Analyzing disease severity of SARS-CoV-2 Omicron variant using RNA dependent RNA polymerase target delay

In a recent study posted to the medRxiv* pre-print server, a team of researchers compared the severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant to the Delta variant using the polymerase chain reaction (PCR) proxy marker of RNA dependent RNA polymerase (RdRp) target delay.

Introduction

The rapid spread of the SARS-CoV-2 Omicron variant of concern (VOC) has made it imperative to understand its implications on public health. There is new evidence that suggests a reduced risk of disease severity in Omicron VOC-infected patients as compared to Delta VOC-infected patients.

In the third wave of coronavirus disease 2019 (COVID-19) infections, the RdRp target delay (RTD) proxy marker was successfully used to investigate the disease severity related to the Delta VOC.

About the study

In the present study, the researchers aimed to assess the clinical implications of the Omicron VOC in the Western Cape Province, South Africa, and compared it to the Delta VOC using the RTD proxy marker.

In diagnostic PCR assays, RTD was used as a proxy marker to detect the Delta VOC in samples. The RTD had a specificity of 89.7% and a sensitivity of 93.6% in the detection of the Delta variant in a sample. With the emerging spread of the Omicron variant, the absence of RTD in the diagnostic assays was used to identify non-Delta or Omicron variants. In this study, RTD was defined as a difference in the cycle threshold value of the RdRp gene target and the E gene target.

This study was conducted on COVID-19-infected patients aged 15 years and older, including 1486 cases without RTD (a proxy for Omicron/non-Delta) and 150 cases with RTD (a proxy for Delta). These COVID-19 cases, recorded from a period from 1 November to 14 December 2021, were diagnosed using PCR assay tests.

The researchers conducted a survival analysis, studying the RTD and non-RTD groups from the date of COVID-19 diagnosis to the date of COVID-19-related hospital admission. One day of follow-up was assigned to patients who were hospitalized either on the day of diagnosis or a day before being diagnosed with COVID-19.

Statistical adjustments were made for factors like gender, age, known comorbidities, prior COVID-19 diagnosis, and vaccination status at the time of diagnosis. An individual was considered fully vaccinated 28 days or more after receiving the Janssen/Johnson & Johnson (Ad26.COV2.S) vaccine or 14 days or more after receiving the second dose of Pfizer–BioNTech (BNT162b2) vaccine.

Results

For the group with the RTD cases and the group with the non-RTD cases, the median age was 33 years. Although the proportions of fully vaccinated individuals were similar in both groups, more partially vaccinated individuals were observed to be COVID-19-infected in the non-RTD group than in the RTD group. Also, the proportion of individuals reinfected with COVID-19 was 11% in both groups.

The number of COVID-19-related hospitalizations was 14% in the RTD group and 6.8% in the non-RTD group. In both groups, 12.5% of individuals who were not hospitalized had a history of COVID-19 infections, while none of the hospitalized individuals had previous COVID-19 infections.

The non-RTD group had a lower hazard of hospital admission as compared to the RTD group. In both groups, complete vaccination was noted to provide substantial protection against COVID-19-related hospitalizations. Therefore, the researchers concluded that vaccination protected the individuals against the severity of infection despite newly emerging VOCs.

Conclusion

The study results show that the non-RTD group, or the group with Omicron-infected cases, exhibited a lower risk of COVID-19-related hospitalizations as compared to Delta-infected cases. Antibodies produced as a result of COVID-19 infections provide considerable protection against the severity of reinfected cases.

Moreover, partially vaccinated patients were discerned to be more protected against the Delta VOC as compared to the Omicron VOC while fully vaccinated patients exhibited a lowered risk of hospitalization in both Omicron VOC and Delta VOC cases. According to the authors, ascertaining the virulence of the Omicron variant as compared to the previous variants or to any non-Delta variants will require further investigation.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.