Researching COVID to enhance recovery (RECOVER) adult study protocol: Rationale, objectives and design (preprint)

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged [≥]18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.

Willingness to accept COVID-19 vaccination among people living with HIV in a high HIV prevalence community (preprint)

Background People living with HIV (PLWH) may have a poorer prognosis with COVID-19 infection and are an important population for COVID-19 vaccination. We assessed the willingness and reasons for COVID-19 vaccine acceptance or hesitancy among PLWH in South Africa.MethodsWe conducted a cross-sectional study consisting of telephone interviews with a randomly selected subset of participants enrolled in a prospective observational cohort study evaluating a decentralized antiretroviral therapy (ART) delivery program in South Africa. Questions assessed willingness to accept a future COVID-19 vaccine, concerns regarding COVID-19 vaccination, and overall vaccine confidence. Interviews were conducted between September 2020 and January 2021. We evaluated participant demographics, sources of COVID-19 information, stigma and medical mistrust, uptake of non-pharmaceutical interventions, and socioeconomic impacts of the COVID-19 pandemic as potential covariates of willingness to accept vaccination. Results We completed interviews with 213 participants; 153 (72%) were female, median age 35y, and 100 (47%) had completed secondary school. Among the participants, 121 (57%) were willing to accept future vaccination, 46 (22%) were unsure, and 45 (21%) stated they did not intend to be vaccinated. Fear of side effects, reported by 42 (20%), was the most common concern about COVID-19 vaccination. Older age was associated with willingness to accept vaccination (aOR 1.75 for every 10-year increase in age, 95% CI 1.10-2.78, p=0.02), while higher medical mistrust related to COVID-19 (aOR 0.21, 95% CI 0.093-0.45, p<0.001) and use of social media for COVID-19 information (aOR 0.30, 95% CI 0.11-0.84, p=0.02) were associated with lower willingness to accept vaccination. Conclusions In this cohort of PLWH in South Africa, over half were willing to accept COVID-19 vaccination, although a substantial proportion remained unsure or were not willing to be vaccinated. Public health messaging should emphasize the safety and efficacy of COVID-19 vaccination and address misinformation and medical mistrust among PLWH. Ongoing efforts to ensure access to COVID-19 vaccines for vulnerable populations are crucial. 

Massachusetts General Hospital Covid-19 Registry reveals two distinct populations of hospitalized patients by race and ethnicity (preprint)

ObjectiveTo evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH). MethodsThe MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N=866 patients hospitalized with Covid-19 from March 11, 2020 - May 4, 2020. ResultsOverall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR=(48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR=(40.6, 61.6) versus 72y; (58.0, 81.7) (p< 0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p=0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p< 0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p< 0.001; OR=1.99, p=0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p< 0.001). ConclusionsHospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.

COVID-19 Outpatient Screening: a Prediction Score for Adverse Events (preprint)

Background. We sought to develop an automatable score to predict hospitalization, critical illness, or death in patients at risk for COVID-19 presenting for urgent care during the Massachusetts outbreak. Methods. Single-center study of adult outpatients seen in respiratory illness clinics (RICs) or the emergency department (ED), including development (n = 9381, March 7-May 2) and prospective (n = 2205, May 3-14) cohorts. Data was queried from Partners Enterprise Data Warehouse. Outcomes were hospitalization, critical illness or death within 7 days. We developed the COVID-19 Acuity Score (CoVA) using automatically extracted data from the electronic medical record and learning-to-rank ordinal logistic regression modeling. Calibration was assessed using predicted-to-observed event ratio (E/O). Discrimination was assessed by C-statistics (AUC). Results. In the development cohort, 27.3%, 7.2%, and 1.1% of patients experienced hospitalization, critical illness, or death, respectively; and in the prospective cohort, 26.1%, 6.3%, and 0.5%. CoVA showed excellent performance in the development cohort (concurrent validation) for hospitalization (E/O: 1.00, AUC: 0.80); for critical illness (E/O: 1.00, AUC: 0.82); and for death (E/O: 1.00, AUC: 0.87). Performance in the prospective cohort (prospective validation) was similar for hospitalization (E/O: 1.01, AUC: 0.76); for critical illness (E/O 1.03, AUC: 0.79); and for death (E/O: 1.63, AUC=0.93). Among 30 predictors, the top five were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. Conclusions. CoVA is a prospectively validated automatable score to assessing risk for adverse outcomes related to COVID-19 infection in the outpatient setting.