COVID-19 and Intracranial Hemorrhage: A Multicenter Case Series, Systematic Review and Pooled Analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). RESULTS: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. CONCLUSION: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.

Plasma exchange with COVID-19 convalescent plasma in a patient with severe ANCA-associated vasculitis and COVID-19 pneumonia after rituximab therapy.

The combination of coronavirus disease 2019 (COVID-19) pneumonia and pulmonary-renal syndrome due to ANCA-associated vasculitis (AAV) poses diagnostic uncertainty and a therapeutic dilemma. According to current limited knowledge of COVID-19, the application of commonly used drugs in AAV, cyclophosphamide (CYC) and rituximab (RTX), must be weighed carefully in active COVID-19 infection. We report a case of a 52-year-old male patient with concurrent severe COVID-19 pneumonia and acute relapse of pulmonary-renal syndrome due to AAV after recent RTX maintenance dose. The patient presented with severe hypoxaemia, complete B-cell depletion and severe acute respiratory syndrome coronavirus 2 viraemia. He was successfully treated with therapeutic plasma exchange employing COVID-19 convalescent plasma.

Reactivation of EBV and CMV in Severe COVID-19-Epiphenomena or Trigger of Hyperinflammation in Need of Treatment? A Large Case Series of Critically ill Patients.

BACKGROUND: Reactivation of viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common in critically ill patients and have been described in patients with severe COVID-19. However, it is unclear whether these reactivations are associated with increased mortality and whether targeted treatments are beneficial. METHODS: In a retrospective single-center cohort study, patients with severe COVID-19 treated on our intensive care unit (ICU) were screened for EBV and CMV reactivation as detected by polymerase chain reaction. If present, patient characteristics, temporal connections to severe acute respiratory syndrome coronavirus 2 diagnosis and corticosteroid use, the use of targeted treatments as well as the course of disease and outcome were analyzed. As control group, non-COVID-19 patients with sepsis, treated within the same time period on our ICU, served as control group to compare incidences of viral reactivation. RESULTS: In 19 (16%) of 117 patients with severe COVID-19 treated on our ICU EBV reactivations were identified, comparable 18 (14%) of 126 in the non-COVID-19 control group (P = .672). Similarly, in 11 (9%) of 117 patients CMV reactivations were identified, comparable to the 16 (13%) of 126 in the non-COVID-19 sepsis patients (P = .296). The majority of EBV (58%) and CMV reactivations (55%) were detected in patients under systemic corticosteroid treatment. 7 (37%) of 19 patients with EBV reactivation survived the ICU stay, 2 (29%) of 7 patients with rituximab treatment and 5 (42%) of 12 patients without treatment (P = .568). Five (50%) of 10 patients with CMV reactivation survived the ICU stay, 5 (83%) of 6 patients with ganciclovir treatment and 0 of 4 patients without treatment (P = .048). Follow-up analysis in these patients showed that the initiation of treatment lead to decrease in viral load. CONCLUSION: Critically ill patients with COVID-19 are at a high risk for EBV and CMV reactivations. Whether these reactivations are a cause of hyperinflammation and require targeted treatment remains uncertain. However, in patients with clinical deterioration or signs of hyperinflammation targeted treatment might be beneficial and warrants further studying.

Clinical Course and Outcome of Patients with SARS-CoV-2 Alpha Variant Infection Compared to Patients with SARS-CoV-2 Wild-Type Infection Admitted to the ICU.

The alpha variant of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is associated with higher transmissibility and possibly higher mortality compared with wild-type SARS-CoV-2. However, few data are available on the clinical course of infections with the alpha variant compared with wild-type SARS-CoV-2 in critically ill patients in intensive care units (ICUs). Therefore, we retrospectively analyzed patients admitted to our ICU due to SARS-CoV-2 Alpha variant infection and compared characteristics and course to patients with SARS-CoV-2 wild-type infection. The median age of patients with Alpha variant infections was 57 years compared to 62 years in the wild-type group. ICU survival was 41/80 (51%) in the Alpha variant group and 35/80 (44%) in the wild-type group (p = 0.429). Results of a matched-pair analysis based on age and sex illustrated that 45/58 patients (77.6%) in the Alpha variant group and 38/58 (65.5%) patients in the wild-type group required mechanical ventilation (p = 0.217). ICU survival was documented for 28/58 patients (48.3%) in the Alpha variant group and 27/58 patients (46.6%) in the wild-type group (p = 1). Thus, ICU mortality among patients with SARS-CoV-2 infections remains high. Although the Alpha variant group included younger patients requiring mechanical ventilation, no significant differences between patients with the SARS-CoV-2 Alpha variant and the SARS-CoV-2 wild-type, respectively, were detected with respect to clinical course and ICU mortality. For future VOCs, we believe it would be important to obtain valid and rapid data on the clinical course of critically ill patients who test positive for COVID-19 in order to perform appropriate epidemiological planning of intensive care capacity.