Comparison of performance between three SARS-CoV-2 molecular assays (Aptima™, Laboratory Developed Test-Fusion, and R-GENE®) with special attention to turnaround time, a key point in laboratory management.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of rapid diagnostic testing to identify individuals with SARS-CoV-2 infections and to limit the spread of the virus. Many molecular assays have become commercially available to cope with this surging demand for timely diagnosis of COVID-19 cases, but identifying individuals requires accurate diagnostic tools. We compared the performance of three molecular SARS-CoV-2 assays: Aptima™ SARS-CoV-2 assay running on the Panther system (Hologic), an in-house assay (Laboratory Developed Test, LDT) running on the Fusion module of the Panther Fusion system (LDT-Fusion; Hologic), and the R-GENE® SARS-CoV-2 assay (bioMérieux). In addition, we also evaluated the turnaround time. This parameter is crucial to managing the SARS-CoV-2 diagnosis and represents a key point in the quality management at the laboratory. Aptima™ and LDT-Fusion assays exhibited an excellent positive percent agreement (PPA) (100.0%), while the R-GENE® assay showed a slightly decreased PPA (98.2%). The Hologic assays have a higher throughput with less hands-on time than the R-GENE® assays (24-25 vs. 71 min). Both Hologic assays are used on a fully automated random-access testing system with on-demand testing capabilities that avoid run series, unlike the R-GENE® assay. Automated random-access testing systems should be preferred during periods of high SARS-CoV-2 prevalence.

Risk of symptomatic venous thromboembolism in mild and moderate COVID-19: A comparison of two prospective European cohorts.

BACKGROUND: Severely ill patients with SARS-CoV-2 have an increased risk of venous thromboembolism (VTE) i.e., deep vein thrombosis and pulmonary embolism. However, the VTE risk in patients with mild and moderate COVID-19, hospitalized or managed at home, remain uncertain. The aims of this study were to assess the rate and the risk factors symptomatic VTE, in patients with mild and moderate COVID-19 and to compare them to a cohort of similar patients without COVID-19. METHODS: Patients presenting to the emergency department (ED) of participating centers for confirmed or probable mild or moderate COVID-19 and not having acute VTE were included. This COVID-19 cohort was retrospectively compared to a prospective cohort of similar ED patients using propensity score matching. The main outcome was the rate of symptomatic VTE within the 28 days after ED presentation. RESULTS: A total of 2292 patients were included in the COVID-19 cohort. The 28-day incidence of symptomatic VTE was 1.3% (n = 29/2292, 95%CI: 0.9 to 1.8), 2.3% (n = 20/866, 95%CI: 1.5 to 3.5) in moderate COVID-19 patients and 0.6% (n = 9/1426; 95%CI: 0.3 to 1.2) in mild COVID-19 patients managed as outpatients. An age over 65 years and hospitalization were independent risk factors of VTE. After adjustment, patients in the COVID-19 cohort had an absolute increase in over symptomatic VTE risk of +1.69% (95%CI, 0.88 to 2.51) versus patients in the comparison cohort (n = 1539). CONCLUSIONS: Patients with moderate COVID-19 presenting to the ED had a high risk of subsequent VTE. TRIAL REGISTRATION: Ethics committee of the CHU of Angers (N°2020/87).

Outpatient Management of Patients With COVID-19: Multicenter Prospective Validation of the Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection Rule to Discharge Patients Safely.

BACKGROUND: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method. RESEARCH QUESTION: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely? STUDY DESIGN AND METHODS: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment. RESULTS: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26). INTERPRETATION: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov.

A 78-Year-Old Woman With Diarrhea and Respiratory Failure.

CASE PRESENTATION: A 78-year-old woman was admitted to the ED with a 10-day history of diarrhea and recent onset of dry cough, fever, and asthenia. She had a medical history of obesity (BMI 32) and arterial hypertension treated with irbesartan. In the context of a large-scale lockdown in France during the COVID-19 pandemic, she only had physical contact with her husband, who did not report any symptoms. She required mechanical ventilation because of severe hypoxemia within 1 hour after admission to the ED.

Definition and Validation of a Risk-Stratification Model for Probable or Proven COVID-19 Patients in Emergency Departments: The Revised HOME-CoV Score. (preprint)

The HOME-CoV rule is a list of clinical criteria defined by experts’ consensus, qualifying patients with probable or proven COVID-19 for home treatment when negative. The aims were to define and validate a revised HOME-CoV score, optimizing the original rule. Definition of the revised HOME-CoV score using logistic regression in a prospective multicenter cohort and validation in another cohort of patients who presented to the emergency department with proven or probable COVID-19. The main outcome was non-invasive or invasive ventilation or all-cause death within the 7 days following inclusion. Two threshold values were defined using a sensitivity of > 0.9 and a specificity of > 0.9 to identify low-risk patients and high-risk patients, respectively. The revised HOME-CoV score included seven clinical criteria. In the definition cohort (n=1696), the AUC was 87.6 (95% CI 84.7 to 90.6). The cutoffs to define low-risk and high-risk patients were <2 and >3, respectively. In the validation cohort (n=1304), the AUC was 85.8 (95% CI 80.6 to 91.0) and 85.5 (95% CI 76.8 to 94.1) in the subgroup of patients with positive RT-PCR for SARS-CoV2. A score of < 2 qualified 73% of patients as low risk with a sensitivity of 0.84 (0.66-0.95) and a negative predictive value of 0.99 (0.99-1.00). The revised HOME-CoV score compared favorably with the original rule and other models. The revised HOME-CoV score may allow accurate risk stratification and safely qualify for home treatment, a significant proportion of patients with probable or proven COVID-19.

[Clinical and epidemiological characteristics of COVID-19]. / Caractéristiques cliniques et épidémiologiques de la Covid-19.

Severe acute respiratory syndrome coronavirus 2, the coronavirus with respiratory tropism responsible for COVID-19, was isolated for the first time in China at the end of 2019. Several months after its discovery and despite its pandemic spread, there are still many grey areas concerning the pathophysiology and treatment of COVID-19. However, we have strong data on its epidemiological characteristics and the clinical expression of this disease is now well described.

Outpatient management or hospitalization of patients with proven or suspected SARS-CoV-2 infection: the HOME-CoV rule.

In the context of the COVID-19 pandemic and overloaded hospitals, a central issue is the need to define reliable and consensual criteria for hospitalization or outpatient management in mild cases of COVID-19. Our aim was to define an easy-to-use clinical rule aiming to help emergency physicians in hospitalization or outpatient management decision-making for patients with suspected or confirmed SARS-CoV-2 infection (the HOME-CoV rule). The Delphi method was used to reach a consensus of a large panel of 51 experts: emergency physicians, geriatricians, infectious disease specialists, and ethical consultants. A preliminary list of eligible criteria was compiled based on a literature review. Four rounds of anonymized expert consultations were performed. The experts were asked to score each item as relevant, possibly relevant and non-relevant, as major or minor, and to choose the cut-off. They were also able make suggestions and remarks. Eight criteria constituting the HOME-CoV were selected: six correspond to the severity of clinical signs, one to the clinical course (clinically significant worsening within the last 24 h), and the last corresponds to the association of a severe comorbidity and an inadequate living context. Hospitalization is deemed necessary if a patient meets one or more of the criteria. In the end, 94.4% of the experts agreed with the defined rule. Thanks to the Delphi method, an absolute consensus was obtained of a large panel of experts on the HOME-CoV rule, a decision-making support mechanism for clinicians to target patients with suspected or confirmed COVID-19 requiring hospitalization.Trial registration: NCT04338841.