Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination

PCORnet, United States, January 2021-January 2022

Jason P. Block, MD; Tegan K. Boehmer, PhD; Christopher B. Forrest, MD, PhD; Thomas W. Carton, PhD; Grace M. Lee, MD; Umed A. Ajani, MBBS; Dimitri A. Christakis, MD; Lindsay G. Cowell, PhD; Christine Draper; Nidhi Ghildayal, PhD; Aaron M. Harris, MD; Michael D. Kappelman, MD; Jean Y. Ko, PhD; Kenneth H. Mayer, MD; Kshema Nagavedu, MPH; Matthew E. Oster, MD; Anuradha Paranjape, MD; Jon Puro, MPA; Matthew D. Ritchey; David K. Shay, MD; Deepika Thacker, MD; Adi V. Gundlapalli, MD, PhD

Disclosures

Morbidity and Mortality Weekly Report. 2022;71(14):517-523.

Discussion

Analysis of EHR data from 40 U.S. health care systems found that the incidences of cardiac complications after SARS-CoV-2 infection or mRNA COVID-19 vaccination were low overall but were higher after infection than after vaccination for both males and females in all age groups. Two studies from Israel^[2] and the United Kingdom^[3] have found similar higher risk for myocarditis after SARS-CoV-2 infection compared with that after mRNA COVID-19 vaccination.

Myocarditis or pericarditis incidence after mRNA COVID-19 vaccination in the current study (0–35.9 per 100,000 for males and 0–10.9 for females across age groups and vaccine cohorts) was similar to estimates found in a study from eight U.S. health systems in the Vaccine Safety Datalink.^[10] Previous CDC estimates found the highest risk for post-vaccination myocarditis among males aged 16–17 years (10.6 per 100,000) during a 7-day risk window after receipt of a second mRNA COVID-19 vaccine dose.^[5] Estimates from the current study (22.0 per 100,000 males aged 12–17 years) are higher, likely because outcomes were captured using ICD-10-CM codes alone rather than through passive reporting with subsequent verification through medical record review. Even among males aged 12–17 years, the group with the highest incidence of cardiac complications after receipt of a second mRNA COVID-19 vaccine dose, the risk was 1.8–5.6 times as high after SARS-CoV-2 infection than after vaccination.

The findings in this report are subject to at least six limitations. First, data were obtained using a query that returned aggregate data from sites, precluding adjustment for potential confounders. Stratification by age and sex was performed because of their clear prior association with cardiac outcomes. Second, outcomes were rare in some cohorts, leading to wide CIs around RR estimates. Third, only SARS-CoV-2 test results and mRNA COVID-19 vaccinations documented in EHRs were available for assessment. SARS-CoV-2 infections were not captured if testing occurred in homes, schools, community sites, or pharmacies. Similarly, EHR data in this study captured ≥1 dose of mRNA COVID-19 vaccine for 28% of persons aged ≥5 years. Nationally, 82% of persons aged ≥5 years were reported to have received any COVID-19 vaccination; 97% of all vaccinations administered were mRNA COVID-19 vaccines.^§§ Underascertainment of SARS-CoV-2 infections and mRNA COVID-19 vaccinations reduced sample size and might have introduced bias if capture of infection or vaccination within the EHR occurred differentially for those with cardiac outcomes.^¶¶ Fourth, case definitions for myocarditis, pericarditis, or MIS were ICD-10-CM code–based; diagnoses were not confirmed with chart review and are subject to misclassification. Fifth, cases of MIS among persons without documented SARS-CoV-2 infection were not included.^[9] Finally, some overlap might have occurred in risk windows for persons who had a SARS-CoV-2 infection soon after vaccination or a vaccination soon after infection. Exclusions were made for persons who received COVID-19 vaccine doses ≤30 days before infection or who had infections ≤30 days before vaccination.

Cardiac complications were rare after SARS-CoV-2 infection or mRNA COVID-19 vaccination. However, the risks for these complications were higher after infection than after vaccination among males and females in all age groups. These findings provide important context for balancing risks and benefits of mRNA COVID-19 vaccination among eligible persons ≥5 years.

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Acknowledgments
All institutions participating in this study; PCORnet, the National Patient-Centered Clinical Research Network, developed with funding from the Patient-Centered Outcomes Research Institute (PCORI); Karen R. Broder, Samantha Chao, Joshua Denson, Julia Fearrington, Bridget Nolan, Sonja A. Rasmussen, Tom Shimabukuro, William E. Trick, leadership of the Data, Analytics, and Visualization Task Force, CDC COVID-19 Emergency Response Team.

^§§ https://covid.cdc.gov/covid-data-tracker/#vaccinations (Accessed March 29, 2022).
^¶¶If patients who received a SARS-CoV-2–positive test result at a health care system were more likely to return to the same health care system for myocarditis, pericarditis, or MIS treatment than were patients who had their mRNA COVID-19 vaccination documented at the health care system, then the underascertainment of outcomes might be higher in the vaccination cohorts, introducing bias away from the null. This scenario might occur if a person was more likely to visit a tertiary care referral center participating in this study if they were more severely ill with a cardiac complication after SARS-CoV-2 infection than a perhaps mild cardiac complication after COVID-19 vaccination. However, if the cardiac complications were more commonly linked to vaccination than infection in the EHR, bias would be toward the null. This scenario might occur if clinicians were more likely to document an mRNA COVID-19 vaccination in the EHR if a cardiac complication was noted after vaccination than if the cardiac complication occurred after SARS-CoV-2 infection.

Table 1. Demographic characteristics of persons who were infected with SARS-CoV-2 or received a first, second, unspecified, or any dose of an mRNA COVID-19 vaccine* — National Patient-Centered Clinical Research Network, United States, January 1, 2021–January 31, 2022
Characteristic	No. (%)
	SARS-CoV-2 infection cohort^†	mRNA COVID-19 vaccination cohort
	SARS-CoV-2 infection cohort^†	First dose*^,§	Second dose*^,§	Unspecified dose*^,¶	Any dose^,*
Cohort total	814,524 (100)	2,548,334 (100)	2,483,597 (100)	1,681,169 (100)	6,713,100 (100)
Age group, yrs
5–11	76,960 (9)	48,986 (2)	41,742 (2)	30,199 (2)	120,927 (2)
12–17	70,336 (9)	190,810 (7)	179,612 (7)	113,775 (7)	484,197 (7)
18–29	151,950 (19)	308,892 (12)	297,560 (12)	241,787 (14)	848,239 (13)
30–50	255,103 (31)	665,876 (26)	652,947 (26)	490,808 (29)	1,809,631 (27)
51–65	152,243 (19)	601,615 (24)	588,873 (24)	404,445 (24)	1,594,933 (24)
≥66	107,932 (13)	732,155 (29)	722,863 (29)	400,155 (24)	1,855,173 (28)
Sex
Female	457,506 (56)	1,497,984 (59)	1,463,746 (59)	997,741 (59)	3,959,471 (59)
Male	357,018 (44)	1,050,350 (41)	1,019,851 (41)	683,428 (41)	2,753,629 (41)
Race/Ethnicity^††
Hispanic	133,784 (16)	309,468 (12)	298,270 (12)	169,688 (10)	777,426 (12)
Asian	23,684 (3)	133,445 (5)	131,205 (5)	83,937 (5)	348,587 (5)
Black or African American	162,434 (20)	408,657 (16)	395,283 (16)	283,534 (17)	1,087,474 (16)
Other	34,473 (4)	93,100 (4)	90,122 (4)	54,305 (3)	237,527 (4)
White	408,152 (50)	1,441,573 (57)	1,407,974 (57)	1,001,686 (60)	3,851,233 (57)
Missing^§§	58,980 (7)	205,834 (8)	204,224 (8)	98,299 (6)	508,357 (8)

*In the first and second dose cohorts, 27% of persons received mRNA-1273 (Moderna) vaccine and 73% received BNT162b2 (Pfizer-BioNTech) vaccine. In the unspecified dose cohort, 36% received Moderna and 64% Pfizer-BioNTech. In the any dose cohort, 29% received Moderna and 71% Pfizer-BioNTech.
^†Persons in the infection cohort included those who received ≥1 positive SARS-CoV-2 molecular or antigen test result.
^§The first dose cohort included persons who had either the first of 2 doses ≥20 days before a second dose or a specific code for a first dose; the second dose cohort included persons who had either the second of 2 doses ≥20 days after a first dose or a specific code for a second dose.
^¶The unspecified dose cohort included persons who had a single dose that was not specified as a first or second dose; doses specified as booster doses were excluded.
**The any dose cohort is the first, second, and unspecified dose cohorts combined; persons who had 2 doses are represented twice in the cohort but had different index dates for their first and second doses.
^††Persons of Hispanic origin could be of any race; Asian, Black or African American, White, or other (which includes American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, multiple race, and other race) persons are not Hispanic.
^§§Missing race category includes no information, refused to answer, unknown, or missing.

Table 2. Incidence of cardiac outcomes among males aged ≥5 years after SARS-CoV-2 infection or mRNA COVID-19 vaccination and risk ratios, by age group and risk window — National Patient-Centered Clinical Research Network, United States, January 1, 2021–January 31, 2022
Age group, yrs/Outcome/Risk window	Incidence* among males					Risk ratio (95% CI) SARS-CoV-2 infection versus mRNA COVID-19 vaccination
	SARS-CoV-2 infection cohort^†	mRNA COVID-19 vaccination cohort				mRNA COVID-19 vaccination cohort
	SARS-CoV-2 infection cohort^†	First dose^§	Second dose^§	Unspecified dose^¶	Any dose**	First dose^§	Second dose^§	Unspecified dose^¶	Any dose**
5–11^††
Myocarditis
7-day	12.6	0	0	0	0	NC	NC	NC	NC
21-day	17.6	4.0	0	6.5	3.2	4.4 (0.5–35.7)	NC	2.7 (0.3–22.1)	5.4 (1.1–26.1)
Myocarditis or pericarditis
7-day	12.6	0	0	0	0	NC	NC	NC	NC
21-day	17.6	4.0	0	6.5	3.2	4.4 (0.5–35.7)	NC	2.7 (0.3–22.1)	5.4 (1.1–26.1)
Myocarditis, pericarditis, or MIS^§§
7-day	93.0	—^¶¶	—	—	—	NC	NC	NC	NC
21-day	103.0	—	—	—	—	25.7 (3.5–187.0)	NC	16.0 (2.2–116.0)	31.7 (7.7–131.2)
42-day	133.2	—	—	—	—	33.3 (4.6–240.5)	28.2 (3.9–203.9)	10.3 (2.5–42.3)	20.5 (7.4–56.7)
12–17 ^††
Myocarditis
7-day	50.1	2.2	22.0	16.7	12.9	23.0 (5.3–99.5)	2.3 (1.2–4.4)	3.0 (1.3–6.7)	3.9 (2.1–7.0)
21-day	59.0	3.3	26.7	20.4	16.0	18.0 (5.4–60.6)	2.2 (1.2–4.0)	2.9 (1.4–6.0)	3.7 (2.1–6.4)
Myocarditis or pericarditis
7-day	56.0	2.2	26.7	22.3	16.0	25.7 (6.0–110.3)	2.1 (1.1–3.9)	2.5 (1.2–5.2)	3.5 (2.0–6.1)
21-day	64.9	3.3	35.9	29.7	21.6	19.8 (5.9–66.2)	1.8 (1.0–3.1)	2.2 (1.1–4.2)	3.0 (1.8–5.0)
Myocarditis, pericarditis, or MIS^§§
7-day	150.5	—	—	—	—	69.0 (16.8–283.2)	5.6 (3.5–9.2)	6.8 (3.6–12.7)	9.4 (6.2–14.4)
21-day	159.3	—	—	—	—	48.7 (15.2–155.7)	4.4 (2.9–6.9)	5.4 (3.1–9.4)	7.4 (5.0–10.8)
42-day	180.0	—	—	—	—	4.9 (3.2–7.4)	4.6 (3.0–6.9)	5.4 (3.2–9.1)	4.9 (3.5–6.7)
18–29
Myocarditis
7-day	55.3	0.9	6.5	7.0	4.6	61.8 (8.5–451.8)	8.5 (3.7–19.1)	7.9 (3.3–19.0)	12.0 (6.4–22.5)
21-day	63.7	3.6	8.4	11.6	7.5	17.8 (6.4–49.8)	7.6 (3.7–15.7)	5.5 (2.7–11.0)	8.4 (5.0–14.2)
Myocarditis or pericarditis
7-day	85.5	2.7	12.1	22.0	11.5	31.8 (9.9–102.0)	7.0 (3.8–12.9)	3.9 (2.3–6.6)	7.4 (4.8–11.5)
21-day	100.6	8.1	15.0	27.8	16.1	12.5 (6.2–25.2)	6.7 (3.9–11.7)	3.6 (2.3–5.8)	6.3 (4.3–9.1)
Myocarditis, pericarditis, or MIS^§§
7-day	97.2	—	—	—	—	36.2 (11.3–115.5)	8.0 (4.4–14.6)	4.4 (2.6–7.4)	8.5 (5.6–12.9)
21-day	112.3	—	—	—	—	13.9 (7.0–28.0)	7.5 (4.4–13.0)	4.0 (2.5–6.4)	7.0 (4.8–10.1)
42-day	140.8	—	—	—	—	7.2 (4.5–11.4)	8.4 (5.0–13.9)	4.5 (2.9–6.9)	6.4 (4.6–8.8)
≥30
Myocarditis
7-day	57.2	0.9	0.5	3.0	1.3	67.2 (31.4–143.8)	115.2 (42.6–311.7)	18.9 (11.2–31.7)	45.7 (30.2–69.2)
21-day	63.0	1.9	1.2	4.2	2.2	32.4 (19.3–54.3)	50.8 (26.7–96.4)	15.1 (9.7–23.7)	28.3 (20.4–39.3)
Myocarditis or pericarditis
7-day	100.2	3.8	3.1	15.0	6.3	26.6 (18.2–38.7)	32.3 (21.3–48.8)	6.7 (5.2–8.6)	16.0 (12.9–19.8)
21-day	114.0	7.3	7.3	20.1	10.4	15.6 (11.8–20.7)	15.6 (11.7–20.7)	5.7 (4.5–7.1)	10.9 (9.1–13.1)
Myocarditis, pericarditis, or MIS^§§
7-day	109.1	—	—	—	—	28.9 (19.9–42.0)	35.1 (23.3–53.0)	7.3 (5.7–9.4)	17.4 (14.1–21.5)
21-day	123.0	—	—	—	—	16.8 (12.7–22.3)	16.8 (12.7–22.2)	6.1 (4.9–7.7)	11.8 (9.9–14.0)
42-day	136.8	—	—	—	—	10.7 (8.6–13.4)	10.8 (8.6–13.5)	5.4 (4.4–6.7)	8.7 (7.4–10.1)

Abbreviations: MIS = multisystem inflammatory syndrome; NC = not calculated.
*Cases per 100,000 persons.
^†Persons in the infection cohort included those who received ≥1 positive SARS-CoV-2 molecular or antigen test result.
^§The first dose cohort included persons who had either the first of 2 doses ≥20 days before a second dose or a specific code for a first dose; the second dose cohort included persons who had either the second of 2 doses ≥20 days after a first dose or a specific code for a second dose.
^¶The unspecified dose cohort included persons who had a single dose that was not specified as a first or second dose; doses specified as booster doses were excluded.
**The any dose cohort is the first, second, and unspecified dose cohorts combined; persons who had 2 doses are represented twice in the cohort but had different index dates for their first and second doses.
^††BNT162b2 (Pfizer-BioNTech) is the only mRNA COVID-19 vaccine approved for persons aged 5–17 years.
^§§Diagnoses of myocarditis, pericarditis, or MIS after a positive SARS-CoV-2 test result compared with diagnoses of myocarditis or pericarditis after vaccination. The 42-day risk ratios were only calculated for this outcome and comparison. The incidence of myocarditis or pericarditis in this risk window was 4.0, 37.1, 19.7, and 12.8 cases per 100,000 for males aged 5–11, 12–17, 18–29, and ≥30 years after a first dose of an mRNA COVID-19 vaccine; 4.7, 39.4, 16.8, and 12.7 cases per 100,000 after a second dose; 12.9, 33.4, 31.3, and 25.3 cases per 100,000 after an unspecified dose; and 6.5, 37.1, 22.0, and 15.8 cases per 100,000 after any dose.
^¶¶Dashes indicate the incidence for vaccination cohorts was not applicable because the comparison for incidence of myocarditis, pericarditis, or MIS after infection was to myocarditis or pericarditis after vaccination.

Table 3. Incidence of cardiac outcomes among females aged ≥5 years after SARS-CoV-2 infection or mRNA COVID-19 vaccination and risk ratios, by age group and risk window — National Patient-Centered Clinical Research Network, United States, January 1, 2021–January 31, 2022
Age group, yrs/Outcome/Risk window	Incidence* among females					Risk ratio (95% CI) SARS-CoV-2 infection versus mRNA COVID-19 vaccination
	SARS-CoV-2 infection cohort^†	mRNA COVID-19 vaccination cohort				mRNA COVID-19 vaccination cohort
	SARS-CoV-2 infection cohort^†	First dose^§	Second dose^§	Unspecified dose^¶	Any dose**	First dose^§	Second dose^§	Unspecified dose^¶	Any dose**
5–11^††
Myocarditis
7-day	5.4	0	0	0	0	NC	NC	NC	NC
21-day	8.1	0	0	0	0	NC	NC	NC	NC
Myocarditis or pericarditis
7-day	8.1	0	0	0	0	NC	NC	NC	NC
21-day	10.8	0	0	0	0	NC	NC	NC	NC
Myocarditis, pericarditis, or MIS^§§
7-day	67.3	—^¶¶	—	—	—	NC	NC	NC	NC
21-day	80.7	—	—	—	—	NC	NC	NC	NC
42-day	94.2	—	—	—	—	NC	NC	NC	NC
12–17^††
Myocarditis
7-day	24.7	1.0	1.1	0	0.8	24.5 (3.1–193.3)	23.1 (2.9–182.0)	NC	31.2 (6.7–144.3)
21-day	35.7	1.0	3.2	1.7	2.0	35.4 (4.6–270.5)	11.1 (3.2–39.0)	21.4 (2.8–163.4)	18.0 (6.4–50.5)
Myocarditis or pericarditis
7-day	24.7	2.0	2.1	0	1.6	12.2 (2.6–56.7)	11.5 (2.5–53.4)	NC	15.6 (4.8–50.6)
21-day	35.7	2.0	5.4	3.3	3.6	17.7 (4.0–78.4)	6.7 (2.4–18.7)	10.7 (2.4–47.4)	10.0 (4.3–23.4)
Myocarditis, pericarditis, or MIS^§§
7-day	63.1	—	—	—	—	31.3 (7.4–132.7)	29.5 (6.9–125.0)	NC	39.8 (13.8–115.2)
21-day	79.6	—	—	—	—	39.5 (9.4–165.4)	14.9 (5.7–38.3)	23.8 (5.7–99.9)	22.3 (10.6–47.2)
42-day	93.3	—	—	—	—	11.6 (5.4–25.0)	12.4 (5.5–28.1)	14.0 (5.0–39.4)	12.4 (7.1–21.7)
18–29
Myocarditis
7-day	11.9	0.5	1.6	3.9	1.8	23.5 (3.0–182.0)	7.6 (2.1–27.1)	3.1 (1.1–8.4)	6.5 (2.8–15.2)
21-day	19.5	1.0	2.1	5.8	2.8	19.2 (4.5–82.9)	9.3 (3.1–27.5)	3.4 (1.5–7.5)	7.1 (3.6–14.0)
Myocarditis or pericarditis
7-day	23.8	2.5	3.1	7.1	4.0	9.4 (3.6–24.8)	7.6 (3.1–18.7)	3.4 (1.6–7.0)	5.9 (3.3–10.6)
21-day	33.6	4.6	5.2	10.9	6.6	7.4 (3.5–15.5)	6.4 (3.1–13.1)	3.1 (1.7–5.6)	5.1 (3.1–8.2)
Myocarditis, pericarditis, or MIS^§§
7-day	27.1	—	—	—	—	10.7 (4.1–27.9)	8.6 (3.5–21.0)	3.8 (1.9–7.8)	6.7 (3.8–11.9)
21-day	40.1	—	—	—	—	8.8 (4.2–18.2)	7.6 (3.8–15.4)	3.7 (2.1–6.5)	6.1 (3.8–9.6)
42-day	67.2	—	—	—	—	8.3 (4.8–14.3)	11.6 (6.1–22.1)	5.2 (3.2–8.7)	7.8 (5.3–11.3)
≥30
Myocarditis
7-day	32.6	0.8	0.5	1.0	0.7	42.6 (21.5–84.4)	62.9 (27.6–143.6)	31.3 (15.2–64.3)	44.0 (27.9–69.3)
21-day	36.3	1.4	0.9	1.6	1.3	25.2 (15.1–42.0)	38.3 (20.6–71.3)	23.2 (12.8–42.2)	28.2 (19.6–40.6)
Myocarditis or pericarditis
7-day	53.8	3.1	1.7	8.2	3.9	17.1 (12.0–24.5)	31.2 (19.6–49.7)	6.6 (4.9–8.8)	13.9 (11.0–17.7)
21-day	61.7	6.2	4.1	10.7	6.5	10.0 (7.6–13.1)	14.9 (10.8–20.5)	5.8 (4.5–7.5)	9.4 (7.7–11.5)
Myocarditis, pericarditis, or MIS^§§
7-day	58.6	—	—	—	—	18.7 (13.1–26.6)	34.0 (21.4–54.0)	7.1 (5.4–9.5)	15.2 (12.0–19.2)
21-day	68.2	—	—	—	—	11.0 (8.4–14.4)	16.5 (12.0–22.6)	6.4 (4.9–8.3)	10.4 (8.6–12.7)
42-day	79.6	—	—	—	—	8.4 (6.7–10.5)	10.0 (7.9–12.8)	5.6 (4.5–7.0)	7.9 (6.7–9.4)

Abbreviations: MIS = multisystem inflammatory syndrome; NC = not calculated.
*Cases per 100,000 persons.
^†Persons in the infection cohort included those who received ≥1 positive SARS-CoV-2 molecular or antigen test result.
^§The first dose cohort included persons who had either the first of 2 doses ≥20 days before a second dose or a specific code for a first dose; the second dose cohort included persons who had either the second of 2 doses ≥20 days after a first dose or a specific code for a second dose.
^¶The unspecified dose cohort included persons who had a single dose that was not specified as a first or second dose; doses specified as booster doses were excluded.
**The any dose cohort is the first, second, and unspecified dose cohorts combined; persons who had 2 doses are represented twice in the cohort but had different index dates for their first and second doses.
^††BNT162b2 (Pfizer-BioNTech) is the only mRNA COVID-19 vaccine approved for persons aged 5–17 years.
^§§Diagnoses of myocarditis, pericarditis, or MIS after a positive SARS-CoV-2 test result compared with diagnoses of myocarditis or pericarditis after vaccination. The 42-day risk ratios were only calculated for this outcome and comparison. The incidence of myocarditis or pericarditis in this risk window was 0, 8.1, 8.1, 9.5 cases per 100,000 for females 5–11, 12–17, 18–29, and ≥30 years after a first dose of an mRNA COVID-19 vaccine; 0, 7.5, 5.8, and 8.0 cases per 100,000 after a second dose; 0, 6.7, 12.9, and 14.2 cases per 100,000 after an unspecified dose; and 0, 7.5, 8.7, and 10.1 cases per 100,000 after any dose.
^¶¶Dashes indicate the incidence for vaccination cohorts was not applicable because the comparison for incidence of myocarditis, pericarditis, or MIS after infection was to myocarditis or pericarditis after vaccination.

Authors and Disclosures

Jason P. Block, MD¹, Tegan K. Boehmer, PhD², Christopher B. Forrest, MD, PhD³, Thomas W. Carton, PhD⁴, Grace M. Lee, MD⁵, Umed A. Ajani, MBBS², Dimitri A. Christakis, MD⁶, Lindsay G. Cowell, PhD⁷, Christine Draper¹, Nidhi Ghildayal, PhD¹, Aaron M. Harris, MD², Michael D. Kappelman, MD⁸, Jean Y. Ko, PhD², Kenneth H. Mayer, MD⁹, Kshema Nagavedu, MPH¹, Matthew E. Oster, MD^2,10, Anuradha Paranjape, MD¹¹, Jon Puro, MPA¹², Matthew D. Ritchey², David K. Shay, MD², Deepika Thacker, MD¹³ and Adi V. Gundlapalli, MD, PhD²

¹Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, Massachusetts; ²CDC COVID-19 Emergency Response Team; ³Applied Clinical Research Center, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; ⁴Louisiana Public Health Institute, New Orleans, Louisiana; ⁵Department of Pediatrics, Stanford University School of Medicine, Stanford, California; ⁶Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle Children's Hospital, Seattle, Washington; ⁷Department of Population and Data Sciences and Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas; ⁸Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, North Carolina; ⁹The Fenway Institute, Fenway Health, Harvard Medical School, Boston, Massachusetts; ¹⁰Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia; ¹¹Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania; ¹²OCHIN, Inc., Portland, Oregon; ¹³Nemours Cardiac Center, Nemours Children's Health System, Wilmington, Delaware.

Corresponding author
Jason P. Block, jblock1@partners.org.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jason P. Block, Christopher B. Forrest, Grace M. Lee, and Thomas W. Carton report support from the National Institutes of Health (NIH) as part of the Researching COVID to Enhance Recovery (RECOVER) program. Nidhi Ghildayal reports NIH funding for a postdoctoral position. Michael D. Kappelman reports grants from NIH, PCORI, Helmsley Trust, Abbvie, Arenapharm, Boehringer Ingelheim, Bristol Myers Squibb, Celtrion, Eli Lilly, Genentech, Janssen (a subsidiary of Johnson & Johnson, Pfizer, and Takeda) and consulting fees from Abbvie, Janssen, Takeda, and Pfizer; payment for service on a data safety monitoring board for Eli Lilly, and payment for service on the editorial board of the American Journal of Gastroenterology. Kenneth H. Mayer reports grant support from NIH's COVID-19 Vaccine Trials Network for a Phase III AstraZeneca SARS-CoV-2 vaccine trial. Matthew E. Oster reports institutional support from NIH's National Heart, Lung, and Blood Institute. No other potential conflicts of interest were disclosed.