Trends in management and outcomes of COVID patients admitted to a Swiss tertiary care hospital.

Two successive COVID-19 flares occurred in Switzerland in spring and autumn 2020. During these periods, therapeutic strategies have been constantly adapted based on emerging evidence. We aimed to describe these adaptations and evaluate their association with patient outcomes in a cohort of COVID-19 patients admitted to the hospital. Consecutive patients admitted to the Geneva Hospitals during two successive COVID-19 flares were included. Characteristics of patients admitted during these two periods were compared as well as therapeutic management including medications, respiratory support strategies and admission to the ICU and intermediate care unit (IMCU). A mutivariable model was computed to compare outcomes across the two successive waves adjusted for demographic characteristics, co-morbidities and severity at baseline. The main outcome was in-hospital mortality. Secondary outcomes included ICU admission, Intermediate care (IMCU) admission, and length of hospital stay. A total of 2'983 patients were included. Of these, 165 patients (16.3%, n = 1014) died during the first wave and 314 (16.0%, n = 1969) during the second (p = 0.819). The proportion of patients admitted to the ICU was lower in second wave compared to first (7.4 vs. 13.9%, p < 0.001) but their mortality was increased (33.6% vs. 25.5%, p < 0.001). Conversely, a greater proportion of patients was admitted to the IMCU in second wave compared to first (26.6% vs. 22.3%, p = 0.011). A third of patients received lopinavir (30.7%) or hydroxychloroquine (33.1%) during the first wave and none during second wave, while corticosteroids were mainly prescribed during second wave (58.1% vs. 9.1%, p < 0.001). In the multivariable analysis, a 25% reduction of mortality was observed during the second wave (HR 0.75; 95% confidence interval 0.59 to 0.96). Among deceased patients, 82.3% (78.2% during first wave and 84.4% during second wave) died without beeing admitted to the ICU. The proportion of patients with therapeutic limitations regarding ICU admission increased during the second wave (48.6% vs. 38.7%, p < 0.001). Adaptation of therapeutic strategies including corticosteroids therapy and higher admission to the IMCU to receive non-invasive respiratory support was associated with a reduction of hospital mortality in multivariable analysis, ICU admission and LOS during the second wave of COVID-19 despite an increased number of admitted patients. More patients had medical decisions restraining ICU admission during the second wave which may reflect better patient selection or implicit triaging.

Electronic monitoring of potential adverse drug events related to lopinavir/ritonavir and hydroxychloroquine during the first wave of COVID-19.

During Switzerland's first wave of COVID-19, clinical pharmacy activities during medical rounds in Geneva University Hospitals were replaced by targeted remote interventions. We describe using the electronic PharmaCheck system to screen high-risk situations of adverse drug events (ADEs), particularly targeting prescriptions of lopinavir/ritonavir (LPVr) and hydroxychloroquine (HCQ) in the presence of contraindications or prescriptions outside institutional guidelines. Of 416 patients receiving LPVr and/or HCQ, 182 alerts were triggered for 164 (39.4%) patients. The main associated risk factors of ADEs were drug-drug interactions, QTc interval prolongation, electrolyte disorder and inadequate LPVr dosage. Therapeutic optimisation recommended by a pharmacist or proposals for additional monitoring were accepted in 80% (n=36) of cases. Combined with pharmacist contextualisation to the clinical context, PharmaCheck made it possible to successfully adapt clinical pharmacist activities by switching from a global to a targeted analysis mode in an emergency context.

Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs.

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.

[Advances in hospital based internal medicine]. / Nouveautés en médecine interne hospitalière.

Hospital based internal medicine has been strongly solicited for over two years with the SARS-CoV-2 epidemic. This epidemic continues to evolve and represents a strain for public health. Numerous studies have addressed issues concerning this epidemic, and multiple novelties concerning other frequent pathologies have also been published. Management strategies of cardiovascular, pulmonary, gastro-intestinal and metabolic diseases are discussed.

La médecine interne hospitalière a été fortement sollicitée depuis 2 ans avec l'épidémie de SARS-CoV-2. Celle-ci continue d'évoluer et reste une épreuve pour la santé publique. Une pléthore d'études a tenté de résoudre les multiples défis que représente cette épidémie, mais de multiples nouveautés concernant d'autres pathologies fréquentes sont également apparues. La prise en charge des maladies cardiovasculaires, pulmonaires, gastro-intestinales et métaboliques est évoquée.

Abdominal pain patterns during COVID-19: an observational study.

Abdominal pain and liver injury have been frequently reported during coronavirus disease-2019 (COVID-19). Our aim was to investigate characteristics of abdominal pain in COVID-19 patients and their association with disease severity and liver injury.Data of all COVID-19 patients hospitalized during the first wave in one hospital were retrieved. Patients admitted exclusively for other pathologies and/or recovered from COVID-19, as well as pregnant women were excluded. Patients whose abdominal pain was related to alternative diagnosis were also excluded.Among the 1026 included patients, 200 (19.5%) exhibited spontaneous abdominal pain and 165 (16.2%) after abdomen palpation. Spontaneous pain was most frequently localized in the epigastric (42.7%) and right upper quadrant (25.5%) regions. Tenderness in the right upper region was associated with severe COVID-19 (hospital mortality and/or admission to intensive/intermediate care unit) with an adjusted odds ratio of 2.81 (95% CI 1.27-6.21, p = 0.010). Patients with history of lower abdomen pain experimented less frequently dyspnea compared to patients with history of upper abdominal pain (25.8 versus 63.0%, p < 0.001). Baseline transaminases elevation was associated with history of pain in epigastric and right upper region and AST elevation was strongly associated with severe COVID-19 with an odds ratio of 16.03 (95% CI 1.95-131.63 p = 0.010).More than one fifth of patients admitted for COVID-19 presented abdominal pain. Those with pain located in the upper abdomen were more at risk of dyspnea, demonstrated more altered transaminases, and presented a higher risk of adverse outcomes.

Comparison of prognostic scores for inpatients with COVID-19: a retrospective monocentric cohort study.

BACKGROUND: The SARS-CoV-2 pandemic led to a steep increase in hospital and intensive care unit (ICU) admissions for acute respiratory failure worldwide. Early identification of patients at risk of clinical deterioration is crucial in terms of appropriate care delivery and resource allocation. We aimed to evaluate and compare the prognostic performance of Sequential Organ Failure Assessment (SOFA), Quick Sequential Organ Failure Assessment (qSOFA), Confusion, Uraemia, Respiratory Rate, Blood Pressure and Age ≥65 (CURB-65), Respiratory Rate and Oxygenation (ROX) index and Coronavirus Clinical Characterisation Consortium (4C) score to predict death and ICU admission among patients admitted to the hospital for acute COVID-19 infection. METHODS AND ANALYSIS: Consecutive adult patients admitted to the Geneva University Hospitals during two successive COVID-19 flares in spring and autumn 2020 were included. Discriminative performance of these prediction rules, obtained during the first 24 hours of hospital admission, were computed to predict death or ICU admission. We further exluded patients with therapeutic limitations and reported areas under the curve (AUCs) for 30-day mortality and ICU admission in sensitivity analyses. RESULTS: A total of 2122 patients were included. 216 patients (10.2%) required ICU admission and 303 (14.3%) died within 30 days post admission. 4C score had the best discriminatory performance to predict 30-day mortality (AUC 0.82, 95% CI 0.80 to 0.85), compared with SOFA (AUC 0.75, 95% CI 0.72 to 0.78), qSOFA (AUC 0.59, 95% CI 0.56 to 0.62), CURB-65 (AUC 0.75, 95% CI 0.72 to 0.78) and ROX index (AUC 0.68, 95% CI 0.65 to 0.72). ROX index had the greatest discriminatory performance (AUC 0.79, 95% CI 0.76 to 0.83) to predict ICU admission compared with 4C score (AUC 0.62, 95% CI 0.59 to 0.66), CURB-65 (AUC 0.60, 95% CI 0.56 to 0.64), SOFA (AUC 0.74, 95% CI 0.71 to 0.77) and qSOFA (AUC 0.59, 95% CI 0.55 to 0.62). CONCLUSION: Scores including age and/or comorbidities (4C and CURB-65) have the best discriminatory performance to predict mortality among inpatients with COVID-19, while scores including quantitative assessment of hypoxaemia (SOFA and ROX index) perform best to predict ICU admission. Exclusion of patients with therapeutic limitations improved the discriminatory performance of prognostic scores relying on age and/or comorbidities to predict ICU admission.

Cohort profile: Actionable Register of Geneva Outpatients and inpatients with SARS-CoV-2 (ARGOS).

PURPOSE: The Actionable Register of Geneva Outpatients and inpatients with SARS-CoV-2 (ARGOS) is an ongoing prospective cohort created by the Geneva Directorate of Health. It consists of an operational database compiling all SARS-CoV-2 test results recorded in the Geneva area since late February 2020. This article aims at presenting this comprehensive cohort, in light of some of the varying public health measures in Geneva, Switzerland, since March 2020. PARTICIPANTS: As of 1 June 2021, the database included 360 525 patients, among which 65 475 had at least one positive test result for SARS-CoV-2. Among all positive patients, 37.6% were contacted only once, 10.6% had one follow-up call, 8.5% had two and 27.7% had three or more follow-up calls. Participation rate among positive patients is 94%. Data collection is ongoing. FINDINGS TO DATE: ARGOS data illustrates the magnitude of COVID-19 pandemic in Geneva, Switzerland, and details a variety of population factors and outcomes. The content of the cohort includes demographic data, comorbidities and risk factors for poor clinical outcome, self-reported COVID-19 symptoms, environmental and socioeconomic factors, prospective and retrospective contact tracing data, travel quarantine data and deaths. The registry has already been used in several publications focusing on symptoms and long COVID-19, infection fatality rate and re-infection. FUTURE PLANS: The data of this large real-world registry provides a valuable resource for various types of research, such as clinical research, epidemiological research or policy assessment as it illustrates the impact of public health policies and overall disease burden of COVID-19.

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.

Role of Intermediate Care Unit Admission and Noninvasive Respiratory Support during the COVID-19 Pandemic: A Retrospective Cohort Study.

BACKGROUND: The COVID-19 pandemic has led to shortage of intensive care unit (ICU) capacity. We developed a triage strategy including noninvasive respiratory support and admission to the intermediate care unit (IMCU). ICU admission was restricted to patients requiring invasive ventilation. OBJECTIVES: The aim of this study is to describe the characteristics and outcomes of patients admitted to the IMCU. METHOD: Retrospective cohort including consecutive patients admitted between March 28 and April 27, 2020. The primary outcome was the proportion of patients with severe hypoxemic respiratory failure avoiding ICU admission. Secondary outcomes included the rate of emergency intubation, 28-day mortality, and predictors of ICU admission. RESULTS: One hundred fifty-seven patients with COVID-19-associated pneumonia were admitted to the IMCU. Among the 85 patients admitted for worsening respiratory failure, 52/85 (61%) avoided ICU admission. In multivariate analysis, PaO2/FiO2 (OR 0.98; 95% CI: 0.96-0.99) and BMI (OR 0.88; 95% CI: 0.78-0.98) were significantly associated with ICU admission. No death or emergency intubation occurred in the IMCU. CONCLUSIONS: IMCU admission including standardized triage criteria, self-proning, and noninvasive respiratory support prevents ICU admission for a large proportion of patients with COVID-19 hypoxemic respiratory failure. In the context of the COVID-19 pandemic, IMCUs may play an important role in preserving ICU capacity by avoiding ICU admission for patients with worsening respiratory failure and allowing early discharge of ICU patients.

Head-to-Head Accuracy Comparison of Three Commercial COVID-19 IgM/IgG Serology Rapid Tests.

BACKGROUND: Comparative data of SARS-CoV-2 IgM/IgG serology rapid diagnostic tests (RDTs) is scarce. We thus performed a head-to-head comparison of three RDTs. METHODS: In this unmatched case-control study, blood samples from 41 RT-PCR-confirmed COVID-19 cases and 50 negative controls were studied. The diagnostic accuracy of three commercially available COVID-19 RDTs: NTBIO (RDT-A), Orient-Gene (RDT-B), and MEDsan (RDT-C), against both a recombinant spike-expressing immunofluorescence assay (rIFA) and Euroimmun IgG ELISA, was assessed. RDT results concordant with the reference methods, and between whole blood and plasma, were established by the Kendall coefficient. RESULTS: COVID-19 cases' median time from RT-PCR to serology was 22 days (interquartile range (IQR) 13-31 days). Whole-blood IgG detection with RDT-A, -B, and -C showed 0.93, 0.83, and 0.98 concordance with rIFA. Against rIFA, RDT-A sensitivity (SN) was 92% (95% CI: 78-98) and specificity (SP) 100% (95% CI: 91-100), RDT-B showed 87% SN (95% CI: 72-95) and 98% SP (95% CI: 88-100), and RDT-C 100% SN (95% CI: 88-100) and 98% SP (95% CI: 88-100). Against ELISA, SN and SP were above 90% for all three RDTs. CONCLUSIONS: RDT-A and RDT-C displayed IgG detection SN and SP above 90% in whole blood. These RDTs could be considered in the absence of routine diagnostic serology facilities.

Diagnostic accuracy of Augurix COVID-19 IgG serology rapid test.

AIMS: To validate the diagnostic accuracy of the Augurix SARS-CoV-2 IgM/IgG rapid immunoassay diagnostic test (RDT) for COVID-19. METHODS: In this unmatched 1:1 case-control study, blood samples from 46 real-time RT-PCR-confirmed SARS-CoV-2 hospitalized cases and 45 healthy donors (negative controls) were studied. Diagnostic accuracy of the IgG RDT was assessed against both an in-house recombinant spike-expressing immunofluorescence assay (rIFA), as an established reference method (primary endpoint), and the Euroimmun SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISA) (secondary endpoint). RESULTS: COVID-19 patients were more likely to be male (61% vs 20%; P = .0001) and older (median 66 vs 47 years old; P < .001) than controls. Whole blood IgG-RDT results showed 86% and 93% overall Kendall concordance with rIFA and IgG ELISA, respectively. IgG RDT performances were similar between plasma and whole blood. Overall, RDT sensitivity was 88% (95% confidence interval [95%CI]: 70-96), specificity 98% (95%CI: 90-100), PPV 97% (95%CI: 80-100) and NPV 94% (95%CI: 84-98). The IgG-RDT carried out from 0 to 6 days, 7 to 14 days and > 14 days after the SARS-CoV-2 RT-PCR test displayed 30%, 73% and 100% positivity rates in the COVID-19 group, respectively. When considering samples taken >14 days after RT-PCR diagnosis, NPV was 100% (95%CI:90-100), and PPV was 100% (95%CI:72-100). CONCLUSIONS: The Augurix IgG-RDT done in whole blood displays a high diagnostic accuracy for SARS-CoV-2 IgG in high COVID-19 prevalence settings, where its use could be considered in the absence of routine diagnostic serology facilities.