The pandemic toll and post-acute sequelae of SARS-CoV-2 in healthcare workers at a Swiss University Hospital.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n = 3083) suffered mostly from fatigue (25.5 %), headache (10.0 %), difficulty concentrating (7.9 %), exhaustion/burnout (7.1 %), insomnia (6.2 %), myalgia (6.7 %) and arthralgia (6.3 %). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n = 3556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19.

Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

BACKGROUND: COVID-19 is a viral prothrombotic respiratory infection. Heparins exert antithrombotic and anti-inflammatory effects, and might have antiviral properties. We aimed to investigate whether thromboprophylaxis with enoxaparin would prevent untoward hospitalisation and death in symptomatic, but clinically stable outpatients with COVID-19. METHODS: OVID was a randomised, open-label, parallel-group, investigator-initiated, phase 3 trial and was done at eight centres in Switzerland and Germany. Outpatients aged 50 years or older with acute COVID-19 were eligible if they presented with respiratory symptoms or body temperature higher than 37·5°C. Eligible participants underwent block-stratified randomisation (by age group 50-70 vs >70 years and by study centre) in a 1:1 ratio to receive either subcutaneous enoxaparin 40 mg once daily for 14 days versus standard of care (no thromboprophylaxis). The primary outcome was a composite of any untoward hospitalisation and all-cause death within 30 days of randomisation. Analysis of the efficacy outcomes was done in the intention-to-treat population. The primary safety outcome was major bleeding. The study was registered in ClinicalTrials.gov (NCT04400799) and has been completed. FINDINGS: At the predefined formal interim analysis for efficacy (50% of total study population), the independent Data Safety Monitoring Board recommended early termination of the trial on the basis of predefined statistical criteria having considered the very low probability of showing superiority of thromboprophylaxis with enoxaparin for the primary outcome under the initial study design assumptions. Between Aug 15, 2020, and Jan 14, 2022, from 3319 participants prescreened, 472 were included in the intention-to-treat population and randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (IQR 53-62) and 217 (46%) were women. The 30-day risk of the primary outcome was similar in participants allocated to receive enoxaparin and in controls (8 [3%] of 234 vs 8 [3%] of 238; adjusted relative risk 0·98; 95% CI 0·37-2·56; p=0·96). All hospitalisations were related to COVID-19. No deaths were reported during the study. No major bleeding events were recorded. Eight serious adverse events were recorded in the enoxaparin group versus nine in the control group. INTERPRETATION: These findings suggest thromboprophylaxis with enoxaparin does not reduce early hospitalisations and deaths among outpatients with symptomatic COVID-19. Futility of the treatment under the initial study design assumptions could not be conclusively assessed owing to under-representation of older patients and consequent low event rates. FUNDING: SNSF (National Research Programme COVID-19 NRP78: 198352), University Hospital Zurich, University of Zurich, Dr-Ing Georg Pollert (Berlin), Johanna Dürmüller-Bol Foundation.

One-year persistent symptoms and functional impairment in SARS-CoV-2 positive and negative individuals.

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

Implementing Lung Ultrasound in the Outpatient Management of COVID-19 Pneumonia: A Pilot Study to Update Local Guidelines.

Background: Lung ultrasound (LUS) has a good performance with a high sensitivity and specificity for the diagnosis of pneumonia compared with chest X-ray, and it has been extensively used to assess patients during the COVID-19 pandemic. This study aims to evaluate the potential advantages of the regular use of LUS for the assessment of the severity and prognosis of COVID-19 pneumonia and to propose an adapted protocol with its inclusion in current local validated and published guidelines. Methods: This is a single-center prospective study conducted during the first (April-May 2020) and second (October 2020-January 2021) waves of the SARS-CoV2 pandemic in Switzerland. All adult patients presenting to dedicated test centers with a suspicion of mild-to-moderate COVID-19 pneumonia and not requiring hospitalization at the time of diagnosis were included. Patients with confirmed COVID-19 pneumonia were referred to an ambulatory follow-up unit at our institution for reassessment, with the inclusion of the use of LUS in a random selection. Descriptive statistics were calculated for demographics using percentages, means, and standard deviations according to the distribution of variables. Results: Eighty-eight ambulatory patients with a confirmed COVID-19 pneumonia were included (men = 57 [59%]; mean age, 52.1 ± 13.5 years). Among these, 19 (21%) were hospitalized and none died. Twenty-five lung assessments by ultrasound were performed during the follow-up consultation. All were consistent with the clinical examination and confirmed the clinician's opinion. Conclusion: The use of a standardized pleuro-pulmonary ultrasound protocol for ambulatory patients with COVID-19 could help to reduce the use of chest X-rays and improve overall management at the time of referral and eventual follow-up. However, a specific study including LUS in a systematic approach should be performed to evaluate the outcome of patients according to findings.

Negative Association Between Smoking and Positive SARS-CoV-2 Testing: Results From a Swiss Outpatient Sample Population.

To date, most of the evidence suggests that smoking is negatively associated with testing positive for SARS-CoV-2. However, evidence has several methodological limitations. Using an outpatient sample population, we analyzed the association of testing positive for SARS-CoV-2 and smoking considering comorbidities, socioeconomic and demographic factors. Baseline data were obtained from a cohort during the first wave of the pandemic in Geneva, Switzerland (March-April 2020). RT-PCR tests were carried out on individuals suspected of having SARS-CoV-2 according to the testing strategy at that time. Logistic regressions were performed to test the association of smoking and testing positive for SARS-CoV-2 and further adjusted for comorbidities, socioeconomic and demographic factors. The sample included 5,169 participants; 60% were women and the mean age was 41 years. The unadjusted OR for testing positive for SARS-CoV-2 was 0.46 (CI: 0.38-0.54). After adjustment for comorbidities, socioeconomic and demographic factors, smoking was still negatively associated with testing positive for SARS-CoV-2 (OR: 0.44; CI: 0.35-0.77). Women (OR: 0.79; CI: 0.69-0.91), higher postal income (OR: 0.97; CI: 0.95-0.99), having respiratory (OR: 0.68; CI: 0.55-0.84) and immunosuppressive disorders (OR: 0.63; CI: 0.44-0.88) also showed independent negative associations with a positive test for SARS-CoV-2. Smoking was negatively associated with a positive test for SARS-CoV-2 independently of comorbidities, socioeconomic and demographic factors. Since having respiratory or immunosuppressive conditions and being females and healthcare workers were similarly negatively associated with SARS-CoV-2 positive testing, we hypothesize that risk factor-related protective or testing behaviors could have induced a negative association with SARS-CoV-2.

Head-to-Head Evaluation of Five Automated SARS-CoV-2 Serology Immunoassays in Various Prevalence Settings.

PURPOSE: To assess the diagnostic performances of five automated anti-SARS-CoV-2 immunoassays, Epitope (N), Diasorin (S1/S2), Euroimmun (S1), Roche N (N), and Roche S (S-RBD), and to provide a testing strategy based on pre-test probability. METHODS: We assessed the receiver operating characteristic (ROC) areas under the curve (AUC) values, along with the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs), of each assay using a validation sample set of 172 COVID-19 sera and 185 negative controls against a validated S1-immunofluorescence as a reference method. The three assays displaying the highest AUCs were selected for further serodetection of 2033 sera of a large population-based cohort. RESULTS: In the validation analysis (pre-test probability: 48.1%), Roche N, Roche S and Euroimmun showed the highest discriminant accuracy (AUCs: 0.99, 0.98, and 0.98) with PPVs and NPVs above 96% and 94%, respectively. In the population-based cohort (pre-test probability: 6.2%) these three assays displayed AUCs above 0.97 and PPVs and NPVs above 90.5% and 99.4%, respectively. A sequential strategy using an anti-S assay as screening test and an anti-N as confirmatory assays resulted in a 96.7% PPV and 99.5% NPV, respectively. CONCLUSIONS: Euroimmun and both Roche assays performed equally well in high pre-test probability settings. At a lower prevalence, sequentially combining anti-S and anti-N assays resulted in the optimal trade-off between diagnostic performances and operational considerations.

Post-exposure Lopinavir-Ritonavir Prophylaxis versus Surveillance for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial.

BACKGROUND: Since the beginning of the COVID-19 pandemic, no direct antiviral treatment is effective as post-exposure prophylaxis (PEP). Lopinavir/ritonavir (LPV/r) was repurposed as a potential PEP agent against COVID-19. METHODS: We conducted a pragmatic open-label, parallel, cluster-randomised superiority trial in four sites in Switzerland and Brazil between March 2020 to March 2021. Clusters were randomised to receive LPV/r PEP (400/100 mg) twice daily for 5 days or no PEP (surveillance). Exposure to SARS-CoV-2 was defined as a close contact of >15 minutes in <2 metres distance or having shared a closed space for ≥2 hours with a person with confirmed SARS-CoV-2 infection. The primary outcome is the occurrence of COVID-19 defined by a SARS-CoV-2 infection (positive oropharyngeal SARS-CoV-2 PCR and/or a seroconversion) and ≥1 compatible symptom within 21 days post-enrolment. ClinicalTrials.gov (Identifier: NCT04364022); Swiss National Clinical Trial Portal: SNCTP 000003732. FINDINGS: Of 318 participants, 157 (49.4%) were women; median age was 39 (interquartile range, 28-50) years. A total of 209 (179 clusters) participants were randomised to LPV/r PEP and 109 (95 clusters) to surveillance. Baseline characteristics were similar, with the exception of baseline SARS-CoV-2 PCR positivity, which was 3-fold more frequent in the LPV/r arm (34/209 [16.3%] vs 6/109 [5.5%], respectively). During 21-day follow-up, 48/318 (15.1%) participants developed COVID-19: 35/209 (16.7%) in the LPV/r group and 13/109 (11.9%) in the surveillance group (unadjusted hazard ratio 1.44; 95% CI, 0.76-2.73). In the primary endpoint analysis, which was adjuted for baseline imbalance, the hazard ratio for developing COVID-19 in the LPV/r group vs surveillance was 0.60 (95% CI, 0.29-1.26; p =0.18). INTERPRETATION: The role of LPV/r as PEP for COVID-19 remains unanswered. Although LPV/r over 5 days did not significantly reduce the incidence of COVID-19 in exposed individuals, we observed a change in the directionality of the effect in favour of LPV/r after adjusting for baseline imbalance. LPV/r for this indication merits further testing against SARS-CoV-2 in clinical trials. FUNDING: Swiss National Science Foundation (project no.: 33IC30_166819) and the Private Foundation of Geneva University Hospitals (Edmond Rothschild (Suisse) SA, Union Bancaire Privée and the Fondation pour la recherche et le traitement médical).

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Kinetics in Symptomatic Children, Adolescents, and Adults.

SARS-CoV-2 viral load (VL) can serve as a correlate for infectious virus presence and transmission. Viral shedding kinetics over the first week of illness for symptomatic children (n = 279), adolescents (n = 639), and adults (n = 7109) show VLs compatible with infectious virus presence, with slightly lower VL in children than adults.

Network Analysis of Outpatients to Identify Predictive Symptoms and Combinations of Symptoms Associated With Positive/Negative SARS-CoV-2 Nasopharyngeal Swabs.

Background: Limited data exist on early predictive clinical symptoms or combinations of symptoms that could be included in the case definition of coronavirus disease 2019 (COVID-19), particularly for mild-to-moderate disease in an outpatient setting. Methods: A cohort study of individuals presenting with clinical symptoms to one of the largest dedicated networks of COVID-19 test centers in Geneva, Switzerland, between March 2 and April 23, 2020. Individuals completed a symptom questionnaire, received a nurse-led check-up, and nasopharyngeal swabs were obtained. An analysis of clinical features predicting the positivity and negativity of the SARS-CoV-2 RT-PCR test was performed to determine the relationship between symptoms and their combinations. Results: Of 3,248 patients included (mean age, 42.2 years; 1,504 [46.3%] male), 713 (22%) had a positive RT-PCR; 1,351 (41.6%) consulted within 3 days of symptom onset. The strongest predictor of a positive SARS-CoV-2 RT-PCR was anosmia, particularly in early disease, followed by fever, myalgia, and cough. Symptoms predictive of a negative test were breathing difficulties, abdominal symptoms, thoracic pain and runny nose. Three distinct networks of symptoms were identified, but did not occur together: respiratory symptoms; systemic symptoms related to fever; and other systemic symptoms related to anosmia. Conclusions: Symptoms and networks of symptoms associated with a positive/negative SARS-CoV-2 RT-PCR are emerging and may help to guide targeted testing. Identification of early COVID-19-related symptoms alone or in combination can contribute to establish a clinical case definition and provide a basis for clinicians and public health authorities to distinguish it from other respiratory viruses early in the course of the disease, particularly in the outpatient setting.

Vulnerable patients forgo health care during the first wave of the Covid-19 pandemic.

During the first wave of the Covid-19 pandemic, access to health care was limited, and patients encountered important delays for scheduled appointments and care. Empirical data relying on patients' reports of forgoing health care are scarce. This study investigated Covid-19-related self-reports of forgoing health care in a sample of vulnerable outpatients in Geneva, Switzerland. We collected data from 1167 adult outpatients, including clinically vulnerable patients (with chronic diseases), geriatric patients (involved in a health care network for people aged 60 or older), and socially vulnerable patients (involved in a migrant health program or a mobile outpatient community care center) in June 2020. Data on sociodemographic factors, forgoing health care, and anti-SARS-CoV-2 antibodies were collected. Of the patients, 38.5% reported forgoing health care. Forgoing health care was more frequent for younger patients, women, patients with a low level of education, and patients with a chronic disease (p < .001). There was no significant association between the presence of anti-SARS-CoV-2 antibodies and forgoing health care (p = .983). As the decrease in routine management of patients might have important and unpredictable adverse health consequences, avoiding delayed health care is crucial.

Development and validation of the OUTCoV score to predict the risk of hospitalisation among patients with SARS-CoV-2 infection in ambulatory settings: a prospective cohort study.

OBJECTIVES: To develop and validate a rule-out prediction model for the risk of hospitalisation among patients with SARS-CoV-2 infection in the ambulatory setting to derive a simple score to determine outpatient follow-up. DESIGN: Prospective cohort study. SETTING: Swiss university hospital. PARTICIPANTS: 1459 individuals with a positive result for SARS-CoV-2 infection between 2 March and 23 April 2020. METHODS: We applied the rule of 10 events per variable to construct our multivariable model and included a maximum of eight covariates. We assessed the model performance in terms of discrimination and calibration and performed internal validation to estimate the statistical optimism of the final model. The final prediction model included age, fever, dyspnoea, hypertension and chronic respiratory disease. To develop the OUTCoV score, we assigned points for each predictor that were proportional to the coefficients of the regression equation. Sensitivity, specificity, positive and negative likelihood ratios were estimated, including positive and negative predictive values in different thresholds. MAIN OUTCOME MEASURE: The primary outcome was COVID-19-related hospitalisation. RESULTS: The OUTCoV score ranged from 0 to 7.5 points. The two threshold parameters with optimal rule-out and rule-in characteristics for the risk of hospitalisation were 3 and 5.5, respectively. Outpatients with a score <3 (997/1459; 68.3%) had no follow-up as at low risk of hospitalisation (1.8%; 95% CI 1.1 to 2.8). For a score ≥5.5 (20/1459; 1.4%), the hospitalisation risk was higher (30%; 95% CI 11.9 to 54.3). CONCLUSIONS: The OUTCoV score allows to rule out two-thirds of outpatients with SARS-CoV-2 infection presenting a low hospitalisation risk and to identify those at high risk that require careful follow-up to assess the need for hospitalisation. The model provides a simple decision-making tool for an effective allocation of resources to maintain quality care for outpatient populations.

Equity in access to COVID-19 testing for undocumented migrants and homeless persons during the initial phase of the pandemic.

INTRODUCTION: The COVID-19 pandemic has excessively affected socially and economically deprived groups of population. There is a dearth of empirical evidence about the effect of policies regulating access to care for such groups. This study aims to document the impact of an equity-based strategy to facilitate access to COVID-19 testing during the initial phase of the pandemic. MATERIALS AND METHODS: This cross-sectional study included all outpatients presenting at the Geneva University Hospital for COVID-19 testing in March and April 2020. We compared the testing program uptake, and the proportions of positive tests and of complicated clinical course between undocumented migrants and homeless persons and the general population. RESULTS: Underserved patients represented 215 (6.5%) of the 3299 participants. There was no significant difference in the time-lag between the first COVID-19 evocative symptoms and the testing, the number of symptoms at presentation, and the participation to the program during its first month of implementation. The proportion of positive tests was significantly higher (32.1% vs. 23.6%, p=.005) among undeserved while the proportion of complicated clinical course was comparable. CONCLUSIONS: Equity-based policies can mitigate disparities in access to care during the pandemic and reduce the spread of COVID-19 in the community by early detection of infective cases. The high proportion of positive test in underserved patients highlight the need to include such groups into future COVID-19 immunization program. More globally, this study highlights the opportunity to reinforce healthcare systems to adapt to new threats and to contribute to a better protection of the whole of society.

SARS-CoV-2 testing strategy: A comparison of restricted and extended strategies in a Swiss outpatient cohort from the community and hospital employees.

BACKGROUND: Testing is a key measure to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we empirically compared two SARS-CoV-2 testing strategies. METHODS: We used data from a Swiss single-centre, outpatient cohort study (n = 6,331 test results). A "restricted" strategy was applied to individuals with respiratory symptoms and/or fever and selected risk factors, or an epidemiological link and an "extended" strategy included any clinical symptoms without restriction, irrespective of risk factors and exposure. Data on infection, symptoms, viral load were collected during the first wave (March 11-April 21, 2020) and patients were followed up for clinical complications and hospitalisations until August 31, 2020. FINDINGS: Infection, clinical complications, and hospitalisation rates were lower for those in the extended strategy compared with the restricted strategy (17.2% vs. 25.0%, 12.3% vs. 20.8%, and 0.7% vs. 2.3%). In the whole cohort, participants included in the extended strategy had a lower number of symptoms (3.51 vs. 4.57; p < .001) and visits occurred earlier after symptom onset (0-3 days: 59.2% vs. 44.2%; p < .001). Among positive cases, the viral load was higher for the extended strategy (p < .001). CONCLUSIONS: These findings highlighted the crucial importance to implement a widespread testing strategy to achieve a better understanding of the infection, to mount an effective control response, by capturing people when their viral load is highest. A widespread test strategy should be available without barriers to help break the chains of transmission.

Deep learning diagnostic and risk-stratification pattern detection for COVID-19 in digital lung auscultations: clinical protocol for a case-control and prospective cohort study.

BACKGROUND: Lung auscultation is fundamental to the clinical diagnosis of respiratory disease. However, auscultation is a subjective practice and interpretations vary widely between users. The digitization of auscultation acquisition and interpretation is a particularly promising strategy for diagnosing and monitoring infectious diseases such as Coronavirus-19 disease (COVID-19) where automated analyses could help decentralise care and better inform decision-making in telemedicine. This protocol describes the standardised collection of lung auscultations in COVID-19 triage sites and a deep learning approach to diagnostic and prognostic modelling for future incorporation into an intelligent autonomous stethoscope benchmarked against human expert interpretation. METHODS: A total of 1000 consecutive, patients aged ≥ 16 years and meeting COVID-19 testing criteria will be recruited at screening sites and amongst inpatients of the internal medicine department at the Geneva University Hospitals, starting from October 2020. COVID-19 is diagnosed by RT-PCR on a nasopharyngeal swab and COVID-positive patients are followed up until outcome (i.e., discharge, hospitalisation, intubation and/or death). At inclusion, demographic and clinical data are collected, such as age, sex, medical history, and signs and symptoms of the current episode. Additionally, lung auscultation will be recorded with a digital stethoscope at 6 thoracic sites in each patient. A deep learning algorithm (DeepBreath) using a Convolutional Neural Network (CNN) and Support Vector Machine classifier will be trained on these audio recordings to derive an automated prediction of diagnostic (COVID positive vs negative) and risk stratification categories (mild to severe). The performance of this model will be compared to a human prediction baseline on a random subset of lung sounds, where blinded physicians are asked to classify the audios into the same categories. DISCUSSION: This approach has broad potential to standardise the evaluation of lung auscultation in COVID-19 at various levels of healthcare, especially in the context of decentralised triage and monitoring. TRIAL REGISTRATION: PB_2016-00500, SwissEthics. Registered on 6 April 2020.

Novel outpatient management of mild to moderate COVID-19 spares hospital capacity and safeguards patient outcome: The Geneva PneumoCoV-Ambu study.

BACKGROUND: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes coronavirus disease (COVID-19), is creating an unprecedented burden on health care systems across the world due to its high rate of pneumonia-related hospitalizations. This study presents recommendations for the outpatient management of moderate SARS-CoV-2 pneumonia implemented at the Geneva University Hospital, Switzerland, from April 4 to June 30, 2020 and evaluated the impact of these recommendations on patient safety, patient satisfaction, and overall hospital capacity. METHODS: Recommendations for the outpatient management of moderate pneumonia implemented in the Geneva University Hospital (PneumoCoV-Ambu) between April 4 and June 30, 2020, were evaluated prospectively. The primary endpoint was hospitalization. Secondary endpoints were: severity of COVID-19 disease based on a 7-points ordinal scale assessed at 1 and 2 months following SARS-CoV-2 infection; patient satisfaction using a satisfaction survey and the analysis of number of beds and costs potentially averted. RESULTS: A total of 36 patients with COVID-19-related pneumonia were followed between April 4 and May 5, 2020. Five patients (14%) were hospitalized and none died over a median of 30 days follow-up. The majority of patients (n = 31; 86%) were satisfied with the ambulatory care they received. These novel recommendations for outpatient management resulted in sparing an estimated potential 124 hospital bed-nights and CHF 6'826 per capita averted hospitalization costs over the three months period. CONCLUSIONS: Recommendations developed for the outpatient management of COVID-19-related pneumonia were able to spare hospital capacity without increasing adverse patient outcomes. Widely implementing such recommendations is crucial in preserving hospital capacity during this pandemic.

Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial.

INTRODUCTION: Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2. METHODS AND ANALYSIS: COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732). REGISTERED REPORT IDENTIFIER: CCER 2020-0864.