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.

Predictors of Mortality in Hospitalized African American Covid-19 Cancer Patients (preprint)

Background: Coronavirus disease 2019 (COVID-19) and associated outcomes manifest differently depending on patients’ background and pre-existing conditions. It remains unclear how African Americans with and without cancer have been affected. Aim: To determine epidemiological, clinical comorbidities, and laboratory test results to identify markers associated with mortality in COVID-19 cancer patients. Methods: : We reviewed all Covid-19 hospitalized patients records from Dec. 2019 to Oct. 2021 at Howard University Hospital. Patients having a history of, or active cancer status were reviewed. All the clinical, treatment, lab values, and pathological data were extracted. Statical analysis of the Covid-19 cancer patients and comparison with non-cancer Covid-19 patients was performed using univariate and multivariate analyses. Results: : Out of 512 COVID-19 infected patients, a total of 49 patients were identified with different types of cancer, with both active and previous history. Females consisted of 26 cancer patients (53%). African American race was predominant in both cases and controls, 83.6% and 66.7% respectively. Cancer patients were older than non-cancer patients (Mean Age-70.6 vs. 56.3 years) and had an increased length of hospital stay (Mean 13.9 vs 9.4 days). Among cancer patients, breast cancer was more prevalent in females and prostate cancer in males, (54% and 52% respectively). Comparison of patients with active vs. previous cancer showed no significant difference in the clinical outcome, death vs. discharge (P=0.34). A higher reduction in albumin level in cancer cases, from the time of admission to day five, was significantly associated with death during the same hospital stay compared to those discharged (n=24, 48.9%, p<0.001). In controls, Lymphopenia (n=436, 94.1%, p=0.05), AST (n=59, 12%, p=0.008) and Albumin (n=40, 10.7%, p=0.02) have shown an association with increased mortality. Conclusion: Albumin level has shown to have an inverse relationship with clinical outcomes among all COVID infected African American patients. Reduction in Albumin level during the hospital stay, particularly in COVID-19 cancer patients should be considered as a predictor of mortality. No significant difference was noticed in the clinical outcome in patients with previous versus active cancer. Further research with a large cohort size is needed to verify and identify other predictors of outcome in Covid-19 cancer patients and develop appropriate treatment modalities.

COVID-19 Patients’ Symptoms: Gastrointestinal Presentations, Comorbidities and Outcomes in a Canadian Hospital Setting (preprint)

ABSTRACT Background The Coronavirus disease 2019 (COVID-19) pandemic has had significant global impact. While public health interventions and universal health insurance has been credited with minimizing transmission rates in Canada relative to neighboring countries, significant morbidity and mortality have occurred nationwide. We sought to determine factors associated with differences in gastrointestinal outcomes in COVID-19 patients at a Canadian hospital. Methods We collected data from 192 hospital records of COVID-19 patients across seven Hamilton Health Sciences hospitals, a network of academic health centres serving one of the largest metropolitan areas in Canada. Statistical and correlative analysis of symptoms, comorbidities, and mortality were performed. Results There were 192 patients. The mean age was 57.6 years (SD=21.0). For patients who died (n=27, 14%), mean age was 79.2 years old (SD=10.6) versus 54 years for survivors (SD=20.1). There was a higher mortality among patients with older age ( p= 0.000), long hospital stay ( p= 0.004), male patients ( p= 0.032), and patients in nursing homes ( p= 0.000). Patients with dyspnea ( p= 0.028) and hypertension ( p= 0.004) were more likely to have a poor outcome. Laboratory test values that were significant in determining outcomes were an elevated INR ( p= 0.007) and elevated creatinine ( p= 0.000). Cough and hypertension were the most common symptom and comorbidity, respectively. Diarrhea was the most prevalent (14.5%) gastrointestinal symptom. Impaired liver function was related to negative outcome (LR 5.6; p =0.018). Conclusions In a Canadian cohort, elevated liver enzymes, prolonged INR and elevated creatinine were associated with poor prognosis. Hypertension was also linked to a higher likelihood of negative outcome. SUMMARY BOX What is already known about this subject? The prevalence of gastrointestinal symptoms in COVID-19 patients across Canada is lacking Gastrointestinal manifestations of COVID-19 are well described, and longterm sequelae of gastrointestinal tract involvement are an ongoing concern What are the new findings? There was a significant prevalence of gastrointestinal symptoms in patients with a confirmed diagnosis of COVID-19 at one of the largest metropolitan regions across Canada Liver enzyme abnormalities were common in patients at diagnosis This report, over an 8-month period, represents the largest cohort of COVID-19 patients reported in Canada How might these results impact on clinical practice in the foreseeable future? Baseline gastrointestinal symptoms and laboratory abnormalities correlate with patient outcome in Canadian COVID-19 patients These results enhance our knowledge of the prevalence of gastrointestinal symptoms and laboratory abnormalities in Canadian patients and offer important baseline data for longitudinal studies in these patients Our findings increase our knowledge of the epidemiology of COVID-19 in Canada and allow future comparison with international data

A Comprehensive Analysis of COVID-19 Impact in Latin America (preprint)

Background: Latin America has now become the epicenter of the global coronavirus disease 2019 (COVID-19) pandemic. In the ongoing COVID -19 pandemic, a profound burden of SARS-COV-2 infection has been reported in Latin America. In the present study, we aim to determine the profiles that are associated with this disease in Latin America. We analyzed symptoms, morbidities and gastrointestinal (GI) manifestations by country.Methods: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 Latin American countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia between March 1 and July 30, 2020.  These countries consist of a total population that exceeds 519 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and lethality were performed.Results: A total of 728,282 patients tested positive for COVID-19 across all the 8 Latin American countries. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years old and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivia had fever as the top symptom (83.3%). GI symptoms including diarrhea (highest in Mexico with 22.9%), nausea, vomiting, and abdominal pain were not associated with higher mortality. Hypertension was among the top (12.1%) comorbidities followed by diabetes with 8.3% and obesity 4.5%. In multivariable analyses, the leading and significant comorbidities were hypertension (r=0.83, p=0.02), diabetes (r=0.91, p=0.01), and obesity (r=0.86, p=0.03). Asthma (r=0.37, p=0.54) and increasing age (0.13 p=0.81) were not independently associated with higher mortality. Lethality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts.Conclusion: Nearly, 10.5%–53% of patients with COVID-19 have GI manifestations. Differential clinical symptoms were associated with COVID-19 in Latin America countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed. Country-specific management and prevention plans can be established from this meta-analysis.