Coronavirus, uses the Angiotensin Converting Enzyme-2 Receptor to enter airway cells. Viral endocytosis is mediated by several factors, including clathrin, the adaptor protein-2 complex (AP2) and the adaptor-associated kinase-1 (AAK1). 2 According to a recent report, 3 COVID-19, the disease caused by SARS-CoV-2, is characterized by three clinical patterns: no symptoms, mild to moderate disease, severe pneumonia requiring admission to Intensive Care Unit (ICU) in up to 31% of the patients. 3 Thus far, there is no specific therapy for COVID-19 infection. No benefit of lopinavir-ritonavir treatment resulted in a recent trial. 4 Hydroxychloroquine, currently used in view of its "in vitro" observed effect of reduction of viral replication, seems unsatisfactory. 5 Elevated proinflammatory cytokine/chemokine responses seem associated with respiratory failure. 3 Recently, tocilizumab, an interleukin-6 inhibitor, was reported as effective in patients with severe COVID-19 pneumonia. 6 Baricitinib, another inhibitor of cytokine-release, seems an interesting anti-inflammatory drug. It is a Janus kinase inhibitor (anti-JAK) licensed for the treatment of rheumatoid arthritis (RA) with good efficacy and safety records. 7 Moreover it seems to have anti-viral effects by its affinity for AP2-associated protein AAK1, reducing SARS-CoV-2 endocytosis. 8 On this basis, we assessed the safety of baricitinib therapy combined with lopinavir-ritonavir in moderate COVID-19 pneumonia patients and we evaluated its clinical impact.All consecutive hospitalized patients (March 16th −30th) with moderate COVID-19 pneumonia, older than 18 years, were treated for 2 weeks with baricitinib tablets 4 mg/day added to ritonavir-lopinavir therapy. The last consecutive patients with moderate COVID-19 pneumonia receiving standard of care therapy (lopinavir/ritonavir tablets 250 mg/bid and hydroxychloroquine 400 mg/day/orally for 2 weeks) admitted before the date of the first baricitinib-treated patient served as controls. Antibiotics were scheduled only in the case of suspected bacterial infection.Inclusion criteria were: a. SARS-Co-V2 positivity in the nasal/oral swabs; b. presence of at least 3 of the following symptoms: fever, cough, myalgia, fatigue; c. evidence of radiological pneumonia . After discharge, patients treated with baricitinib were planned to be followed for additional 6 weeks. Exclusion criteria: history of thrombophlebitis (TP), latent tuberculosis infection (QuantiFERON Plus-test positivity, Qiagen, Germany 9 ), pregnancy and lactation.Mild to moderate COVID-19 disease definition: presence of bilateral pneumonia with or without ground glass opacity and in absence of consolidation, not requiring intubation at enrollment; arterial oxygen saturation (SpO2) > 92% at room-air, and ratio arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) 10 0-30 0 mmHg. Parameters daily accessed were: fever, pulmonary function, Modified Early Warning Score (MEWS), 10 pulse rate, blood pressure. After the initial execution, r...

Background This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC—COV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018. Methods Between September 28 and November 13 2020, 77 participants were screened. Of these, 45 healthy adults from 20 to 49 years of age were to be administered two doses of MVC—COV1901 in doses of 5 μg, 15 μg, or 25 μg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second dose at the time of the interim analysis. Adverse events and laboratory data were recorded for the safety evaluation. Blood samples were collected for humoral, and cellular immune response at various time points. Trial Registration: ClinicalTrials.gov NCT 04487210. Findings Solicited adverse events were mostly mild and similar. No subject experienced fever. After the second dose, the geometric mean titers (GMTs) for SARS-CoV-2 spike-specific immunoglobulin G were 7178.2, 7746.1, 11,220.6 in the 5 μg, 15 μg, and 25 μg dose groups, respectively. The neutralizing activity were detected in both methods. (Day 43 GMTs, 538.5, 993.1, and 1905.8 for pseudovirus; and 33.3, 76.3, and 167.4 for wild-type virus). The cellular immune response induced by MVC—COV1901 demonstrated substantially higher numbers of IFN-γ- producing cells, suggesting a Th1-skewed immune response. Interpretation The MVC—COV1901 vaccine was well tolerated and elicited robust immune responses and is suitable for further development. Funding Medigen Vaccine Biologics Corporation

Background/Purpose To investigate the characteristics of dysosmia and dysgeusia among patients diagnosed with coronavirus disease 2019 (COVID-19) in Taiwan. Methods Prospective data collection between January 22, 2020 to May 7, 2020 of nucleic acid confirmed COVID-19 hospitalized patients in northern Taiwan by the Taiwan Centers for Disease Control were analyzed. Results Of 217 patients enrolled, 78 (35.9%) reported dysosmia (n = 73, 33.6%) and/or dysgeusia (n = 62, 28.6%). The median duration of COVID-19 associated symptom-onset to development of dysosmia and/or dysgeusia was <1 days (interquartile range [IQR], <1 to 6 days) and 53 of 78 (67.9%) patients developed dysosmia and/or dysgeusia as one of the initial symptoms of COVID-19. Of 59 closely monitored patients, 41 (69.5%) patients recovered within 3 weeks after symptoms onset and the median time to recovery was 12 days (IQR, 7 to 20 days). Only 6 of the 59 (10.2%) patients reported persistent dysosmia and/or dysgeusia before discharge from hospitals. Multivariate analysis showed that younger individuals (adjusted hazard ratio [AHR], 0.93 per one-year increase; 95% confidence interval [95% CI], 0.89-0.97; P = 0.001), women (AHR, 2.76; 95% CI, 1.05-7.25; P = 0.04) and travel to North America (AHR, 2.35; 95% CI, 1.05-5.26; P = 0.04) were the significant factors associated with dysosmia and/or dysgeusia. Conclusion Dysosmia and/or dysgeusia are common symptoms and clues for the diagnosis of COVID-19, particularly in the early stage of the disease. Physicians should be alerted to these symptoms to make timely diagnosis and management for COVID-19 to limit spread.

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