Table 1.
Demographic and clinical characteristics of patients with MIS-C according to SARS-CoV-2 variant era.
| Variable | Total, N = 436a | MIS-C during Alpha era, N = 275 | MIS-C during Delta era, N = 87 | MIS-C during Omicron era, N = 74 |
Delta compared to Alpha |
Omicron compared to Alpha |
||
|---|---|---|---|---|---|---|---|---|
| Pooled RD or ES (95% CI) | P value | Pooled RD or ES (95% CI) | P value | |||||
| Age, years, pooled mean (pooled SD) [N] | 9.7 (4.5) [N = 598] | 10.3 (4.8) [N = 383] | 9.0 (3.9) [N = 111] | 8.2 (3.8) [N = 104] | −1.183 (−2.049, −0.317) | 0.007 | −1.649 (−2.535, −0.763) | <0.001 |
| Sex, N (%) | ||||||||
| Male | 365 (61.0) | 231 (60.3) | 68 (61.3) | 66 (63.5) | 0.012 (−0.097, −0.118)b | 0.884 | 0.045 (−0.178, 0.195)b | 1.000 |
| Female | 233 (39.0), [N = 598] | 152 (39.7) [N = 383] | 43 (38.7) [N = 111] | 38 (36.5) [N = 104] | ||||
| Baseline comorbidities | ||||||||
| Overweight or obesity, N (%) | 28 (6.4) | 23 (8.4) | 2 (2.2) | 3 (4.0) | −0.065 (−0.131, 0.021) | 0.176 | −0.088 (−0.145, 0.047) | 0.229 |
| Asthma, N (%) | 36 (8.3) | 23 (8.4) | 5 (5.7) | 8 (10.8) | −0.036 (−0.120, 0.042) | 0.573 | 0.032 (−0.087, 0.146) | 1.000 |
| Generalized symptoms (other than fever) or muco-cutaneous involvement, N (%) | 310 (71.1) | 201 (73.1) | 58 (66.7) | 51 (68.9) | −0.013 (−0.213, 0.102) | 1.000 | −0.047 (−0.265, 0.156) | 1.000 |
| Fatigue, asthenia | 91 (20.9) | 62 (22.5) | 15 (17.2) | 14 (18.9) | −0.035 (−0.124, 0.113) | 0.799 | −0.000 (−0.193, 0.128) | 1.000 |
| Rash | 143 (32.8) | 95 (34.5) | 24 (27.5) | 24 (32.4) | 0.036 (−0.153, 0.166) | 0.935 | −0.002 (−0.124, 0.124) | 1.000 |
| Conjunctivitis | 155 (35.5) | 99 (36.0) | 31 (35.6) | 25 (33.8) | 0.118 (−0.072, 0.234) | 0.184 | 0.008 (−0.122, 0.166) | 1.000 |
| Mucositis | 52 (11.9) | 38 (13.8) | 7 (8.1) | 7 (9.5) | −0.008 (−0.126, 0.071) | 0.961 | −0.057 (−0.120, 0.032) | 0.174 |
| Lymphadenitis/lymphadenopathy | 72 (16.5) | 47 (17.1) | 11 (12.6) | 14 (18.9) | −0.072 (−0.210, 0.057) | 0.986 | 0.000 (−0.129, 0.120) | 1.000 |
| Gastrointestinal involvement, N (%) | 248 (56.9) | 165 (60.0) | 49 (56.3) | 34 (45.9) | 0.069 (−0.133, 0.265) | 0.647 | 0.049 (−0.341, 0.273) | 1.000 |
| Abdominal pain | 148 (33.9) | 101 (36.7) | 30 (34.5) | 17 (23.0) | 0.018 (−0.143, 0.232) | 1.000 | −0.033 (−0.256, 0.184) | 1.000 |
| Nausea or vomiting | 97 (22.2) | 65 (23.6) | 18 (20.7) | 14 (18.9) | −0.011 (−0.170, 0.161) | 1.000 | −0.015 (−0.252, 0.243) | 1.000 |
| Diarrhea, enteritis, ileitis | 101 (23.2) | 75 (27.3) | 15 (17.2) | 11 (14.9) | −0.077 (−0.194, 0.137) | 0.687 | −0.014 (−0.186, 0.110) | 1.000 |
| Appendicitis, peritonitis | 3 (0.7) | 1 (0.4) | 0 (0.0) | 2 (2.7) | −0.001 (−0.030, 0.044) | 1.000 | 0.032 (−0.018, 0.111) | 0.659 |
| Respiratory involvement, N (%) | 222 (50.9) | 162 (58.9) | 29 (33.3) | 31 (41.9) | −0.148 (−0.327, −0.043) | 0.005 | −0.145 (−0.356, 0.054) | 0.376 |
| Cough | 28 (6.4) | 24 (8.7) | 2 (2.3) | 2 (2.7) | −0.037 (−0.096, 0.036) | 0.300 | −0.073 (−0.130, 0.024) | 0.116 |
| Rhinitis/Rhinorrhea | 7 (1.6) | 4 (1.4) | 1 (1.1) | 2 (2.7) | 0.000 (−0.041, 0.067) | 1.000 | 0.015 (−0.050, 0.089) | 1.000 |
| Sore throat | 26 (6.0) | 20 (7.3) | 2 (2.3) | 4 (5.4) | −0.035 (−0.085, 0.038) | 0.513 | 0.000 (−0.093, 0.099) | 1.000 |
| Respiratory failure/dyspnea | 47 (10.8) | 30 (10.9) | 9 (10.3) | 8 (10.8) | −0.023 (−0.097, 0.067) | 0.909 | −0.035 (−0.121, 0.054) | 0.924 |
| Pleural effusion | 81 (18.6) | 59 (21.4) | 11 (12.6) | 11 (14.9) | −0.040 (−0.157, 0.056) | 1.000 | −0.021 (−0.181, 0.109) | 1.000 |
| Pulmonary edema | 26 (6.0) | 17 (6.2) | 3 (3.4) | 6 (8.1) | −0.001 (−0.052, 0.064) | 1.000 | 0.051 (−0.030, 0.155) | 0.258 |
| Pneumonia | 55 (12.6) | 52 (18.9) | 1 (1.1) | 2 (2.7) | −0.129 (−0.258, −0.036) | 0.005 | −0.145 (−0.295, 0.033) | 0.223 |
| ARDS | 9 (2.1) | 6 (2.2) | 1 (1.1) | 2 (2.7) | 0.002 (−0.043, 0.060) | 1.000 | −0.025 (−0.066, 0.045) | 0.496 |
| Cardiovascular involvement, N (%) | 321 (73.6) | 223 (81.1) | 53 (60.9) | 45 (60.8) | −0.043 (−0.332, 0.075) | 0.825 | −0.020 (−0.415, 0.130) | 1.000 |
| Chest pain | 18 (4.1) | 15 (5.4) | 1 (1.1) | 2 (2.7) | −0.020 (−0.072, 0.031) | 0.511 | −0.027 (−0.095, 0.051) | 0.591 |
| Hypotension | 174 (39.9) | 117 (42.5) | 31 (35.6) | 26 (35.1) | −0.029 (−0.146, 0.224) | 1.000 | 0.003 (−0.160, 0.401) | 1.000 |
| Pre-syncope, syncope | 54 (12.4) | 36 (13.1) | 13 (14.9) | 5 (6.7) | 0.068 (−0.012, 0.156) | 0.234 | −0.010 (−0.096, 0.080) | 0.898 |
| Arrhythmias | 97 (22.2) | 69 (25.1) | 14 (16.1) | 14 (18.9) | −0.003 (−0.075, 0.076) | 1.000 | −0.032 (−0.119, 0.064) | 0.645 |
| Myocarditis | 58 (13.3) | 41 (14.9) | 7 (8.0) | 10 (13.5) | −0.075 (−0.245, 0.024) | 0.166 | −0.059 (−0.298, 0.063) | 0.585 |
| Pericarditis/pericardial effusion | 107 (24.5) | 74 (26.9) | 19 (21.8) | 14 (18.9) | 0.036 (−0.088, 0.138) | 0.898 | −0.014 (−0.146, 0.123) | 1.000 |
| Left ventricular dysfunction | 60 (13.8) | 43 (15.6) | 6 (6.9) | 11 (14.9) | −0.032 (−0.084, 0.031) | 0.318 | −0.012 (−0.103, 0.117) | 1.000 |
| Heart failure | 56 (12.8) | 41 (14.9) | 10 (11.5) | 5 (6.8) | −0.022 (−0.084, 0.089) | 1.000 | 0.067 (−0.178, 0.043) | 0.553 |
| Cardiogenic shock | 84 (19.3) | 52 (18.9) | 16 (18.4) | 16 (21.6) | −0.076 (−0.169, 0.103) | 0.652 | 0.017 (−0.201, 0.192) | 1.000 |
| Shock (non-cardiogenic)/SIRS, N (%) | 187 (42.9) | 146 (53.1) | 16 (18.4) | 23 (31.1) | −0.348 (−0.645, −0.067) | 0.006 | −0.101 (−0.288, 0.041) | 0.207 |
| Septic shock | 45 (10.3) | 36 (13.1) | 5 (5.7) | 4 (5.4) | −0.107 (−0.175, 0.021) | 0.106 | −0.011 (−0.110, 0.057) | 1.000 |
| Hypovolemic shock | 8 (1.83) | 4 (1.4) | 2 (2.3) | 2 (2.7) | −0.004 (−0.037, 0.060) | 1.000 | 0.047 (−0.029, 0.129) | 0.266 |
| Shock, others (non-cardiogenic) | 90 (20.6) | 63 (22.9) | 14 (16.1) | 13 (17.6) | −0.135 (−0.281, 0.064) | 0.342 | −0.001 (−0.179, 0.175) | 1.000 |
| SIRS | 104 (23.8) | 93 (33.8) | 3 (3.4) | 8 (10.8) | −0.278 (−0.463, −0.024) | 0.010 | −0.181 (−0.304, −0.050) | 0.004 |
| Neurologic involvement, N (%) | 163 (37.4) | 130 (47.3) | 19 (21.8) | 14 (18.9) | −0.130 (−0.297, 0.026) | 0.317 | −0.048 (−0.371, 0.104) | 0.958 |
| Headache | 54 (12.4) | 43 (15.6) | 4 (4.6) | 7 (9.5) | −0.088 (−0.168, 0.002) | 0.059 | 0.002 (−0.188, 0.117) | 1.000 |
| Disorientation/Confusion | 27 (6.2) | 23 (8.4) | 2 (2.3) | 2 (2.7) | −0.044 (0.120, 0.044) | 0.437 | −0.047 (−0.106, 0.044) | 0.317 |
| Seizures | 9 (2.1) | 6 (2.2) | 2 (2.3) | 1 (1.3) | 0.013 (−0.037, 0.065) | 0.948 | −0.021 (−0.063, 0.042) | 0.509 |
| Muscle weakness/myalgia/myositis | 47 (10.8) | 35 (12.7) | 9 (10.3) | 3 (4.0) | 0.031 (−0.070, 0.134) | 0.935 | 0.021 (−0.146, 0.095) | 1.000 |
| Encephalopathy/meningoencephalitis | 9 (2.1) | 6 (2.2) | 2 (2.3) | 1 (1.3) | −0.047 (−0.186, 0.071) | 0.841 | −0.003 (−0.167, 0.048) | 1.000 |
| Stroke | 3 (0.7) | 2 (0.7) | 0 (0) | 1 (1.3) | 0.000 (−0.032, 0.047) | 1.000 | 0.017 (−0.039, 0.086) | 0.749 |
| Kidney dysfunction, N (%) | 92 (21.1) | 66 (24.0) | 14 (16.1) | 12 (16.2) | −0.048 (−0.233, 0.058) | 0.540 | 0.000 (−0.273, 0.161) | 1.000 |
| Liver dysfunction, N (%) | 50 (11.5) | 32 (11.6) | 7 (8.0) | 11 (14.9) | −0.013 (−0.297, 0.026) | 0.460 | 0.045 (−0.011, 0.217) | 0.950 |
A detailed definition of the variables based on EHR data or ICD-10 codes is reported as Supplementary Material.
Aggregate counts and summary statistics for the total sample and the MIS-C era subgroups were calculated for descriptive purposes only. Meta-analyses were computed by pooling risk differences (RD, categorical variables) or effect sizes (ES, continuous variables) and their 95% confidence intervals (CIs) previously calculated at site-level. A detailed definition of the variables based on EHR data or ICD-10 codes is reported as Supplementary Material.
ES: effect size; MIS-C: multisystem inflammatory syndrome; RD: risk difference; SD: standard deviation; SIRS: systemic inflammatory response syndrome.
a
ICD-10-code-based data from one centre, which did not pass the quality check, were excluded from analysis, thereby reducing sample size.
b
Male as reference category.