Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
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Long-term symptoms associated with SARS-cov-2 infection among blood donors
Shah MM , Spencer BR , James-Gist J , Haynes JM , Feldstein LR , Stramer SL , Jones JM , Saydah SH . JAMA Netw Open 2024 7 (4) e245611 IMPORTANCE: Long-term symptoms, lasting more than 4 consecutive weeks after acute COVID-19 disease, are an important consequence of SARS-CoV-2 infection. Many prior studies have lacked a non-SARS-CoV-2-infected control population to distinguish background prevalence of symptoms from the direct impact of COVID-19 disease. OBJECTIVE: To examine the prevalence of long-term physical and mental health symptoms associated with SARS-CoV-2 infection in a large population of blood donors based on self-report and serologic test results. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included American Red Cross blood donors (aged ≥18 years) who were surveyed between February 22 and April 21, 2022, about new long-term symptoms arising after March 2020 and their SARS-CoV-2 infection status. All participants underwent at least 1 serologic test for antinucleocapsid antibodies between June 15, 2020, and December 31, 2021. EXPOSURES: SARS-CoV-2 infection as defined by a self-reported, confirmed acute infection or antinucleocapsid antibody positivity. MAIN OUTCOMES AND MEASURES: New long-term symptoms since March 2020, including 5 symptom categories (neurologic, gastrointestinal, respiratory and cardiac, mental health, and other). RESULTS: Among 818 361 individuals who received the survey, 272 965 (33.4%) responded, with 238 828 meeting the inclusion criteria (138 576 [58.0%] female; median [IQR] age, 59.0 [47.0-67.0] years). Of the 83 015 individuals with a history of SARS-CoV-2 infection, 43.3% reported new long-term symptoms compared with 22.1% of those without a history of SARS-CoV-2 infection. After controlling for age, sex, race and ethnicity, and number of underlying conditions, those with a history of SARS-CoV-2 infection had an increased odds of new long-term symptoms compared with those without (adjusted odds ratio [AOR], 2.55; 95% CI, 2.51-2.61). Female sex and a history of chronic conditions were associated with new long-term symptoms. Long-term symptoms in the other category (AOR, 4.14; 95% CI, 4.03-4.25), which included changes in taste or smell, and the respiratory and cardiac symptom categories (AOR, 3.21; 95% CI, 3.12-3.31) were most associated with prior SARS-CoV-2 infection. Mental health long-term symptoms were also associated with prior SARS-CoV-2 infection (AOR, 1.05; 95%, CI, 1.02-1.08). CONCLUSIONS AND RELEVANCE: This study's findings suggest that long-term symptoms lasting more than 4 weeks are common in the adult population, but there is a significantly higher prevalence among those with SARS-CoV-2 infection. Continued efforts to define and track long-term sequelae of SARS-CoV-2 using a control group without infection and serologic information to include those who had asymptomatic or unidentified infections are needed. |
Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period
King JP , Chung JR , Donahue JG , Martin ET , Leis AM , Monto AS , Gaglani M , Dunnigan K , Raiyani C , Saydah S , Flannery B , Belongia EA . BMC Infect Dis 2024 24 (1) 300 BACKGROUND: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. METHODS: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants' SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. RESULTS: During September 22, 2020 - February 13, 2021, 2712 eligible adults were enrolled, 1541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. CONCLUSION: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset. |
Differences in report of post-covid conditions among adults tested for SARS-cov-2 by race and ethnicity: 2022 Porter Novelli SummerStyles Survey, U.S
Feldstein LR , Edwards D , Cope JR , Hagen MB , Saydah S . AJPM Focus 2024 3 (2) 100181 INTRODUCTION: Since March 2020, Hispanic and Black/African American persons have made up a disproportionate number of COVID-19 cases, hospitalizations, and deaths. However, little is known about whether the prevalence of postacute sequelae or post-COVID conditions differs by race/ethnicity. METHODS: This study used cross-sectional survey data collected by Porter Novelli Public Services to determine the prevalence of ≥1 ongoing symptom lasting ≥4 weeks by SARS-CoV-2 test status and racial/ethnic groups among 2,890 adults in the U.S. RESULTS: Overall, 57% (95% CI=54%, 60%) of respondents with positive SARS-CoV-2 tests reported ≥1 ongoing symptom, compared with 22% (95% CI=20%, 24%) of respondents who tested negative. Among those with positive SARS-CoV-2 tests, Hispanic respondents had higher AORs of experiencing ≥1 ongoing symptom (AOR=1.79, 95% CI=1.27, 2.53) than non-Hispanic White respondents. In addition, Hispanic respondents had significantly higher ORs of experiencing 2 or more ongoing symptoms (AOR=2.03, 95% CI=1.45, 2.86), respiratory/cardiac symptoms (AOR=1.47, 95% CI=1.03, 2.07), neurologic symptoms (AOR=1.77, 95% CI=1.26, 2.48), and other symptoms (AOR=1.53, 95% CI=1.09, 2.14) than non-Hispanic White respondents. Non-Hispanic other respondents who reported at least 1 positive SARS-CoV-2 test had significantly higher ORs of experiencing gastrointestinal symptoms (AOR=4.06, 95% CI=1.78, 8.89) than non-Hispanic White respondents. CONCLUSIONS: These results highlight potential disparities in ongoing symptoms, even after accounting for demographic differences, and reinforce the need for culturally appropriate and targeted strategies to increase access to health care and reduce SARS-CoV-2 infections. |
Notes from the field: Long COVID prevalence among adults - United States, 2022
Ford ND , Agedew A , Dalton AF , Singleton J , Perrine CG , Saydah S . MMWR Morb Mortal Wkly Rep 2024 73 (6) 135-136 |
Ethnic and racial differences in self-reported symptoms, health status, activity level, and missed work at 3 and 6 months following SARS-CoV-2 infection
O'Laughlin KN , Klabbers RE , Ebna Mannan I , Gentile NL , Geyer RE , Zheng Z , Yu H , Li SX , Chan KCG , Spatz ES , Wang RC , L'Hommedieu M , Weinstein RA , Plumb ID , Gottlieb M , Huebinger RM , Hagen M , Elmore JG , Hill MJ , Kelly M , McDonald S , Rising KL , Rodriguez RM , Venkatesh A , Idris AH , Santangelo M , Koo K , Saydah S , Nichol G , Stephens KA . Front Public Health 2023 11 1324636 INTRODUCTION: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. METHODS: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. RESULTS: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). DISCUSSION: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes. |
Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults
Zhang Y , Romieu-Hernandez A , Boehmer TK , Azziz-Baumgartner E , Carton TW , Gundlapalli AV , Fearrington J , Nagavedu K , Dea K , Moyneur E , Cowell LG , Kaushal R , Mayer KH , Puro J , Rasmussen SA , Thacker D , Weiner MG , Saydah S , Block JP . BMC Infect Dis 2024 24 (1) 181 BACKGROUND: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. RESULTS: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection. |
Effectiveness of bivalent mRNA COVID-19 vaccines in preventing SARS-cov-2 infection in children and adolescents aged 5 to 17 years
Feldstein LR , Britton A , Grant L , Wiegand R , Ruffin J , Babu TM , Briggs Hagen M , Burgess JL , Caban-Martinez AJ , Chu HY , Ellingson KD , Englund JA , Hegmann KT , Jeddy Z , Lauring AS , Lutrick K , Martin ET , Mathenge C , Meece J , Midgley CM , Monto AS , Newes-Adeyi G , Odame-Bamfo L , Olsho LEW , Phillips AL , Rai RP , Saydah S , Smith N , Steinhardt L , Tyner H , Vandermeer M , Vaughan M , Yoon SK , Gaglani M , Naleway AL . Jama 2024 331 (5) 408-416 IMPORTANCE: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. OBJECTIVE: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. EXPOSURE: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. MAIN OUTCOME AND MEASURES: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. RESULTS: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. CONCLUSION AND RELEVANCE: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations. |
Prevalence of COVID-19 and long COVID in collegiate student athletes from Spring 2020 to Fall 2021: A retrospective survey
Massey D , Saydah S , Adamson B , Lincoln A , Aukerman DF , Berke EM , Sikka R , Krumholz HM . BMC Infect Dis 2023 23 (1) 876 BACKGROUND: Symptomatic COVID-19 and Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 (PASC) or post-COVID conditions, have been widely reported in young, healthy people, but their prevalence has not yet been determined in student athletes. We sought to estimate the prevalence of reported COVID-19, symptomatic COVID-19, and Long COVID in college athletes in the United States attending 18 schools from spring 2020 to fall 2021. METHODS: We developed an online survey to measure the prevalence of student athletes who tested positive for COVID-19, developed Long COVID, and did not return to their sport during the relevant time period. We surveyed a convenience sample of 18 collegiate school administrators, representing about 7,000 student athletes. Of those schools surveyed, 16 responded regarding the spring 2020 semester, and 18 responded regarding the full academic year of fall 2020 to spring 2021 (both semesters). RESULTS: According to the survey responses, there were 9.8% of student athletes who tested positive for COVID-19 in spring 2020 and 25.4% who tested positive in the academic year of fall 2020 to spring 2021. About 4% of student athletes who tested positive from spring 2020 to spring 2021 developed Long COVID, defined as new, recurring, or ongoing physical or mental health consequences occurring 4 or more weeks after SARS-CoV-2 infection. CONCLUSIONS: This study highlights that Long COVID occurs among young, healthy athletes and is a real consequence of COVID-19. Understanding the prevalence of Long COVID in this population requires longer follow-up and further study. |
Prevalence of SARS-CoV-2 infection among US blood donors by industry, May-December 2021
Shi DS , McDonald E , Shah M , Groenewold MR , Haynes JM , Spencer BR , Stramer S , Feldstein LR , Saydah S , Jones J , Chiu SK , Rinsky JL . Am J Ind Med 2023 BACKGROUND: Work is a social determinant of health that is often overlooked. There are major work-related differences in the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death, but there have been few analyses of infection rates across industry groups. To date, only one national assessment of SARS-CoV-2 infection prevalence by industry based on self-report has been completed. No study has looked at seroprevalence of COVID-19 by industry. METHODS: During May-December 2021, blood donors with SARS-CoV-2 antinucleocapsid testing were sent an electronic survey about their work. Free-text industry responses were classified using the North American Industry Classification System. We estimated seroprevalence and 95% confidence intervals (CIs) of SARS-CoV-2 infection by industry. RESULTS: Of 57,726 donors, 7040 (12%, 95% CI: 11.9%-12.5%) had prior SARS-CoV-2 infection. Seroprevalence was highest among Accommodation & Food Services (19.3%, 95% CI: 17.1%-21.6%), Mining, Quarrying, and Oil and Gas Extraction (19.2%, 95% CI: 12.8%-27.8%), Healthcare & Social Assistance (15.6%, 95% CI: 14.9%-16.4%), and Construction (14.7%, 95% CI: 13.1%-16.3%). Seroprevalence was lowest among Management of Companies & Enterprises (6.5%, 95% CI: 3.5%-11.5%), Professional Scientific & Technical Services (8.4%, 95% CI: 7.7%-9.0%), and Information (9.9%, 95% CI: 8.5%-11.5%). CONCLUSIONS: While workers in all industries had serologic evidence of SARS-CoV-2 infection, certain sectors were disproportionately impacted. Disease surveillance systems should routinely collect work characteristics so public health and industry leaders can address health disparities using sector-specific policies. |
Use of updated COVID-19 vaccines 2023-2024 formula for persons aged ≥6 months: Recommendations of the Advisory Committee on Immunization Practices - United States, September 2023
Regan JJ , Moulia DL , Link-Gelles R , Godfrey M , Mak J , Najdowski M , Rosenblum HG , Shah MM , Twentyman E , Meyer S , Peacock G , Thornburg N , Havers FP , Saydah S , Brooks O , Talbot HK , Lee GM , Bell BP , Mahon BE , Daley MF , Fleming-Dutra KE , Wallace M . MMWR Morb Mortal Wkly Rep 2023 72 (42) 1140-1146 COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated. |
Viral determinants of acute COVID-19 symptoms in a nonhospitalized adult population in the pre-Omicron era
Goldberg SA , Lu S , Garcia-Knight M , Davidson MC , Tassetto M , Anglin K , Pineda-Ramirez J , Chen JY , Rugart PR , Mathur S , Forman CA , Donohue KC , Abedi GR , Saydah S , Briggs-Hagen M , Midgley CM , Andino R , Peluso MJ , Glidden DV , Martin JN , Kelly JD . Open Forum Infect Dis 2023 10 (8) ofad396 BACKGROUND: The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood, particularly among nonhospitalized individuals. METHODS: The study included 85 nonhospitalized, symptomatic adults, who were enrolled from September 2020 to November 2021. Data from a longitudinal cohort studied over 28 days was used to analyze the association of individual symptoms with SARS-CoV-2 viral RNA load, or the presence or level of infectious (culturable) virus. Presence of infectious virus and viral RNA load were assessed daily, depending on specimen availability, and amount of infectious virus was assessed on the day of maximum RNA load. Participants were surveyed for the start and end dates of 31 symptoms at enrollment and at days 9, 14, 21, and 28; daily symptom presence was determined analytically. We describe symptoms and investigate their possible association with viral determinants through a series of single or pooled (multiple days across acute period) cross-sectional analyses. RESULTS: There was an association between viral RNA load and the same-day presence of many individual symptoms. Additionally, individuals with infectious virus were more than three times as likely to have a concurrent fever than individuals without infectious virus, and more than two times as likely to have concurrent myalgia, chills, headache, or sore throat. CONCLUSIONS: We found evidence to support the association of viral RNA load and infectious virus on some, but not all symptoms. Fever was most strongly associated with the presence of infectious virus; this may support the potential for symptom-based isolation guidance for COVID-19. |
Long COVID and significant activity limitation among adults, by age - United States, June 1-13, 2022, to June 7-19, 2023
Ford ND , Slaughter D , Edwards D , Dalton A , Perrine C , Vahratian A , Saydah S . MMWR Morb Mortal Wkly Rep 2023 72 (32) 866-870 Long COVID is a condition encompassing a wide range of health problems that emerge, persist, or return following COVID-19. CDC analyzed national repeat cross-sectional Household Pulse Survey data to estimate the prevalence of long COVID and significant related activity limitation among U.S. adults aged ≥18 years by age group. Data from surveys completed between June 1-13, 2022, and June 7-19, 2023, indicated that long COVID prevalence decreased from 7.5% (95% CI = 7.1-7.9) to 6.0% (95% CI = 5.7-6.3) among the overall U.S. adult population, irrespective of history of previous COVID-19, and from 18.9% (95% CI = 17.9-19.8) to 11.0% (95% CI = 10.4-11.6) among U.S. adults reporting previous COVID-19. Among both groups, prevalence decreased from June 1-13, 2022, through January 4-16, 2023, before stabilizing. When stratified by age, only adults aged <60 years experienced significant rates of decline (p<0.01). Among adults reporting previous COVID-19, prevalence decreased among those aged 30-79 years through fall or winter and then stabilized. During June 7-19, 2023, 26.4% (95% CI = 24.0-28.9) of adults with long COVID reported significant activity limitation, the prevalence of which did not change over time. These findings help guide the ongoing COVID-19 prevention efforts and planning for long COVID symptom management and future health care service needs. |
Prevalence of symptoms 12 months after acute illness, by COVID-19 testing status among adults - United States, December 2020-March 2023
Montoy JCC , Ford J , Yu H , Gottlieb M , Morse D , Santangelo M , O'Laughlin KN , Schaeffer K , Logan P , Rising K , Hill MJ , Wisk LE , Salah W , Idris AH , Huebinger RM , Spatz ES , Rodriguez RM , Klabbers RE , Gatling K , Wang RC , Elmore JG , McDonald SA , Stephens KA , Weinstein RA , Venkatesh AK , Saydah S . MMWR Morb Mortal Wkly Rep 2023 72 (32) 859-865 To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline and the 3-month follow-up, from 98.4% to 48.2% for persons who received a positive SARS-CoV-2 test results (COVID test-positive participants) and from 88.2% to 36.6% for persons who received negative SARS-CoV-2 test results (COVID test-negative participants). Persistent symptoms decreased through 12 months; no difference between the groups was observed at 12 months (prevalence among COVID test-positive and COVID test-negative participants = 18.3% and 16.1%, respectively; p>0.05). Both groups reported symptoms that emerged or reemerged at 6, 9, and 12 months. Thus, these symptoms are not unique to COVID-19 or to post-COVID conditions. Awareness that symptoms might persist for up to 12 months, and that many symptoms might emerge or reemerge in the year after COVID-like illness, can assist health care providers in understanding the clinical signs and symptoms associated with post-COVID-like conditions. |
CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design
Babu TM , Feldstein LR , Saydah S , Acker Z , Boisvert CL , Briggs-Hagen M , Carone M , Casto A , Cox SN , Ehmen B , Englund JA , Fortmann SP , Frivold CJ , Groom H , Han PD , Kuntz JL , Lockwood T , Midgley CM , Mularski RA , Ogilvie T , Reich SL , Schmidt MA , Smith N , Starita L , Stone J , Vandermeer M , Weil AA , Wolf CR , Chu HY , Naleway AL . BMJ Open 2023 13 (7) e071446 INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media. |
Longitudinal and Quantitative Fecal Shedding Dynamics of SARS-CoV-2, Pepper Mild Mottle Virus and CrAssphage (preprint)
Arts PJ , Kelly JD , Midgley CM , Anglin K , Lu S , Abedi GR , Andino R , Bakker KM , Banman B , Boehm AB , Briggs-Hagen M , Brouwer AF , Davidson MC , Eisenberg MC , Garcia-Knight M , Knight S , Peluso MJ , Pineda-Ramirez J , Sanchez RD , Saydah S , Tassetto M , Martin JN , Wigginton KR . medRxiv 2023 07 e0013223 Wastewater-based epidemiology (WBE) emerged during the COVID-19 pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden, though the lack of high-quality, longitudinal fecal shedding data of SARS-CoV-2 and other viruses limits the interpretation and applicability of wastewater measurements. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as the commonly used fecal indicators Pepper Mild Mottle Virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2 infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding, with individual measurements varying from below limit of detection to 2.79x106 gene copies/mg - dry mass of stool (gc/mg-dw). Of individuals that contributed at least 3 samples covering a range of at least 15 of the first 30 days after initial acute symptom onset, 77.4% had at least one positive SARS-CoV-2 RNA stool sample measurement. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall; and measured crAssphage DNA above detection limits in 80% (38/48) of individuals and 48% (179/371) of samples. Median shedding values for PMMoV and crAssphage nucleic acids were 1x105 gc/mg-dw and 1.86x103 gc/mgdw, respectively. These results can be used to inform and build mechanistic models to significantly broaden the potential of WBE modeling and to provide more accurate insight into SARS-CoV-2 prevalence estimates. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
CASCADIA: A prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults utilizing a remote nasal swab collection and web-based survey design (preprint)
Babu TM , Feldstein LR , Saydah S , Acker Z , Boisvert CL , Briggs-Hagen M , Carone M , Casto A , Cox SN , Ehmen B , Englund JA , Fortmann SP , Frivold CJ , Groom H , Han P , Kuntz JL , Lockwood T , Midgley CM , Mularski RA , Ogilvie T , Reich S , Schmidt MA , Smith N , Starita L , Stone J , Vandermeer M , Weil AA , Wolf CR , Chu HY , Naleway AL . medRxiv 2023 07 Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Method(s): CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. Ethics and dissemination: All study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Self-Reported Mask Use among Persons with or without SARS CoV-2 Vaccination -United States, December 2020-August 2021 (preprint)
Calamari LE , Weintraub WS , Santos R , Gibbs M , Bertoni AG , Ward LM , Saydah S , Plumb ID , Runyon MS , Wierzba TF , Sanders JW , Herrington D , Espeland MA , Williamson J , Mongraw-Chaffin M , Bertoni A , Alexander-Miller MA , Castri P , Mathews A , Munawar I , Seals AL , Ostasiewski B , Ballard CAP , Gurcan M , Ivanov A , Zapata GM , Westcott M , Blinson K , Blinson L , Mistysyn M , Davis D , Doomy L , Henderson P , Jessup A , Lane K , Levine B , McCanless J , McDaniel S , Melius K , O'Neill C , Pack A , Rathee R , Rushing S , Sheets J , Soots S , Wall M , Wheeler S , White J , Wilkerson L , Wilson R , Wilson K , Burcombe D , Saylor G , Lunn M , Ordonez K , O'Steen A , Wagner L , McCurdy LH , Gibbs MA , Taylor YJ , Calamari L , Tapp H , Ahmed A , Brennan M , Munn L , Dantuluri KL , Hetherington T , Lu LC , Dunn C , Hogg M , Price A , Leonidas M , Manning M , Rossman W , Gohs FX , Harris A , Priem JS , Tochiki P , Wellinsky N , Silva C , Ludden T , Hernandez J , Spencer K , McAlister L , Weintraub W , Miller K , Washington C , Moses A , Dolman S , Zelaya-Portillo J , Erkus J , Blumenthal J , Romero Barrientos RE , Bennett S , Shah S , Mathur S , Boxley C , Kolm P , Franklin E , Ahmed N , Larsen M , Oberhelman R , Keating J , Kissinger P , Schieffelin J , Yukich J , Beron A , Teigen J , Kotloff K , Chen WH , Friedman-Klabanoff D , Berry AA , Powell H , Roane L , Datar R , Correa A , Navalkele B , Min YI , Castillo A , Ward L , Santos RP , Anugu P , Gao Y , Green J , Sandlin R , Moore D , Drake L , Horton D , Johnson KL , Stover M , Lagarde WH , Daniel L , Maguire PD , Hanlon CL , McFayden L , Rigo I , Hines K , Smith L , Harris M , Lissor B , Cook V , Eversole M , Herrin T , Murphy D , Kinney L , Diehl P , Abromitis N , Pierre TSt , Heckman B , Evans D , March J , Whitlock B , Moore W , Arthur S , Conway J , Gallaher TR , Johanson M , Brown S , Dixon T , Reavis M , Henderson S , Zimmer M , Oliver D , Jackson K , Menon M , Bishop B , Roeth R , King-Thiele R , Hamrick TS , Ihmeidan A , Hinkelman A , Okafor C , Bray Brown RB , Brewster A , Bouyi D , Lamont K , Yoshinaga K , Vinod P , Peela AS , Denbel G , Lo J , Mayet-Khan M , Mittal A , Motwani R , Raafat M , Schultz E , Joseph A , Parkeh A , Patel D , Afridi B , Uschner D , Edelstein SL , Santacatterina M , Strylewicz G , Burke B , Gunaratne M , Turney M , Zhou SQ , Tjaden AH , Fette L , Buahin A , Bott M , Graziani S , Soni A , Mores C , Porzucek A , Laborde R , Acharya P , Guill L , Lamphier D , Schaefer A , Satterwhite WM , McKeague A , Ward J , Naranjo DP , Darko N , Castellon K , Brink R , Shehzad H , Kuprianov D , McGlasson D , Hayes D , Edwards S , Daphnis S , Todd B , Goodwin A , Berkelman R , Hanson K , Zeger S , Hopkins J , Reilly C , Edwards K , Gayle H , Redd S . medRxiv 2022 10 Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Presence of Symptoms 6 Weeks After COVID-19 Among Vaccinated and Unvaccinated U.S. Healthcare Personnel (preprint)
Mohr NM , Plumb ID , Harland KK , Pilishvili T , Fleming-Dutra KE , Krishnadasan A , Hoth KF , Saydah SH , Mankoff Z , Haran JP , Leon ES , Talan DA , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Steele MT , Beiser DG , Faine B , Nandi U , Schrading WA , Chinnock B , Chipman A , Fuentes M , LoVecchio F , Clinansmith B , Landers S , Horcher A , Wallace K , Uribe L , Pathmarajah K , Poronsky KE , Hashimoto DM , Bahamon M , Romain MSt , Kean E , Krebs E , Stubbs A , Roy S , Volturo G , Higgins A , Galbraith J , Crosby JC , Mulrow M , Gonzalez E , Gierke R , Farrar JL , Xing W , Chung Y , Yousaf A , Okaro JO , Briggs-Hagen M , Abedi GR , Nyanseor S , Watts CK . medRxiv 2022 25 Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Prevalence of COVID-19 and Long COVID in Collegiate Student Athletes from Spring 2020 to Fall 2021: A Retrospective Survey (preprint)
Massey D , Saydah S , Adamson B , Lincoln A , Aukerman DF , Berke EM , Sikka R , Krumholz HM . medRxiv 2022 16 Symptomatic COVID-19 and post-COVID conditions, also referred to as post-acute sequelae of SARS-CoV-2 (PASC) or Long COVID, have been widely reported in young, healthy people, but their prevalence has not yet been determined in student athletes. We surveyed a convenience sample of 18 collegiate school administrators, representing about 7,000 student athletes. According to their survey responses, 9.8% of student athletes tested positive for COVID-19 in spring 2020 and 25.4% tested positive in the academic year of fall 2020 to spring 2021. About 4% of student athletes who tested positive from spring 2020 to spring 2021 developed Long COVID, defined as new, recurring, or ongoing physical or mental health consequences occurring 4 or more weeks after SARS-CoV-2 infection. This study highlights that Long COVID occurs in healthy collegiate athletes and merits a larger study to determine population-wide prevalence. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study (preprint)
Garcia-Knight M , Anglin K , Tassetto M , Lu S , Zhang A , Goldberg SA , Catching A , Davidson MC , Shak JR , Romero M , Pineda-Ramirez J , Sanchez RD , Rugart P , Donohue K , Massachi J , Sans HM , Djomaleu M , Mathur S , Servellita V , McIlwain D , Gaudiliere B , Chen J , Martinez EO , Tavs JM , Bronstone G , Weiss J , Watson JT , Briggs-Hagen M , Abedi GR , Rutherford GW , Deeks SG , Chiu C , Saydah S , Peluso MJ , Midgley CM , Martin JN , Andino R , Kelly JD . medRxiv 2022 19 (9) e1010802 The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): a longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection (preprint)
O'Laughlin KN , Thompson M , Hota B , Gottlieb M , Plumb ID , Chang AM , Wisk LE , Hall AJ , Wang RC , Spatz ES , Stephens KA , Huebinger RM , McDonald SA , Venkatesh A , Gentile N , Slovis BH , Hill M , Saydah S , Idris AH , Rodriguez R , Krumholz HM , Elmore JG , Weinstein RA , Nichol G . medRxiv 2021 05 BACKGROUND: Reports 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. METHOD(S): INSPIRE 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. RESULT(S): Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSION(S): This 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. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Long COVID clinical phenotypes up to 6 months after infection identified by latent class analysis of self-reported symptoms
Gottlieb M , Spatz ES , Yu H , Wisk LE , Elmore JG , Gentile NL , Hill M , Huebinger RM , Idris AH , Kean ER , Koo K , Li SX , McDonald S , Montoy JCC , Nichol G , O'Laughlin KN , Plumb ID , Rising KL , Santangelo M , Saydah S , Wang RC , Venkatesh A , Stephens KA , Weinstein RA . Open Forum Infect Dis 2023 10 (7) ofad277 BACKGROUND: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. METHODS: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. RESULTS: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. CONCLUSIONS: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515. |
Association between SARS-CoV-2 variants and frequency of acute symptoms: Analysis of a multi-institutional prospective cohort study-December 20, 2020-June 20, 2022
Wang RC , Gottlieb M , Montoy JCC , Rodriguez RM , Yu H , Spatz ES , Chandler CW , Elmore JG , Hannikainen PA , Chang AM , Hill M , Huebinger RM , Idris AH , Koo K , Li SX , McDonald S , Nichol G , O'Laughlin KN , Plumb ID , Santangelo M , Saydah S , Stephens KA , Venkatesh AK , Weinstein RA . Open Forum Infect Dis 2023 10 (7) ofad275 BACKGROUND: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. METHODS: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. RESULTS: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). CONCLUSIONS: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. TRIAL REGISTRATION: NCT04610515. |
Longitudinal and quantitative fecal shedding dynamics of SARS-CoV-2, pepper mild mottle virus, and crAssphage
Arts PJ , Kelly JD , Midgley CM , Anglin K , Lu S , Abedi GR , Andino R , Bakker KM , Banman B , Boehm AB , Briggs-Hagen M , Brouwer AF , Davidson MC , Eisenberg MC , Garcia-Knight M , Knight S , Peluso MJ , Pineda-Ramirez J , Diaz Sanchez R , Saydah S , Tassetto M , Martin JN , Wigginton KR . mSphere 2023 8 (4) e0013223 Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 10(4) and 1.4 × 10(4) gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE. |
Factors associated with COVID-19 vaccination during June-October 2021: A multi-site prospective study
Datar RS , Fette LM , Hinkelman AN , Hammershaimb EA , Friedman-Klabanoff DJ , Mongraw-Chaffin M , Weintraub WS , Ahmed N , Gibbs MA , Runyon MS , Plumb ID , Thompson W , Saydah S , Edelstein SL , Berry AA . Vaccine 2023 INTRODUCTION: Vaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs associated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership. METHODS: In June 2021, we assessed attitudes and beliefs associated with COVID-19 vaccination using an online survey. Self-reported vaccination data were requested daily through October 2021. We compared responses between vaccinated and unvaccinated respondents using absolute standardized mean differences (ASMD). We assessed validity and reliability using exploratory factor analysis and identified latent factors associated with a subset of survey items. Cox proportional hazards models and mediation analyses assessed predictors of subsequent vaccination among those initially unvaccinated. RESULTS: In June 2021, 29,522 vaccinated and 1,272 unvaccinated participants completed surveys. Among those unvaccinated in June 2021, 559 (43.9 %) became vaccinated by October 31, 2021. In June, unvaccinated participants were less likely to feel "very concerned" about getting COVID-19 than vaccinated participants (10.6 % vs. 43.3 %, ASMD 0.792). Among those initially unvaccinated, greater intent to become vaccinated was associated with getting vaccinated and shorter time to vaccination. However, even among participants who reported no intention to become vaccinated, 28.5 % reported vaccination before study end. Two latent factors predicted subsequent vaccination-being 'more receptive' was derived from motivation to protect one's own or others' health and resume usual activities; being 'less receptive' was derived from concerns about COVID-19 vaccines. In a Cox model, both factors were partially mediated by vaccination intention. CONCLUSION: This study characterizes vaccine hesitant individuals and identifies predictors of eventual COVID-19 vaccination through October 31, 2021. Even individuals with no intention to be vaccinated can shift to vaccine uptake. Our data suggest factors of perceived severity of COVID-19 disease, vaccine safety, and trust in the vaccine development process are predictive of vaccination and may be important opportunities for ongoing interventions. |
Estimated COVID-19 vaccine effectiveness against seroconversion from SARS-CoV-2 Infection, March-October, 2021.
Plumb ID , Fette LM , Tjaden AH , Feldstein L , Saydah S , Ahmed A , Link-Gelles R , Wierzba TF , Berry AA , Friedman-Klabanoff D , Larsen MP , Runyon MS , Ward LM , Santos RP , Ward J , Weintraub WS , Edelstein S , Uschner D . Vaccine 2023 41 (15) 2596-2604 BACKGROUND: Monitoring the effectiveness of COVID-19 vaccines against SARS-CoV-2 infections remains important to inform public health responses. Estimation of vaccine effectiveness (VE) against serological evidence of SARS-CoV-2 infection might provide an alternative measure of the benefit of vaccination against infection. METHODS: We estimated mRNA COVID-19 vaccine effectiveness (VE) against development of SARS-CoV-2 anti-nucleocapsid antibodies in March-October 2021, during which the Delta variant became predominant. Participants were enrolled from four participating healthcare systems in the United States, and completed electronic surveys that included vaccination history. Dried blood spot specimens collected on a monthly basis were analyzed for anti-spike antibodies, and, if positive, anti-nucleocapsid antibodies. We used detection of new anti-nucleocapsid antibodies to indicate SARS-CoV-2 infection, and estimated VE by comparing 154 case-participants with new detection of anti-nucleocapsid antibodies to 1,540 seronegative control-participants matched by calendar period. Using conditional logistic regression, we estimated VE ≥ 14 days after the 2nd dose of an mRNA vaccine compared with no receipt of a COVID-19 vaccine dose, adjusting for age group, healthcare worker occupation, urban/suburban/rural residence, healthcare system region, and reported contact with a person testing positive for SARS-CoV-2. RESULTS: Among individuals who completed a primary series, estimated VE against seroconversion from SARS-CoV-2 infection was 88.8% (95% confidence interval [CI], 79.6%-93.9%) after any mRNA vaccine, 87.8% (95% CI, 75.9%-93.8%) after BioNTech vaccine and 91.7% (95% CI, 75.7%-97.2%) after Moderna vaccine. VE was estimated to be lower ≥ 3 months after dose 2 compared with < 3 months after dose 2, and among participants who were older or had underlying health conditions, although confidence intervals overlapped between subgroups. CONCLUSIONS: VE estimates generated using infection-induced antibodies were consistent with published estimates from clinical trials and observational studies that used virologic tests to confirm infection during the same period. Our findings support recommendations for eligible adults to remain up to date with COVID-19 vaccination. |
School-based interventions to increase student COVID-19 vaccination coverage in public school populations with low coverage - Seattle, Washington, December 2021-June 2022
Fairlie T , Chu B , Thomas ES , Querns AK , Lyons A , Koziol M , Englund JA , Anderson EM , Graff K , Rigel S , Bell TR , Saydah S , Chatham-Stephens K , Vogt TM , Hoag S , Briggs-Hagen M . MMWR Morb Mortal Wkly Rep 2023 72 (11) 283-287 COVID-19 can lead to severe outcomes in children (1). Vaccination decreases risk for COVID-19 illness, severe disease, and death (2). On December 13, 2020, CDC recommended COVID-19 vaccination for persons aged ≥16 years, with expansion on May 12, 2021, to children and adolescents (children) aged 12-15 years, and on November 2, 2021, to children aged 5-11 years (3). As of March 8, 2023, COVID-19 vaccination coverage among school-aged children remained low nationwide, with 61.7% of children aged 12-17 years and approximately one third (32.7%) of those aged 5-11 years having completed the primary series (3). Intention to receive COVID-19 vaccine and vaccination coverage vary by demographic characteristics, including race and ethnicity and socioeconomic status (4-6). Seattle Public Schools (SPS) implemented a program to increase COVID-19 vaccination coverage during the 2021-22 school year, focusing on children aged 5-11 years during November 2021-June 2022, with an added focus on populations with low vaccine coverage during January 2022-June 2022.(†) The program included strategic messaging, school-located vaccination clinics, and school-led community engagement. Vaccination data from the Washington State Immunization Information System (WAIIS) were analyzed to examine disparities in COVID-19 vaccination by demographic and school characteristics and trends over time. In December 2021, 56.5% of all SPS students, 33.7% of children aged 5-11 years, and 81.3% of children aged 12-18 years had completed a COVID-19 primary vaccination series. By June 2022, overall series completion had increased to 80.3% and was 74.0% and 86.6% among children aged 5-11 years and 12-18 years, respectively. School-led vaccination programs can leverage community partnerships and relationships with families to improve COVID-19 vaccine access and coverage. |
Estimating incidence of type 1 and type 2 diabetes using prevalence data: the SEARCH for Diabetes in Youth study
Hoyer A , Brinks R , Tönnies T , Saydah SH , D'Agostino RB Jr , Divers J , Isom S , Dabelea D , Lawrence JM , Mayer-Davis EJ , Pihoker C , Dolan L , Imperatore G . BMC Med Res Methodol 2023 23 (1) 39 BACKGROUND: Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts. The aim of this study was to examine whether a partial differential equation (PDE) can be used to estimate diabetes incidence from prevalence in youth. METHODS: We used age-, sex-, and race/ethnicity-specific estimates of prevalence in 2001 and 2009 as reported in the SEARCH for Diabetes in Youth study. Using these data, a PDE was applied to estimate the average incidence rates of type 1 and type 2 diabetes for the period between 2001 and 2009. Estimates were compared to annual incidence rates observed in SEARCH. Precision of the estimates was evaluated using 95% bootstrap confidence intervals. RESULTS: Despite the long period between prevalence measures, the estimated average incidence rates mirror the average of the observed annual incidence rates. Absolute values of the age-standardized sex- and type-specific mean relative errors are below 8%. CONCLUSIONS: Incidence of diabetes can be accurately estimated from prevalence. Since only cross-sectional prevalence data is required, employing this methodology in future studies may result in considerable cost savings. |
Direct medical costs associated with post-COVID-19 conditions among privately insured children and adults
Pike J , Kompaniyets L , Lindley MC , Saydah S , Miller G . Prev Chronic Dis 2023 20 E06 INTRODUCTION: SARS-CoV-2, the virus that causes COVID-19, has caused more than 100.2 million infections and more than 1 million deaths in the US as of November 2022, yet information on the economic burden associated with post-COVID-19 conditions is lacking. We estimated the possible economic burden associated with post-COVID-19 conditions by comparing direct medical costs among patients younger than 65 years with and without COVID-19 in the postacute period. METHODS: Commercially insured children and adults with a COVID-19 diagnosis (cases) during April-August 2020 were matched to those without COVID-19 (controls) on a 1:4 ratio. Direct medical costs represented 1-, 3-, and 6-month total expenditures per person starting 31 days after the diagnosis date. We used a 2-part model to evaluate cost differences among individuals with and without COVID-19, adjusted for patient characteristics. RESULTS: Costs were higher among cases compared with controls. Direct medical costs among child cases were 1.82, 1.72, and 1.70 times higher than controls over 1, 3, and 6 months, respectively. Direct medical costs among adult cases were 1.69, 1.54, and 1.46 times higher than costs among controls over 1, 3, and 6 months, respectively. Relative differences in costs were highest among adults aged 50 to 64 years. In a subset of people with COVID-19, costs were higher among hospitalized cases compared with nonhospitalized cases. CONCLUSION: Our findings suggest a considerable economic burden of COVID-19 even after the resolution of acute illness, highlighting the importance of prevention and mitigation measures to reduce the economic impact of COVID-19 on the US health care system. |
Presence of symptoms 6 weeks after COVID-19 among vaccinated and unvaccinated US healthcare personnel: a prospective cohort study
Mohr NM , Plumb ID , Harland KK , Pilishvili T , Fleming-Dutra KE , Krishnadasan A , Hoth KF , Saydah SH , Mankoff Z , Haran JP , Briggs-Hagen M , León ES , Talan DA . BMJ Open 2023 13 (2) e063141 OBJECTIVES: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work. DESIGN: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. SETTING: Health systems in 12 US states. PARTICIPANTS: HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset. EXPOSURES: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. MAIN OUTCOME MEASURES: Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work. RESULTS: Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79). CONCLUSIONS: Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work. |
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