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.

Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: a combined retrospective epidemiological and genomic study.

Background: There is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings. Methods: We performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, to determine who infected whom. We evaluated general transmission patterns according to case type (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each case type across all posterior trees and comparing them to random expectations. Results: During the study period (1 March to 7 May 2020), we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10% to 19% for patients, and 21% for HCWs. We estimated that 16 importation events occurred with high confidence (4 patients, 12 HCWs) that jointly led to up to 41 secondary cases; in six additional cases (5 HCWs, 1 patient), importation was possible with a posterior probability between 10% and 50%. Most patient-to-patient transmission events involved patients having shared a ward (95.2%, 95% credible interval [CrI] 84.2%-100%), in contrast to those having shared a room (19.7%, 95% CrI 6.7%-33.3%). Transmission events tended to cluster by case type: patientnoso were almost twice as likely to be infected by other patientnoso than expected (observed:expected ratio 2.16, 95% CrI 1.17-4.20, p=0.006); similarly, HCWoutbreak were more than twice as likely to be infected by other HCWoutbreak than expected (2.72, 95% CrI 0.87-9.00, p=0.06). The proportion of infectors being HCWcovid was as expected as random. We found a trend towards a greater proportion of high transmitters (≥2 secondary cases) among HCWoutbreak than patientnoso in the late phases (28.6% vs. 11.8%) of the outbreak, although this was not statistically significant. Conclusions: Most importation events were linked to HCW. Unexpectedly, transmission between HCWcovid was more limited than transmission between patients and HCWoutbreak. This finding highlights gaps in infection control and suggests the possible areas of improvements to limit the extent of nosocomial transmission. Funding: This study was supported by a grant from the Swiss National Science Foundation under the NRP78 funding scheme (Grant no. 4078P0_198363).

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.

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.

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.