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1.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21266812

RESUMEN

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.

2.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21257987

RESUMEN

BACKGROUNDInformation is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions. METHODSProspective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020--April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). VE was calculated as 100%x(1-hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation. RESULTSSARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially ([≥]14 days post-dose-1 to 13 days after dose-2) or fully ([≥]14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%-97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants. CONCLUSIONSAuthorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.

3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20161810

RESUMEN

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.

4.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20140384

RESUMEN

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.

5.
Rachel M Burke; Sharon Balter; Emily Barnes; Vaughn Barry; Karri Bartlett; Karlyn D Beer; Isaac Benowitz; Holly M Biggs; Hollianne Bruce; Jonathan Bryant-Genevier; Jordan Cates; Kevin Chatham-Stephens; Nora Chea; Howard Chiou; Demian Christiansen; Victoria Chu; Shauna Clark; Sara H. Cody; Max Cohen; Erin E Conners; Vishal Dasari; Patrick Dawson; Traci DeSalvo; Matthew Donahue; Alissa Dratch; Lindsey Duca; Jeffrey Duchin; Jonathan W Dyal; Leora R Feldstein; Marty Fenstersheib; Marc Fischer; Rebecca Fisher; Chelsea Foo; Brandi Freeman-Ponder; Alicia M Fry; Jessica Gant; Romesh Gautom; Isaac Ghinai; Prabhu Gounder; Cheri T Grigg; Jeffrey Gunzenhauser; Aron J Hall; George S Han; Thomas Haupt; Michelle Holshue; Jennifer Hunter; Mireille B Ibrahim; Max W Jacobs; M. Claire Jarashow; Kiran Joshi; Talar Kamali; Vance Kawakami; Moon Kim; Hannah Kirking; Amanda Kita-Yarbro; Rachel Klos; Miwako Kobayashi; Anna Kocharian; Misty Lang; Jennifer Layden; Eva Leidman; Scott Lindquist; Stephen Lindstrom; Ruth Link-Gelles; Mariel Marlow; Claire P Mattison; Nancy McClung; Tristan McPherson; Lynn Mello; Claire M Midgley; Shannon Novosad; Megan T Patel; Kristen Pettrone; Satish K Pillai; Ian W Pray; Heather E Reese; Heather Rhodes; Susan Robinson; Melissa Rolfes; Janell Routh; Rachel Rubin; Sarah L Rudman; Denny Russell; Sarah Scott; Varun Shetty; Sarah E Smith-Jeffcoat; Elizabeth A Soda; Chris Spitters; Bryan Stierman; Rebecca Sunenshine; Dawn Terashita; Elizabeth Traub; Grace E Vahey; Jennifer R Verani; Megan Wallace; Matthew Westercamp; Jonathan Wortham; Amy Xie; Anna Yousaf; Matthew Zahn.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20081901

RESUMEN

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.

6.
Stephanie A. Kujawski; Karen K Wong; Jennifer P. Collins; Lauren Epstein; Marie E. Killerby; Claire M. Midgley; Glen R. Abedi; N. Seema Ahmed; Olivia Almendares; Francisco N. Alvarez; Kayla N. Anderson; Sharon Balter; Vaughn Barry; Karri Bartlett; Karlyn Beer; Michael A. Ben-Aderet; Isaac Benowitz; Holly Biggs; Alison M. Binder; Stephanie R. Black; Brandon Bonin; Catherine M. Brown; Hollianne Bruce; Jonathan Bryant-Genevier; Alicia Budd; Diane Buell; Rachel Bystritsky; Jordan Cates; E. Matt Charles; Kevin Chatham-Stephens; Nora Chea; Howard Chiou; Demian Christiansen; Victoria Chu; Sara Cody; Max Cohen; Erin Conners; Aaron Curns; Vishal Dasari; Patrick Dawson; Traci DeSalvo; George Diaz; Matthew Donahue; Suzanne Donovan; Lindsey M. Duca; Keith Erickson; Mathew D. Esona; Suzanne Evans; Jeremy Falk; Leora R. Feldstein; Martin Fenstersheib; Marc Fischer; Rebecca Fisher; Chelsea Foo; Marielle J. Fricchione; Oren Friedman; Alicia M. Fry; Romeo R. Galang; Melissa M. Garcia; Susa I. Gerber; Graham Gerrard; Isaac Ghinai; Prabhu Gounder; Jonathan Grein; Cheri Grigg; Jeffrey D. Gunzenhauser; Gary I. Gutkin; Meredith Haddix; Aron J. Hall; George Han; Jennifer Harcourt; Kathleen Harriman; Thomas Haupt; Amber Haynes; Michelle Holshue; Cora Hoover; Jennifer C. Hunter; Max W. Jacobs; Claire Jarashow; Michael A. Jhung; Kiran Joshi; Talar Kamali; Shifaq Kamili; Lindsay Kim; Moon Kim; Jan King; Hannah L. Kirking; Amanda Kita-Yarbro; Rachel Klos; Miwako Kobayashi; Anna Kocharian; Kenneth K. Komatsu; Ram Koppaka; Jennifer E. Layden; Yan Li; Scott Lindquist; Stephen Lindstrom; Ruth Link-Gelles; Joana Lively; Michelle Livingston; Kelly Lo; Jennifer Lo; Xiaoyan Lu; Brian Lynch; Larry Madoff; Lakshmi Malapati; Gregory Marks; Mariel Marlow; Glenn E. Mathisen; Nancy McClung; Olivia McGovern; Tristan D. McPherson; Mitali Mehta; Audrey Meier; Lynn Mello; Sung-sil Moon; Margie Morgan; Ruth N. Moro; Janna' Murray; Rekha Murthy; Shannon Novosad; Sara E. Oliver; Jennifer O'Shea; Massimo Pacilli; Clinton R. Paden; Mark A. Pallansch; Manisha Patel; Sajan Patel; Isabel Pedraza; Satish K. Pillai; Talia Pindyck; Ian Pray; Krista Queen; Nichole Quick; Heather Reese; Brian Rha; Heather Rhodes; Susan Robinson; Philip Robinson; Melissa Rolfes; Janell Routh; Rachel Rubin; Sarah L. Rudman; Senthilkumar K. Sakthivel; Sarah Scott; Christopher Shepherd; Varun Shetty; Ethan A. Smith; Shanon Smith; Bryan Stierman; William Stoecker; Rebecca Sunenshine; Regina Sy-Santos; Azaibi Tamin; Ying Tao; Dawn Terashita; Natalie J. Thornburg; Suxiang Tong; Elizabeth Traub; Ahmet Tural; Anna Uehara; Timothy M. Uyeki; Grace Vahey; Jennifer R. Verani; Elsa Villarino; Megan Wallace; Lijuan Wang; John T. Watson; Matthew Westercamp; Brett Whitaker; Sarah Wilkerson; Rebecca C. Woodruff; Jonathan M. Wortham; Tiffany Wu; Amy Xie; Anna Yousaf; Matthew Zahn; Jing Zhang.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20032896

RESUMEN

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.

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