Clinical characteristics of the severe acute respiratory syndrome coronavirus 2 omicron variant compared with the delta variant: a retrospective case-control study of 318 outpatients from a single sight institute in Japan

Study design and participants

This retrospective case-control study was conducted in a single hospital. Patients newly diagnosed with COVID-19 who visited Asahikawa City Hospital as new patients and underwent blood tests were enrolled in the study. We divided them into two groups: the Delta group from April 2021 to October 2021 and the Omicron group from January 2022 to April 2022 (Fig. 1). All patients were diagnosed using polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes, antigen quantification testing, or both from April 2021 to January 2022. According to the notification in February 2022 from the Ministry of Health, Labour, and Welfare of Japan, some symptomatic patients who lived in close contact with confirmed patients with COVID-19 were deemed positive with no testing. Our study included only patients over 15 years of age. Patients who had been treated at other hospitals were excluded. Furthermore, we divided the patients into two groups: those categorized as mild and those with pneumonia (Fig. 1). Multivariate logistic analysis was used to identify pneumonia-related factors in patients with the Omicron variant.

All demographic, clinical, and outcome data were retrospectively extracted from the records of the Asahikawa City Hospital. Demographic characteristics of the patients (age, sex, body mass index (BMI)); white blood cell count (WBC); neutrophil-lymphocyte ratio (NLR); lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), D-dimer, and ferritin levels, and comorbidities were recorded. All blood samples were collected before patients received treatment for COVID-19.

Statistics

Continuous data were analyzed using the Mann–Whitney U test and presented as the mean (interquartile range). Fisher’s exact test or chi-square test was used for categorical variables, as appropriate.

Statistical significance was set at P < 0.05. Statistical analysis was performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a 120 graphical user interface for R (The R Foundation for Statistical Computing, Vienna, 121 Austria) (Kanda, 2013).

We created matched Omicron and Delta groups by age and comorbidities using a caliper width of 0.2.

Ethics

This study was approved by the ethics committee of Asahikawa City Hospital (No. 8, 2021) and was conducted in accordance with the ethical standards outlined in the Declaration of Helsinki (1983). An opt-out method was used to obtain patient consent.

Characteristics

A total of 332 outpatients with COVID-19 who visited Asahikawa City Hospital and underwent blood tests were enrolled in the study. We excluded 14 patients treated in other hospitals after our hospital owing to missing clinical course data. The number of Delta phase patients was 167 from April 2021 to October 2021, and the number of Omicron phase patients was 151. All blood samples were collected in an outpatient setting.

Table 1 presents the characteristics of the 318 patients. The median patient age was significantly higher in the Omicron phase than in the Delta phase, 62 (44.0–78.5) years versus 48 (39–56) years (p < 0.001). The patient comorbidity rate is higher in the Omicron group (64.9%) than in the Delta group (42.5%) (p < 0.001). The proportion of vaccinated patients was significantly higher in the Omicron group than in the Delta group (82.9% vs. 11.4%, p < 0.001). Patients with pneumonia, admission rate, and oxygen requirements were significantly lower in the Omicron group (31.8% vs. 62.9%, p < 0.001), 40.4% compared in the Delta group 56.9% (p = 0.004), and 12.6% in the Omicron group compared to 24.0% in the Delta group (p = 0.010). No significant differences were found in sex, BMI, or smoking history between the two groups. Table S1 shows the types of oxygen therapy used by the patients. There were no patients who died in the Omicron phase, and one patient died in the Delta phase. None of the patients required intensive care unit therapy. In the Omicron group, higher WBC (5,440/µL [3,980–6,755] vs. 4,700/µL [3,845–5,685]/µL, P = 0.005), higher Platelet (Plt) (182*10³/µL [147–230*10³] vs.. 155*10³ /µL[131–196*10³], P < 0.001), lower LDH (200 U/L [173–220] vs. 238 U/L [195–305], P < 0.001), lower NLR (2.87 [1.82–4.35] vs.. 3.42 [2.23–5.33], P = 0.035), lower CRP (0.975 mg/dL [0.36–3.55] vs. 2.43 mg/dL [0.87–4.89], P = 0.001), lower ferritin (184.4 ng/mL [88.6–290] vs. 284 ng/mL [106–523], P = 0.004), lower AST (25.0 U/L [19.0–34.0] vs. 31.0 U/L [23.0–41.0], P < 0.001), lower ALT (21.0 U/L [14.0–35.0] vs. 24.0 U/L[17.0–43.0], P = 0.002) and higher D-dimer (0.6 µg/mL [0.3–1.2] vs. 0.5 µg/mL [0.2–1.0], P = 0.046) were found compared to the Delta group.

Table 2 shows the data of the matched groups in terms of age and comorbidities. The proportion of vaccinated patients was significantly higher in the Omicron group (83.7% vs. 8.8%, p < 0.001). Patients who developed pneumonia, required oxygen, or required admission were significantly lower in the Omicron group, 25.2% versus 71.8% (p < 0.001), 32.0% versus 66.0% (p < 0.001), and 5.8% versus 29.1% (p < 0.001). No significant differences were found in sex, BMI, or smoking history between the two groups.

In the Omicron group, higher WBC (5,610/µL [4,010–6,780] vs. 4,510/µL [3,775–5,470]/µL, P = 0.004), higher Platelet (193*10³/µl [156–235*10³] vs. 150*10³/µl [129–195*10³], P < 0.001), lower LDH (197 U/L [172–220] vs. 250 U/L [199–325], P < 0.001), lower NLR (2.96 [1.74–4.31] vs. 3.48 [2.25–5.39], P = 0.035), lower CRP (0.91 mg/dL [0.31–3.11] vs. 2.74 mg/dL [1.25–5.63], P < 0.001), lower ferritin (169 ng/mL [86–340] vs. 272 ng/mL [103–568], P = 0.028), and lower AST (18.5 U/L [13.0–34.5] vs. 31.0 U/L [24.5–39.5], P < 0.001) were found compared to the Delta group. ALT and D-dimer levels did not differ between the groups.

In the Omicron phase, 103 patients were categorized into the mild group and 48 into the pneumonia group. Table 3 shows the data of 151 patients with the Omicron variant. The median patient age was significantly higher in the pneumonia group than in the mild group, 71.5 (56.8–84.0) years versus 56.0 (42.0–74.5) years (p = 0.001). The proportion of men was significantly higher in the pneumonia group (70.8% vs. 49.5%) (p = 0.015). The median BMI was higher in the pneumonia group, 25.3 (23.0–27.8) vs. 23.4 (20.8–26.3) (p = 0.029). There were no significant differences in smoking, vaccination, and comorbidities.

In the pneumonia group, lower Plt (167*10³/µl [133–215*10³] vs. 185*10³/µl [156–235*10³], P = 0.027), higher LDH (221 U/L [199–254] vs. 189 U/L [170–207], P < 0.001), higher CRP (3.13 mg/dL [0.83–6.33] vs. 0.72 mg/dL [0.22–1.83], P < 0.001), higher ferritin (274 ng/mL [172–578] vs. 134 ng/mL [71–240], P < 0.001), higher D-dimer (0.7 µg/mL [0.5–1.5] vs. 0.5 µg/mL [0.3–1.1], P = 0.012) and higher AST (31.0 U/L [22.0–36.0] vs. 23.0 U/L [18.0–33.5], P = 0.006) were found compared to the mild group. The WBC, NLR and ALT levels did not differ between the groups. Multivariate logistic regression analysis was performed on the data. To address the problem of multicollinearity, we excluded the categories smoking, WBC, AST, and ALT. The adjusted odds ratio of age was 1.06 (1.01–1.11, P = 0.020), BMI was 1.19 (1.02–1.40, P = 0.030), SARS-CoV-2 vaccines was 0.12 (0.02–0.55, P = 0.006), LDH was 1.03 (1.01–1.05, P = 0.006) and CRP was 1.50 (1.19–1.89, P = 0.001) (Table 4). There were no significant differences in sex, comorbidities, Plt, NLR, D-dimer and Ferritin. The multivariate analysis showed that older age, higher BMI, more non-vaccination, higher LDH, and higher CRP levels were associated with the pneumonia group.