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Abstract
Introduction Initial reports suggest the B.1.1.529 (Omicron) variant of SARS-CoV-2 causes less severe disease compared with the B.1.617.2 (Delta) variant, though more widespread vaccination contributed to these findings. Little is known about clinical characteristics and outcomes of patients with SARS-CoV-2 infection requiring intensive care during periods of Delta and Omicron variant predominance.
Aim To examine and compare characteristics of critically ill adults with SARS-CoV-2 infection during periods of Delta and Omicron variant predominance.
Methods We conducted a retrospective cohort study of critically ill adults with SARS-CoV-2 infection at one academic hospital in Los Angeles during Delta (15 July 2021–23 September 2021) and Omicron (21 December 2021–27 January 2022) predominance. Patient characteristics were compared between Delta-period and Omicron-period hospitalisations, overall and stratified by vaccination status.
Results 79 adults required intensive care during the Delta predominance period and 116 during the Omicron predominance period. We found similar proportions of intensive care unit admissions occurring in fully vaccinated patients between the two periods, despite Los Angeles County data revealing an almost 60% increase in the proportion of SARS-CoV-2 hospitalisations occurring in fully vaccinated persons. There was no difference in the need for invasive mechanical ventilation (IMV). Among those who required IMV, the median duration of IMV was shorter overall (Delta=18 days; Omicron=8 days; p=0.006) and among unvaccinated persons (Delta=19 days; Omicron=8.5 days; p=0.018). Among unvaccinated persons, the median intensive care unit length of stay was shorter (Delta=12 days; Omicron=5 days; p=0.037) during Omicron predominance. There was no difference in the proportion of patients who died while hospitalised.
Conclusions In this single-hospital study, critically ill patients with SARS-CoV-2 infection experienced less severe respiratory disease during Omicron predominance, likely due to reduced variant-specific virulence. Vaccination likely reduced development of critical illness in adults with SARS-CoV-2 infection during Omicron predominance.
- COVID-19
Data availability statement
Data are available on reasonable request.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Initial reports suggest the B.1.1.529 (Omicron) variant of SARS-CoV-2 causes less severe disease in hospitalised adults compared with the B.1.617.2 (Delta) variant, though little is known about clinical characteristics and outcomes of critically ill adults during these periods.
WHAT THIS STUDY ADDS
We found similar proportions of intensive care unit admissions occurring in fully vaccinated patients between Delta and Omicron predominance periods, despite county-wide evidence of a 60% increase in the proportion of SARS-CoV-2 hospitalisations occurring in fully vaccinated persons. Among unvaccinated persons, the median intensive care unit length of stay was 7 days shorter and duration of invasive mechanical ventilation was 10.5 days shorter during Omicron predominance.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Vaccination remains important, as it likely reduced development of critical illness in adults with SARS-CoV-2 infection during Omicron predominance. Adults who became critically ill with SARS-CoV-2 infection experienced less severe respiratory disease during Omicron predominance, likely due to reduced variant-specific virulence.
Introduction
The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, overtook the B.1.617.2 (Delta) variant as the dominant strain in California in mid-December 2021.1 Initial reports suggest the Omicron variant causes less severe illness,2 though more widespread vaccination contributed to these findings.3 Little is known about clinical characteristics and outcomes of patients requiring intensive care during periods of Delta and Omicron predominance. The aim of this study was to examine and compare characteristics of critically ill adults with SARS-CoV-2 infection during periods of Delta and Omicron variant predominance.
Methods
We conducted a retrospective cohort study of adults aged >18 years with positive reverse transcription-PCR (RT-PCR) SARS-CoV-2 test results admitted to intensive care units (ICUs) at one academic hospital in Los Angeles, California, during 15 July 2021–23 September 2021 (Delta predominant period) and 21 December 2021–27 January 2022 (Omicron predominant period). Predominance periods were selected to reflect peaks in SARS-CoV-2 hospitalisations when each variant accounted for >50% of sequenced SARS-CoV-2 isolates in California.1 A longer duration for the Delta predominant period was chosen because the incidence of COVID-19 cases and hospitalisations in Los Angeles County was substantially lower during Delta predominance as compared with Omicron predominance.4 The hospital’s internal flagging system for SARS-CoV-2 admissions was used to identify RT-PCR positive test results. This system is triggered by a laboratory report of a positive SARS-CoV-2 RT-PCR test result during hospital admission or 14 days prior to admission, or by admitting physician confirmation of RT-PCR positivity from an outside facility through patient or family interview. Adults hospitalised with a positive SARS-CoV-2 test result during the preceding 90 days were excluded unless the patient’s symptoms resolved before readmission as determined by the admitting provider. Vaccination status was determined by electronic linkage from the electronic health record (EHR) to the California Immunisation Registry. Following the Centers for Disease Control and Prevention definition,5 fully vaccinated adults were those who received the second dose of a two-dose COVID-19 vaccine series (or a third dose if immunocompromised) or a single dose of a one-dose product >14 days before receiving a positive SARS-CoV-2 test result associated with their hospitalisation. Adults without documented receipt of any COVID-19 vaccine before the SARS-CoV-2 test date were considered unvaccinated. Patient demographic, clinical characteristics and outcomes were abstracted from the EHR. Using prior published methods,3 investigators (KS, NM and AP) conducted detailed chart review using prespecified criteria to determine whether the reason for ICU admission was likely or not likely due to COVID-19. In brief, ICU admissions were classified as likely due to COVID-19 if chart review could not clearly identify an alternative reason for ICU admission that was not plausibly linked to SARS-CoV-2 infection. Patient characteristics were compared between Delta-period and Omicron-period hospitalisations, overall and stratified by vaccination status. Categorical variables were compared with Fisher’s exact tests and continuous variables with the Mann-Whitney U test. Two-sided p values <0.05 were considered statistically significant. All analyses were conducted in Stata (V.17.0).
Patient and public involvement
None.
Results
There was no difference in vaccination status between the 79 adults requiring intensive care during the Delta predominant period and the 116 adults requiring intensive care during the Omicron predominant period (table 1). The median age of unvaccinated patients was older during Omicron predominance as compared with during Delta predominance (Delta=45 years; Omicron=63 years; p=0.002), while the median age of vaccinated patients was younger during Omicron predominance as compared with during Delta predominance (Delta=75 years; Omicron=68 years; p=0.037). The proportion of patients with chronic pulmonary disease was lower overall (7.6% vs 0.9%; p=0.018) and among unvaccinated persons (10.9% vs 0%; p=0.005) during Omicron predominance. Fewer patients during Omicron predominance received COVID-19 directed therapies (87.3% vs 74.1%; p=0.030). There was no difference in need for invasive mechanical ventilation (IMV). Among those who required IMV, the median duration of IMV was shorter overall (Delta=18 days; Omicron=8 days; p=0.006) and among unvaccinated persons (Delta=19 days; Omicron=8.5 days; p=0.018) during Omicron predominance. Among adults who required IMV, the proportion who received rescue therapies was lower overall (80.4% vs 49.2%; p=0.001) and among unvaccinated persons (86.5% vs 50.0%; p=0.001), and the proportion who required tracheostomy was lower among unvaccinated persons (40.5% vs 19.1%; p=0.048), during Omicron predominance. Among unvaccinated persons, the median ICU length of stay was shorter (Delta=12 days; Omicron=5 days; p=0.037) during Omicron predominance. There was no difference in the proportion of patients who died while hospitalised.
Demographic characteristics, clinical characteristics and clinical outcomes among 195 adults admitted to intensive care units (ICU) with SARS-CoV-2 infection by vaccination status and period of variant predominance—one hospital, California, 15 July 2021–23 September 2021 (Delta period) and 21 December 2021–27 January 2022 (Omicron period)
Discussion
At a single hospital in California, critically ill adults with SARS-CoV-2 infection during Omicron predominance experienced fewer days in hospital as compared with during Delta predominance. This difference was driven by fewer days in the ICU among unvaccinated persons, which stemmed from fewer days of IMV among those unvaccinated persons requiring IMV. Among unvaccinated persons requiring IMV, smaller proportions received therapies used to treat refractory hypoxaemia and required tracheostomy during Omicron predominance. Taken together, our results suggest critically ill patients experienced less severe respiratory disease during Omicron predominance. That we found no difference in mortality is not incompatible with these findings, as patients requiring therapies for refractory hypoxaemia and tracheostomy may still survive after a more prolonged period of mechanical ventilation. These findings appear primarily due to lower virulence of the Omicron variant, consistent with studies demonstrating the Omicron variant has lower replication competence in lung parenchyma.6 7
We found that fewer patients in the Omicron predominant period received COVID-19 directed therapies. This may be due to changes in prescribing practices over time. Alternatively, lower use of COVID-19 directed therapies may reflect a higher proportion of patients perceived by providers to have incidental COVID-19 instead of direct sequalae of SARS-CoV-2 infection during Omicron predominance. Another possibility is high population-level immunity from vaccination, prior infection or both resulted in different clinical presentations of patients with COVID-19 during Omicron predominance that may have been under-recognised.
Between mid-July and mid-December 2021, the proportion of fully vaccinated adults in Los Angeles County increased by approximately 20% and the proportion of SARS-CoV-2 hospitalisations occurring in fully vaccinated persons increased almost 60%.3 8 Despite this, we found the proportion of ICU admissions occurring in fully vaccinated persons were not substantially different between the two periods. This suggests vaccination was protective against development of severe disease during Omicron predominance.
This study has several limitations. First, sequencing data were unavailable to identify the SARS-CoV-2 variant. However, genomic surveillance data suggest each variant accounted for most sequenced isolates in its respective predominance period.9 10 Second, small sample size limits the ability to detect differences in vaccination status, incidental COVID-19 and variant-specific outcomes. Third, we could not account for time between last dose of COVID-19 vaccine. Fourth, our analysis was confounded by differences in age and chronic pulmonary disease. However, if both variants were equally virulent then we would expect worse outcomes among unvaccinated patients during Omicron predominance given their older age and this was not observed. It is possible more chronic pulmonary disease during Delta predominance contributed to more challenges weaning from the ventilator. Finally, these findings are from a single hospital in Los Angeles, limiting generalisability. However, the hospital captures a racially and ethnically diverse population.
In this single-hospital study, critically ill patients with SARS-CoV-2 infection experienced less severe respiratory disease during Omicron predominance, likely due to reduced variant-specific virulence. Vaccination likely reduced development of critical illness in adults with SARS-CoV-2 infection during Omicron predominance.
Supplemental material
Data availability statement
Data are available on reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
This study was Institutional Review Board approved (Cedars-Sinai STUDY00001967).
Acknowledgments
The authors thank Haoshu Yang, PharmD, Priya Chaudhary, MBBS, Susan Bartolini, Keren Dunn and Michael Melgar, MD for their contributions.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
NM and AP are joint first authors.
PC and MEM are joint senior authors.
Contributors MEM acts as guarantor and had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. KS, NM, AP, IP, PC and MEM substantially contributed to the design of the study, data acquisition, data analysis, interpretation of the data, drafting and/or revising the manuscript for critically important intellectual content. Final approval was given for the version to be published. All agree to be accountable for all aspects of the work. MPD, LRJ, NK, SKI substantially contributed to the data acquisition, data analysis, revising the manuscript for critically important intellectual content. Final approval was given for the version to be published. All agreed to be accountable for all aspects of the work.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Author note MEM is the guarantor of the content of the manuscript, including the data and analysis.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.