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.

A Cellular Assay for Spike/ACE2 Fusion: Quantification of Fusion-Inhibitory Antibodies after COVID-19 and Vaccination.

Not all antibodies against SARS-CoV-2 inhibit viral entry, and hence, infection. Neutralizing antibodies are more likely to reflect real immunity; however, certain tests investigate protein/protein interaction rather than the fusion event. Viral and pseudoviral entry assays detect functionally active antibodies but are limited by biosafety and standardization issues. We have developed a Spike/ACE2-dependent fusion assay, based on a split luciferase. Hela cells stably transduced with Spike and a large fragment of luciferase were co-cultured with Hela cells transduced with ACE2 and the complementary small fragment of luciferase. Cell fusion occurred rapidly allowing the measurement of luminescence. Light emission was abolished in the absence of Spike and reduced in the presence of proteases. Sera from COVID-19-negative, non-vaccinated individuals or from patients at the moment of first symptoms did not lead to a significant reduction of fusion. Sera from COVID-19-positive patients as well as from vaccinated individuals reduced the fusion. This assay was more correlated to pseudotyped-based entry assay rather than serology or competitive ELISA. In conclusion, we report a new method measuring fusion-inhibitory antibodies in serum, combining the advantage of a complete Spike/ACE2 interaction active on entry with a high degree of standardization, easily allowing automation in a standard bio-safety environment.

Decreased Levels of SARS-CoV-2 Fusion-Inhibitory Antibodies in the Serum of Aged COVID-19 Patients.

BACKGROUND: The SARS-CoV-2 pandemic was particularly devastating for elderly people, and the underlying mechanisms of the disease are still poorly understood. In this study, we investigated fusion inhibitory antibodies (fiAbs) in elderly and younger COVID-19 patients and analyzed predictive factors for their occurrence. METHODS: Data and samples were collected in two cohorts of hospitalized patients. A fusion assay of SARS-CoV-2 spike-expressing cells with ACE2-expressing cells was used to quantify fiAbs in the serum of patients. RESULTS: A total of 108 patients (52 elderly (mean age 85 ± 7 years); 56 young (mean age 52 ± 10 years)) were studied. The concentrations of fiAbs were lower in geriatric patients, as evidenced at high serum dilutions (1/512). The association between fiAbs and anti-Spike Ig levels was weak (correlation coefficient < 0.3), but statistically significant. Variables associated with fusion were the delay between the onset of symptoms and testing (HR = -2.69; p < 0.001), clinical frailty scale (HR = 4.71; p = 0.035), and WHO severity score (HR = -6.01, p = 0.048). CONCLUSIONS: Elderly patients had lower fiAbs levels after COVID-19 infection. The decreased fiAbs levels were associated with frailty.

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.

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.