• Jensby Camp posted an update 13 hours, 52 minutes ago

    We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. buy DuP-697 These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic tall around the world. Effective treatments to mitigate this virus infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation as well as human corneal epithelial cells in culture challenged with IFNγ to study this issue. We explore ways to block the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to angiotensin-converting enzyme 2 (ACE2). Elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i), among the lipid mediators studied, consistently decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ stimulated human corneal epithelial cells (HCEC). There was also a concomitant decrease in the binding of spike RBD with the lipid treatments. Concurrently, we uncovered that the lipid mediators also attenuated the expression of cytokines that participate in the cytokine storm, hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to opening therapeutic avenues for COVID-19 by counteracting virus attachment and entrance to the eye and other cells and the ensuing disruptions of homeostasis.The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections and ARDS, but their benefit has not been assessed in COVID-19. Thus, we sought to determine whether antecedent statin use is associated with lower in-hospital mortality in patients hospitalized for COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1 st through May 12 th , 2020 with study period ending on June 11 th , 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline socio-demographic and clinical characteristics, and outpatient medications. The primary endpoint included in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 11 propensity-score matching, demographic, baseline, and outpatient medication information were well balanced. Statin use was significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.48, 95% CI 0.36 — 0.64, p less then 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 was associated with lower inpatient mortality. Randomized clinical trials evaluating the utility of statin therapy in patients with COVID-19 are needed.Background Even people living with HIV/AIDS (PLWHA) were considered to be at increased risk of SARS-CoV-2 infection, the driving force among this group of individuals is still not clear. Methods We investigated 1,701 PLWHA through a telephone interview and found 11 COVID-19 patients in four districts of Wuhan, China. The demographic features and major clinical characteristics of these patients were retrieved from the information management systems for COVID-19 patients of four districts’ CDC. Statistical analysis was performed to find out the driving force of COVID-19 among PLWHA. Results The incidence proportion of COVID-19 in PLWHA is 0.6% (95% CI 0.2% – 1.0%), which is comparable to the overall population incidence rate in Wuhan city (0.6%). Nine out of the 11 COVID-19/AIDS patients had relatively high CD4+ T lymphocyte count (>200/μl) and undetectable HIV viral load (<20 copies/ml), and ten of them were on antiretroviral therapy. PLWHA who were old, had low CD4+ T lymphocyte count, infected HIV through homosexual activity, and had been diagnosed for HIV for a long time, were more likely to develop COVID-19. Conclusions PLWHA has comparable COVID-19 morbidity rates as the general population, and older age, low CD4 count, long length since HIV diagnosis, and treatment-naive were potential driving forces of COVID-19 occurrence among PLWHA. Strategies in preventing SARS-CoV-2 infection among PLWHA with worse immune responses are needed. Article Summary Line As COVID-19 continues to spread around the world, people living with HIV/AIDS (PLWHA) are also at risk of infection with SARS-CoV-2. We investigated the factors associated with SARS-CoV-2 infection among PLWHA in Wuhan, China.