Advertisement

Infection with the Omicron variant of SARS-CoV-2 is associated with less severe disease in hospitalized patients with COVID-19

Published:August 05, 2022DOI:https://doi.org/10.1016/j.jinf.2022.07.029
      Dear editor,
      We read with interest a recent letter by Lippi and colleagues, who suggest that Sars-Cov-2 Omicron variant causes less severe illness compared to outbreaks with previous strains.
      • Giuseppe Lippi
      • Riccardo Nocini
      • Henry Brandon M.
      Analysis of online search trends suggests that SARS-CoV-2 Omicron (B.1.1.529) variant causes different symptoms.
      The evolution of SARS-CoV-2 has led to several variants, each one with its own characteristics. Therefore, monitoring the potential implications of these new variants in terms of virulence or transmissibility is of the utmost importance. Omicron was considered a variant of concern (VoC) by the World Health Organization (WHO).
      WHO
      2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern.
      Due to the high number of mutations on the spike protein and its increased transmissibility, Omicron has become the predominant variant worldwide in a remarkably short time.
      • Ensheng Dong
      • Hongru Du
      • Lauren Gardner
      An interactive web-based dashboard to track COVID-19 in real time.
      ,

      Epidemiological update: omicron variant of concern (VOC) – data as of 9 December 2021 (12:00). Available at https://www.ecdc.europa.eu/en/news-events/epidemiological-update-omicron-data-9-december. Accessed March 8, 2022, n.d.

      Similar to other regions, the emergence of the Omicron variant in Spain coincided with a record number of patients diagnosed with COVID-19.

      Report 50 - hospitalisation risk for Omicron cases in England | Faculty of Medicine | Imperial College London. Available at https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/. Accessed February 24, 2022, n.d.

      However, the percentage of patients infected in the community who required hospital admission has been lower than in previous waves. Data on the characteristics and outcomes of patients hospitalized with this new variant could help define the most appropriate epidemiological measures and treatment protocols to address breakthrough scenarios.
      Here, we present a detailed description of the clinical characteristics, viral load, frequency of inflammatory phenotype, and outcomes in hospitalized patients with SARS-CoV-2 infection caused by the Omicron variant, comparing these data with previous admissions.
      We included all consecutive adults hospitalized at the Hospital Clinic of Barcelona >48 hours for SARS-CoV-2 infection between February 19th, 2020 and February 24th, 2021, presumably alpha and beta variants. We then compared with the first 90 patients both hospitalized in our center and identified with SARS-CoV-2 caused by the Omicron variant.
      During the first peak of the pandemic (March-April 2020), COVID-19 diagnoses (hereafter referred to as the Non-Omicron group) were confirmed by real-time polymerase chain reaction (RT-PCR) testing performed on nasal and oropharyngeal throat-swabs, and/or by clinical diagnostic criteria for SARS-CoV-2. The Omicron variant was identified through a multiplex RT-PCR Allplex SARS-CoV-2 Variants I assay and II assay (Seegene Inc., Korea).
      This study was approved by the Institutional Ethics Committee of the Hospital Clinic of Barcelona, which waived individual patients’ consent for the retrospective data review (HCB/2020/0273).
      We retrieved high-quality data from electronic health records on demographic characteristics, clinical signs, laboratory tests, microbiological results, treatments, and outcomes.
      We defined four clinical phenotypes: viral, inflammatory, co-infection and thrombotic. The viral phenotype comprised patients with a cycle threshold (Ct) value of less than 28 in RT–PCR at COVID-19 diagnosis. The inflammatory phenotype comprised patients with a C-RP higher than 8 mg/dL and/or ferritin higher than 1000 ng/mL and/or LDH higher than 320 U/L. The co-infection phenotype comprised patients with clinically suspected co-infection, given procalcitonin levels being higher than 0.2ng/mL. Finally, the thrombotic phenotype comprised patients with D-dimer levels higher than 1000 ng/mL. Patients may have one or more of these phenotypes at the same time.
      Categorical variables were described using the absolute number and percentage, while continuous variables were presented using the median and interquartile range (IQR). Categorical variables were compared using either a chi-squared (χ²) test and quantitative variables with the Mann-Whitney U test. Analyses were performed using Microsoft SPSS-PC+, version 22.0 (SPSS, Chicago, IL, USA).
      We included 3224 adults (3134 in the non-Omicron group and 90 in the Omicron group) in the study. In the Omicron group, 84% of patients had been vaccinated; 2.2% had had a COVID-19 episode.
      Table S1 summarizes these patients’ epidemiological, clinical characteristics, treatment and outcomes. Data for SARS-CoV-2 PCR Ct value was available in 1573 patients, of whom 1507 belonged to the non-Omicron group and 66, the Omicron group. A viral phenotype with a Ct value of under 28 presented in a total of 97% vs 61.8% (p<0.001) in the Omicron and non-Omicron groups, respectively. An inflammatory phenotype was present in 48 of 90 (53.3%) patients in the Omicron group and 2096 of 3080 (68.1%) patients in the non-Omicron group (p = 0.003). Specifically, when comparing the non-Omicron and Omicron groups, elevated C-RP, ferritin and LDH were documented in 49.6% versus 33.3% (p = 0.002); 33.1% versus 18.3% (p = 0.009); and 44.8% versus 33.3 (p = 0.041), respectively. A co-infection phenotype was present in 50% of patients belonging to the non-Omicron group and 31% of patients belonging to the Omicron group (p = 0.001).
      Table S2 details data on patients with specific characteristics (immunocompromised status, and either Intensive Care Unit (ICU) or conventional ward admission).
      This study compared the epidemiological characteristics and clinical picture of patients diagnosed with the Omicron variant to those infected by COVID-19 in earlier waves. Most patients in the Omicron group were older, they had mores comorbidities and less systemic inflammation and often presented bacterial co-infections. Also immunocompromised patients were admitted for early treatment to minimize the likelihood of progression to severe COVID-19. In both clinical situations, respiratory failure was infrequent and pro-inflammatory phenotype uncommon. To date, we have not hospitalized any patient with the Omicron variant presenting without comorbidities and under the age of 70 years who required mechanical ventilation or died. Our results are consistent with previous population-based studies documenting better outcomes in patients infected with the Omicron variant.

      Wolter Nicole, Jassat Waasila, Walaza Sibongile, Welch Richard, Moultrie Harry, Groome Michelle, et al. Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa. MedRxiv2021:2021.12.21.21268116. 10.1101/2021.12.21.21268116.

      Severity of Omicron Variant of Concern And Vaccine Effectiveness against Symptomatic Disease: National Cohort with Nested Test Negative Design Study in Scotland.
      • Tommy Nyberg
      • M Ferguson Neil
      • G Nash Sophie
      • H Webster Harriet
      • Seth Flaxman
      • Nick Andrews
      • et al.
      Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
      • Caroline Maslo
      • Richard Friedland
      • Mande Toubkin
      • Anchen Laubscher
      • Teshlin Akaloo
      • Boniswa Kama
      Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves.
      A plausible, biological explanation of our results is that the Omicron variant replicates faster than all other SARS-CoV-2 variants in the upper respiratory tract, but it multiplies less efficiently in the lung parenchyma.
      • Hui Kenrie P.Y.
      • Ho John C.W.
      • Man-Chun Cheung
      • Ka-Chun Ng
      • Ching Rachel .H .H
      • Ka-Ling Lai
      • et al.
      SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo.
      Due to its high affinity for the upper airway, it is unlikely that the Ct values detected in PCRs of nasopharyngeal samples from Omicron patients will provide us with the same information compared to previous waves.
      The high number of older patients in the Omicron group may also explain the mortality rate documented in subjects with this variant.
      Finally, hospitalized patients with SARS-CoV-2 Omicron infection had a different clinical picture: most were older and immunocompromised and had comorbidities. Clinical characteristics showed high viral burdens in the nasopharynx and a low systemic inflammatory response. Fever and respiratory failure were less frequent.
      As long as the Omicron variant remains predominant, we recommend that epidemiological and treatment protocols should be adjusted to lower the risk of progression to respiratory failure and death.

      Funding

      This work has been supported by funds for research ad hoc COVID-19 from citizens and organizations’ patronage to Hospital Clínic de Barcelona-Fundació Clínic per a la Recerca Biomèdica . This study has been also supported by Instituto de Salud Carlos III (ISCIII) through the project PI18/01061 , PI21/00498 and PI21/01640 , co-funded by the European Union. The funders had neither a specific role in study design or collection of data, nor in the writing of the paper or decision to submit.

      Transparency declarations

      CG-V has received honoraria for talks on behalf of Gilead Science, MSD, Novartis, Pfizer, Janssen and Lilly, as well as a grant from Gilead Science and MSD. PP-A has received honoraria for talks on behalf of Merck Sharp and Dohme, Lilly, ViiV Healthcare and Gilead Science. AS has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, Angelini, as well as grant support from Pfizer. JM has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis and Angelini.

      Other acknowledgements

      We would like to thank Anthony Armenta for providing medical language editing assistance for the manuscript at hand.

      Data availability statement

      The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

      Acknowledgments

      Hospital Clinic of Barcelona COVID-19 Research Group:
      Infectious Disease Research Group: Gerard Dueñas, Laia Serra, Nicole Garcia-Pouton, Daiana Agüero, Sabina Herrera, Rodrigo Alonso, Juan Ambrosioni, Jose Luis Blanco, Josep Mallolas, Alexy Inciarte, Esteban Martínez, María Martínez, Jose María Miró, Montse Solà, Ainhoa Ugarte, Lorena de la Mora and all the staff members.
      Medical Intensive Care Unit: Pedro Castro, Fernando Fuentes, Adrian Téllez, Sara Fernández, and all the staff members.
      Department of Microbiology: Mikel Martinez, Elisa Rubio, Alvar Simarro, Genoveva Cuesta-Charco, Míriam Alvarez, Jordi Bosch, Josep Costa, Julià Gonzàlez, Francesc Marco, Sofia Narvaez, Cristina Pitart, Elisa Rubio, Andrea Vergara, Mª Eugenia Valls, Jordi Vila and all the staff members.
      Department of Pharmacy: Esther López, Montse Tuset and all the staff members.

      Appendix. Supplementary materials

      References

        • Giuseppe Lippi
        • Riccardo Nocini
        • Henry Brandon M.
        Analysis of online search trends suggests that SARS-CoV-2 Omicron (B.1.1.529) variant causes different symptoms.
        J Infect. 2022; 84: e76-e77https://doi.org/10.1016/J.JINF.2022.02.011
        • WHO
        2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern.
        Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. WHO, 2021: 2021 (Available at) (Accessed December 15)
        • Ensheng Dong
        • Hongru Du
        • Lauren Gardner
        An interactive web-based dashboard to track COVID-19 in real time.
        Lancet Infect Dis. 2020; 20: 533-534https://doi.org/10.1016/S1473-3099(20)30120-1
      1. Epidemiological update: omicron variant of concern (VOC) – data as of 9 December 2021 (12:00). Available at https://www.ecdc.europa.eu/en/news-events/epidemiological-update-omicron-data-9-december. Accessed March 8, 2022, n.d.

      2. Report 50 - hospitalisation risk for Omicron cases in England | Faculty of Medicine | Imperial College London. Available at https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/. Accessed February 24, 2022, n.d.

      3. Wolter Nicole, Jassat Waasila, Walaza Sibongile, Welch Richard, Moultrie Harry, Groome Michelle, et al. Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa. MedRxiv2021:2021.12.21.21268116. 10.1101/2021.12.21.21268116.

      4. Severity of Omicron Variant of Concern And Vaccine Effectiveness against Symptomatic Disease: National Cohort with Nested Test Negative Design Study in Scotland.
        University of Edinburgh Research Explorer, 2022 (Available at) (Accessed February 24n.d)
        • Tommy Nyberg
        • M Ferguson Neil
        • G Nash Sophie
        • H Webster Harriet
        • Seth Flaxman
        • Nick Andrews
        • et al.
        Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
        Lancet. 2022; 399: 1303-1312https://doi.org/10.1016/S0140-6736(22)00462-7
        • Caroline Maslo
        • Richard Friedland
        • Mande Toubkin
        • Anchen Laubscher
        • Teshlin Akaloo
        • Boniswa Kama
        Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves.
        JAMA. 2022; 327: 583-584https://doi.org/10.1001/JAMA.2021.24868
        • Hui Kenrie P.Y.
        • Ho John C.W.
        • Man-Chun Cheung
        • Ka-Chun Ng
        • Ching Rachel .H .H
        • Ka-Ling Lai
        • et al.
        SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo.
        Nature. 2022; https://doi.org/10.1038/S41586-022-04479-6