In a recent study posted to the Preprints with The Lancet* server, a large team of researchers estimated the comparative risk of hospitalization after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and Delta variants of concern (VOCs) in Denmark.
Compared to other countries, Denmark has a higher coronavirus disease 2019 (COVID-19) vaccination coverage and an extensive free-of-charge reverse transcriptase-polymerase chain reaction (RT-PCR) test capacity. Such demographics allow the stratification of population by vaccination status, making it easier to carry out studies addressing the public health impact of the rapidly disseminating Omicron variant.
In Denmark, surveillance of SARS-CoV-2 VOCs is performed via extensive whole-genome sequencing (WGS) efforts and variant RT-PCR (vRT-PCR) efforts. Upon detection of new VOCs, the Test Center Denmark (TCDK) develops vRT-PCRs to survey those VOCs in real-time. For Omicron, TCDK used a 452L marker, implemented on December 1, 2021. In addition, Omicron-specific vPCR solutions were set up in eight of 10 local departments of clinical microbiology (CMDs).
Study: Reduced Risk of Hospitalisation Associated With Infection With SARS-CoV-2 Omicron Relative to Delta: A Danish Cohort Study. Image Credit: NIAID
About the study
The present observational cohort study included samples of all RT-PCR confirmed SARS-CoV-2 cases in Denmark from 21 November-19 December 2021. The starting time point of the study coincided with the date of the first Omicron case, detected by a positive Omicron-specific variant RT-PCR (vRT-PCR) test result.
The researchers used samples from cases found to be RT-PCR-positive for the Omicron variant, either by TCDK or CMD vPCR, and subsequently subjected them to WGS according to capacity, which maxed at 15,000 WGS per week.
From November 24, 2021, >95% of all positive samples were screened with the TCDK’s Omicron vPCR. As the Omicron cases surged, the screening was discontinued, which limited the study population to samples taken before December 20, 2021.
In the study, a COVID-19 hospitalization within 14 days of the first positive SARS-CoV-2 RT-PCR test or during an ongoing hospitalization was recorded using the three data sources, the national patient register, the snapshot data, and the Danish microbiology database. The study thus only included hospitalized cases with a first positive SARS-CoV-2 RT-PCR test before and up to 48 hours after hospital admission, with the latest possible admission for COVID-19 on January 4, 2022.
The researchers also included a multitude of co-variates associated with both SARS-CoV-2 infection variant and hospitalization. The basic co-variates at sampling time were sex, age, calendar week, geographical region of sampling, co-morbidities, re-infection status (a positive RT-PCR test 60 days or more after the first RT-PCR positive test), and SARS-CoV-2 vaccination status based on the Danish Vaccination Register. Additional co-variates for later sensitivity analyses included test-track and ethnicity.
For statistical analyses, the researchers applied a log-linear Poisson regression model with standard errors (SE) to estimate the risk ratios (RRs) of SARS-CoV-2-related hospitalization by Omicron infection compared to Delta infection. While all p-values from the Poisson regression model were estimated using score-tests, the researchers evaluated differences in proportions using the Chi-square test and the difference in median age using a Wilcoxon test.
With an adjusted RR of hospital admission of 0.64, the risk of hospitalization due to Omicron was 36% lower than the Delta variant as observed across unvaccinated, two-dose vaccinated, and three-dose vaccinated individuals.
The risk of hospitalization among Omicron cases was lesser among the population that had received two doses and one dose with RR values of 0.71 and 0.57, respectively, compared to the non-vaccinated individuals. The finding indicates that the vaccine effectiveness declined faster for Omicron relative to Delta after the second dose of vaccine, further supporting the notion that the vaccine masks the severity after a Delta infection more than after an Omicron-induced infection. Also, no significant difference in hospital admission was observed in the first four months after the second COVID-19 vaccine dose (RR=1.20).
When followed up for a longer time, Omicron cases showed reduced severity even in the population of double-vaccinated individuals. Furthermore, Omicron cases had a shorter duration of hospital admission and showed a much-reduced probability of being transferred to the intensive care unit.
The study results demonstrated an intrinsic lowered risk of hospitalization for Omicron cases following both the first and second vaccination dose compared to the risk in the unvaccinated Delta-infected population. However, the extensive spread of Omicron due to its higher transmissibility can rapidly offset any benefits of its reduced severity.
These findings emphasize the importance of a fast roll-out of vaccination programs during the ongoing Omicron wave to mitigate the adverse impact on the public health care system. In addition, the observations support the need for hospital preparedness given the rapid spread of Omicron globally.
Preprints with The Lancet 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.
- Reduced Risk of Hospitalisation Associated With Infection With SARS-CoV-2 Omicron Relative to Delta: A Danish Cohort Study, Bager, Peter and Wohlfahrt, Jan and Bhatt, Samir and Edslev, Sofie Marie and Sieber, Raphael Niklaus and Ingham, Anna Cäcilia and Stegger, Marc and Legarth, Rebecca and Holten Møller, Camilla and Skov, Robert Leo and Valentiner-Branth, Palle and Overvad, Maria and Gram, Mie Agermose and Lomholt, Frederikke Kristensen and Hallundbæk, Louise and Espensen, Caroline Hjorth and Gubbels, Sophie Madeleine and Voldstedlund, Marianne and Karakis, Marianne and Møller, Karina Lauenborg and Olsen, Stefan Schytte and Fischer, Thea K. and Barrella Harboe, Zitta and Johannesen, Caroline Klint and Wiehe, Maarten Van and Holler, Jon Gitz and Simonsen, Lone and Dessau, Ram Benny Christian and Friis, Martin Barfred and Fuglsang-Damgaard, David and Pinholt, Mette and Kirkby, Nikolai Søren and Thomsen, Marianne Kragh and Sydenham, Thomas Vognbjerg and Coia, John Eugenio and Marmolin, Ea Sofie and Fomsgaard, Anders and Fonager, Jannik and Rasmussen, Morten and Spiess, Katja and Marving, Ellinor and Cohen, Arieh and Larsen, Nicolai Balle and Lillebaek, Troels and Ullum, Henrik and Mølbak, Kåre and Grove Krause, Tyra, SSRN 4008930 (2022) doi http://dx.doi.org/10.2139/ssrn.4008930, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4008930