regression

The Lancet

In The Lancet, Nicole Wolter and colleagues1Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; (published online Jan 19.)https://doi.org/10.1016/S0140-6736(22)00017-4Google Scholar report data from more than 11 000 individuals (>80·0% aged 19–59 years; 55·9% women) with COVID-19 in South Africa indicative of significantly reduced odds of hospital admission for patients infected with the omicron SARS-CoV-2 variant of concern (B.1.1.529) versus other SARS-CoV-2 variants during the same period (Oct 1–Nov 30, 2021; adjusted odds ratio [aOR] 0·2, 95% CI 0·1–0·3) and significantly reduced odds of severe disease among patients infected by the omicron variant than among patients infected with the delta variant (B.1.617.2) in earlier epidemic waves (aOR 0·3, 0·2–0·5). These useful findings—derived from national-level COVID-19 hospital surveillance data linked with case, laboratory, and genomic data—represent a reassuring confirmation of early indicators that the omicron variant might lead to less severe disease and societal disruption, and have a reduced effect on hospital resources, than variants that dominated earlier pandemic waves. In the absence of widespread genotyping of confirmed SARS-CoV-2 infections, Wolter and colleagues1Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; (published online Jan 19.)https://doi.org/10.1016/S0140-6736(22)00017-4Google Scholar used amplification failure of the spike gene (S gene target failure [SGTF]) on the TaqPath PCR assay as a proxy for the omicron variant. SGTF is a reasonable marker for the omicron variant given that other circulating variants did not have this characteristic during the period of study.1Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; (published online Jan 19.)https://doi.org/10.1016/S0140-6736(22)00017-4Google Scholar In the context of expanding omicron variant epidemics, the level of generalisability of these South African data to other jurisdictions and timepoints is of paramount global importance. If this reduction in the risk of severe disease with the omicron variant, similar to that observed in England,2UK Health Security AgencySARS-CoV-2 variants of concern and variants under investigation in England. Technical briefing: update on hospitalisation and vaccine effectiveness for omicron VOC-21NOV-01 (B.1.1.529).https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdfDate: Dec 31, 2021Date accessed: January 9, 2022Google Scholar could be attributed to lower intrinsic virulence, it would provide reassurance to the public and health authorities that the recent alarming spike in COVID-19 case numbers observed globally would not translate to unmanageable increases in hospitalisations, with implications for the tightening or relaxation of disease control policies. However, South Africa has had repeated waves of infection and the extent to which this factor could explain the reduced effect of SGTF infections in late 2021 is unclear. SARS-CoV-2 reinfections are milder on average than primary infections,3Abu-Raddad LJ Chemaitelly H Bertollini R Severity of SARS-CoV-2 reinfections as compared with primary infections.N Engl J Med. 2021; 385: 2487-2489Google Scholar and, by December, 2021, more than 70% of South Africans had existing anti-SARS-CoV-2 antibodies as a consequence of either natural infection or vaccination.4Madhi SA Kwatra G Myers JE et al.South African population immunity and severe Covid-19 with omicron variant.medRxiv. 2021; (published online Dec 21.) (preprint).https://doi.org/10.1101/2021.12.20.21268096Google Scholar In the study by Wolter and colleagues,1Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; (published online Jan 19.)https://doi.org/10.1016/S0140-6736(22)00017-4Google Scholar the odds of previous infection were around 23-times higher in SGTF-infected versus delta variant-infected patients, which could be due to the omicron variant's capacity for immune escape that could increase the proportion of milder reinfections.5Cao Y Wang J Jian F et al.Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.Nature. 2021; (published online Dec 23.)https://doi.org/10.1038/s41586-021-04385-3Google Scholar The possibility of some patients being hospitalised with, rather than for, SARS-CoV-2 infection could also affect severity analyses given near universal, pre-hospitalisation COVID-19 testing and the increasing population prevalence of infection.6Sastry SR Pryor R Raybould JE et al.Universal screening for the SARS-CoV-2 virus on hospital admission in an area with low COVID-19 prevalence.Infect Control Hosp Epidemiol. 2020; 41: 1231-1233Google Scholar In an attempt to disentangle intrinsic severity from population immunity, Wolter and colleagues1Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; (published online Jan 19.)https://doi.org/10.1016/S0140-6736(22)00017-4Google Scholar analysed disease severity by comparing contemporaneous, hospitalised individuals with the omicron (SGTF) versus other variants (non-SGTF) using a composite measure of severity, which included admission to an intensive care unit, acute respiratory distress, oxygen treatment, and death.1Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; (published online Jan 19.)https://doi.org/10.1016/S0140-6736(22)00017-4Google Scholar This analysis was inconclusive, possibly due to the small number of severe outcomes; however, there is biological plausibility for some reduction in the intrinsic severity of omicron infections, as indicated by laboratory studies that report reduced pathogenesis in an animal model7Diamond M Halfmann P Maemura T et al.The SARS-CoV-2 B.1.1.529 omicron virus causes attenuated infection and disease in mice and hamsters.In Review Nature Portfolio. 2021; (published online Dec 29.) (preprint).https://doi.org/10.21203/rs.3.rs-1211792/v1Google Scholar and lower replication competence in human lung cells for omicron versus other variants.8Chan MCW Hui KPY Ho J et al.SARS-CoV-2 omicron variant replication in human respiratory tract ex vivo.https://doi.org/10.21203/rs.3.rs-1189219/v1Date: 2021Google Scholar Knowing how frequently omicron causes severe disease is important. But, even a milder average clinical presentation could be offset by an increased incidence of infection with the omicron variant, with the potential for considerable societal disruption through sickness, lost productivity, and distress, and the exertion of additional pressure on health-care systems due to staff absences. For example, on Jan 6, 2022, it was estimated that one in 25 individuals in the UK had symptomatic COVID-19.9ZOE COVID StudyData press release. Omicron spread slows but cases hit vulnerable over 75s.https://covid.joinzoe.com/post/omicron-spread-slows-but-cases-hit-vulnerable-over-75sDate: Jan 6, 2022Date accessed: January 9, 2022Google Scholar Self-isolation of cases, and either voluntary or mandatory quarantine of their contacts, can consequently impact large numbers of individuals. Community epidemics of the omicron variant will probably have less of an impact on health compared with previous COVID-19 waves in most locations because of increased levels of population immunity and the possible reduced intrinsic severity of omicron infections. Nonetheless, in this generally young South African population, 21% of hospitalised patients infected with the SARS-CoV-2 omicron variant had a severe clinical outcome,1Wolter N Jassat W Walaza S et al.Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.Lancet. 2022; (published online Jan 19.)https://doi.org/10.1016/S0140-6736(22)00017-4Google Scholar a proportion that might increase and cause substantial impact during outbreaks in populations with different demographics and lower levels of infection-derived or vaccine-derived immunity. This report of typically milder disease following infection with the omicron versus delta variant in South Africa is encouraging, but we should not assume that omicron variant epidemics will have such a low health effect elsewhere. BJC reports honoraria from AstraZeneca, GSK, Moderna, Roche, and Sanofi, outside the area of work commented on here. JN was previously employed by, and owns shares in, Sanofi, outside the area of work commented on here. We thank Julie Au for technical assistance. Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage studyOur early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. Full-Text PDF Open Access

Omicron severity: milder but not mild