Table 2.
MIS-C bivariable analysis for epidemiological, clinical, laboratory, echocardiography, and hospital outcomes according to SARS-CoV-2 variant periods
|
All MIS-C n: 152, 100% |
Wuhan period n: 73, 48% |
Alpha period n: 5, 3% |
Delta period n: 44, 29% |
Omicron period n: 30, 20% |
p-vala | |
|---|---|---|---|---|---|---|
| Rate (× 106)b | 273 | 926 | 173 | 538 | 82 | < 0.001 |
| Monthly incidence (× 106) | 4.1 | 4.6 | 0.8 | 4.9 | 4.6 | < 0.001 |
| Demographic and COVID-19 related findings | ||||||
| Gender, n (%) | ||||||
| Male | 95 (62.5) | 46 (63.0) | 1 (20.0) | 26 (59.1) | 22 (73.3) | 0.83 |
| Female | 57 (37.5) | 27 (37.0) | 4 (80.0) | 18 (40.9) | 8 (26.7) | - |
| Age (years), median (IQR) | 8 (4–11) | 8 (4–12) | 4 (2–5) | 8 (5–10) | 8 (5.25–11.75) | 0.87 |
| Ethnicity/race, n (%) | ||||||
| Caucasian | 91 (59.9) | 48 (65.8) | 2 (40.0) | 20 (45.5) | 21 (70.0) | 0.47 |
| Hispanic (Latin America) | 23 (15.1) | 8 (11.0) | 1 (20.0) | 10 (22.7) | 4 (13.3) | 0.69 |
| Black African | 13 (8.6) | 8 (11.0) | 1 (20.0) | 3 (6.8) | 1 (3.3) | 0.83 |
| Arabic | 12 (7.9) | 3 (4.1) | 0 (0.0) | 7 (15.9) | 2 (6.7) | 0.47 |
| Asian | 7 (4.6) | 3 (4.1) | 1 (20.0) | 1 (2.3) | 2 (6.7) | 1 |
| Other/mixed | 6 (4.0) | 3 (4.1) | 0 (0.0) | 3 (6.8) | 0 (0.0) | 0.83 |
| Recent COVID-19 infection, n (%) | 69 (45.4) | 29 (42.7) | 2 (40.0) | 23 (52.3) | 15 (50.0) | 0.83 |
| SARS-CoV-2 at MIS-C diagnosis, n (%) | ||||||
| RT-PCR positive | 33 (21.7) | 19 (26.0) | 2 (40.0) | 8 (18.2) | 4 (13.3) | 0.47 |
| RAT positive | 5 (3.3) | 0 (0.0) | 0 (0.0) | 1 (2.3) | 4 (13.3) | 0.13 |
| IgG SARS-CoV-2 positive at MIS-C diagnosis, n (%) | 131 (86.2) | 64 (87.7) | 3 (60.0) | 41 (93.2) | 23 (76.7) | 0.47 |
| Clinical findings (n (%)) | ||||||
| Fever at admission | 150 (98.7) | 71 (97.3) | 5 (100.0) | 44 (100.0) | 30 (100.0) | 1 |
| Fever (> 39) | 124 (81.6) | 57 (78.1) | 5 (100.0) | 36 (81.8) | 26 (86.7) | 1 |
| Rash | 90 (59.2) | 42 (58.3) | 4 (80.0) | 25 (56.8) | 19 (63.3) | 1 |
| Conjunctivitis | 83 (54.6) | 33 (45.2) | 4 (80.0) | 22 (50.0) | 24 (80.0) | 0.13 |
| Oral lesions | 55 (36.2) | 25 (34.3) | 1 (20.0) | 13 (29.6) | 16 (53.3) | 0.47 |
| Cervical lymphadenopathy (> 1.5 cm) | 29 (19.1) | 11 (15.1) | 0 (0.0) | 11 (25.0) | 7 (23.3) | 0.79 |
| Gastrointestinal symptoms | 134 (88.2) | 65 (89.0) | 2 (40.0) | 39 (88.6) | 28 (93.3) | 1 |
| Respiratory symptoms | 35 (23.0) | 16 (21.9) | 1 (20.0) | 11 (25.0) | 7 (23.3) | 1 |
| Neurologic symptoms | 19 (12.5) | 11 (15.1) | 0 (0.0) | 8 (18.2) | 1 (3.3) | 0.66 |
| Hypotension/shock | 81 (53.3) | 42 (57.5) | 0 (0.0) | 23 (52.3) | 16 (53.3) | 1 |
| PICU admission | 68 (44.7) | 36 (49.3) | 0 (0.0) | 19 (43.2) | 13 (43.3) | 1 |
| Laboratory results | ||||||
| Hemoglobin (g/dL), median (IQR) | 11.8 (10.9–12.7) | 12 (11.0–12.6) | 11.1 (10.7–11.9) | 11.4 (10.8–12.0) | 12.5 (11.1–12.9) | 0.69 |
| Leukocytes (109/L), median (IQR) | 9.45 (6.35–13.00) | 9.55 (6.4–13.3) | 9.8 (7.7–10.93) | 8.19 (5.64–11.4) | 9.55 (6.4–13.3) | 0.47 |
| Platelets (109/L) median (IQR) | 171 (114–232.25) | 162 (110–230) | 327 (211–330) | 170.5 (132.5–227.5) | 167 (103.5–229) | 0.47 |
| Platelets < 150 (109/L), n (%) | 92 (60.5) | 30 (41.1) | 0 (0.0) | 17 (38.6) | 13 (43.3) | 1 |
| Lymphocytes < 1.0 (109/L), n (%) | 75 (49.3) | 37 (50.7) | 2 (40.0) | 22 (50.0) | 16 (53.3) | 1 |
| CPR (mg/dL), median (IQR) | 17.25 (11.28–24.82) | 17.2 (10.73–25.7) | 21.8 (15.9–23.39) | 16.5 (12.55–22.36) | 17.75 (10.95–25.57) | 1 |
| Procalcitonin (ng/mL), median (IQR) | 3.7 (1.43–10.67) | 3.67 (1.45–7.43) | 3.16 (2.25–4.07) | 2.46 (1.24–6.48 | 7.0 (2.6–17.45) | 0.78 |
| Ferritin (ng/mL), median (IQR) | 399 (237–640) | 393 (193.5–569.5) | 547 (496.25–592.92) | 350 (240.0–575.25) | 631.5 (332.75–1460.25) | 0.47 |
| IL-6 (ng/L), median (IQR) | 162.29 (52–380.9) | 100.6 (31.37–248.52) | 308 (275.45–387.35) | 182.55 (92.27–385.17) | 206.75 (82.75–392.17) | 0.67 |
| Pro-BNP (pg/mL), median (IQR) | 2411.0 (583.1–5804.5) | 3277.0 (1006.0–7726.5) | 1093.0 (306.475–2212.5) | 1401.5 (301.5–4132.0) | 2230.5 (675.5–10,049.7) | 0.47 |
| D-dimer (ng/mL), median (IQR) | 2150.5 (1187.75–4192.5) | 1999 (854–5030) | 1719 (1624–1857.5) | 2652 (1487.5–3948.5) | 2039 (1630–5130) | 0.96 |
| ALT (IU/L), n (%) | ||||||
| < 50 | 91 (59.9) | 42 (57.5) | 1 (20.0) | 32 (72.7) | 16 (53.3) | 0.76 |
| > 250 | 4 (2.6) | 3 (4.1) | 1 (20.0) | 0 (0.0) | 0 (0.0) | 0.96 |
| Echocardiography | ||||||
| Pathologic echocardiography | 60 (39.5) | 31 (42.5) | 2 (40.0) | 16 (36.4) | 11 (36.7) | 0.96 |
| Ventricular dysfunction | 22 (14.5) | 12 (16.4) | 0 (0.0) | 6 (13.6) | 4 (13.3) | 0.83 |
| Coronary abnormalities | 15 (9.8) | 9 (12.3) | 0 | 4 (9.1) | 2 (6.7) | 0.96 |
| Hospital stay | ||||||
| Length of hospital stay (days), median (IQR) | 7 (5–9) | 7 (5–10.25) | 6 (5–9) | 7 (5–8) | 5 (4–8) | 0.75 |
| PICU admission, n (%) | 68 (44.7) | 36 (49.3) | 0 (0.0) | 19 (43.2) | 13 (43.3) | 1 |
| Length of PICU stay (days), median (IQR) | 4 (2–5) | 5 (3–5.25) | - | 3 (2–5) | 3 (2–5) | 0.67 |
The periods were Wuhan type variant April 2020–December 2020, Alpha variant January 2021–July 2021, Delta variant July 2021–December 2021, Omicron variant December 21–February 2022
ECMO extracorporeal membrane oxygenation, PICU pediatric intensive care unit, IL-6 interleukin 6, IQR interquartile range, MIS-C multisystem inflammatory syndrome in children, NT-proBNP N-terminal pro b-type natriuretic peptide, RT-PCR reverse transcription polymerase chain reaction, RAT rapid antigen test, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
aP-values (α = 0.05) come from Kruskal–Wallis tests in the case of quantitative variables and Fisher’s exact tests in the case of categorical variables (except for MIS-C rate and incidence, where z-tests were performed). The Alpha period has been excluded from all tests except from MIS-C rate. p-values reported, except for MIS-C rate and incidence, have been adjusted, together for Tables 2 and 3, using the Benjamini and Hochberg method, to account for multi-testing
bFor the analysis of the rate between MIS-C cases and COVID-19 cases across SARS-CoV-2 variants, the Wuhan period is excluded for the calculation of the p-value due to the lack of COVID-19 diagnosis occurring in the first pandemic wave (no access to diagnosis methods such as RT-PCR or RAT). This leads to a bias for the estimation of the ratio (overestimated) in this period