Treatment effect modifiers in hospitalised patients with COVID-19 receiving remdesivir and dexamethasone.

BACKGROUND: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated. METHODS: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics. RESULTS: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration. CONCLUSIONS: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

Venous Thromboembolism and Major Bleeding in Patients With Coronavirus Disease 2019 (COVID-19): A Nationwide, Population-Based Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and thromboprophylaxis should be balanced against risk of bleeding. This study examined risks of VTE and major bleeding in hospitalized and community-managed SARS-CoV-2 patients compared with control populations. METHODS: Using nationwide population-based registries, 30-day risks of VTE and major bleeding in SARS-CoV-2 positive patients were compared with those of SARS-CoV-2 test-negative patients and with an external cohort of influenza patients. Medical records of all COVID-19 patients at 6 departments of infectious diseases in Denmark were reviewed in detail. RESULTS: The overall 30-day risk of VTE was 0.4% (40/9460) among SARS-CoV-2 patients (16% hospitalized), 0.3% (649/226 510) among SARS-CoV-2 negative subjects (12% hospitalized), and 1.0% (158/16 281) among influenza patients (59% hospitalized). VTE risks were higher and comparable in hospitalized SARS-CoV-2 positive (1.5%), SARS-CoV-2 negative (1.8%), and influenza patients (1.5%). Diagnosis of major bleeding was registered in 0.5% (47/9460) of all SARS-CoV-2 positive individuals and in 2.3% of those hospitalized. Medical record review of 582 hospitalized SARS-CoV-2 patients observed VTE in 4% (19/450) and major bleeding in 0.4% (2/450) of ward patients, of whom 31% received thromboprophylaxis. Among intensive care patients (100% received thromboprophylaxis), risks were 7% (9/132) for VTE and 11% (15/132) for major bleeding. CONCLUSIONS: Among people with SARS-CoV-2 infection in a population-based setting, VTE risks were low to moderate and were not substantially increased compared with SARS-CoV-2 test-negative and influenza patients. Risk of severe bleeding was low for ward patients, but mirrored VTE risk in the intensive care setting.

Improved Survival Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Treated With Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study.

BACKGROUND: There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone. METHODS: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The 30-days mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI: .38-.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36; 95% CI: .29-.46). CONCLUSIONS: Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.

SARS-CoV-2 viral load as a predictor for disease severity in outpatients and hospitalised patients with COVID-19: A prospective cohort study.

INTRODUCTION: We aimed to examine if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) cycle quantification (Cq) value, as a surrogate for SARS-CoV-2 viral load, could predict hospitalisation and disease severity in adult patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a prospective cohort study of adult patients with PCR positive SARS-CoV-2 airway samples including all out-patients registered at the Department of Infectious Diseases, Odense University Hospital (OUH) March 9-March 17 2020, and all hospitalised patients at OUH March 10-April 21 2020. To identify associations between Cq-values and a) hospital admission and b) a severe outcome, logistic regression analyses were used to compute odds ratios (OR) and 95% Confidence Intervals (CI), adjusting for confounding factors (aOR). RESULTS: We included 87 non-hospitalised and 82 hospitalised patients. The median baseline Cq-value was 25.5 (interquartile range 22.3-29.0). We found a significant association between increasing Cq-value and hospital-admission in univariate analysis (OR 1.11, 95% CI 1.04-1.19). However, this was due to an association between time from symptom onset to testing and Cq-values, and no association was found in the adjusted analysis (aOR 1.08, 95% CI 0.94-1.23). In hospitalised patients, a significant association between lower Cq-values and higher risk of severe disease was found (aOR 0.89, 95% CI 0.81-0.98), independent of timing of testing. CONCLUSIONS: SARS-CoV-2 PCR Cq-values in outpatients correlated with time after symptom onset, but was not a predictor of hospitalisation. However, in hospitalised patients lower Cq-values were associated with higher risk of severe disease.

Positive Predictive Value of ICD-10 Diagnosis Codes for COVID-19.

PURPOSE: To examine the positive predictive value (PPV) of International Classification version 10 (ICD-10) diagnosis codes for Coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: Medical record review of all patients assigned a diagnosis code of COVID-19 (DB342A or DB972A) at six Danish departments of infectious diseases from February 27 through May 4, 2020. Confirmed COVID-19 diagnosis was defined as either: 1) definite, a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) on a respiratory sample combined with symptoms suggestive of COVID-19: 2) probable, clinical presentation of COVID-19 without detection of SARS-CoV-2 and no alternative diagnoses considered more likely; or 3) possible, clinical presentation of COVID-19 without detection of SARS-CoV-2, and the patient was discharged or deceased before further investigations were carried out. We computed the PPV with 95% confidence intervals (CI) as the number of patients with confirmed (i.e., definite, probable, and possible) COVID-19 divided by the number of patients assigned a diagnosis code for COVID-19. RESULTS: The study included 710 patients with a median age of 61 years (interquartile range [IQR] 47-74) and 285/710 (40%) were female. COVID-19 was confirmed in 706/710 (99%) with 705/710 (99%) categorized as definite, 1/710 (0.1%) as probable, and 0 patients as possible COVID-19. The diagnosis was disproven in 4/710 (0.6%) patients who were hospitalized due to bacterial pneumonia (n = 2), influenza (n = 1), and urinary tract infection (n = 1). The overall PPV for COVID-19 was 99% (95% CI 99-100) and remained consistently high among all subgroups including sex, age groups, calendar period, and stratified by diagnosis code and department of infectious diseases (range 97-100%). CONCLUSION: The overall PPV of diagnosis codes for COVID-19 in Denmark was high and may be suitable for future registry-based prognosis studies of COVID-19.

Lung ultrasound may be a valuable aid in decision making for patients admitted with COVID-19 disease.

INTRODUCTION: COVID-19 is associated with a risk of severe pneumonia and acute respiratory distress syndrome (ARDS), requiring treatment at an intensive care unit (ICU). Since clinical deterioration may occur rapidly, a simple, fast, bedside, non-invasive method for assessment of lung changes is warranted. The primary aim of this study was to investigate whether lung ultrasound (LUS) findings within 72 hours of admission were predictive of clinical deterioration in hospitalized patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS: Patients admitted to a dedicated COVID-19 unit were subject to daily LUS examinations. Number of present consolidations and pleural effusions were registered and a Mongodi score was calculated. These findings were correlated with initial chest x-ray and clinical deterioration, defined as ICU-admission, ARDS diagnosis, death. RESULTS: In total, 29 of 83 patients had LUS performed during admission, 18 within 72 h of admission. Of these, four patients died during admission, six were transferred to the ICU and 13 were diagnosed with ARDS. Initial Mongodi-score did not differ significantly between patients with and without clinical deterioration (p = 0.95). Agreement between initial LUS and chest x-ray findings were fair with Cohen's Kappa at 0.21. CONCLUSION: LUS performed within 72 h in patients admitted to a dedicated COVID-19 unit could not predict ARDS, ICU admission or death. However, consecutive investigations may be of value, as sudden substantial changes may herald disease progression, enabling earlier supplementary diagnostics and treatment initiation.

Low mortality of hospitalised patients with COVID-19 in a tertiary Danish hospital setting.

OBJECTIVES: We aimed to describe clinical characteristics and outcomes of admitted COVID-19 patients in a Danish hospital setting where an early active government intervention was taken. METHODS: Prospective cohort study including all admitted patients to the COVID-19 unit at Odense University Hospital from March 10 to April 21, 2020. Patients were assessed by a multidisciplinary team at admission. Outcome parameters were development of acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, death and admission time. RESULTS: We included 83 patients (median age 62 years, 62.7% male). At hospitalization, 31.3% needed oxygen supplementation and the median National Early Warning Score was four. Median admission time was 7 days (Interquartile ranges (IQR) 3-12). In total, ARDS was diagnosed in 33.7% (28/83) of the patients corresponding to an incidence rate of 7.1 per 100 person days (95% CI: 4.1-10.2). Overall 13 patients (15.7%) were transferred to the ICU of whom 11 (84.6%) received corticosteroids.. No patients died while admitted to the ICU. Four patients (4.8%) died during admission. CONCLUSION: Despite similar patient characteristics compared to those reported by others, we found a low overall mortality of < 5%.