Non-hospitalized Participants Research Articles

Lopinavir/ritonavir for treatment of non-hospitalized patients with COVID-19: a randomized clinical trial

ObjectivesEffective and widely available therapies are still needed for outpatients with COVID-19. We aimed to evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) for early treatment of non-hospitalized individuals diagnosed with COVID-19. MethodsThis randomized, placebo (Plb)-controlled, double-blind, multi-site decentralized clinical trial enrolled non-hospitalized adults with confirmed SARS-CoV-2 infection and six or fewer days of acute respiratory infection symptoms who were randomized to either twice-daily oral LPV/r (400 mg/100 mg) or Plb for 14 days. Daily surveys on study days 1 through 16 and again on study day 28 evaluated symptoms, daily activities, and hospitalization status. The primary outcome was longitudinal change in an ordinal scale based on a combination of symptoms, activity, and hospitalization status through day 15 and was analyzed by use of a Bayesian longitudinal proportional odds logistic regression model for estimating the probability of a superior recovery for LPV/r over Plb (odds ratio >1). ResultsBetween June 2020 and December 2021, 448 participants were randomized to receive either LPV/r (n = 216) or Plb (n = 221). The mean symptom duration before randomization was 4.3 days (SD 1.3). There were no differences between treatment groups through the first 15 days for the ordinal primary outcome (odds ratio 0.96; 95% credible interval: 0.66 to 1.41). There were 3.2% (n = 7) of LPV/r and 2.7% (n = 6) of Plb participants hospitalized by day 28. Serious adverse events did not differ between groups. ConclusionLPV/r did not significantly improve symptom resolution or reduce hospitalization in non-hospitalized participants with COVID-19. Trial registrationClinicalTrials.gov Identifier: NCT04372628

Systemic corticosteroids for the treatment of COVID-19: Equity-related analyses and update on evidence.

Systemic corticosteroids for the treatment of COVID-19: Equity-related analyses and update on evidence.

Abstract A050: Analysis of methods to improve engagement of under-represented and socioeconomically deprived patients in clinical research

Abstract The current under-representation of racial and ethnic minorities and socio-economically disadvantaged participants in clinical trials represents an important problem, because it reduces generalizability of trial results and should urgently be addressed in all diseases. Decentralized trials may improve engagement of under-represented populations with long-standing health disparities and may be relevant to patients with pancreatic cancer who would benefit from at home trial participation. We completed a fully decentralized randomized double-blind phase II clinical trial in New York State for participants with mild-to-moderate COVID-19. Electronic data were collected for 28 days (5 vital readings and 1 survey with 20 questions per day) from 55 non-hospitalized participants. Home monitoring devices, HIPAA compliant data submission technology, and internet access were provided free-of-charge. We enrolled 40% White, 33% Black or African American and 27% Other/Mixed/Unknown participants. Of these, 25% self-identified as Hispanic or Latino. This exceeded national and New York state averages of minority populations, in contrast with the current clinical trial landscape. We found that the local area within a 30-minute return car journey from our main research hospital disproportionately over-represented socio-economically advantaged white inhabitants. We found that decentralization enabled the inclusion of participants living up to a 2-hour journey from this hospital in socio-economically deprived geographies with higher minority race representation. We excluded selection bias, by demonstrating that our trial population represented the differences of social deprivation observed between races at the national and state level (p = 0.003). In addition to trial enrollment, completeness of trial data has an important impact on the veracity of trial results. Half our participants were assigned a dedicated team member to make telephone call reminders if participants had not submitted data by mid-day despite of a pre-ceding automated notification to the supplied electronic device. Daily telephone follow-up significantly reduced missing electronic data in participants living above the median deprivation index (submitted data per day 4 out of 6 vs 6 out of 6: p = 0.03), thereby aiding equitable data collection from traditionally under-represented participant groups. Our findings require further validation and refinement from multiple centers and expansion to patients with reduced mobility and cachexia due to progressing pancreatic cancer. Also, other factors such as language assistance and recruitment methods, need to be addressed in clinical trials to mitigate against their negative impact on equitable recruitment. Nevertheless, for now we identify decentralization combined with engagement telephone calls as readily actionable methods to improve inclusion of under-represented participants in clinical trials. Citation Format: Hassal Lee, Alexander Shakeel Bates, Richard Dima, Sandeep Nadella, Nicole Jordan-Martin, Christina Brennan, Tobias Janowitz. Analysis of methods to improve engagement of under-represented and socioeconomically deprived patients in clinical research [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A050.

Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients.

The coronavirus disease (COVID) 2019 pandemic remains a great challenge for the healthcare system. The widely reported prolonged signs and symptoms resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (Long-COVID) require medical care. The aim of the study was to assess factors, including lifestyle variables, related to the course of COVID-19 infection and to assess their impact on prolonged symptoms in non-hospitalized patients with COVID-19. A total of 1,847 (637 men and 1,210 women) non-hospitalized participants of the STOP-COVID registry of the PoLoCOV-Study who, following the COVID-19, underwent check-up examinations at the cardiology outpatient clinic were included in the analysis. The study participants (median age 51 [41-62] years) were evaluated at 13.4 (8.4-23.6) weeks following the diagnosis of COVID-19. Female sex (odds ratio [OR] 1.46 [95% CI 1.19-1.78]), body mass index (BMI; per 1 kg/m2: 1.02 [1.00-1.04]), hypertension (1.39 [1.07-1.81]), asthma (1.55 [1.06-2.27]), stress or overworking (1.54 [1.25-1.90]), and nightshift work (1.51 [1.06-2.14]) were independently related to the severity of symptoms during acute phase of the COVID-19 infection. The Long-COVID syndrome was independently related to the female sex (1.42 [1.13-1.79]), history of myocardial infarction (2.57 [1.04-6.32]), asthma (1.56 [1.01-2.41]), and severe course of the acute phase of the COVID-19 infection (2.27 [1.82-2.83]). Female sex, BMI, asthma, hypertension, nightshifts, and stress or overworking are significantly related to the severity of the acute phase of the COVID-19 infection, while female sex, asthma, history of myocardial infarction, and the severity of symptoms in the acute phase of COVID-19 are the predictors of Long-COVID in non-hospitalized patients. We did not find an independent relation between Long-COVID and the studied lifestyle factors.

Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults.

Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown. To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction. Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021. 2,413 adults ages 18-64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone. The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction. Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06]. Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.

Body composition and cardiorespiratory fitness in overweight or obese people post COVID-19: A comparative study.

The present study aimed to evaluate the body composition and cardiorespiratory fitness of overweight or obese people after COVID-19. 171 volunteers of both sexes (men, n = 93 and women, n = 78) between 19 and 65 years old were allocated into three groups according to the severity of their symptoms of COVID-19: non-hospitalized people/mild symptoms (n = 61), hospitalized (n = 58), and hospitalized in an intensive care unit-ICU (n = 52). Two laboratory visits were carried out 24 h apart. First, a medical consultation was carried out, with subsequent measurement of body weight and height (calculation of body mass index) and body composition assessment via electrical bioimpedance. After 24 h, a cardiorespiratory test was performed using the Bruce protocol, with a direct gas exchange analysis. Hospitalized individuals had significantly higher values for fat mass and body fat percentage than non-hospitalized individuals (p < 0.05). Significantly higher values were found for heart rate (HR) and peak oxygen consumption (VO2peak) for individuals who were not hospitalized when compared to those hospitalized in the ICU (p < 0.05). Significantly higher values for distance, ventilation, and the relationship between respiratory quotient were found for non-hospitalized individuals compared to hospitalized individuals and those in the ICU (p < 0.05). After the cardiorespiratory test, higher values for peripheral oxygen saturation (SpO2) were observed for non-hospitalized individuals than for all hospitalized individuals (p < 0.05). Diastolic blood pressure was significantly higher at the tenth and fifteenth minute post-Bruce test in hospitalized than in non-hospitalized participants (p < 0.05). Based on these results, proposals for cardiopulmonary rehabilitation are indispensable for hospitalized groups considering the responses of blood pressure. Monitoring HR, SpO2, and blood pressure are necessary during rehabilitation to avoid possible physical complications. Volume and intensity of exercise prescription should respect the physiologic adaptation. Given lower physical conditioning among all the groups, proposals for recovering from health conditions are urgent and indispensable for COVID-19 survivors.

Detection of Higher Cycle Threshold Values in Culturable SARS-CoV-2 Omicron BA.1 Sublineage Compared with Pre-Omicron Variant Specimens - San Francisco Bay Area, California, July 2021-March 2022.

Before emergence in late 2021 of the highly transmissible B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19 (1,2), several studies demonstrated that SARS-CoV-2 was unlikely to be cultured from specimens with high cycle threshold (Ct) values§ from real-time reverse transcription-polymerase chain reaction (RT-PCR) tests (suggesting low viral RNA levels) (3). Although CDC and others do not recommend attempting to correlate Ct values with the amount of infectious virus in the original specimen (4,5), low Ct values are sometimes used as surrogate markers for infectiousness in clinical, public health, or research settings without access to virus culture (5). However, the consistency in reliability of this practice across SARS-CoV-2 variants remains uncertain because Omicron-specific data on infectious virus shedding, including its relationship with RNA levels, are limited. In the current analysis, nasal specimens collected from an ongoing longitudinal cohort¶ (6,7) of nonhospitalized participants with positive SARS-CoV-2 test results living in the San Francisco Bay Area** were used to generate Ct values and assess for the presence of culturable SARS-CoV-2 virus; findings were compared between specimens from participants infected with pre-Omicron variants and those infected with the Omicron BA.1 sublineage. Among specimens with culturable virus detected, Ct values were higher (suggesting lower RNA levels) during Omicron BA.1 infections than during pre-Omicron infections, suggesting variant-specific differences in viral dynamics. Supporting CDC guidance, these data show that Ct values likely do not provide a consistent proxy for infectiousness across SARS-CoV-2 variants.

Lung Abnormalities Detected with Hyperpolarized 129Xe MRI in Patients with Long COVID.

BackgroundPost-Covid-19 condition describes symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is common.PurposeThe purpose of this study was to determine whether the previously described lung abnormalities on Hp-XeMRI in post-hospitalised COVID-19 participants are also present in non-hospitalised participants with Post-Covid-19 condition.MethodsIn this prospective study, non-hospitalised Post-Covid-19 condition (NHLC) and post-hospitalised COVID-19 (PHC) participants were enrolled from 06/2020 to 08/2021. Participants had chest CT, hyperpolarized pulmonary 129Xenon MRI (Hp-XeMRI), pulmonary function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Control subjects underwent HP-XeMRI only. CT scans were analysed for post COVID interstitial lung disease severity using a previously published scoring system, and Full-scale Airway Network (FAN) modelling. Analysis used group and pair-wise comparisons between participants and controls, and correlations between participant clinical and imaging data.ResultsA total of 11 NHLC (4:7 Male: Female, 44 ± 11 years, [37-50], (mean ± SD, [95% CI]) and 12 PHC (10:2, Male: Female, 58 ± 10 years, [52-64]) participants were included, with a significant difference in age between groups, p = 0.05. NHLC participants were 287 ± 79, [240-334] and PHC 143 ± 72, [105-190] days from infection, respectively. NHLC and PHC participants had normal or near normal CT scans (0.3/25 ± 0.6, [0-0.63] and 7/25 ± 5, [4-10], respectively). Gas transfer (DLco (%)) was different between NHLC and PHC participants (76 ± 8%, [73-83] vs 86 ± 8%, [80-91] respectively, p = 0.04) but there was no evidence of other differences in lung function. Red Blood Cell:Tissue Plasma (RBC:TP) mean was different between volunteers vs PHC (0.45 ± 0.07, [0.43-0.47] vs (0.31 ± 0.10, [0.24-0.37], respectively, p = 0.02) and volunteers vs NHLC (0.37 ± 0.10, [0.31-0.44], p = 0.03) participants, but not between NHLC and PHC participants (p = 0.26). FAN results did not correlate with DLco or Hp- XeMRI.ConclusionNHLC and PHC subjects showed Hp-XeMRI RBC:TP abnormalities, with NHLC participants demonstrating lower DLco than PHC participants despite having normal CT scans.See also the editorial by Parraga and Matheson.

Genetic risk factors and COVID-19 severity in Brazil: results from BRACOVID study.

The coronavirus disease 2019 (COVID-19) pandemic has changed the paradigms for disease surveillance and rapid deployment of scientific-based evidence for understanding disease biology, susceptibility and treatment. We have organized a large-scale genome-wide association study (GWAS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals in Sao Paulo, Brazil, one of the most affected areas of the pandemic in the country, itself one of the most affected in the world. Here, we present the results of the initial analysis in the first 5233 participants of the BRACOVID study. We have conducted a GWAS for COVID-19 hospitalization enrolling 3533 cases (hospitalized COVID-19 participants) and 1700 controls (non-hospitalized COVID-19 participants). Models were adjusted by age, sex and the 4 first principal components. A meta-analysis was also conducted merging BRACOVID hospitalization data with the Human Genetic Initiative (HGI) Consortia results. BRACOVID results validated most loci previously identified in the HGI meta-analysis. In addition, no significant heterogeneity according to ancestral group within the Brazilian population was observed for the two most important COVID-19 severity associated loci: 3p21.31 and Chr21 near IFNAR2. Using only data provided by BRACOVID, a new genome-wide significant locus was identified on Chr1 near the genes DSTYK and RBBP5. The associated haplotype has also been previously associated with a number of blood cell related traits and might play a role in modulating the immune response in COVID-19 cases.

Longitudinal surveillance of Post-Acute Sequelae of SARS-CoV-2 among Long Beach City residents, April-December, 2020

PurposeThere have been limited studies on the post-acute sequelae of SARS-CoV-2 (PASC) throughout the course of the disease and recovery. The purpose of this study was to identify the prevalence and associated factors of PASC in a diverse population to inform patients’ expectations and public health policy.Methods & MaterialsConfirmed Coronavirus Disease 2019 (COVID-19) surveillance data was obtained from the California Reportable Disease Information Exchange (CalREDIE) surveillance system between April 1, 2020 and December 10, 2020. Simple random sampling without replacement was used to select participants for the study. Interview questions, guided by the CalREDIE COVID-19 case investigation questionnaire, focused on tracking self-reported symptoms prior to diagnosis, at time of positive test result, one-month post-testing, two months post-testing, and on the date of the final interview.ResultsOne third of participants reported PASC two months post-testing, most commonly reporting fatigue, anosmia, and dyspnea. Individuals forty years and older, female, Black/African American, and with asthma or obesity had the highest odds of developing PASC in our study population.ConclusionAge, gender, pre-existing conditions, and ethnicity/race were associated with developing PASC in a diverse sample of hospitalized and non-hospitalized participants. As the number of recovered COVID-19 patients increases, it is critical to understand the impacts of PASC and differential access to care and recovery among diverse populations in order to guide patient expectations and equitable public health policies.

Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection part 2: Psychological functioning

Objective: Limited research investigating the long-term psychological and emotional correlates of COVID-19 infection has been completed. The current study begins to address this limitation in patients experiencing Post-Acute Sequelae SARS-CoV-2 (PASC; e.g. “Long COVID”). Participants and methods: Participants were 43 consecutive neuropsychological outpatients diagnosed with PASC and who completed the Personality Assessment Inventory (PAI). The sample was predominantly female (n = 36) and white (n = 32). Effect sizes compared to the normative mean T scores and base rates of elevated (T > 69) scores were calculated. Results: PAI scales measuring somatic preoccupation and depression had large effect sizes and the highest base rates of scale elevations, with the mean T score at approximately the normative cutoff for clinical significance (T = 70). The Schizophrenia Thought Disorder subscale (SCZ-T) also had a large effect size and high base rate of elevation, likely reflecting cognitive concerns. Scales measuring anxiety had medium effect sizes. The other PAI scales generally had small to negligible effect sizes. There were no significant differences between hospitalized and non-hospitalized participants on the PAI. Conclusions: Overall, PAI scales measuring psychological distress, particularly somatic preoccupation and depression, were the most frequently elevated in the participants. The specific reasons for somatic preoccupation could not be determined in this study. Potential explanations include a vulnerability to distress in Long COVID patients, premorbid somatic preoccupation perhaps motivating these patients to seek clinical attention, or socioenvironmental factors leading some COVID patients to be somatically preoccupied with minor physiological changes and attribute those changes to COVID-19.

A Cohort Study of Post COVID-19 Condition Across the Beta, Delta and Omicron Waves in South Africa: 6-Month Follow Up of Hospitalised and Non-Hospitalised Participants

A Cohort Study of Post COVID-19 Condition Across the Beta, Delta and Omicron Waves in South Africa: 6-Month Follow Up of Hospitalised and Non-Hospitalised Participants

511. Treatment with Molnupiravir in the MOVe-In and MOVe-Out Clinical Trials Results in an Increase in Transition Mutations Across the SARS-CoV-2 Genome

BackgroundMolnupiravir (MOV), (MK-4482, EIDD-2801) is being clinically developed for the treatment of COVID-19 disease caused by SARS-CoV-2. MOV is the orally administered 5′-isobutyrate prodrug of the active, antiviral ribonucleoside analogue, N-hydroxycytidine (NHC, EIDD-1931) which inhibits viral replication by induction of mutations in the viral genome, leading to viral error catastrophe. In 2 clinical studies, hospitalized (MOVe-In) and non-hospitalized (MOVe-Out) participants were treated for 5 days with MOV and followed up to Day 29. Viral RNA isolated from nasal swab samples were sequenced to determine the rate, distribution and type of viral mutations observed after MOV treatment. MethodsRNA isolated from nasopharangeal swab samples collected during study conduct was quantified by RT-PCR. Samples containing >22,000 copies/mL of RNA underwent complete genome NGS using the Ion AmpliSeq SARS-CoV-2 research panel and Ion Torrent sequencing. Mutation rates were calculated by determining the number of nucleotide changes observed across the entire genome at Day 3 and/or Day 5 compared to baseline. ResultsCombined data from both studies showed an increase of ~2-4 fold in the viral mutation rate post-baseline in MOV treated compared with placebo. Mutations were distributed across the entire genome with only a minority being observed in more than one sample. The most frequent mutations were transitions of C to U observed in the highest MOV dose group (800 mg/BID).ConclusionConsistent with the proposed mechanism of action of MOV, an increase in the rate of transition mutations in the virus was observed in post-baseline nasal swab samples from participants treated with MOV compared with placebo. Disclosures Julie Strizki, PhD, Merck & Co., Inc. (Employee, Shareholder) Jay Grobler, PhD, Merck & Co., Inc. (Employee, Shareholder) Ying Zhang, PhD, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Shunbing Zhao, PhD, Merck & Co., Inc. (Employee, Shareholder) Diane Levitan, PhD, Merck & Co., Inc. (Employee, Shareholder) Alex Therien, PhD, Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Nicholas Murgolo, PhD, Merck & Co., Inc. (Employee, Shareholder)

Prevalence and predictors of post-traumatic stress symptoms in 2200 hospitalised and non-hospitalised injured New Zealanders.

Post-traumatic stress disorder following injuries unrelated to mass casualty events has received little research attention in New Zealand. Internationally, most studies investigating predictors of post-injury post-traumatic stress disorder focus on hospitalised patients although most survivors are not hospitalised. We compared the prevalence and predictors of symptoms suggestive of post-traumatic stress disorder 12 months following injury among hospitalised and non-hospitalised entitlement claimants in New Zealand's Accident Compensation Corporation. This government-funded universal no-fault insurance scheme replaced tort-based compensation for injuries in 1974 since when civil litigation (which can bias post-traumatic stress disorder estimates) has been rare. A total of 2220 Accident Compensation Corporation claimants aged 18-64 years recruited to the Prospective Outcomes of Injury Study were interviewed at 12 months post-injury to identify symptoms suggestive of post-traumatic stress disorder using the Impact of Events Scale. Multivariable models examined the extent to which baseline sociodemographic, injury, health status and service interaction factors predicted the risk of post-traumatic stress disorder symptoms among hospitalised and non-hospitalised groups. Symptoms suggestive of post-traumatic stress disorder were reported by 17% of hospitalised and 12% of non-hospitalised participants. Perceived threat to life at the time of the injury doubled this risk among hospitalised (adjusted relative risk: 2.0; 95% confidence interval: 1.2-3.2) and non-hospitalised (relative risk: 1.8; 95% confidence interval: 1.2-2.8) participants. Among hospitalised participants, other predictors included female gender, Pacific and 'other' minority ethnic groups, pre-injury depressive symptoms, financial insecurity and perceived inadequacies in healthcare interactions, specifically information and time to discuss problems. Among non-hospitalised survivors, predictors included smoking, hazardous drinking, assault and poor expectations of recovery. One in six hospitalised and one in eight non-hospitalised people reported post-traumatic stress disorder symptoms 12 months following injury. Perceived threat to life was a strong predictor of this risk in both groups. Identifying early predictors of post-traumatic stress disorder, regardless of whether the injury required hospitalisation, could help target tailored interventions that can reduce longer-term psychosocial morbidity.

Efficacy of Inhaled Ciclesonide for Outpatient Treatment of Adolescents and Adults With Symptomatic COVID-19

Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear. To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection. This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020. Participants were randomly assigned to receive ciclesonide MDI, 160 μg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 μg) or placebo for 30 days. The primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19. A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study. The results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms. ClinicalTrials.gov Identifier: NCT04377711.

Genome-wide association study of hospitalized COVID-19 patients in the United Arab Emirates.

BackgroundThe heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. The objective of this manuscript is to conduct a trans-ancestry genome wide association study (GWAS) meta-analysis of COVID-19 severity to improve the understanding of potentially causal targets for SARS-CoV-2.MethodsThis cross-sectional study recruited 646 participants in the UAE that were divided into two phenotypic groups based on the severity of COVID-19 phenotypes, hospitalized (n=482) and non-hospitalized (n=164) participants. Hospitalized participants were COVID-19 patients that developed acute respiratory distress syndrome (ARDS), pneumonia or progression to respiratory failure that required supplemental oxygen therapy or mechanical ventilation support or had severe complications such as septic shock or multi-organ failure. We conducted a trans-ancestry meta-analysis GWAS of European (n=302), American (n=102), South Asian (n=99), and East Asian (n=107) ancestry populations. We also carried out comprehensive post-GWAS analysis, including enrichment of SNP associations in tissues and cell-types, expression quantitative trait loci and differential expression analysis.FindingsEight genes demonstrated a strong association signal: VWA8 gene in locus 13p14·11 (SNP rs10507497; p=9·54 x10-7), PDE8B gene in locus 5q13·3 (SNP rs7715119; p=2·19 x10-6), CTSC gene in locus 11q14·2 (rs72953026; p=2·38 x10-6), THSD7B gene in locus 2q22·1 (rs7605851; p=3·07x10-6), STK39 gene in locus 2q24·3 (rs7595310; p=4·55 x10-6), FBXO34 gene in locus 14q22·3 (rs10140801; p=8·26 x10-6), RPL6P27 gene in locus 18p11·31 (rs11659676; p=8·88 x10-6), and METTL21C gene in locus 13q33·1 (rs599976; p=8·95 x10-6). The genes are expressed in the lung, associated to tumour progression, emphysema, airway obstruction, and surface tension within the lung, as well as an association to T-cell-mediated inflammation and the production of inflammatory cytokines.InterpretationWe have discovered eight highly plausible genetic association with hospitalized cases in COVID-19. Further studies must be conducted on worldwide population genetics to facilitate the development of population specific therapeutics to mitigate this worldwide challenge.FundingThis review was commissioned as part of a project to study the host cell receptors of coronaviruses funded by Khalifa University's CPRA grant (Reference number 2020-004).

Post-COVID-19 conditions in Ecuadorian patients: an observational study

BackgroundPost-COVID-19 disease is not yet clearly described, presenting significant clinical variability across populations and patients. This paper compares post-COVID symptoms in three patient groups with mild, moderate, and severe infections in Ecuadorian outpatients.MethodsAn epidemiological, observational, descriptive, and cross-sectional study was performed, and carried out in Quito, Ecuador. 1,366 non-hospitalized participants between 12 to 85 years, diagnosed with COVID-19 infection by molecular RT-PCR were included in the study. Demographic characteristics, including age groups, sex, ethnic group, work type, residence type, comorbidities, diagnosis, symptoms, and treatment were studied.Findings1,366 outpatient Ecuadorian patients were analysed with SARS-CoV2 infection confirmed with a PCR+ test. The mean age was 39 (± 10) years, distributed by age groups ranging between 12 and 85 years; 81.41% were between 18 and 54 years. 50.29% were men, and 49.71% were women.Interpretation64.3% of patients had symptoms between 4 to 6 weeks after infection, 21.1% showed ongoing symptoms between 6 to 12 weeks, and 14.6% had symptoms for more than 12 weeks. The most common symptom was fatigue in 67.3% of patients, followed by headache in 45.2%, body pain in 42.3%, and sleep disorders (insomnia, sleep apnoea, restless leg syndrome) in 36.5%. 69.3% of patients showed mild infection, 21.7% moderate, and 9.0% severe infection. On average, patients’ daily life activities showed a 6.8% mean degree of impact following infection. A sedentary lifestyle (walking less than 30 minutes a day) was the most critical risk factor (40.3%), followed by being a health worker (11.87%). Patients aged ≥55 years with HTN, CKD, smoking, and sedentary lifestyle were 4.39, 1.92, 9.19, 4.07, and 2.42 times more likely to have a severe infection level. At least 30% of patients do not feel recovered from COVID-19 infection.FundingThe author declares that the financial resources for the preparation of this research come from their self-management.

Colchicine for the treatment of COVID-19.

Colchicine for the treatment of COVID-19.

Covid-19: Signs and symptoms related to the feeding behavior

COVID-19 reached pandemic level in March 2020 and the number of confirmed cases continued to increase worldwide. The clinical course of the disease has not yet been fully characterized, and some specific symptoms related to smell, taste, and feeding behavior require further examination. The present study aimed to assess the presence of symptoms related to the feeding behavior occurred during and/or after COVID-19 in adults residing in Portugal and to link them to disease severity using a multivariate approach. Data were collected from May to September 2020, through a questionnaire answered online containing questions about general and specific symptoms before, during and after COVID-19. 362 participants were included: 201 were symptomatic, being 15 hospitalized and 186 non-hospitalized. Cluster analysis grouped the symptomatic non-hospitalized participants as mild and severe cases. For these patients, the most frequent symptoms related to the feeding process were smell disorders in 40% and 62%, taste disorders in 37% and 60%, and dry mouth, in 23% and 48% of the mild and severe cases, respectively. Dry mouth was significantly associated with difficulty to swallow, pain during swallow, choking when eating or drinking, and preference for mushy/pasty foods (p < 0.01; Chi-squared test). Among the severe cases, the incidence of coughing during the meal (31%), difficulty (19%) and pain during swallow (17%), preference for mushy/pasty foods (10%) and choking when eating or drinking (6%) were clinically relevant and may indicate the presence of swallowing disorders. This group also showed a higher frequency of general symptoms, such as fever, headache, abdominal pain, tiredness, diarrhea, nausea, and shortness of breath (p < 0.05; Chi-squared test). Smell disorders, taste disorders and dry mouth were the most frequent symptoms related to the feeding behavior for both mild and severe cases. Dry mouth was significantly associated with swallowing difficulties and future research should investigate it as a frequent symptom and as a predictive of the presence of eating and swallowing disorders in COVID-19 cases.

SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.

SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.