Occupations Associated with SARS-CoV-2 Infection and Vaccination, U.S. Blood Donors, July 2021-December 2021.

BACKGROUND: There are limited data on the risk of SARS-CoV-2 infection in the U.S. by occupation. We identified occupations at higher risk for prior SARS-CoV-2 infection as defined by the presence of infection-induced antibodies among U.S. blood donors. METHODS: Using a nested case-control study design, blood donors during May-December 2021 with anti-nucleocapsid (anti-N) testing were sent an electronic survey on employment status, vaccination, and occupation. The association between previous SARS-CoV-2 infection and occupation-specific in-person work was estimated using multivariable logistic regression adjusting for sex, age, month of donation, race/ethnicity, education, vaccination, and telework. RESULTS: Among 85,986 included survey respondents, 9,504 (11.1%) were anti-N reactive. Healthcare support (20.3%), protective service (19.9%), and food preparation and serving related occupations (19.7%) had the highest proportion of prior infection. After adjustment, prior SARS-CoV-2 infection was associated with healthcare practitioners (adjusted OR [aOR] 2.10, 95% CI 1.74-2.54) and healthcare support (aOR 1.83, 95% CI 1.39-2.40) occupations compared with computer and mathematical occupations as the referent group. Lack of COVID-19 vaccination (aOR 16.13, 95% CI 15.01-17.34) and never teleworking (aOR 1.17, 95% CI 1.05-1.30) were also independently associated with prior SARS-CoV-2 infection. Protective service occupations had the highest proportion of unvaccinated workers (30.0%). CONCLUSIONS: Workers in healthcare, protective services, and food preparation had the highest prevalence of prior SARS-CoV-2 infection. Occupational risks for SARS-CoV-2 infection remained after adjusting for vaccination, telework, and demographic factors. These findings underscore the need for mitigation measures and personal protection in healthcare settings and other workplaces.

Post-COVID conditions and healthcare utilization among adults with and without disabilities-2021 Porter Novelli FallStyles survey.

BACKGROUND: Adults with disabilities are at increased risk for SARS-CoV-2 infection and severe disease; whether adults with disabilities are at an increased risk for ongoing symptoms after acute SARS-CoV-2 infection is unknown. OBJECTIVES: To estimate the frequency and duration of long-term symptoms (>4 weeks) and health care utilization among adults with and without disabilities who self-report positive or negative SARS-CoV-2 test results. METHODS: Data from a nationwide survey of 4510 U.S. adults administered from September 24, 2021-October 7, 2021, were analyzed for 3251 (79%) participants who self-reported disability status, symptom(s), and SARS-CoV-2 test results (a positive test or only negative tests). Multivariable models were used to estimate the odds of having ≥1 COVID-19-like symptom(s) lasting >4 weeks by test result and disability status, weighted and adjusted for socio-demographics. RESULTS: Respondents who tested positive for SARS-CoV-2 had higher odds of reporting ≥1 long-term symptom (with disability: aOR = 4.50 [95% CI: 2.37, 8.54] and without disability: aOR = 9.88 [95% CI: 7.13, 13.71]) compared to respondents testing negative. Among respondents who tested positive, those with disabilities were not significantly more likely to experience long-term symptoms compared to respondents without disabilities (aOR = 1.65 [95% CI: 0.78, 3.50]). Health care utilization for reported symptoms was higher among respondents with disabilities who tested positive (40%) than among respondents without disabilities who tested positive (18%). CONCLUSIONS: Ongoing symptoms among adults with and without disabilities who also test positive for SARS-CoV-2 are common; however, the frequency of health care utilization for ongoing symptoms is two-fold among adults with disabilities.

Risk Factors for Reinfection with SARS-CoV-2 Omicron Variant among Previously Infected Frontline Workers.

In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities.

Post-COVID Conditions and Healthcare Utilization Among Adults With and Without Disabilities—2021 Porter Novelli FallStyles Survey

Background Adults with disabilities are at increased risk for SARS-CoV-2 infection and severe disease;whether adults with disabilities are at an increased risk for ongoing symptoms after acute SARS-CoV-2 infection is unknown. Objectives To estimate the frequency and duration of long-term symptoms (> 4 weeks) and health care utilization among adults with and without disabilities who self-report positive or negative SARS-CoV-2 test results. Methods Data from a nationwide survey of 4,510 U.S. adults administered from September 24, 2021 – October 7, 2021, were analyzed for 3,251 (79%) participants who self-reported disability status, symptom(s), and SARS-CoV-2 test results (a positive test or only negative tests). Multivariable models were used to estimate the odds of having ≥1 COVID-19–like symptom(s) lasting >4 weeks by test result and disability status, weighted and adjusted for socio-demographics. Results Respondents who tested positive for SARS-CoV-2 had higher odds of reporting ≥ 1 long-term symptom (with disability: aOR=4.50 [95% CI: 2.37, 8.54] and without disability: aOR=9.88 [95% CI: 7.13, 13.71]) compared to respondents testing negative. Among respondents who tested positive, those with disabilities were not significantly more likely to experience long-term symptoms compared to respondents without disabilities (aOR=1.65 [95% CI: 0.78, 3.50]). Healthcare utilization for reported symptoms was higher among respondents with disabilities who tested positive (40%) than among respondents without disabilities who tested positive (18%). Conclusions Ongoing symptoms among adults with and without disabilities who also test positive for SARS-CoV-2 are common;however, frequency of healthcare utilization for ongoing symptoms is two-fold among adults with disabilities.

CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 - United States, April-September 2022.

Nirmatrelvir-ritonavir (Paxlovid), an oral antiviral treatment, is authorized for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness. However, real-world evidence on the benefit of Paxlovid, according to vaccination status, age group, and underlying health conditions, is limited. To examine the benefit of Paxlovid in adults aged ≥18 years in the United States, a large electronic health record (EHR) data set (Cosmos†) was analyzed to assess the association between receiving a prescription for Paxlovid and hospitalization with a COVID-19 diagnosis in the ensuing 30 days. A Cox proportional hazards model was used to estimate this association, adjusted for demographic characteristics, geographic location, vaccination, previous infection, and number of underlying health conditions. Among 699,848 adults aged ≥18 years eligible for Paxlovid during April-August 2022, 28.4% received a Paxlovid prescription within 5 days of COVID-19 diagnosis. Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population (adjusted hazard ratio [aHR] = 0.49), among those who had received ≥3 mRNA COVID-19 vaccines (aHR = 0.50), and across age groups (18-49 years: aHR = 0.59; 50-64 years: aHR = 0.40; and ≥65 years: aHR = 0.53). Paxlovid should be prescribed to eligible adults to reduce the risk of COVID-19-associated hospitalization.

Coronavirus Disease 2019 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection in the United States Before the Delta- and Omicron-Associated Surges: A Retrospective Cohort Study of Repeat Blood Donors.

BACKGROUND: To inform public health policy, it is critical to monitor coronavirus disease 2019 vaccine effectiveness (VE), including against acquiring infection. METHODS: We estimated VE using self-reported vaccination in a retrospective cohort of repeat blood donors who donated during the first half of 2021, and we demonstrated a viable approach for monitoring VE via serological surveillance. RESULTS: Using Poisson regression, we estimated an overall VE of 88.8% (95% confidence interval, 86.2-91.1), adjusted for demographic covariates and variable baseline risk. CONCLUSIONS: The time since first reporting vaccination, age, race and/or ethnicity, region, and calendar time were statistically significant predictors of incident infection.

Investigating Health Disparities Associated With Multisystem Inflammatory Syndrome in Children After SARS-CoV-2 Infection.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities. METHODS: This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression. RESULTS: We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28). CONCLUSIONS: In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.

Health Impairments in Children and Adolescents After Hospitalization for Acute COVID-19 or MIS-C.

OBJECTIVES: To evaluate risk factors for postdischarge sequelae in children and adolescents hospitalized for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter prospective cohort study conducted in 25 United States pediatric hospitals. Patients <21-years-old, hospitalized May 2020 to May 2021 for acute COVID-19 or MIS-C with follow-up 2 to 4 months after admission. We assessed readmissions, persistent symptoms or activity impairment, and new morbidities. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). RESULTS: Of 358 eligible patients, 2 to 4 month survey data were available for 119 of 155 (76.8%) with acute COVID-19 and 160 of 203 (78.8%) with MIS-C. Thirteen (11%) patients with acute COVID-19 and 12 (8%) with MIS-C had a readmission. Thirty-two (26.9%) patients with acute COVID-19 had persistent symptoms (22.7%) or activity impairment (14.3%) and 48 (30.0%) with MIS-C had persistent symptoms (20.0%) or activity impairment (21.3%). For patients with acute COVID-19, persistent symptoms (aRR, 1.29 [95% CI, 1.04-1.59]) and activity impairment (aRR, 1.37 [95% CI, 1.06-1.78]) were associated with more organ systems involved. Patients with MIS-C and pre-existing respiratory conditions more frequently had persistent symptoms (aRR, 3.09 [95% CI, 1.55-6.14]) and those with obesity more frequently had activity impairment (aRR, 2.52 [95% CI, 1.35-4.69]). New morbidities were infrequent (9% COVID-19, 1% MIS-C). CONCLUSIONS: Over 1 in 4 children hospitalized with acute COVID-19 or MIS-C experienced persistent symptoms or activity impairment for at least 2 months. Patients with MIS-C and respiratory conditions or obesity are at higher risk of prolonged recovery.

Effectiveness of COVID-19 mRNA Vaccination in Preventing COVID-19-Associated Hospitalization Among Adults with Previous SARS-CoV-2 Infection - United States, June 2021-February 2022.

Previous infection with SARS-CoV-2, the virus that causes COVID-19, has been estimated to confer up to 90% protection against reinfection, although this protection was lower against the Omicron variant compared with that against other SARS-CoV-2 variants (1-3). A test-negative design was used to estimate effectiveness of COVID-19 mRNA vaccines in preventing subsequent COVID-19-associated hospitalization among adults aged ≥18 years with a previous positive nucleic acid amplification test (NAAT) or diagnosis of COVID-19.† The analysis used data from Cosmos, an electronic health record (EHR)-aggregated data set (4), and compared vaccination status of 3,761 case-patients (positive NAAT result associated with hospitalization) with 7,522 matched control-patients (negative NAAT result). After previous SARS-CoV-2 infection, estimated vaccine effectiveness (VE) against COVID-19-associated hospitalization was 47.5% (95% CI = 38.8%-54.9%) after 2 vaccine doses and 57.8% (95% CI = 32.1%-73.8%) after a booster dose during the Delta-predominant period (June 20-December 18, 2021), and 34.6% (95% CI = 25.5%-42.5%) after 2 doses and 67.6% (95% CI = 61.4%-72.8%) after a booster dose during the Omicron-predominant period (December 19, 2021-February 24, 2022). Vaccination provides protection against COVID-19-associated hospitalization among adults with previous SARS-CoV-2 infection, with the highest level of protection conferred by a booster dose. All eligible persons, including those with previous SARS-CoV-2 infection, should stay up to date with vaccination to prevent COVID-19-associated hospitalization.

A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020.

BACKGROUND: It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. METHODS: Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. RESULTS: Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). CONCLUSION: Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.

Influenza Vaccine Effectiveness for Prevention of Severe Influenza-Associated Illness Among Adults in the United States, 2019-2020: A Test-Negative Study.

BACKGROUND: Influenza vaccine effectiveness (VE) against a spectrum of severe disease, including critical illness and death, remains poorly characterized. METHODS: We conducted a test-negative study in an intensive care unit (ICU) network at 10 US hospitals to evaluate VE for preventing influenza-associated severe acute respiratory infection (SARI) during the 2019-2020 season, which was characterized by circulation of drifted A/H1N1 and B-lineage viruses. Cases were adults hospitalized in the ICU and a targeted number outside the ICU (to capture a spectrum of severity) with laboratory-confirmed, influenza-associated SARI. Test-negative controls were frequency-matched based on hospital, timing of admission, and care location (ICU vs non-ICU). Estimates were adjusted for age, comorbidities, and other confounders. RESULTS: Among 638 patients, the median (interquartile) age was 57 (44-68) years; 286 (44.8%) patients were treated in the ICU and 42 (6.6%) died during hospitalization. Forty-five percent of cases and 61% of controls were vaccinated, which resulted in an overall VE of 32% (95% CI: 2-53%), including 28% (-9% to 52%) against influenza A and 52% (13-74%) against influenza B. VE was higher in adults 18-49 years old (62%; 95% CI: 27-81%) than those aged 50-64 years (20%; -48% to 57%) and ≥65 years old (-3%; 95% CI: -97% to 46%) (P = .0789 for interaction). VE was significantly higher against influenza-associated death (80%; 95% CI: 4-96%) than nonfatal influenza illness. CONCLUSIONS: During a season with drifted viruses, vaccination reduced severe influenza-associated illness among adults by 32%. VE was high among young adults.

Decline in SARS-CoV-2 Antibodies After Mild Infection Among Frontline Health Care Personnel in a Multistate Hospital Network - 12 States, April-August 2020.

Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline. The percentage of participants who experienced seroreversion, defined as an antibody signal-to-threshold ratio >1.0 at baseline and <1.0 at the follow-up visit, was assessed. Overall, 194 (6.0%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline (1). Upon repeat testing approximately 60 days later (range = 50-91 days), 146 (93.6%) of 156 participants experienced a decline in antibody response indicated by a lower signal-to-threshold ratio at the follow-up visit, compared with the baseline visit, and 44 (28.2%) experienced seroreversion. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response. Whether decay in these antibodies increases risk for reinfection and disease remains unanswered. However, these results suggest that serology testing at a single time point is likely to underestimate the number of persons with previous SARS-CoV-2 infection, and a negative serologic test result might not reliably exclude prior infection.

Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network - 13 Academic Medical Centers, April-June 2020.

Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission.

Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. METHODS: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. FINDINGS: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. INTERPRETATION: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.

Influenza vaccine acceptance and hesitancy among adults hospitalized with severe acute respiratory illnesses, United States 2019-2020.

INTRODUCTION: Understanding patient factors associated with not being vaccinated is essential for successful implementation of influenza vaccination programs. METHODS: We enrolled adults hospitalized with severe acute respiratory illness at 10 United States (US) hospitals during the 2019-2020 influenza season. We interviewed patients to collect data about influenza vaccination, sociodemographic characteristics, and vaccine perceptions. RESULTS: Among 679 participants, 264 (38.9%) reported not receiving influenza vaccination. Among those not vaccinated, 135 (51.1%) reported choosing not to receive a vaccine because of perceived ineffectiveness (36.7%) or risk (14.4%) of influenza vaccination. Sociodemographic factors associated with not being vaccinated included no medical insurance (aOR = 6.42; 95% CI: 2.52-16.38) and being non-White or Hispanic (aOR = 1.54, 95% CI: 1.02-2.32). CONCLUSIONS: Optimizing uptake of influenza vaccination in the US may be improved by educational programs regarding vaccine safety and effectiveness and enhancing vaccine access, particularly among non-White and Hispanic Americans and those without medical insurance.

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. Objective: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. Design, Setting, and Participants: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Exposures: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Main Outcomes and Measures: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. Results: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). Conclusions and Relevance: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).