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BackgroundInfluenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. MethodsInfluenza and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, two population-based surveillance systems with similar catchment areas and methodology. The annual COVID-19-associated hospitalization rate per 100 000 during the ongoing COVID-19 pandemic (October 1, 2020-September 30, 2021) was compared to influenza-associated hospitalization rates during the 2017-18 through 2019-20 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared. ResultsAmong children <18 years old, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-18 (33.5), 2018-19 (33.8), and 2019-20 (41.7). The COVID-19-associated hospitalization rate was higher among adolescents 12-17 years old (COVID-19: 59.9; influenza range: 12.2-14.1), but similar or lower among children 5-11 (COVID-19: 25.0; influenza range: 24.3-31.7) and 0-4 (COVID-19: 66.8; influenza range: 70.9-91.5) years old. Among children <18 years old, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; p<0.01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; p=0.28). ConclusionsIn the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19-associated hospitalization rate during 2020-2021 was higher among adolescents and similar or lower among children <12 years old compared with influenza during the three seasons before the COVID-19 pandemic. COVID-19 adds substantially to the existing burden of pediatric hospitalizations and severe outcomes caused by influenza and other respiratory viruses. SummaryAnnual hospitalization rates and proportions of hospitalized children experiencing severe outcomes were as high or higher for COVID-19 during October 2020-September 2021 compared with influenza during the three seasons before the COVID-19 pandemic, based on U.S. population-based surveillance data.
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Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, [~]88% of neutralizing and [~]63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; [~]30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19.
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BACKGROUNDReports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODSINSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTSParticipating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONSThis study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.
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BackgroundPregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection. MethodsPregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020-January 8, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics. ResultsAmong 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30-39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions. ConclusionsPregnant women with moderate-to-severe or critical COVID-19 illness were more likely to be older and have underlying medical conditions compared to pregnant women with asymptomatic infection or mild COVID-19 illness. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging. SummaryAmong pregnant women with COVID-19, older age and underlying medical conditions were risk factors for increased illness severity. These findings can be used to inform pregnant women about their risk for severe COVID-19 illness and public health messaging.
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BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), presents with a broad range of symptoms. Existing COVID-19 case definitions were developed from early reports of severely ill, primarily hospitalized, patients. Symptom-based case definitions that guide public health surveillance and individual patient management in the community must be optimized for COVID-19 pandemic control. MethodsWe collected daily symptom diaries and performed RT-PCR on respiratory specimens over a 14-day period in 185 community members exposed to a household contact with COVID-19 in the Milwaukee, Wisconsin and Salt Lake City, Utah metropolitan areas. We interpreted the discriminatory performance (sensitivity, specificity, predictive values, F1 score, Youdens index, and prevalence estimation) of individual symptoms and common case definitions according to two principal surveillance applications (i.e., individual screening and case counting). We also constructed novel case definitions using an exhaustive search with over 73 million symptom combinations and calculated bias-corrected and accelerated bootstrap confidence intervals stratified by children versus adults. FindingsCommon COVID-19 case definitions generally showed high sensitivity (8696%) but low positive predictive value (PPV) (3649%; F1 score 5263) in this community cohort. The top performing novel symptom combinations included taste or smell dysfunction. They also improved the balance of sensitivity and PPV (F1 score 7880) and reduced the number of false positive symptom screens. Performance indicators were generally lower for children (<18 years of age). InterpretationExisting COVID-19 case definitions appropriately screened in community members with COVID-19. However, they led to many false positive symptom screens and poorly estimated community prevalence. Absent unlimited, timely testing capacity, more accurate case definitions may help focus public health resources. Novel symptom combinations incorporating taste or smell dysfunction as a primary component better balanced sensitivity and specificity. Case definitions tailored specifically for children versus adults should be further explored. FundingThis research was wholly supported by the U.S. Centers for Disease Control and Prevention. DisclaimerThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSCoronavirus disease 2019 (COVID-19) incidence has accelerated globally over the last several months. As the full spectrum of clinical presentations has come into clearer focus, symptom-based clinical screening and case surveillance has also evolved. Preliminary understanding of the clinical manifestation of COVID-19 was driven primarily by descriptions of hospitalized patients, as early testing algorithms prioritized more severely ill persons with classic lower respiratory symptoms and fever. Since then, more data from ambulatory settings have emerged. We searched PubMed from 1 December 2019 to 21 August 2020 for studies that assessed the diagnostic performance of case surveillance definitions for COVID-19. We found no studies examining the discriminatory performance of case surveillance definitions among contacts with mild to moderate symptoms with documented exposure to persons with COVID-19. Nonetheless, we found nine highly relevant studies: seven original reports and two review articles. Five original studies evaluated individual, self-reported symptoms (two among healthcare workers in the United States, one among healthcare workers in the Netherlands, and one online survey for the general public in Somalia) and concluded that using dysfunction of taste or smell for routine COVID-19 screening likely had utility. The fifth study had a similar conclusion based on self-reported symptoms and laboratory results collected via smartphone from the general public in the United States and the United Kingdom. Another original study modeled the substantial effect that multiple revisions to the COVID-19 case definition had on the reported disease burden in the Chinese population. Lastly, an original study illustrated the shift in discriminatory performance of established influenza surveillance case definitions for influenza between adults and children. Age-specific differences in case definition performance may also apply to COVID-19. Two articles reviewed predictive algorithms to define outpatient COVID-19 illness and risk of hospitalization. The reviewed studies were limited in that they were either restricted to individual signs or symptoms, or they incorporated blood tests or imaging that required in-person access to medical care. Added value of this studyThe discriminatory performance of case surveillance definitions for COVID-19 is important for implementing effective epidemic mitigation strategies. Our study illustrates the performance of case definitions in community members with household exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based solely on symptom profiles. Prior work overrepresented healthcare workers or otherwise studied non-representative populations, and they did not examine across the age spectrum. Our study also provides a novel framework for refining definitions. Using 15 symptoms associated with COVID-19 for all contacts regardless of disease status, we systematically evaluated the discriminatory performance of individual symptoms and previously defined case surveillance definitions across ages and according to two core surveillance applications: 1) screening non-hospitalized individuals to prioritize public health interventions, and 2) estimating the number of non-hospitalized persons with COVID-19 (i.e., community-based syndromic surveillance). We also constructed novel symptom combinations that effectively performed both functions and improved upon widely used case surveillance definitions that may help to target interventions in the absence of unlimited laboratory diagnostic capacity. Our analyses highlight the importance of ongoing re-evaluation of symptom-based surveillance definitions to suit the intended purpose and population under surveillance. Based on our results, which were derived from household members of all ages, case surveillance definition performance may improve if developed separately for adults and children. Implications of all the available evidenceCase definitions for COVID-19 should be tailored to maximize the discriminatory performance dependent upon its intended use. Existing COVID-19 case definitions screened in most community members with COVID-19, but also yielded a high number of false positive results. When unlimited, timely diagnostic testing is not available symptom combinations with improved accuracy (i.e., more balanced sensitivity and specificity) may help focus resources, such as recommending self-isolation among community contacts.
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BackgroundIdentification of risk factors for COVID-19-associated hospitalization is needed to guide prevention and clinical care. ObjectiveTo examine if age, sex, race/ethnicity, and underlying medical conditions is independently associated with COVID-19-associated hospitalizations. DesignCross-sectional. Setting70 counties within 12 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) and a population-based sample of non-hospitalized adults residing in the COVID-NET catchment area from the Behavioral Risk Factor Surveillance System. ParticipantsU.S. community-dwelling adults ([≥]18 years) with laboratory-confirmed COVID-19-associated hospitalizations, March 1- June 23, 2020. MeasurementsAdjusted rate ratios (aRR) of hospitalization by age, sex, race/ethnicity and underlying medical conditions (hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI [≥]30 kg/m2], severe obesity [BMI[≥]40 kg/m2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease). ResultsOur sample included 5,416 adults with COVID-19-associated hospitalizations. Adults with (versus without) severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7) had higher rates of hospitalization, after adjusting for age, sex, and race/ethnicity. In models adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults [≥]65 years, 45-64 years (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites). LimitationsInterim analysis limited to hospitalizations with underlying medical condition data. ConclusionOur findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.
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ImportanceReported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. ObjectiveTo estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States. DesignSerologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies. SettingConnecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington States (WA) Puget Sound region. ParticipantsPersons of all ages with serum collected during intervals from March 23 through May 3, 2020. ExposureSARS-CoV-2 virus infection. Main outcomes and measuresWe estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date. ResultsWe tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site. Conclusions and relevanceOur seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures. Key findingsO_ST_ABSQuestionC_ST_ABSWhat proportion of persons in six U.S. sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020? FindingsWe tested 11,933 residual clinical specimens. We estimate that from 1.1% of persons in the Puget Sound to 6.9% in New York City (collected March 23-April 1) had detectable antibodies. Estimates ranged from 1.9% in south Florida to 4.9% in Connecticut with specimens collected during intervals from April 6-May 3. Six to 24 times more infections were estimated per site with seroprevalence than with case report data. MeaningFor most sites, evidence suggests >10 times more SARS-CoV-2 infections occurred than reported cases. Most persons in each site likely had no detectable SARS-CoV-2 antibodies.
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BackgroundCoronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. MethodsClose contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention. ResultsThere were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had [≥]1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had [≥]1 respiratory sample tested, was 13% (95% CI: 4 - 38%). ConclusionsThe enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.
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IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. ResultsAmong the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.
