Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial.

Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients. Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707). Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034). Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens. Funding: French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole.

Pulmonary Nocardiosis as an Opportunistic Infection in COVID-19.

Secondary bacterial pneumonia infection is frequent in COVID-19 patients. Nocardia are responsible for opportunistic pulmonary infections especially after steroid treatment. We describe a case of pulmonary nocardiosis following critical COVID-19 pneumonia in an 83-year-old male. Two weeks after initiation of dexamethasone 6 mg/L, the patient developed a new episode of acute dyspnea. The sputum cultures identified Nocardia cyriacigeorgica. In spite of intravenous imipenem and cotrimoxazole treatment the patient died. Physicians should be aware of the possibility of nocardiosis in case of deterioration of respiratory status of severe COVID-19 inpatients and perform Nocardia evaluation. This evaluation requires prolonged culture. LEARNING POINTS: Nocardia are responsible for opportunistic pulmonary infections after steroid treatment.We describe a case of pulmonary nocardiosis following critical COVID-19 pneumonia.Physicians should be aware of the possibility of secondary nocardiosis in COVID-19 inpatients.

The challenge of diagnosing Guillain-Barre syndrome in patients with COVID-19 in the intensive care unit.

Various neurological complications have been described in COVID-19 patients, especially Guillain-Barre syndrome (GBS). The underlying mechanisms on the association between SARS-CoV-2 infection and GBS remain unclear, but several hypotheses have been proposed. It seems that post-SARS-CoV-2 GBS shares many characteristics with classic post-infectious GBS; however, it may occur in sedated and intubated patients hospitalized in the intensive care unit for SARS-CoV-2 acute respiratory distress syndrome, which presents challenges in the diagnosis and treatment of GBS. In this study, we describe three cases of post-SARS-CoV-2 GBS that were hospitalized in the intensive care unit.

Factors associated with mechanical ventilation in SARS-CoV-2 patients treated with high-flow nasal cannula oxygen and outcomes.

Five percent of patients infected with SARS-CoV-2 require advanced respiratory support. The high-flow nasal cannula oxygenotherapy (HFNCO) appears to be effective and safe to reduce the need for mechanical ventilation. However, the factors associated with HFNCO failure as well as the outcomes of patients receiving this noninvasive respiratory strategy remain unclear. Thus, we performed this study to determine factors leading to intubation of SARS-CoV-2 patients treated with HFNCO and patients' outcomes. We retrospectively analyzed the medical charts of patients admitted in our ICU center for acute respiratory failure due to SARS-CoV-2 infection and who initially benefited from HFNCO, between September 1, 2020, and March 1, 2021. We included all adults patients who received HFNCO and compared two groups: those treated with HFNCO alone and those who failed HFNCO. Patients treated with HFNCO and secondarily limited to the use of mechanical ventilation were excluded from the analysis. Sixty-nine patients were included, 33 were treated with HFNCO alone and 36 failed HFNCO. We found more patients with shock in the HFNCO failure group (p = 0.001). The mean IGSII score was higher in the HFNCO failure group (p < 0.001). The minimum PaO2 /FiO2 was lower in the HFNCO failure group (p = 0.024). The length of stay in ICU was higher in the HFNCO failure group (p < 0.001). The mean duration of HFNCO before intubation was 1.77 days. Six-week mortality was higher in the HFNCO failure group (p = 0.034). Ten patients had a complication during intubation. The HFNCO leads to reduce the intubation rate, the length of stay in ICU, and the mortality. Determining the factors associated with HFNCO failure is important to avoid complications following late intubation.

Multifocal and Microvascular Involvement in Ischemic Stroke During COVID-19: A Cohort Study With Comparison With Non-COVID-19 Stroke.

Introduction: Thromboembolic events, including ischemic stroke, are major complications of coronavirus disease 2019 (COVID-19). The clinical characteristics of COVID-19-related stroke are not clearly defined, and few controlled studies assessed the underlying mechanisms of cerebrovascular complications of COVID-19. This single-center retrospective observational study compared stroke characteristics between patients with and without COVID-19. Methods: This study included all patients hospitalized between March 1, 2020, and April 30, 2020, in Colmar Hospital for ischemic stroke as confirmed by imaging. The characteristics of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by real-time reverse transcriptase polymerase chain reaction or serology were compared with those without SARS-CoV-2 infection. Result: Among 772 patients, nine COVID-19 patients were compared with 50 patients without COVID-19. The following inflammatory and procoagulant marker levels were significantly higher in the COVID-19 group than those in the control group: C-reactive protein, 57.3 ± 43.4 vs. 15.0 ± 30.6 mg/L, p < 0.001; fibrinogen, 5.89 ± 1.75 vs. 4.03 ± 1.26 g/L, p < 0.001; and D-dimer, 4,833.9 ± 6,549.4 vs. 1,028.6 ± 942.6 ng/ml, p < 0.001. The rates of multifocal cerebral territory involvement (4 vs. 7, p = 0.05), microvascular involvement (4 vs. 6, p = 0.04), and thrombophilia (4 vs. 4, p = 0.014) were significantly higher in the COVID-19 group than in the control group, whereas no significant intergroup differences were found in the stroke mechanisms, i.e., cardio-embolic, atherosclerotic, small vessel disease, and cryptogenic. Conclusion: COVID-19-related stroke is characterized by hypercoagulability and hyperinflammation that may favor strokes via microvascular circulation abnormalities, microthrombus formation, and multifocal lesions.

Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.

The BAS2IC Score: A Useful Tool to Identify Patients at High Risk of Early Progression to Severe Coronavirus Disease 2019.

We developed a score, with easily accessible data (age, sex, body mass index, dyspnea, inflammatory parameters), to predict the risk of rapid progression to severe coronavirus disease 2019. Using a cutoff of >6 points, the negative predictive value was 87%.

Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19.

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.