Clinical Characteristics and Outcomes Among Adults Hospitalized With Laboratory-Confirmed SARS-CoV-2 Infection During Periods of B.1.617.2 (Delta) and B.1.1.529 (Omicron) Variant Predominance

One Hospital, California, July 15-September 23, 2021, and December 21, 2021-January 27, 2022

Matthew E Modes, MD; Michael P. Directo, MD; Michael Melgar, MD; Lily R. Johnson, MPH; Haoshu Yang, PharmD; Priya Chaudhary, MBBS; Susan Bartolini; Norling Kho; Paul W. Noble, MD; Sharon Isonaka, MD; Peter Chen, MD

Disclosures

Morbidity and Mortality Weekly Report. 2022;71(6):217-223.

Discussion

Among adults hospitalized with SARS-CoV-2 infection at a single hospital in California during the Omicron-predominant period (December 21, 2021–January 27, 2022), COVID-19 vaccination, particularly receipt of a booster dose, was associated with lower likelihood of ICU admission, and, among adults aged ≥65 years, lower likelihood of death while hospitalized. Compared with the period of Delta predominance, a higher proportion of adults hospitalized during Omicron predominance were fully vaccinated. Consistent with earlier findings,^[3] Omicron-period hospitalizations were associated with a lower likelihood of ICU admission, IMV, and death while hospitalized, compared with Delta-period hospitalizations. However, the proportion requiring ICU admission and IMV did not differ significantly when stratified by vaccination status, suggesting that much of the lower disease severity observed during Omicron predominance might be driven by increased population-level vaccine-conferred immunity. These findings support the continued importance of COVID-19 vaccination, including booster doses, in mitigating the risk of severe illness associated with SARS-CoV-2 infection.

From mid-July through mid-December 2021, the proportion of fully vaccinated adults in Los Angeles County increased nearly 20%, from approximately 65% to 77%,*** but the proportion of SARS-CoV-2 hospitalizations occurring in fully vaccinated adults increased almost 60%, from approximately 25% to 40%. The increase in the percentage of fully vaccinated Hispanic adults and the decrease in the percentage of non-Hispanic White adults hospitalized between the two periods likely reflect increased vaccination coverage among Hispanic persons during fall 2021. Increases in infections among vaccinated persons during the period of Omicron predominance were likely driven both by waning vaccine-derived immunity over time and by relative resistance to vaccine neutralization in the Omicron variant compared with the Delta variant.^[2,4] This is consistent with the observed decline in effectiveness of 2-dose vaccination against COVID-19 hospitalization during the Omicron period.^[5] A previous study also found that, compared with the period of Delta predominance, the period of Omicron predominance in Los Angeles County was associated with a decrease in the degree of protection against COVID-19 and hospitalization.^[6] Despite this, COVID-19 vaccination, including a booster dose, was associated with lower likelihood of ICU admission during the Omicron period, and lower likelihood of death among adults aged ≥65 years, who are at higher risk for severe outcomes when hospitalized with COVID-19.^[7,8]

Early reports suggest that the Omicron variant has lower replication competence in lung parenchyma,^{†††,§§§} possibly contributing to a decreased severity of illness compared with earlier variants.^[3] However, among patients hospitalized for COVID-19 during the early Omicron predominant period, most had lower respiratory symptoms and abnormal chest imaging, approximately one third had hypoxemia, and 10% required IMV. These findings demonstrate that, despite observed changes compared with Delta, Omicron variant infection still causes severe lower respiratory illness. Similar data on patient symptoms were not available for Delta-period hospitalizations. However, fewer Omicron-period patients received COVID-19-directed therapies, which might suggest lower proportion with hypoxemia, compared with Delta-period patients. Alternatively, this change might have been driven by changes in prescribing practices or other unmeasured factors.

Approximately 20% of SARS-CoV-2 admissions during early Omicron predominance were likely for reasons other than COVID-19, a proportion even higher among young and vaccinated adults. Given high rates of SARS-CoV-2 community transmission, this is not unexpected. This estimate stands in contrast to an estimated 63% of patients admitted with incidental SARS-CoV-2 infection reported from South Africa.^[9] While this difference might be driven, in part, by differences in demographics and population immunity, the present study's classification methodology might have overestimated the number of persons whose admission was driven by COVID-19. One third of patients classified as having been admitted for COVID-19 received no COVID-19–directed therapies. Alternatively, high population-level immunity from vaccination, previous SARS-CoV-2 infection, or both might have modulated the clinical presentation of patients with COVID-19 during Omicron predominance and atypical presentations might have been underrecognized (e.g., exacerbations of chronic medical conditions), or lesser illness severity might have resulted in fewer therapies. However, the pandemic health care burden is not limited to hospitalizations for symptomatic COVID-19. Even patients with positive SARS-CoV-2 test results admitted for non-COVID-19 conditions require isolation rooms and use of personal protective equipment and might transmit infection to health care workers, exacerbating staff shortages.

The findings in this report are subject to at least six limitations. First, sequencing data were not available to identify the SARS-CoV-2 variant. However, based on California genomic surveillance data, which is based on sequencing of ≥10% of all positive RT-PCR tests in the state,^¶¶¶ and on recent genomic surveillance for Los Angeles County,^[7] the Delta and Omicron variants accounted for the majority of sequenced isolates throughout their respective predominance periods. Second, the proportion of Omicron-period hospitalizations attributed to COVID-19 could not be compared with earlier periods, so it is unclear whether the proportion represented a change from an earlier period. Third, the study might have been underpowered to detect Omicron-specific reductions in illness severity after stratifying by vaccination status. Fourth, the analysis could not account for the interval since the last dose of COVID-19 vaccine, which might have been longer among Omicron-period patients. Fifth, there might have been incomplete ascertainment of deaths in the recent weeks of Omicron predominance; severely ill patients might remain hospitalized and might be at high risk of death. A longer period of observation might have reduced differences in death between the two periods. Finally, these findings are from a single hospital in Los Angeles and cannot be generalized to the United States. However, the hospital has a large catchment area in a racially and ethnically diverse region.

In this single-hospital study, adults hospitalized with SARS-CoV-2 infection during Omicron predominance had less severe illness compared with adults hospitalized during Delta predominance. Much of this effect appears to be driven by increased proportion of patients who were fully vaccinated. Approximately 20% of Omicron-period hospitalizations among adults with a positive SARS-CoV-2 RT-PCR result were driven by non–COVID-19 conditions, which might be attributed to high SARS-CoV-2 community transmission and high population vaccination coverage. COVID-19 vaccination was associated with lower likelihood of ICU admission during Omicron predominance. COVID-19 vaccination, including a booster dose for those who are fully vaccinated, is critical to minimizing the risk for severe health outcomes among adults with COVID-19.

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Acknowledgments
Keren Dunn, Cedars-Sinai Medical Center; Meredith McMorrow, CDC COVID-19 Emergency Response Team.

***https://covid19.ca.gov/vaccination-progress-data/
^††† https://www.researchsquare.com/article/rs-1189219/v1
^§§§ https://www.researchsquare.com/article/rs-1211792/v1
^¶¶¶ https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/COVID-19/COVID-Variants.aspx

Table 1. Demographic characteristics, clinical characteristics, and clinical outcomes among 1,076 hospitalized adults with SARS-CoV-2 infection by vaccination status and period of variant predominance — one hospital, California, July 15–September 23, 2021 (Delta period) and December 21, 2021–January 27, 2022 (Omicron period)
Characteristic	No. (%)
	Total hospitalizations (N = 1,076)			Unvaccinated (n = 657)			Fully vaccinated (n = 377)
	Delta period	Omicron period	p-value	Delta period	Omicron period	p-value	Delta period	Omicron period	p-value
Total	339	737	—	241	416	—	85	292	—
*Vaccination status^,†**
Unvaccinated	241 (71.1)	416 (56.4)	<0.01	241 (100)	416 (100)	—	—	—	—
At least 1 dose	98 (28.9)	321 (43.6)	<0.01	—	—	—	85 (100)	292 (100)	—
Fully vaccinated	85 (25.1)	292 (39.6)	<0.01	—	—	—	85 (100)	292 (100)	—
Fully vaccinated and booster dose	—^§	70 (9.5)	—	—	—	—	—^§	70 (24.0)	—
Age, yrs, median (IQR)	60 (43–73)	66 (49–79)	<0.01	54 (38–68)	64 (48–78)	<0.01	71 (5–82)	69 (51–80)	0.36
Sex
Men	190 (56.0)	377 (51.2)	0.15	130 (53.9)	221 (53.1)	0.87	52 (61.2)	142 (48.6)	0.05
Women	149 (44.0)	360 (48.8)	0.15	111 (46.1)	195 (46.9)	0.87	33 (38.8)	150 (51.4)	0.05
Race and ethnicity
White, non-Hispanic	163 (48.1)	336 (45.6)	0.47	105 (43.6)	184 (44.2)	0.94	53 (62.4)	136 (46.6)	0.01
Black, non-Hispanic	69 (20.4)	145 (19.7)	0.81	54 (22.4)	87 (20.9)	0.69	12 (14.1)	52 (17.8)	0.51
Hispanic	56 (16.5)	157 (21.3)	0.07	45 (18.7)	87 (20.9)	0.54	9 (10.6)	64 (21.9)	0.02
Asian, non-Hispanic	10 (2.9)	33 (4.5)	0.31	4 (1.7)	17 (4.1)	0.11	6 (7.1)	16 (5.5)	0.60
Other, non-Hispanic^¶	41 (12.1)	66 (9.0)	0.12	33 (13.7)	41 (9.9)	0.16	5 (5.9)	24 (8.2)	0.64
COVID-19 therapies received
Any	273 (80.5)	412 (55.9)	<0.01	197 (81.7)	241 (57.9)	<0.01	65 (76.5)	153 (52.4)	<0.01
Dexamethasone	245 (72.3)	360 (48.8)	<0.01	178 (73.9)	216 (51.9)	<0.01	57 (67.1)	129 (44.2)	<0.01
Remdesivir	234 (69.0)	293 (39.8)	<0.01	170 (70.5)	173 (41.6)	<0.01	54 (63.5)	106 (36.3)	<0.01
Other therapies**	76 (22.4)	92 (12.5)	<0.01	47 (19.5)	58 (13.9)	0.08	23 (27.1)	30 (10.3)	<0.01
Intensive care unit admission	79 (23.3)	124 (16.8)	0.01	55 (22.8)	79 (19.0)	0.27	20 (23.5)	34 (15.3)^††	0.10
Invasive mechanical ventilation	46 (13.6)	68 (9.2)	0.03	37 (15.4)	45 (10.8)	0.11	8 (9.4)	19 (8.6)^††	0.82
Death while hospitalized	28 (8.3)	22 (4.0)^§§	0.01	19 (7.9)	14 (4.9)^¶¶	0.21	9 (10.6)	6 (3.4)***	0.02

*Vaccination status was ascertained from the California Immunization Registry. Fully vaccinated adults were those who were not immunocompromised and had received the second dose of a 2-dose COVID-19 vaccine series or a single dose of a 1-dose product ≥14 days before receiving a positive SARS-CoV-2 test result associated with their hospitalization. Immunocompromised adults were considered fully vaccinated if they had received a third dose of a 3-dose primary series or a single dose of a 1-dose product ≥14 days before receiving a positive SARS-CoV-2 test result associated with their hospitalization. Fully vaccinated adults were considered to have received a booster dose if they had received an additional dose (third or fourth) of an mRNA COVID-19 vaccine ≥14 days before receiving a positive SARS-CoV-2 test result associated with their hospitalization. Adults whose positive SARS-CoV-2 test date was ≥14 days after the first dose of a 2-dose series (or second dose of a 3-dose series) but <14 days after receipt of the second dose (or third dose) were considered partially vaccinated, as were those who had received only a single dose of a 2-dose product (or 1 or 2 doses of a 3-dose series). Adults with no documented receipt of any COVID-19 vaccine dose before the test date were considered unvaccinated.
^†Partially vaccinated adults were not included in analyses stratified by vaccination status because of small sample size. However, they were included in overall proportions and comparisons not stratified by vaccination status; thus, the total number of patients exceeds the sum of fully vaccinated and unvaccinated patients.
^§Vaccination status was ascertained from the California Immunization Registry. Booster status was unavailable for hospitalizations before December 1, 2021.
^¶Includes Native Hawaiian, other Pacific Islander, American Indian, and Alaska Native persons, and persons of unknown race or ethnicity.
**Includes baricitinib, casirivimab-imdevimab, convalescent plasma, sotrovimab, and tocilizumab.
^††Denominator excludes 70 fully vaccinated patients who also received a booster dose.
^§§Denominator excludes 188 patients who remained hospitalized as of January 27, 2022.
^¶¶Denominator excludes 129 patients who remained hospitalized as of January 27, 2022
***Denominator excludes 70 fully vaccinated patients who also received a booster dose and 43 patients who remained hospitalized as of January 27, 2022.

Table 2. Demographic and clinical characteristics and clinical outcomes among 131 adults hospitalized with SARS-CoV-2 infection during early Omicron variant predominance, by primary reason for admission — one hospital, California, December 21, 2021–January 2, 2022
Characteristic	No. (column %)			p-value
Characteristic	Total hospitalizations (N = 131)	Hospitalizations not likely due to COVID-19 (n = 26)	Hospitalizations likely due to COVID-19 (n = 105)	p-value
Age, yrs, median (IQR)	63 (38–79)	38 (29–62)	67 (47–79)	<0.01
Sex
Men	61 (46.6)	11 (42.3)	50 (47.6)
Women	70 (53.4)	15 (57.7)	55 (52.4)	0.67
Race and ethnicity
White, non-Hispanic	59 (45.0)	9 (34.6)	50 (47.6)	0.28
Hispanic	32 (24.4)	10 (38.5)	22 (21.0)	0.08
Black, non-Hispanic	26 (19.8)	5 (19.2)	21 (20.0)	>0.99
Asian, non-Hispanic	5 (3.8)	2 (7.7)	3 (2.9)	0.26
Other, non-Hispanic*	9 (6.9)	0 (—)	9 (8.6)	0.20
Vaccination status^†
Unvaccinated	45 (34.4)	4 (15.4)	41 (39.0)	0.02
At least 1 dose	86 (65.6)	22 (84.6)	64 (61.0)	0.02
Fully vaccinated	80 (61.1)	20 (76.9)	60 (57.1)	0.07
Fully vaccinated and booster dose	18 (13.7)	4 (15.4)	14 (13.3)	0.76
Initial symptoms and signs
Lower respiratory symptoms^§	68 (51.9)	1 (3.8)	67 (63.8)	<0.01
Abnormal chest radiograph^¶	55 (42.0)	1 (3.8)	54 (51.4)	<0.01
Hypoxemia	41 (31.3)	0 (—)	41 (39.0)	<0.01
Fever**	39 (29.8)	5 (19.2)	34 (32.4)	0.24
Gastrointestinal symptoms^††	32 (24.4)	7 (26.9)	25 (23.8)	0.80
Underlying medical conditions
Obesity (BMI ≥30)	46 (35.1)	8 (30.8)	38 (36.2)	0.65
Renal disease	14 (10.7)	2 (7.7)	12 (11.4)	0.74
Hypertension	13 (9.9)	0 (—)	13 (12.4)	0.07
Cardiovascular disease^§§	11 (8.4)	0 (—)	11 (10.5)	0.11
Diabetes mellitus	6 (4.6)	0 (—)	6 (5.7)	0.60
Chronic pulmonary disease^¶¶	2 (1.5)	0 (—)	2 (1.9)	>0.99
COVID-19 therapies administered
Any	73 (55.7)	4 (15.4)	69 (65.7)	<0.01
Dexamethasone	63 (48.1)	3 (11.5)***	60 (57.1)	<0.01
Remdesivir	51 (38.9)	2 (7.7)^†††	49 (46.7)	<0.01
Other therapies^§§§	29 (19.8)	0 (—)	26 (24.8)	<0.01
Intensive care unit admission	17 (13.0)	2 (7.7)	15 (14.3)	0.52
Invasive mechanical ventilation	12 (9.2)	2 (7.7)	10 (9.5)	>0.99
Death while hospitalized	2 (1.9)^¶¶¶	0 (—)****	2 (2.4)^††††	>0.99

Abbreviation: BMI = body mass index.
*Includes Native Hawaiian, other Pacific Islander, American Indian, and Alaska Native persons, and persons of unknown race or ethnicity.
^†Fully vaccinated adults were those who were not immunocompromised and had received the second dose of a 2-dose COVID-19 vaccine series or a single dose of a 1-dose product ≥14 days before receiving a positive SARS-CoV-2 test result associated with their hospitalization. Immunocompromised adults were considered fully vaccinated if they had received a third dose of a 3-dose primary series or a single dose of a 1-dose product ≥14 days before receiving a positive SARS-CoV-2 test result associated with their hospitalization. Fully vaccinated adults were considered to have received a booster dose if they had received an additional (third or fourth) dose of an mRNA COVID-19 vaccine ≥14 days before receiving a positive SARS-CoV-2 test result associated with their hospitalization. Adults whose positive SARS-CoV-2 test date was ≥14 days after the first dose of a 2-dose series (or second dose of a 3-dose series) but <14 days after receipt of the second dose (or third dose) were considered partially vaccinated, as were those who had received only a single dose of a 2-dose product (or 1 or 2 doses of a 3-dose series). Adults with no documented receipt of any COVID-19 vaccine dose before the test date were considered unvaccinated.
^§Includes dyspnea, cough, and wheezing.
^¶Includes presence of opacities or nonspecific densities.
**Either documented temperature >100.4°F (38°C) on admission or identification of fever in a clinical note by the emergency physician or admitting provider.
^††Includes nausea, vomiting, and diarrhea.
^§§Includes coronary artery disease, congestive heart failure, arrhythmias, valvular heart disease, stroke, and peripheral vascular disease.
^¶¶Includes chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma.
***Dexamethasone was administered for neurosurgical indications (two) and for suspected bacterial meningitis (one).
^†††Remdesivir was administered in the setting of difficulty extubating after a gastrointestinal procedure (one) and for unclear indication in a patient admitted for psychiatric care (one).
^§§§Includes baricitinib, casirivimab-imdevimab, convalescent plasma, sotrovimab, and tocilizumab.
^¶¶¶Denominator does not include 25 patients who remained hospitalized as of January 11, 2022.
****Denominator does not include two patients who remained hospitalized as of January 11, 2022.
^††††Denominator does not include 23 patients who remained hospitalized as of January 11, 2022.