Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD).

Background and Objectives: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions: We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.

Discovery of Zika Virus NS2B/NS3 Inhibitors That Prevent Mice from Life-Threatening Infection and Brain Damage.

Zika virus (ZIKV) infection, which initially was endemic only in Africa and Asia, is rapidly spreading throughout Europe, Oceania, and the Americas. Although there have been enormous efforts, there is still no approved drug to treat ZIKV infection. Herein, we report the synthesis and biological evaluation of agents with noncompetitive mechanism of the ZIKV NS2B/NS3 protease inhibition through the binding to an allosteric site. Compounds 1 and 2 showed potent activity in both enzymatic and cellular assays. Derivative 1 efficiently reduced the ZIKV protein synthesis and the RNA replication and prevented the mice from life-threatening infection and the brain damage caused by ZIKV infection in a ZIKV mouse model.

The value of colour Doppler sonography of the knee joint: a useful tool to discriminate inflammatory from non-inflammatory disease?

OBJECTIVE: To determine the diagnostic value of colour Doppler ultrasound (CDUS) in patients with inflammatory arthritis (IA) vs non-inflammatory disease (e.g. OA) of the knee joint. METHODS: Standardized CDUS examinations were performed in 111 knee joints of 106 patients (70 women and 36 men) presenting with severe OA (n = 72) or confirmed IA (n = 39) of one or both knee joints to determine the degree of synovial inflammation in a semiquantitative fashion. To definitely distinguish inflammatory from non-inflammatory disease, SF was obtained from every patient within 24 h after sonography and analysed SFs containing ≤1000 white blood cells (WBC)/µl were considered non-inflammatory, whereas ≥5000 WBC/µl were classified as inflammatory. RESULTS: The CDUS sum score of OA patients was determined to be 3.3 (range 0-8). In contrast, IA patients exhibited significantly elevated synovitis score of 5.3 (range 3-9) (P < 0.001). However, high synovial CDUS activity could be observed in OA patients sporadically. Therefore, there is no definitive CDUS threshold that clearly separates OA from IA patients. CONCLUSION: CDUS is a valuable instrument to assist clinicians in distinguishing OA from IA of the knee joint, but nevertheless should always be interpreted within the clinical context.