Multisystem Inflammatory Syndrome After Breakthrough SARS-CoV-2 Infection in 2 Immunized Adolescents, United States

Lyndsey D. Cole; Molly Slate; Samantha Minneman; Michael J. Bozzella

Emerging Infectious Diseases. 2022;28(7):1456-1459.

Abstract and Introduction

Abstract

Eight weeks after having laboratory-confirmed SARS-CoV-2 breakthrough infections, 2 otherwise healthy, fully immunized adolescent patients in the United States who were experiencing related signs and symptoms were diagnosed with multisystem inflammatory syndrome in children. Our findings indicate that COVID-19 vaccination does not completely protect adolescents against multisystem inflammatory syndrome.

Introduction

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory illness occurring after SARS-CoV-2 infection; ≈30% of case-patients are adolescents.^[1] The United States reported 7,880 MIS-C cases and 66 deaths as of March 28, 2022.^[1] MIS-C is an exception to the lower incidence and death from SARS-CoV-2–associated health conditions in children than adults.^[2] In April–June 2020, estimated MIS-C incidence across 7 US jurisdictions was 316 (95% CI 278–357) cases per 1 million SARS-CoV-2 infections in persons <21 years of age.^[3] The small but serious risk of MIS-C has been cited in support of pediatric SARS-CoV-2 immunization.^[4,5]

The BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine (https://www.pfizer.com) was approved in December 2020 for children ≥16 years of age and in May 2021 for children 12–15 years of age.^[6] As of April 20, 2022, a total of 68% of US children 12–17 years of age had been fully immunized.^[6] Data about the effects of SARS-CoV-2 immunization on MIS-C are limited, although some evidence suggests the vaccine offers protection against MIS-C in adolescents.^[7,8] We describe 2 cases of MIS-C after breakthrough SARS-CoV-2 infection in fully immunized adolescents.

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Next Section

Abstract and Introduction
The Study
Conclusions
References

Table 1. Laboratory results for 2 adolescent MIS-C case-patients, by day in hospital, United States*
Result†	Case-patient 1, hospitalization for MIS-C						Case-patient 2‡
	Case-patient 1, hospitalization for MIS-C						Pre–MIS-C hospitalization		Hospitalization for MIS-C
	HD1	HD2	HD3	HD4	HD5	HD6	HD1	HD4	HD1	HD3	HD5	HD7	HD9
Leukocytes, × 10⁹ cells/L	↓3.6	↓4.1	↓2.3	↓2.6	↓3.1	↓2.7	11.9	NA	7.8	5.8	↓2.9	5.4	9.0
Hemoglobin, g/dL	12.5	13.1	12.4	12.2	12.4	↓10.5	13.5	NA	13.8	↓10.8	↓10.4	↓10.3	↓10.5
Platelets, 10⁹/L	↓98	↓109	188	237	321	362	290	NA	373	265	NA	305	331
Absolute neutrophil count, × 10⁹ cells/L	2.4	3.3	↓1	↓0.9	↓1	↓0.6	NA	NA	↓1.4	1.8	2.0	3.6	4.7
Absolute lymphocyte count, × 10⁹ cells/L	1	↓0.6	1.1	1.3	1.7	1.8	NA	NA	5.8	2.3	↓0.6	1.2	2.8
ESR, mm/h	NA	6	7	↑23	↑24	↑25	↑18	NA	↑22	↑96	NA	NA	NA
Sodium, mmol/L	↓130	↓136	↓134	↓133	↓132	137	↓135	NA	↓136	137	↓127	↓136	139
Creatinine, mg/dL	↑1.2	↑1.0	↑0.9	0.7	↑0.8	0.6	0.7	NA	↑1.0	↑2.2	↑3.9	↑2.3	↑1.3
AST, U/L	↑165	↑207	↑131	↑114	↑200	↑164	↑297	↑164	↑102	↑169	↑53	28	33
ALT, U/L	↑221	↑243	↑196	↑167	↑195	↑162	↑249	↑269	↑188	↑177	↑123	↑57	45
GGT, U/L	↑126	↑137	↑129	↑128	↑136	NA	NA	NA	↑342	↑209	NA	NA	NA
LDH, U/L	↑1,484	NA	↑1,155	↑928	↑863	NA	↑1,313	NA	↑982	NA	NA	NA	NA
C-reactive protein, mg/L	↑135	↑86	↑64	↑36	↑19	↑11	↑23	NA	↑17	↑47	↑56	↑19	10
Ferritin, ng/mL	↑750	NA	↑576	↑626	↑754	↑578	↑593	NA	191	284	NA	NA	NA
Albumin, g/dL	NA	↓2.9	↓2.8	↓2.8	↓3.1	↓3.1	↓3.1	↓3.2	3.6	↓2.6	3.0	↓3.1	↓3.1
aPTT, s	↑42.9	36.5	↑38.9	↑39.4	NA	NA	↓20.5	NA	28.9	31.3	NA	NA	NA
PT, s	14	12.6	13.5	13.7	14.1	13.5	13.4	NA	13.5	14.7	NA	NA	NA
Fibrinogen, mg/dL	328	354	302	269	317	NA	258	NA	413	NA	NA	NA	NA
D-dimer, μg/mL	NA	↑>4	↑>4	↑>4	↑3.1	NA	NA	NA	↑2.8	NA	NA	NA	NA
Troponin-I, ng/mL	0.03	↑0.04	↑0.05	0.03	0.02	NA	<0.02	NA	<0.02	NA	NA	NA	NA
NT-proBNP, pg/mL	↑365	↑477	↑601	↑1,020	↑212	NA	66	NA	85	↑3,190	↑3,360	↑1,300	↑1,590

*ALT, alanine aminotransferase; aPTT, activated partial thromboplastin time; AST, aspartate aminotransferase; ESR, erythrocyte sedimentation rate; GGT, gamma-glutamyl transpeptidase; HD, hospital day; LDH, lactate dehydrogenase; MIS-C, multisystem inflammatory syndrome in children; NT-proBNP, N-type pro-brain natriuretic peptide; PT, prothrombin time; ↑, increased outside of reference range; ↓, decreased outside of reference range. †Reference ranges: leukocytes, 5.2–9.7 × 10⁹ cells/L; hemoglobin, 11.8–15.8 g/dL; platelets, 150–500 × 10⁹/L; absolute neutrophil count, 1.8–6.6 × 10⁹ cells/L; absolute lymphocyte count, 1.0–4.8 × 10⁹/L; ESR, <15 mm/h; sodium, 137–145 mmol/L; creatinine, 0.2–0.7 mg/dL; AST, 15–40 U/L; ALT, <50 U/L; GGT, 10–28 U/L; LDH, 360–730 U/L; C-reactive protein, 0–10 mg/L; ferritin, 6–464 ng/mL; albumin 3.5–5 g/dL; aPTT, 23.5–37.5 s; PT, 11.5–15.0 s; fibrinogen, 200–450 mg/dL; D-dimer, <0.5 μg/mL; troponin-I, <0.03 ng/mL; NT-proBNP, <125 pg/mL
‡Omitted data for case-patient 2 from HD2 and HD3 of pre–MIS-C hospitalization and data from HD4, HD6, and HD8 of hospitalization for MIS-C were unnecessary for demonstrating clinical trends

Table 2. Infectious laboratory results for 2 adolescents after multisystem inflammatory syndrome in children symptom onset and throughout hospitalization, United States*
Laboratory test	Case-patient 1	Case-patient 2
SARS-CoV-2 spike IgG	Positive	NA
SARS-CoV-2 nucleocapsid IgG	Positive	Positive
SARS-CoV-2 PCR	Negative	Positive†
Other respiratory pathogen panel PCR	Negative	Negative
Blood culture, peripheral, 2 sets	Negative	Negative
Urine culture	Negative	Negative
Epstein Barr virus ab panel	Consistent with prior infection	Negative
Gastrointestinal pathogen panel PCR	Negative	NA
Group A Streptococcus throat PCR	Negative	NA
Quantiferon tuberculosis gold	Negative	NA
HIV Ag/Ab, 4th-generation	NA	Nonreactive
Rapid plasma regain	NA	Nonreactive
Parvovirus IgM and IgG	NA	Negative
Anti-streptolysin-O	NA	Negative
Anti-deoxyribonuclease B	NA	Negative

*Ag, antigen; Ab, antibody.
†Case-patient 2 had a positive SARS-CoV-2 PCR result on day-of-illness 11, followed by a negative result on day-of-illness 19.