Abstract Background Validated tools to assess gender are essential for clinical and population research but remain scarce and unstandardized. Understanding how sociocultural gender interacts with biological sex in shaping disease risk is critical for precision medicine. We aimed to investigate the association of sex and gender with cardiovascular risk factors and common comorbidities, and to refine an existing composite Gender score in a Swiss cohort. Methods This multicenter prospective study conducted in three tertiary and one regional hospital included outpatients and inpatients with PCR-confirmed SARS-CoV-2 infection (n = 2,690; estimation and internal validation sets) and outpatients with periodontitis (n = 337; external validation set). Gender-related variables were acquired via questionnaire. Logistic regression models and propensity score matching were used to assess associations between sex, gender, and the prevalence of cardiometabolic and chronic health conditions. Results A total of 3,027 individuals (46.3% women; mean age 45 ± 17 years) were included. The composite Gender Score predicted biological sex with good accuracy (ROC 0.776–0.809). Biological sex was more strongly associated with most cardiometabolic risk factors, stroke, immune disorders, and bone diseases, whereas gender showed limited independent associations. For diabetes, female sex was inversely associated with diabetes prevalence, while a more feminine gender profile was positively associated. These opposing associations persisted after accounting for gender in matched analyses, illustrating that sex and gender may contribute differently to specific metabolic outcomes. Conclusion Sociocultural variables can accurately approximate biological sex and are differentially associated with health outcomes. In this cohort, biological sex explained most associations with cardiometabolic and chronic conditions, while gender effects were modest and condition-specific. The divergent associations observed for diabetes highlight that sex and gender are related but distinct constructs that should be considered jointly. Integrating both dimensions may improve future approaches to risk stratification, although these findings require confirmation in prospective and diverse populations.

OBJECTIVES:To improve estimation of cohort coverage in the Swiss HIV Cohort Study (SHCS) using a data triangulation framework that compares SHCS data with multiple external data sources. DESIGN:Retrospective longitudinal analysis of the SHCS. METHODS:Cohort coverage of HIV diagnoses, AIDS diagnoses, and antiretroviral therapy (ART) uptake was triangulated across SHCS data (1985-2023), national HIV/AIDS surveillance (1985-2023), longitudinal antiretroviral therapy (ART) sales data (2017-2024), and a targeted literature comparison. Temporal trends in cohort coverage were assessed, and demographic representativeness was evaluated by sex, age, HIV acquisition mode, and region. Mean cohort coverage estimates were calculated for three outcomes: HIV and AIDS diagnoses (Step 1) and ART uptake (Step 2). RESULTS:Over 38 years, mean SHCS coverage was 62.4% for HIV diagnoses, 74.0% for AIDS, and 64.9% for ART uptake, consistent with literature-based estimates. Coverage of HIV diagnoses declined in recent years, and geographical heterogeneity was observed. The SHCS remained broadly representative across most subgroups; however, females, older adults, and people with heterosexually acquired HIV or using psychoactive substances were underrepresented, while people on single-tablet and salvage ART regimens were overrepresented. CONCLUSIONS:A data triangulation framework provides a practical approach for monitoring cohort coverage and representativeness. While the SHCS captures a broadly representative sample of diagnosed individuals, tailored strategies are needed to improve inclusion of underrepresented subgroups and maintain cohort coverage. Sustained monitoring is essential to ensure that cohort-based research remains generalizable and continues to inform clinical care and public health responses in Switzerland and beyond.

Tick-borne encephalitis virus (TBEV) infection can manifest as disease of variable severity, ranging from subclinical infection to severe disease with neurological involvement and potentially fatal outcome. Although TBE is recognized as a major public health problem in Europe, the true burden of disease is potentially underestimated. Here, we investigated TBEV-specific antibody prevalence, infection incidence, and seroreversion and antibody decline rates in a prospective Swiss healthcare worker (HCW) cohort. We screened serum samples from 1444 HCWs between June and October 2020, and from a subset again between August and September 2021, using a TBEV envelope (E) protein IgG ELISA. Positive samples underwent further analysis with a TBEV non-structural protein 1 (NS1) IgG ELISA, and seroconversions in unvaccinated individuals were confirmed by seroneutralization testing. Questionnaire data were used to determine vaccination status and risk factors. TBEV E protein-specific IgG prevalence was 72.1% (95% CI 68.2–75.7%) in TBEV-vaccinated and 6% (95% CI 4.4–7.8%) in unvaccinated individuals. The estimated annual incidence of infection was 735/100,000. Age was the only factor significantly associated with seroprevalence. The seroreversion rate in unvaccinated individuals was 30.3% within one year, which is almost ten times higher than in vaccinated individuals (3.4%, annual decline rate 8.0%). NS1-specific IgG antibodies were six times more common in vaccinated than unvaccinated HCWs. In conclusion, undetected TBEV infections are common, and infection incidence is much higher than reported clinical cases. Individuals with abortive infections have high antibody decline and seroreversion rates. Whether lifelong protection is conferred and by which immune subsets remain unclear.

Background Personal protective equipment (PPE) should effectively protect health care workers (HCWs) when treating infectious patients. However, during doffing contamination from outside of the PPE could be transferred and might cause serious infection. Therefore, complex doffing procedures have been developed, which include disinfection steps and would thereby protect the HCWs even if a contamination event occurred during doffing. However, assessing these complex multi-step procedures regarding risk of contamination and infection is challenging. The use of harmless surrogates with pathogen mimicking properties such as lipid nanoparticles encapsulating DNA (LNPs) could provide valuable insights into the effectiveness of doffing and disinfection procedures. Compared to the state-of-the-art method of contamination monitoring using fluorescent lotions LNPs promise to be more sensitive and give additional insights into the value of the disinfection steps. Methods After pre-testing the suitability of LNPs as viral surrogates in terms of detection limit and susceptibility to ethanolic disinfection, LNPs with different barcodes were used to evaluate the PPE doffing procedure in place at the Cantonal Hospital Baden (Switzerland). During the biannual HCWs’ PPE training, several sites of the PPE were deliberately contaminated with LNPs after donning. After completion of the doffing procedure, the hands and faces of the HCWs and several environmental sites were analysed for LNP contamination via qPCR. Results The analysis showed that no contamination of HCWs’ hands and faces was detectable, indicating the effective protection of HCWs. But some environmental sites were contaminated during the doffing procedure. Owing to the disinfection sensitivity of the LNPs it could be shown that the LNPs detected were disintegrated during one of the disinfection steps of the procedure. Conclusions This study demonstrates that LNPs can be used as viral surrogates during the evaluation of PPE doffing procedures. LNPs can lead to insightful results due to their low detection limit and the susceptibility towards disinfection, making this method superior to fluorescent lotions. Consequently, indications for the procedures’ effectivity in inhibiting pathogen transfer to HCWs were found using LNPs. At the same time, blind spots in environmental contamination were uncovered, and the necessity of the disinfection steps in the protocol was displayed.

Background Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim We assessed the impact of sex and gender on PASC in a Swiss population. Method Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection. Results Among those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41–1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03–1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74–1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01–1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03–1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29–2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60–0.97; p = 0.030). Conclusion Specific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Abstract Background Disentangling the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. Methods We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in north-eastern Switzerland. HCWs were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCWs without positive swab and with negative serology served as controls. The sum of 18 self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyze the association of mean symptom number with viral variant and vaccination status. Results Among 2912 participants (median age: 44 years; 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number: 1.12; P < .001; median time since infection: 18.3 months), after Alpha/Delta infection (0.67 symptoms; P < .001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms; P = .005; 3.1 months) versus uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals versus 0.71 with 1–2 vaccinations (P = .028) and 0.49 with ≥3 prior vaccinations (P = .30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR]: 2.81; 95% confidence interval [CI]: 2.08–3.83) and Alpha/Delta infections (aRR: 1.93; 95% CI: 1.10–3.46) were significantly associated with the outcome. Conclusions Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCWs. Vaccination before Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population.

Background Disentangling the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. Methods We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in north-eastern Switzerland. HCWs were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCWs without positive swab and with negative serology served as controls. The sum of 18 self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyze the association of mean symptom number with viral variant and vaccination status. Results Among 2912 participants (median age: 44 years; 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number: 1.12; P < .001; median time since infection: 18.3 months), after Alpha/Delta infection (0.67 symptoms; P < .001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms; P = .005; 3.1 months) versus uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals versus 0.71 with 1-2 vaccinations (P = .028) and 0.49 with >= 3 prior vaccinations (P = .30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR]: 2.81; 95% confidence interval [CI]: 2.08-3.83) and Alpha/Delta infections (aRR: 1.93; 95% CI: 1.10-3.46) were significantly associated with the outcome. Conclusions Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCWs. Vaccination before Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population. Within this healthcare worker cohort, the frequency of post-acute sequelae of SARS-CoV-2 symptoms was highest after wild-type infection. In contrast, symptoms were only slightly more common after Omicron BA.1 infection compared with uninfected controls, independent of SARS-CoV-2 vaccination status.

The effects of different types of pre-existing immunity on the frequency of clinical symptoms caused by the SARS-CoV-2 breakthrough infection were prospectively assessed in healthcare workers during the Omicron period. Among 518 participants, hybrid immunity was associated with symptom reduction for dizziness, muscle or limb pain and headache as compared to vaccination only. Moreover, the frequencies of dizziness, cough and muscle or limb pain were lower in participants who had received a booster vaccine dose. Thus, hybrid immunity appeared to be superior in preventing specific symptoms during breakthrough infection compared to vaccination alone. A booster vaccine dose conferred additional symptom reduction.

Background Few studies have assessed whether the increased SARS-CoV-2 risk of healthcare workers (HCW) is carried on to their household contacts. Within a prospective HCW cohort, we assessed the SARS-CoV-2 risk of household contacts of HCW depending on the HCWs cumulative exposure to COVID-19 patients and identified factors influencing this association. Methods HCW aged ≥ 16 years from nine Swiss healthcare networks participated. HCW without any household contacts were excluded. For HCW, cumulative patient exposure (number of COVID-19 patient contacts times average contact duration during a 12-month follow-up) was calculated. During follow-up, HCW reported SARS-CoV-2 nasopharyngeal swab results and positive swab results of their household contacts. We used multivariable logistic regression to identify variables associated with SARS-CoV-2 household positivity. Results Of 2406 HCW, 466 (19%) reported ≥ 1 SARS-CoV-2 positive household. In multivariable analysis, patient exposure of HCW (adjusted OR [aOR] 1.08 per category, 95% CI 1.04–1.12), household size (aOR 1.53 per household member, 95% CI 1.35–1.73) and having children (aOR 0.70, 95% CI 0.53–0.94) remained associated with household positivity. Vaccinated HCW had a lower risk (aOR 0.54, 95% CI 0.38–0.77) of reporting a positive contact, as were those using respirator masks in contact with COVID-19 patients (aOR 0.65, 95% CI 0.49–0.86). Among vaccinated HCW, delayed first vaccination was associated with increased household SARS-CoV-2 positivity (aOR 1.14 per month, 95% CI 1.08–1.21). Conclusions SARS-CoV-2 positivity in household contacts of HCW increases with higher cumulative COVID-19 patient exposure of HCWs. Measures reducing the SARS-CoV-2 risk in HCW might indirectly reduce the infection risk of their households.

This cohort study compares the risk of infection with SARS-CoV-2 among health care workers by mask preference and level of patient exposure.

Background Knowledge about protection conferred by previous Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and/or vaccination against emerging viral variants allows clinicians, epidemiologists, and health authorities to predict and reduce the future Coronavirus Disease 2019 (COVID-19) burden. We investigated the risk and symptoms of SARS-CoV-2 (re)infection and vaccine breakthrough infection during the Delta and Omicron waves, depending on baseline immune status and subsequent vaccinations. Methods and findings In this prospective, multicentre cohort performed between August 2020 and March 2022, we recruited hospital employees from ten acute/nonacute healthcare networks in Eastern/Northern Switzerland. We determined immune status in September 2021 based on serology and previous SARS-CoV-2 infections/vaccinations: Group N (no immunity); Group V (twice vaccinated, uninfected); Group I (infected, unvaccinated); Group H (hybrid: infected and ≥1 vaccination). Date and symptoms of (re)infections and subsequent (booster) vaccinations were recorded until March 2022. We compared the time to positive SARS-CoV-2 swab and number of symptoms according to immune status, viral variant (i.e., Delta-dominant before December 27, 2021; Omicron-dominant on/after this date), and subsequent vaccinations, adjusting for exposure/behavior variables. Among 2,595 participants (median follow-up 171 days), we observed 764 (29%) (re)infections, thereof 591 during the Omicron period. Compared to group N, the hazard ratio (HR) for (re)infection was 0.33 (95% confidence interval [CI] 0.22 to 0.50, p < 0.001) for V, 0.25 (95% CI 0.11 to 0.57, p = 0.001) for I, and 0.04 (95% CI 0.02 to 0.10, p < 0.001) for H in the Delta period. HRs substantially increased during the Omicron period for all groups; in multivariable analyses, only belonging to group H was associated with protection (adjusted HR [aHR] 0.52, 95% CI 0.35 to 0.77, p = 0.001); booster vaccination was associated with reduction of breakthrough infection risk in groups V (aHR 0.68, 95% CI 0.54 to 0.85, p = 0.001) and H (aHR 0.67, 95% CI 0.45 to 1.00, p = 0.048), largely observed in the early Omicron period. Group H (versus N, risk ratio (RR) 0.80, 95% CI 0.66 to 0.97, p = 0.021) and participants with booster vaccination (versus nonboosted, RR 0.79, 95% CI 0.71 to 0.88, p < 0.001) reported less symptoms during infection. Important limitations are that SARS-CoV-2 swab results were self-reported and that results on viral variants were inferred from the predominating strain circulating in the community at that time, rather than sequencing. Conclusions Our data suggest that hybrid immunity and booster vaccination are associated with a reduced risk and reduced symptom number of SARS-CoV-2 infection during Delta- and Omicron-dominant periods. For previously noninfected individuals, booster vaccination might reduce the risk of symptomatic Omicron infection, although this benefit seems to wane over time.

BACKGROUND/AIM:To assess the diagnostic performance of reverse transcriptase polymerase chain reaction (RT-PCR), low-dose chest computed tomography (CT), and serological testing, alone and in combinations, as well as routine inflammatory markers in patients evaluated for COVID-19 during the first wave in early 2020.PATIENTS AND METHODS:We retrospectively analyzed data of all patients who were admitted to the emergency department due to fever and/or respiratory symptoms. CT scans were rated using the COVID-19 Reporting and Data System (CO-RADS) suspicion score. True disease status (COVID-19 - positive vs. negative) was adjudicated by two independent clinicians. Receiver-operating characteristic curves and areas under the curves were calculated for inflammatory markers. Sensitivities and specificities were calculated for RT-PCR, CT, and serology alone, as well as the combinations of RT-PCR+CT, RT-PCR+serology, CT+serology, and all three modalities.RESULTS:Of 221 patients with a median age of 72 years, 113 were classified as COVID-19 positive. Among 180 patients from which data on CT and RT-PCR were available, RT-PCR had the highest sensitivity to detect COVID-19 (0.87; 95%CI=0.78-0.93). Notably, the addition of CT in the analysis increased sensitivity to 0.89 (95%CI=0.8-0.94), but lowered specificity from 1 (95%CI=0.96-1) to 0.9 (95%CI=0.83-0.95). The combination of RT-PCR, CT and serology (n=60 patients with complete dataset) yielded a sensitivity of 0.83 (95%CI=0.61-0.94) and specificity of 0.86 (95%CI=0.72-0.93).CONCLUSION:RT-PCR was the best single test in patients evaluated for COVID-19. Conversely, the routine performance of chest CT adds little sensitivity and decreases specificity.

Abstract Background There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. We analysed the impact of filtering facepiece class 2 (FFP2) versus surgical masks on the risk of SARS-CoV-2 acquisition among Swiss healthcare workers (HCW). Methods Our prospective multicentre cohort enrolled HCW from June to August 2020. Participants were asked about COVID-19 risk exposures/behaviours, including preferentially worn mask type when caring for COVID-19 patients outside of aerosol-generating procedures. The impact of FFP2 on (1) self-reported SARS-CoV-2-positive nasopharyngeal PCR/rapid antigen tests captured during weekly surveys, and (2) SARS-CoV-2 seroconversion between baseline and January/February 2021 was assessed. Results We enrolled 3259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users; seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was non-significantly associated with decreased risk for SARS-CoV-2-positive swab (adjusted hazard ratio [aHR] 0.8, 95% CI 0.6–1.0) and seroconversion (adjusted odds ratio [aOR] 0.7, 95% CI 0.5–1.0); household exposure was the strongest risk factor (aHR 10.1, 95% CI 7.5–13.5; aOR 5.0, 95% CI 3.9–6.5). In subgroup analysis, FFP2 use was clearly protective among those with frequent (> 20 patients) COVID-19 exposure (aHR 0.7 for positive swab, 95% CI 0.5–0.8; aOR 0.6 for seroconversion, 95% CI 0.4–1.0). Conclusions Respirators compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients.

BACKGROUND:The burden of long-term symptoms (ie, long COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCWs), frequency and risk factors for symptoms compatible with long COVID are assessed. METHODS:Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long COVID (including psychometric scores) were asked and compared between HCWs with positive NPS, seropositive HCWs without positive NPS (presumable asymptomatic/pauci-symptomatic infections), and negative controls. The effect of time since diagnosis and quantitative anti-spike protein antibodies (anti-S) was evaluated. Poisson regression was used to identify risk factors for symptom occurrence. RESULTS:Of 3334 HCWs (median, 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCWs with positive NPS more frequently reported ≥1 symptom compared with controls (73% vs 52%, P < .001); seropositive HCWs without positive NPS did not score higher than controls (58% vs 52%, P = .13), although impaired taste/olfaction (16% vs 6%, P < .001) and hair loss (17% vs 10%, P = .004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores. CONCLUSIONS:Seropositive HCWs without positive NPS are only mildly affected by long COVID. Exhaustion/burnout is common, even in noninfected HCWs. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Background Women are overrepresented amongst individuals suffering from post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Methods and Findings By using Bayesian models comprising >200 co-variates, we assessed the impact of social context in addition to biological data on PASC in a multi-centre prospective cohort study of 2927 (46% women) individuals in Switzerland. Women more often reported at least one persistent symptom than men (43.5% vs 32.0% of men, p<0.001) six (IQR 5–9) months after SARS-CoV-2 infection. Adjusted models showed that women with personality traits stereotypically attributed to women were most often affected by PASC (OR 2.50[1.25-4.98], p<0.001), in particular when they were living alone (OR 1.84[1.25-2.74]), had an increased stress level (OR 1.06[1.03-1.09]), had undergone higher education (OR 1.30[1.08-1.54]), preferred pre-pandemic physical greeting over verbal greeting (OR 1.71[1.44-2.03]), and had experienced an increased number of symptoms during index infection (OR 1.27[1.22-1.33]). Conclusion Besides gender- and sex-sensitive biological parameters, sociocultural variables play an important role in producing sex differences in PASC. Our results indicate that predictor variables of PASC can be easily identified without extensive diagnostic testing and are targets of interventions aiming at stress coping and social support. ### Competing Interest Statement CG has received research grants from the Novartis Foundation and speakers fees from Sanofi Genzyme, Switzerland outside of the submitted work. The University Hospital Zurich (CG, RRB, APP, MM, PAK) holds a research contract with GE Healthcare outside of the submitted work. CG and AM have received research grants from Bayer Pharmaceuticals outside of the submitted work. JCS and TS reports (full departmental disclosure) grants from Orion Pharma, Abbott Nutrition International, B. Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, Pierre Fabre Pharma AG, Pfizer, Bard Medica S.A., Abbott AG, Anandic Medical Systems, Pan Gas AG Healthcare, Bracco, Hamilton Medical AG, Fresenius Kabi, Getinge Group Maquet AG, Draeger AG, Teleflex Medical GmbH, Glaxo Smith Kline, Merck Sharp and Dohme AG, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Nycomed, and Phagenesis, outside of the submitted work. The money went into departmental funds, no personal financial gain applies. All other authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work. ### Funding Statement This project is funded by the Swiss National Science Foundation (Project #196140, to CG, CEG, and VRZ), the LOOP Zurich (CG, VRZ, UH) and an unrestricted research grant from the intensive care unit (ICU) research foundation of the University Hospital of Basel (CEG). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to the anonymized data in the study and share final responsibility for the decision to submit for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the responsible ethics committee of the Canton of Basel (EKNZ, ethics approval #2020-01311). Informed consent was obtained from all participants or their legal representative. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Based on the Business Administration System for Ethics Committees (BASEC) ethics approval, the non-anonymized raw data cannot be shared publicly. However, anonymised data that underlie the results reported in this article will become available to interested parties for non-commercial reasons, after the publication upon reasonable requests made to the corresponding author. Data requestors will need to sign a data access agreement.

BackgroundThe Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.MethodsSolidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89–1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76–0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46–1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76–0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77–1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75–0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.InterpretationRemdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).FundingWHO.

ABSTRACTImportanceDisentangling the effects of different SARS-CoV-2 variants and of vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and potentially reduce the future burden of PASC.ObjectiveTo determine the association of primary SARS-CoV-2 infection on the frequency of PASC symptoms by viral variant and vaccination status.DesignCross-sectional questionnaire and SARS-CoV-2 serology (May/June 2022) performed within a prospective healthcare worker cohort (SURPRISE study).SettingMulticenter study in nine healthcare networks from North-Eastern Switzerland.ParticipantsVolunteer sample of healthcare workers (HCW) from participating institutions. Of approximately 20’000 eligible participants, 3’870 registered for the cohort and 2’912 were included in this analysis.ExposuresSARS-CoV-2 infection documented by positive nasopharyngeal swab (>4 weeks ago), stratified by viral variant and vaccination status at time of infection, compared to absence of documented infection (no positive swab, negative serology).Main OutcomeSum score of eighteen self-reported PASC symptoms.ResultsAmong 2’912 participants (median age 44 years, 81.3% female), SARS-CoV-2 infection was reported by 1’685 (55.9%) participants, thereof 315 (18.7%) during Wild-type, 288 (17.1%) during Alpha/Delta, and 1’082 (64.2%) during Omicron circulation. Mean symptom number in previously infected participants significantly exceeded that of uninfected controls (0.39), but decreased with recency of the viral variant: 1.12 (p<0.001) for Wild-type (median time since infection 18.5 months), 0.67 (p<0.001) for Alpha/Delta (6.6 months), and 0.52 (p=0.005) for Omicron BA.1 (3.1 months) infected participants. After Omicron BA.1 infection, the mean symptom score was 0.49 (p=0.30) for those with ≥3 prior vaccinations and 0.71 (p=0.028) with 1-2 previous vaccinations compared to 0.36 for unvaccinated individuals. Adjusting for confounders, Wild-type (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) showed significant associations with the outcome, whereas Omicron BA.1 infection (aRR 1.29, 95% CI 0.69–2.43) and vaccination before infection (aRR 1.27, 95% CI 0.82–1.94) did not.Conclusions and RelevancePrevious infection with pre-Omicron variants was the strongest risk factor for reporting PASC symptoms in this HCW cohort. A definite influence of prior vaccination on the prevention of PASC after Omicron BA.1 infection was not measurable.

The COVID-19 pandemic has challenged institutions' diagnostic processes worldwide. The aim of this study was to assess the feasibility of an artificial intelligence (AI)-based software tool that automatically evaluates chest computed tomography for findings of suspected COVID-19. Two groups were retrospectively evaluated for COVID-19-associated ground glass opacities of the lungs (group A: real-time polymerase chain reaction positive COVID patients, n = 108; group B: asymptomatic pre-operative group, n = 88). The performance of an AI-based software assessment tool for detection of COVID-associated abnormalities was compared with human evaluation based on COVID-19 reporting and data system (CO-RADS) scores performed by 3 readers. All evaluated variables of the AI-based assessment showed significant differences between the 2 groups (P < .01). The inter-reader reliability of CO-RADS scoring was 0.87. The CO-RADS scores were substantially higher in group A (mean 4.28) than group B (mean 1.50). The difference between CO-RADS scoring and AI assessment was statistically significant for all variables but showed good correlation with the clinical context of the CO-RADS score. AI allowed to predict COVID positive cases with an accuracy of 0.94. The evaluated AI-based algorithm detects COVID-19-associated findings with high sensitivity and may support radiologic workflows during the pandemic.

Background: The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed. Methods: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence. Results: Of 3334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported [≥]1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores. Conclusions: Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Abstract The COVID-19 pandemic has challenged institutions’ diagnostic processes worldwide. The aim of this study was to assess the feasibility of an artificial intelligence (AI)-based software tool that automatically evaluates chest computed tomography for findings of suspected COVID-19. Two groups were retrospectively evaluated for COVID-19-associated ground glass opacities of the lungs (group A: real-time polymerase chain reaction positive COVID patients, n = 108; group B: asymptomatic pre-operative group, n = 88). The performance of an AI-based software assessment tool for detection of COVID-associated abnormalities was compared with human evaluation based on COVID-19 reporting and data system (CO-RADS) scores performed by 3 readers. All evaluated variables of the AI-based assessment showed significant differences between the 2 groups (P < .01). The inter-reader reliability of CO-RADS scoring was 0.87. The CO-RADS scores were substantially higher in group A (mean 4.28) than group B (mean 1.50). The difference between CO-RADS scoring and AI assessment was statistically significant for all variables but showed good correlation with the clinical context of the CO-RADS score. AI allowed to predict COVID positive cases with an accuracy of 0.94. The evaluated AI-based algorithm detects COVID-19-associated findings with high sensitivity and may support radiologic workflows during the pandemic.