Post‑COVID‑19 Syndrome in Outpatients: A Cohort Study (preprint)

Background: Some patients experience persistent symptoms after COVID-19, but data on outpatients with mild-to-moderate COVID-19 are scarce. We aimed to describe the post-COVID-19 syndrome in confirmed COVID-19 outpatients and to identify its predictors.Methods: This monocentric prospective cohort study included symptomatic outpatients with PCR-confirmed COVID-19 (COVID-positive) and SARS-CoV-2 negative PCR (COVID-negative). Predefined persistent symptoms were evaluated though a phone interview between more than three to ten months after diagnosis. Associations between long-term symptoms and PCR test result, as well predictors of persistent symptoms in COVID-positive were evaluated by multivariate logistic regression.Findings: The study population consisted mostly of young (median of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p=0·020) health care workers (67% versus 82%; p=0·006). Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative ( p =0·006). Overall, 21% COVID-positive and 15% COVID-negative (p=0·182) consulted a doctor for these symptoms. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio [aOR] 2·14, 95%CI 1·04-4·41), smell/taste disorder (26·5, 3·46-202), dyspnea (2·81, 1·10-7·16) and memory impairment (5·71, 1·53-21·3). Among COVID-positive, female gender (aOR 1·67, 95% CI 1·09-2·56) and overweight/obesity (1·67, 1·10-2·56) were predictors of persistent symptoms.Interpretation: More than half of COVID-positive outpatients report persistent symptoms up to ten months after infection and 21% seek medical care for this reason. The symptoms and predictors of post-COVID-19 syndrome need further characterization as it places a significant burden on society and especially healthcare systems.Funding: This work was supported by an academic award of the Leenaards Foundation.Declaration of Interests: None to declare. Ethics Approval Statement: The project was approved by the Ethics Committee of the Canton of Vaud, Switzerland. All participants gave their verbal consent to participate in this study during the phone interview (project-ID CER-VD 2020-01107 and 2019-02283).

Post-COVID-19 syndrome in outpatients: a cohort study (preprint)

BackgroundAfter mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. ObjectivesTo characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. ParticipantsOutpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). DesignMonocentric cohort study with prospective phone interview between more than three months to ten months after initial visit to the emergency department and outpatient clinics. Main MeasuresData of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. Key resultsThe study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p=0.020) and health care workers (67% versus 82%; p=0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p=0.006). Overall, 21% COVID-positive and 15% COVID-negative patients (p=0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio [or] 2.14, 95%CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16) and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms. ConclusionsMore than half of COVID-positive outpatients report persistent symptoms up to ten months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.

HGF and CXCL13, Two Antagonizing Cytokines in Lung Inflammation and Fibrosis, Predict the Severity and the Mortality of COVID-19 (preprint)

The objective of the present study was to identify biological signatures of severe COVID-19 predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a ‘discovery’ cohort (n=98 patients) of the Lausanne University Hospital (LUH-1). While cellular immunological markers lacked power in discriminating between ICU and non-ICU patients, 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P<0.05 to P<0.001). The cytokine results were confirmed in two ‘validation’ cohorts, i.e. the French COVID-19 Study (FCS; n=62) and a second LUH-2 cohort (n=47). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. The two cytokines in combination were the best predictors of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.

Epidemiology, risk factors and clinical course of SARS-CoV-2 infected patients in a Swiss university hospital: an observational retrospective study (preprint)

BackgroundCoronavirus disease 2019 (COVID-19) is now a global pandemic with Europe and the USA at its epicenter. Little is known about risk factors for progression to severe disease in Europe. This study aims to describe the epidemiology of COVID-19 patients in a Swiss university hospital. MethodsThis retrospective observational study included all adult patients hospitalized with a laboratory confirmed SARS-CoV-2 infection from March 1 to March 25, 2020. We extracted data from electronic health records. The primary outcome was the need to mechanical ventilation at day 14. We used multivariate logistic regression to identify risk factors for mechanical ventilation. Follow-up was of at least 14 days. Results200 patients were included, of whom 37 (18{middle dot}5%) needed mechanical ventilation at 14 days. The median time from symptoms onset to mechanical ventilation was 9{middle dot}5 days (IQR 7.00, 12.75). Multivariable regression showed increased odds of mechanical ventilation in males (3.26, 1.21-9.8; p=0.025), in patients who presented with a qSOFA score [≥]2 (6.02, 2.09-18.82; p=0.001), with bilateral infiltrate (5.75, 1.91-21.06; p=0.004) or with a CRP of 40 mg/l or greater (4.73, 1.51-18.58; p=0.013). ConclusionsThis study gives some insight in the epidemiology and clinical course of patients admitted in a European tertiary hospital with SARS-CoV-2 infection. Male sex, high qSOFA score, CRP of 40 mg/l or greater and a bilateral radiological infiltrate could help clinicians identify patients at high risk for mechanical ventilation.