Assessing the clinical severity of the SARS-CoV-2 Omicron variant

By Dr. Liji Thomas, MDDec 23 2021Reviewed by Aimee Molineux

The Omicron variant of concern (VOC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rose to dominance in South Africa after its initial reporting at the end of November 2021, and triggered a fourth wave of coronavirus disease 2019 (COVID-19).

A recent preprint on the medRxiv* server examines the proportion of Omicron infection and the risk of severe disease with this variant. The investigators used S gene target failure SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 polymerase chain reaction (PCR) as a proxy for the presence of the Omicron variant.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

South Africa is now experiencing its fourth wave of COVID-19, the first being driven by the wildtype virus, the second by the Beta VOC and the third by the Delta VOC. The Network for Genomics Surveillance of South Africa (NGS-SA) reported the Omicron VOC for the first time on November 24, 2021, using samples collected from patients on November 14, 2021. This was accompanied by a fourth surge in cases in Gauteng Province, where the variant was first detected.

This was marked by an increase in the number of samples with SGTF. Soon after, other provinces began to report SGTF and increased numbers of infections. In approximately three weeks, Omicron was being detected around the world, in 87 countries, many of them reporting community transmission.

The Omicron VOC has multiple mutations that are often associated with predicted immune escape and increased infectivity. This includes some found in the C.1.1, Beta and Delta, but also as many as 22 other mutations, deletions, and insertions unique to this variant. The Δ69-70 spike gene deletion, also seen in the Alpha VOC, is associated with SGTF on this platform.

The public health strategy dealing with this outbreak depends heavily on data availability. The current study aimed to examine the severity of disease due to the Omicron variant.

What did the study show?

The researchers used DATCOV-Gen4, a prospective monitoring network that connects genomic data with epidemiologic and clinical data from hospitalized cases, to allow severity assessment. This included over 160,000 cases of COVID-19 with over 38,000 of them being tested using TaqPath PCR, yielding almost 30,000 SGTF infections.

In these patients, the S gene target was undetectable, with the cycle threshold (Ct) being 30 or less for the ORF1ab or Nucleocapsid (N) gene targets.

While only 3% of COVID-19 infections were SGTF, early in October, by early December, it had gone up to 98% - from week 39 to week 48. After adjusting for hospitalization-associated factors, it was found that SGTF infections were at 80% lower odds of being hospitalized than non-SGTF cases. When factors related to disease severity were matched, SGTF and non-SGTF cases were found to have the same odds for severe disease occurring during the same time period.

Conversely, the risk of severe disease was 70% less for SGTF compared to Delta VOC infections. The Ct value was markedly lower, at 24, during the early Omicron period, compared to 27 in the early Delta wave. This could be due to higher viral loads in those infected with Omicron.

Other risk factors included age: those between 50-59 years, and 60 years or more, had twice or four times the odds of severe disease, while those 13-18 years old had 80% lower odds of severe disease, compared to those aged 19-24 years. Any co-existing illness increased the odds by three times.

The hospitalization data from DATCoV also confirms that when known outcomes are measured, two-thirds of hospitalized patients during the early part of the third wave had severe disease vs one-third of admissions during the first part of the fourth wave. This could be either due to the nature of the variant, or because by this time, a large proportion of the population had markers of adaptive immunity, elicited by natural infection or by vaccination, or by both – hybrid immunity.

In fact, 60%-70% of the population had signs of prior infection with the virus, after the Delta wave ended. By December 9, 2021, single- or double-dose vaccination had also extended to cover two-thirds of those aged 60 years or more, 61% aged 50-59 years, about half of those between 35-49 years, and ~30% of young adults (18-34 years).

The completely vaccinated population at this point included 58% and 55% of those aged 60 years or more, and 50-59 years, respectively, while for adults aged 35-49 and 18-34 years, the fully vaccinated percentage was 43% and 24%, respectively.

Implications

The high population immunity probably interacted with lower virulence to reduce disease severity. The major contribution may have come from population immunity, judging by the gross difference in severity between those who contracted non-SGTF (Omicron) infection vs those who had SGTF infection over the same period. This immunity might have come from either vaccination or natural infection.

The researchers found it difficult to compensate for the impact of prior immunity on the severity outcomes because vaccination data was incomplete, and most reinfections escaped undetected. The study had its limitations, with probably underestimated SGTF infection data. The proxy method is likely to have captured the vast majority of Omicron accurately, but ongoing sequencing will pick up any faults. Thus, the analysis indicates that the proportion of severe cases remained unchanged over successive waves.

Early analyses indicate a reduced risk of hospital admission and a reduced risk of severe disease among SGTF-infected individuals when compared to earlier Delta-infected individuals.”

The underlying reason appears to be a high level of vaccine- and/or infection-induced immunity that protects against severe disease.

These are early data and findings may change as the epidemic progresses, and with additional follow-up time for the more recently diagnosed SGTF-infected individuals.”

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources