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Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

Author/s: 
Feldstein, L.R., et al.

Abstract

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.)

Physical Distancing, Face Masks, and Eye Protection to Prevent Person-To-Person Transmission of SARS-CoV-2 and COVID-19: A Systematic Review and Meta-Analysis

Author/s: 
Chu, D.K., Akl, E.A., Duda, S., Solo, K., Yaacoub, S., Schünemann, H.J., COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings.

Methods: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047.

Findings: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] -10·2%, 95% CI -11·5 to -7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD -14·3%, -15·9 to -10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12-16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD -10·6%, 95% CI -12·5 to -7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings.

Interpretation: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance.

Funding: World Health Organization.

Keywords 
face masks social distancing eye shields

Active Case Finding With Case Management: The Key to Tackling the COVID-19 Pandemic

Author/s: 
China CDC COVID-19 Emergency Response Strategy Team

Abstract

COVID-19 was declared a pandemic by WHO on March 11, 2020, the first non-influenza pandemic, affecting more than 200 countries and areas, with more than 5·9 million cases by May 31, 2020. Countries have developed strategies to deal with the COVID-19 pandemic that fit their epidemiological situations, capacities, and values. We describe China's strategies for prevention and control of COVID-19 (containment and suppression) and their application, from the perspective of the COVID-19 experience to date in China. Although China has contained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and nearly stopped indigenous transmission, a strong suppression effort must continue to prevent re-establishment of community transmission from importation-related cases. We believe that case finding and management, with identification and quarantine of close contacts, are vitally important containment measures and are essential in China's pathway forward. We describe the next steps planned in China that follow the containment effort. We believe that sharing countries' experiences will help the global community manage the COVID-19 pandemic by identifying what works in the struggle against SARS-CoV-2.

Copyright © 2020 Elsevier Ltd. All rights reserved.

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Author/s: 
Lauer, S.A., Grantz, K.A, Bi, Q, Jones, F.K., Zheng, Q., Meredith, H.R., Azman, A.S., Reich, N.G., Lessler, J.

Abstract

Background:

A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities.

Objective:

To estimate the length of the incubation period of COVID-19 and describe its public health implications.

Design:

Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020.

Setting:

News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China.

Participants:

Persons with confirmed SARS-CoV-2 infection outside Hubei province, China.

Measurements:

Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization.

Results:

There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine.

Limitation:

Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases.

Conclusion:

This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases.

Primary Funding Source:

U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.

In December 2019, a cluster of severe pneumonia cases of unknown cause was reported in Wuhan, Hubei province, China. The initial cluster was epidemiologically linked to a seafood wholesale market in Wuhan, although many of the initial 41 cases were later reported to have no known exposure to the market (1). A novel strain of coronavirus belonging to the same family of viruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as the 4 human coronaviruses associated with the common cold, was subsequently isolated from lower respiratory tract samples of 4 cases on 7 January 2020 (2). Infection with the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be asymptomatic or can result in mild to severe symptomatic disease (coronavirus disease 2019 [COVID-19]) (3). On 30 January 2020, the World Health Organization declared that the SARS-CoV-2 outbreak constituted a Public Health Emergency of International Concern, and more than 80 000 confirmed cases had been reported worldwide as of 28 February 2020 (4, 5). On 31 January 2020, the U.S. Centers for Disease Control and Prevention announced that all citizens returning from Hubei province, China, would be subject to mandatory quarantine for up to 14 days (6).

Our current understanding of the incubation period for COVID-19 is limited. An early analysis based on 88 confirmed cases in Chinese provinces outside Wuhan, using data on known travel to and from Wuhan to estimate the exposure interval, indicated a mean incubation period of 6.4 days (95% CI, 5.6 to 7.7 days), with a range of 2.1 to 11.1 days (7). Another analysis based on 158 confirmed cases outside Wuhan estimated a median incubation period of 5.0 days (CI, 4.4 to 5.6 days), with a range of 2 to 14 days (8). These estimates are generally consistent with estimates from 10 confirmed cases in China (mean incubation period, 5.2 days [CI, 4.1 to 7.0 days] [9]) and from clinical reports of a familial cluster of COVID-19 in which symptom onset occurred 3 to 6 days after assumed exposure in Wuhan (1). These estimates of the incubation period of SARS-CoV-2 are also in line with those of other known human coronaviruses, including SARS (mean, 5 days; range, 2 to 14 days [10]), MERS (mean, 5 to 7 days; range, 2 to 14 days [11]), and non-SARS human coronavirus (mean, 3 days; range, 2 to 5 days [12]).

The incubation period can inform several important public health activities for infectious diseases, including active monitoring, surveillance, control, and modeling. Active monitoring requires potentially exposed persons to contact local health authorities to report their health status every day. Understanding the length of active monitoring needed to limit the risk for missing SARS-CoV-2 infections is necessary for health departments to effectively use limited resources. In this article, we provide estimates of the incubation period of COVID-19 and the number of symptomatic infections missed under different active monitoring scenarios.

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