Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimics the influenza A (H1N1) virus in terms of clinical presentation, transmission mechanism, and seasonal coincidence. Comprehensive data for the clinical severity of adult patients co-infected by both H1N1 and SARS-CoV-2, and, particularly, the relationship with PCR cycle threshold (Ct) values are not yet available. All participants in this study were tested for H1N1 and SARS-CoV-2 simultaneously at admission. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records and compared among adults hospitalized for H1N1 infection, SARS-CoV-2 infection and co-infection with both viruses. Ct values for viral RNA detection were further compared within SARS-CoV-2 and co-infection groups. Score on seven-category ordinal scale of clinical status at day 7 and day 14 were assessed. Among patients with monoinfection, H1N1 infection had higher frequency of onset symptoms but lower incidence of adverse events during hospitalization than SAR-CoV-2 infection (P < 0.05). Co-infection had an increased odds of acute kidney injury, acute heart failure, secondary bacterial infections, multilobar infiltrates and admittance to ICU than monoinfection. Score on seven-category scale at day 7 and day 14 was higher in patients with coinfection than patients with SAR-CoV-2 monoinfection (P<0.05). Co-infected patients had lower initial Ct values (referring to higher viral load) (median 32) than patients with SAR-CoV-2 monoinfection (median 36). Among co-infected patients, low Ct values were significantly and positively correlated with acute kidney injury and ARDS (P = 0.03 and 0.02, respectively). Co-infection by SARS-CoV-2 and H1N1 caused more severe disease than monoinfection by either virus in adult inpatients. Early Ct value could provide clues for the later trajectory of the co-infection. Multiplex molecular diagnostics for both viruses and early assessment of SAR-CoV-2 Ct values are recommended to achieve optimal treatment for improved clinical outcome.
Project description:BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has led to a surge in clinical trials evaluating investigational and approved drugs. Retrospective analysis of drugs taken by COVID-19 inpatients provides key information on drugs associated with better or worse outcomes.MethodsWe conducted a retrospective cohort study of 10 741 patients testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 3 days of admission to compare risk of 30-day all-cause mortality in patients receiving ondansetron using multivariate Cox proportional hazard models. All-cause mortality, length of hospital stay, adverse events such as ischemic cerebral infarction, and subsequent positive COVID-19 tests were measured.ResultsAdministration of ≥8 mg of ondansetron within 48 hours of admission was correlated with an adjusted hazard ratio for 30-day all-cause mortality of 0.55 (95% CI, 0.42-0.70; P < .001) and 0.52 (95% CI, 0.31-0.87; P = .012) for all and intensive care unit-admitted patients, respectively. Decreased lengths of stay (9.2 vs 11.6; P < .001), frequencies of subsequent positive SARS-CoV-2 tests (53.6% vs 75.0%; P = .01), and long-term risks of ischemic cerebral ischemia (3.2% vs 6.1%; P < .001) were also noted.ConclusionsIf confirmed by prospective clinical trials, our results suggest that ondansetron, a safe, widely available drug, could be used to decrease morbidity and mortality in at-risk populations.
Project description:Host-virus protein-protein interactions play key roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a comprehensive interactome study between the virus and host cells using tandem affinity purification and proximity labeling strategies and identified 437 human proteins as the high-confidence interacting proteins. Further characterization of these interactions and comparison to other large-scale study of cellular responses to SARS-CoV-2 infection elucidated how distinct SARS-CoV-2 viral proteins participate in its lifecycle. With these data mining, we discovered potential drug targets for the treatment of COVID-19. The interactomes of two key SARS-CoV-2-encoded viral proteins, NSP1 and N, were compared with the interactomes of their counterparts in other human coronaviruses. These comparisons not only revealed common host pathways these viruses manipulate for their survival, but also showed divergent protein-protein interactions that may explain differences in disease pathology. This comprehensive interactome of SARS-CoV-2 provides valuable resources for the understanding and treating of this disease.
Project description:Asthma exacerbation may require a visit to the emergency room as well as hospitalization and can occasionally be fatal. However, there is limited information about the prognostic factors for asthma exacerbation requiring hospitalization, and no methods are available to predict an inpatient's prognosis. We investigated the clinical features and factors affecting in-hospital mortality of patients with asthma exacerbation and generated a nomogram to predict in-hospital death using a national inpatient database in Japan.We retrospectively collected data concerning hospitalization of adult patients with asthma exacerbation between July 2010 and March 2013 using the Japanese Diagnosis Procedure Combination database. We recorded patient characteristics and performed Cox proportional hazards regression analysis to assess the factors associated with all-cause in-hospital mortality. Then, we constructed a nomogram to predict in-hospital death.A total of 19,684 patients with asthma exacerbation were identified; their mean age was 58.8 years (standard deviation, 19.7 years) and median length of hospital stay was 8 days (interquartile range, 5-12 days). Among study patients, 118 died in the hospital (0.6%). Factors associated with higher in-hospital mortality included older age, male sex, reduced level of consciousness, pneumonia, and heart failure. A nomogram was generated to predict the in-hospital death based on the existence of seven variables at admission. The nomogram allowed us to estimate the probability of in-hospital death, and the calibration plot based on these results was well fitted to predict the in-hospital prognosis.Our nomogram allows physicians to predict individual risk of in-hospital death in patients with asthma exacerbation.
Project description:BackgroundWe investigated factors associated with prolonged viral clearance of SARS-CoV-2 among non-severe adult patients in Osaka, Japan. A total of 706 laboratory-confirmed COVID-19 patients were enrolled in this longitudinal observational study between 29 January 2020 and 31 May 2020, across 62 hospitals and three non-hospital recuperation facilities.MethodsLogistic regression analysis was performed to investigate the factors associated with prolonged (29 days: upper 25% in duration) viral clearance of SARS-CoV-2. Linear regression analysis was conducted to assess these factors 14 days after symptom onset.ResultsThe median duration of viral clearance was 22 days from symptom onset. After adjustment for sex, age, symptoms, comorbidity, and location of recuperation, comorbidities were associated with prolonged duration: (OR, 1.77 [95% CI, 1.11-2.82]) for one, (OR, 2.47 [95% CI, 1.32-4.61]) for two or more comorbidities. Viral clearance 14 days after symptom onset was 3 days longer for one comorbidity and 4 days longer for two or more comorbidities compared to clearance when there was no comorbidity.ConclusionThe presence of comorbidity was a robust factor associated with a longer duration of viral clearance, extending by 3 to 4 days compared to patients with no comorbidity.
Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
Project description:SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed "Nanotraps," completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines. The Nanotraps effectively captured SARS-CoV-2 and completely blocked SARS-CoV-2 infection to ACE2-expressing human cell lines and primary lung cells; the phosphatidylserine triggered subsequent phagocytosis of the virus-bound, biodegradable Nanotraps by macrophages, leading to the clearance of pseudotyped and authentic virus in vitro. Furthermore, the Nanotraps demonstrated an excellent biosafety profile in vitro and in vivo. Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an ex vivo lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.
Project description:Impaired mucus clearance and airway mucus plugging have been shown to occur in moderate-severe asthma, especially during acute exacerbations. In cystic fibrosis, where airway mucus is dehydrated, it has been shown that inhaled hypertonic saline (HS) produces both acute and sustained enhancement of mucociliary clearance (MCC). The current study was designed to assess the acute and sustained effect of inhaled 7% HS on MCC in adult asthma. Well-controlled, moderate-severe female asthmatic patients (n=8) were screened with a single test dose of albuterol (four puffs by metered-dose inhaler) followed by HS (7% sodium chloride, 4 mL using PARI LC Star nebuliser). Spirometry was measured pre-treatment and 5 and 30 min post-treatment for safety. MCC was measured using γ-scintigraphy on three separate visits: at baseline, during inhalation and 4 h after a single dose of HS. MCC was acutely enhanced during HS treatment; mean±sd clearance over 60 min of dynamic imaging (Ave60Clr) was 8.9±7.9% (baseline) versus 23.4±7.6% (acute HS) (p<0.005). However, this enhancement was not maintained over a 4-h period where post-HS treatment Ave60Clr was 9.3±8.2%. In this small cohort we found no decrements in lung function up to 30 min post-treatment (forced expiratory volume in 1 s 97.4±10.0% predicted pre-treatment and 98.9±10.7% predicted 30 min post-treatment). While MCC was rapidly enhanced during 7% HS treatment there was no effect on MCC at 4 h post-treatment. While these findings may not support aerosolised HS use for maintenance therapy, they do suggest a benefit of treating acute exacerbations in patients with moderate-severe asthma.