1. Study papulation
Of 621 hospitalized adult patients confirmed as COVID-19, 467 (75%) had radiologic evidence of pneumonia and were included in this study (Fig. 1). Their median age was 64 years, and 184 (39%) were female. Of the 467 patients, 86 (18%) were severely immunocompromised; 29 (33%) were SOT, 57 (66%) had hematologic malignancies and 1 (1%) had primary immunodeficiency. The remaining 382 (75%) patients were classified as the comparator group. The baseline clinical characteristics of the two groups are shown in Tables 1 and 2. The SI patients were younger (median 61.5 [interquartile range, IQR, 56-67] vs 64 [55-74] years, p = 0.02), and more likely than the comparators to have chronic kidney disease (46 [54%] vs 36 [9%]; p < 0.001), and chronic liver disease (15 [17%] vs 23 [6%]; p = 0.001). However, members of the SI group were less likely to be obese (24 [28%] vs 161 [42%]; p = 0.02). Although most of the patients in the comparator group were infected by SARS-CoV-2 before the omicron-dominant era (328 [86%]), most of the SI patients were infected during the omicron-dominant era (65 [76%]; p < 0.001)(Table 1).
2. Comparison of clinical characteristics and viral clearance according to severely immunocompromised status
The median (IQR) time to pneumonia development was significantly longer in the SI group (10 [7-15] days) than the comparator group (6 [3-8] days, p < 0.001)(Fig. 2). Cases of critical illness were less common among the SI patients (24 [28%]) than the comparator group (209 [55%]; p < 0.001). In addition, SI patients were less likely to use a mechanical ventilator (15 [17%] vs 116 [30%]; p < 0.001) and be admitted to the ICU (23 [27%] vs 187 [49%]; p < 0.001). There were no significant differences between the two groups in terms of COVID-19-specific treatments, except that tocilizumab was less often administrated to the SI group (14 [16%] vs 151 [40%]; p < 0.001)(Table 2).
Excluding 22 patients whose Ct value was not available, a total of 361 (81%) patients had Ct >30 at some point during hospitalization, and SI patients were less likely to reach the point of viral clearance than the comparators (50 [61%] vs 311 [86%]; p < 0.001). Among the 361 patients who achieved viral clearance, there was a significant difference in median (IQR) time to viral clearance between the SI group (19 [13-25] days) and the comparator group (11 [9-15] days, p < 0.001). Similar results were obtained in a survival analysis estimating rates of viral clearance (median 22 vs 12 days, p < 0.001)(Online Resource, Fig. S1-A). There was no significant different in time to viral clearance between SOT and hematologic malignancies (median 22 vs 24 days, p value = 0.10)(Online Resource, Fig. S1-B).
3. Characteristics and variables associated with COVID-19-related death.
Seventy-six (16%) patients died within 90 days of the date of SARS-CoV-2 pneumonia, and detailed causes of death are shown in Table 2. Of these patients, 54 (12%) died from SARS-CoV-2 pneumonia, and COVID-19-related deaths were comparable in the SI group (11 [13%]) and the comparator group (43 [11%], p = 0.84)(Table 2). Clinical characteristics according to COVID-19-related death are shown in Table 3. Patients who died from SARS-CoV-2 pneumonia were older (median 76 [IQR, 68-85] vs 62 [52-70] years, p < 0.001), and had more cardiovascular disease (16 [30%] vs 57 [14%]; p = 0.005), and solid tumors (8 [15%] vs 22 [5%]; p = 0.02).
Multivariate analysis revealed that age (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 1.11-1.20; p < 0.001), solid tumor (aOR, 5.26; 95% CI, 1.75-15.85; p = 0.003), and SI status (aOR, 5.70; 95% CI, 2.09-15.56; p < 0.001) were independently associated with COVID-19-related death (Table 4). However, the omicron-dominant era (aOR, 0.37; 95% CI, 0.15-.0.91; p = 0.03) was associated with less COVID-19-related death. Although no significant difference in survival rate was observed between two groups (p = 0.76)(Fig. 3-A), after adjustment for age, solid tumor, and dominant variant of the period. the survival rate in SI patients was significantly lower than that in the comparator group (p = 0.001)(Fig. 3-B).
4. Subgroup analysis for variables associated with COVID-19-related death.
Patients who died due to SARS-CoV-2 pneumonia were more likely to be older in both the non-omicron-dominant era (median 76 [IQR, 70-85] vs 62 [53-70] years, p < 0.001) and the omicron-dominant era (median 75 [IQR, 66-85] vs 62 [52-69] years, p = 0.001)(Online Resource, Table S1). Age (aOR, 1.16; 95% CI, 1.11-1.22; p < 0.001) was independently associated with COVID-19-related death during the non-omicron-dominant era. In addition, age (aOR, 1.12; 95% CI, 1.04-1.20; p = 0.004) and solid tumor (aOR, 8.57; 95% CI, 1.60-45.86; p = 0.01) were independent risk factors for COVID-19-related death during the omicron-dominant era. Multivariate analysis revealed that SI status was an independent risk factor for COVID-19-related death in the non-omicron-dominant era (aOR, 8.78; 95% CI, 2.62-29.43; p < 0.001) but not in the omicron-dominant era (aOR, 2.40; 95% CI, 0.42-13.64; p = 0.32)(Online Resource, Table S2). In the survival analysis, there was a significant difference in survival rate, adjusted for age, between the SI group and the comparator group, during the non-omicron-dominant era (p < 0.001)(Online Resource, Fig. S2-A), whereas during the omicron-dominant era, survival rates, adjusted for age and solid tumor, were similar in the two groups (p = 0.50)( Online Resource, Fig. S2-B).