In total, 646 patients with COVID-19 were admitted to Tokoname City Hospital between 2021 and 2022. Patients were excluded if the purpose of hospitalization was isolation, including passengers from foreign countries who had been confirmed to be positive for SARS-CoV-2 at the time of airport quarantine (n = 139), for monoclonal antibody therapy in elderly or immunocompromised hosts (n = 13), or transfer from other hospitals after improvement (n = 12). The four hundred and eighty-two remaining patients were divided into those admitted during the Omicron period (n = 225) and those admitted during the pre-Omicron period (n = 257).
The patient characteristics are shown in Table 1. Patients in the Omicron period were older by approximately 20 years (half were ≥ 80 years of age) when compared with those in the pre-Omicron period, were leaner, had more comorbidities, and were hospitalized sooner after symptom onset (by 4 days). Vaccination for SARS-CoV-2 was started for citizens aged ≥ 65 years in April 2021 in Japan, and more patients received at least one vaccination dose in the Omicron period than in the pre-Omicron period (79.6% versus 8.6%, p < 0.001). Moreover, 41.8% of patients received a booster dose during the Omicron period. In total, 84.0% of patients in the Omicron period and 97.3% of the patients in the pre-Omicron period had viral/bacterial pneumonia on admission. The critical illness rate was similar, being less than 10% in both periods.
Secondary infection was present in two patients on admission and in 13 after admission during the pre-Omicron period and in 100 and 20 patients, respectively, during the Omicron period. Coinfections on admission were more common in the Omicron period than in the pre-Omicron period (44.4% versus 0.8%, p < 0.001). However, there was no significant difference in the incidence of hospital-onset infection between the two periods (5.5% versus 8.9%, p = 0.141). Although there was no significant difference in the serum C-reactive protein concentration on admission between the two periods, the median serum procalcitonin level was significantly higher in the Omicron period than the pre-Omicron period (0.20 [interquartile range 0.08, 0.65] versus 0.09 [interquartile range 0.06, 0.16], p < 0.001).
The types of secondary infection are shown in supplementary Table 1. During the Omicron period, 93% of coinfections on admission was respiratory tract infections while 50% of hospital-onset infections was respiratory tract infections followed by catheter-related bloodstream infections (30.0%) and urinary tract infections (20.0%). In the pre-Omicron period, the most common type of hospital-onset infection was respiratory tract infection (46.2%) followed by urinary tract infection (38.5%). Fungal infection was diagnosed in only one patient during the study period. Features of the shadows characteristic of pneumonia seen on CT scans are shown in Table 2. Ground-glass opacities, bilateral shadows, and a peripheral distribution, which represent the typical characteristic appearance of COVID-19 pneumonia on CT [18], were observed in most patients in the pre-Omicron period (94.6%, 94.8%, and 95.6% [peripheral and peripheral/central], respectively) and there were significant differences in comparison with patients in the Omicron period. As prominent features, consolidation shadows were detected in 27.5% of patients in the pre-Omicron period and in 6.4% of patients in the pre-Omicron period (p < 0.001).
More patients in the Omicron period had secondary infection, which was a main cause of admission. Therefore, fewer patients received COVID-19-directed therapy (Fig. 1), including antiviral treatment for SARS-CoV-2 (74.7% versus 90.3%, p < 0.001; remdesivir was exclusively used in both periods), steroids (16.9% versus 61.1%, p < 0.001), tocilizumab or baricitinib (4.9% versus 12.8%, p = 0.003), and anticoagulants (31.1% versus 61.9%, p < 0.001).
The organisms isolated in patients with secondary infections are shown in Table 3. Methicillin-resistant Staphylococcus aureus was isolated from hospital-onset infections in four (20.0%) of 20 patients in the Omicron period and two (15.4%) of 13 in the pre-Omicron period. Neither carbapenemase-producing Enterobacterale nor MDR Acinetobacter baumannii or Pseudomonas aeruginosa was isolated during the study period. Supplementary Table 2 shows the antibiotics used for secondary infections. Ceftriaxone and piperacillin/tazobactam were used in one patient each for infections on admission during the pre-Omicron period. However, during the Omicron period, 146 antimicrobial agents were used in 100 patients who had infections on admission. The most frequently used antibiotics were ampicillin/sulbactam (n = 58) and ceftriaxone (n = 42), followed by piperacillin/tazobactam (n = 6), levofloxacin (n = 6), cefepime/ceftazidime (n = 5), meropenem (n = 5), vancomycin (n = 2), and teicoplanin (n = 2). The antibiotics predominantly used for HAIs were administered in seven (53.8%) of 13 patients during the pre-Omicron period and in nine (45.0%) of 20 patients during the Omicron period. Overall, piperacillin/tazobactam (n = 14), cefepime/ceftazidime (n = 11), carbapenems (n = 8), and fluoroquinolone (n = 6) were used in 135 patients with secondary infections throughout the 2-year study period.
The DOT was compared between patients admitted to the COVID-19 ward and those admitted to general acute care wards (Fig. 2). During the pre-Omicron period, the DOT of antibiotics for CAIs was significantly lower in the COVID-19 ward than in the general acute care wards (3.60 ± 3.15 versus 10.04 ± 1.83, p < 0.001). However, in the Omicron period, the DOT in the COVID-19 ward increased to 17.83 ± 10.00, which was significantly higher than the DOT in the general acute care wards during the same period (7.97 ± 1.21, p = 0.006). There was no significant difference in the DOT of antibiotics for HAIs between the COVID-19 ward and the general acute care wards in either period (pre-Omicron, 3.33 ± 6.09 versus 6.37 ± 1.10, p = 0.103; Omicron, 3.84 ± 2.93 versus 5.22 ± 0.79, p = 0.129). The DOT for the antibiotics predominantly used for resistant gram-positive infections was 0.11 in the COVID-19 ward and 0.97 in the general acute care wards during the pre-Omicron period and 1.87 and 1.39, respectively, in the Omicron period. The DOT for antifungal agents was 0.35 in the COVID-19 ward and 1.57 in the general acute care wards during the pre-Omicron period and 2.59 and 1.76, respectively, during the Omicron period.
During hospitalization, high-flow oxygen (≥ 5 L/min) was required in 17.8% of patients (5.8% via high-flow nasal cannula [HFNC]) in the Omicron period and 16.0% (9.7% via HFNC) in the pre-Omicron period. Invasive mechanical ventilation was initiated in three patients (1.3%) and in four patients (1.6%), respectively. In addition, vasopressor support was used in four patients (1.8%) and three patients (1.2%), respectively. Thirty-day mortality was significantly higher in the Omicron period than in the pre-Omicron period (11.1% versus 2.3%, p < 0.001); composite adverse events occurred in 21.3% and 16.3% of patients, respectively (p = 0.161).
In multivariate analyses, independent risk factors associated with composite adverse events were current smoking or a history of smoking (adjusted OR 2.607, 95% CI 1.270–5.349), diabetes (adjusted OR 2.292, 95% CI 1.063–4.942), and secondary infections (adjusted OR 3.767, 95% CI 1.127–12.594) in the pre-Omicron period. While, independent risk factors during the Omicron period were chronic renal failure (adjusted OR 3.993, 95% CI 1.508–10.571) and secondary infections (adjusted OR 9.145, 95% CI 3.846–21.743) (Table 4).