Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium.

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron variants (including BA.1, BQ.1 and XBB.1). Time-of-addition and drug withdrawal assays revealed that early treatment (continuously incubated after viral absorption) of DCM could markedly inhibit Omicron replication in AECs, but DCM did not affect the absorption, exocytosis and spread of viruses or directly eliminate viruses. Mechanistically, we performed single-cell sequencing analysis (a database of 77,969 cells from different airway locations from 10 healthy volunteers) and immunofluorescence staining, and showed that the expression of NAD(P)H quinone oxidoreductase 1 (NQO1), one of the known DCM targets, was predominantly localised in ciliated AECs. We further found that the NQO1 expression level was positively correlated with both the disease severity of COVID-19 patients and virus copy levels in cultured AECs. In addition, DCM treatment downregulated NQO1 expression and disrupted signalling pathways associated with SARS-CoV-2 disease outcomes (e.g., Endocytosis and COVID-19 signalling pathways) in cultured AECs. Collectively, we demonstrated that DCM is an effective post-exposure prophylactic for SARS-CoV-2 infection in the human AECs, and these findings could help physicians formulate novel treatment strategies for COVID-19.

Epidemiological investigation of bovine viral diarrhea virus infection in swinery

From 2017 to 2020, 1 078 piglet diarrhea samples were collected from 6 pig farms in different districts of Shanghai. Multiple RT-PCR method was used for detection and analysis to study the infection status of bovine viral diarrhea virus (BVDV) in swinery in Shanghai. The results showed that the overall detection rate of BVDV in swinery in Shanghai was 7.14% (77/1 078), and showed an increasing trend year by year. The mixed infection rate of BVDV and other diarrhea pathogens was high, with the highest dual infection rate (65%, 26/40), mainly BVDV/PASTV (61.54%, 16/26). On this basis, the triple infection rate was 25% (10/40), mainly BVDV/PAStV/PKoV (40%, 4/10) infection mode;The quadruple infection rate was 10% (4/40), which was dominated by BVDV/PAStV/PEDV/PSV (50%, 2/4) infection. The BVDV prevalence in swinery was seasonal, and the prevalence in spring (10.36%) and autumn (13.59%) was higher than that in summer (6.8%) and winter (2.66%). The positive rate of BVDV in different pig farms was significantly different by 0-24.07%. In view of the detection rate of diarrhea virus dominated by PEDV in pig farm 2 had been high in recent years, this study further monitored the infection of BVDV in this pig farm, and found that the detection rate of BVDV in this pig farm was increasing year by year from 2017 to 2019, with the highest detection rate in 2019 (8.61%, 42/488);The mixed infection of BVDV and other diarrhea pathogens was also serious, with the dual infection rate of 57.58% (19/32), triple infection rate of 21.21% (7/32), quadruple infection rate of 21.21% (7/32), respectively. This study enriched the epidemic data of BVDV in swinery in Shanghai, and could provide reference for the prevention and control of pig epidemics.

Risks of Occupational-Related Adverse Events (ORAEs) and Effect of Bundled Interventions Among Health Care Workers in Novel Coronavirus Pneumonia Wards.

OBJECTIVE: The aims of the study were to investigate the burden for health care workers (HCWs) who suffer from occupational-related adverse events (ORAEs) while working in contaminated areas in a specialized hospital for novel coronavirus pneumonia, to explore related risk factors, to evaluate the effectiveness of bundled interventions, as well as to provide scientific evidence regarding the reduction of risks concerning ORAEs and occupational exposure events. METHODS: The study was completed using a special team of 138 HCWs assembled for a specialized hospital for novel coronavirus pneumonia in Wuhan, dated from February 16 to March 26, 2020. The incidence of occupational exposure was determined by data reported from the hospital, while the prevalence of ORAEs was derived from questionnaire results. The relation coefficients of ORAEs and the variable potential risk factors are analyzed by logistic regression. After the risk factors were identified, targeted organized intervention was implemented and chi-square tests were performed to compare the incidence of occupational exposure and the prevalence of ORAEs in contaminated areas before and after the interventions. RESULTS: Ninety one out of 138 (65.94%) had reported ORAEs with 300 (27.96%) cases of ORAEs being recorded in a total of 1073 entries into contaminated areas. The prevalence of different ORAEs include 205 tenderness (24.73%), 182 headache/dizziness (21.95%), 138 dyspnea (16.65%), 130 blurred vision (15.68%), and 95 nausea/vomiting (11.46%). Personal protective equipment (PPE) is significantly associated with ORAEs in contaminated areas (P < 0.05). Among non-PPE-related factors, insomnia is associated with the majority of ORAEs in contaminated areas. Significant differences were achieved after organized interventions in the incidence of occupational exposure of HCWs (χ2 = 39.07, P < 0.001) and the prevalence of ORAEs in contaminated areas (χ2 = 22.95, P < 0.001). CONCLUSION: During the epidemic period of novel severe respiratory infectious disease, the burden of the ORAEs in contaminated areas and the risk of occupational exposure of HCWs were relatively high. In time, comprehensive and multi-level bundled interventions may help decrease the risk of both ORAEs and occupational exposure.

Immunological and metabolic characteristics of the Omicron variants infection.

The Omicron variants of SARS-CoV-2, primarily authenticated in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wildtype SARS-CoV-2. Omicron could hardly be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescents infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8 + T cell epitopes, compared with Delta. These epitopes could induce robust CD8 + T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8 + T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells. Consistently, a greater fraction of memory CD8 + T cells existed in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.

Unmet health-related needs of community-dwelling older adults during COVID-19 lockdown in a diverse urban cohort.

BACKGROUND: Shelter-in-place orders during the COVID-19 pandemic created unmet health-related and access-related needs among older adults. We sought to understand the prevalence of these needs among community-dwelling older adults. METHODS: We performed a retrospective chart review of pandemic-related outreach calls to older adults between March and July 2020 at four urban, primary care clinics: a home-based practice, a safety net adult medicine clinic, an academic geriatrics practice, and a safety net clinic for adults living with HIV. Participants included those 60 or older at three sites, and those 65 or older with a chronic health condition at the fourth. We describe unmet health-related needs (the need for medication refills, medical supplies, or food) and access-related needs (ability to perform a telehealth visit, need for a call back from the primary care provider). We performed bivariate and multivariate analyses to examine the association between unmet needs and demographics, medical conditions, and healthcare utilization. RESULTS: Sixty-two percent of people had at least one unmet need. Twenty-six percent had at least one unmet health-related need; 14.0% needed medication refills, 12.5% needed medical supplies, and 3.0% had food insecurity. Among access-related needs, 33% were not ready for video visits, and 36.4% asked for a return call from their provider. Prevalence of any unmet health-related need was the highest among Asian versus White (36.4% vs. 19.1%) and in the highest versus lowest poverty zip codes (30.8% vs. 18.2%). Those with diabetes and COPD had higher unmet health-related needs than those without, and there was no change in healthcare utilization. CONCLUSIONS: During COVID, we found that disruptions in access to services created unmet needs among older adults, particularly for those who self-identified as Asian. We must foreground the needs of this older population group in the response to future public health crises.

COVID-19 symptom duration: associations with age, severity and vaccination status in Brunei Darussalam, 2021.

Objective: This retrospective, cross-sectional, observational study assessed the duration of coronavirus disease 2019 (COVID-19) symptoms during the second wave in Brunei Darussalam. Methods: Data from COVID-19 cases admitted to the National Isolation Centre during 7-30 August 2021 were included in the study. Symptom onset and daily symptom assessments were entered into a database during hospitalization and disease was categorized by severity. The time between symptom onset and hospital admission, the duration of symptoms and length of hospitalization were assessed separately by age group, disease severity and vaccination status using one-way analysis of variance with Bonferroni post hoc corrections. Results: Data from 548 cases were included in the study: 55.7% (305) of cases were male, and cases had a mean age of 33.7 years. Overall, 81.3% (446) reported symptoms at admission (mean number of symptoms and standard deviation: 2.8 ± 1.6), with cough (59.1%; 324), fever (38.9%; 213) and sore throat (18.4%; 101) being the most common. Being older, having more severe disease and being unvaccinated were significantly associated with the time between symptom onset and hospital admission, symptom duration and length of hospitalization. Discussion: Knowing which factors predict the duration of COVID-19 symptoms can help in planning management strategies, such as the duration of isolation, predict the length of hospitalization and treatment, and provide more accurate counselling to patients regarding their illness.

Investigation and analysis of the characteristics of a family cluster of coronavirus disease 2019 in Zibo. (Special Issue: Spatio-temporal dynamics analysis, risk assessment and emergency management for COVID-19 epidemic.) [Chinese]

Objective: To investigate a family cluster of coronavirus disease 2019(COVID-19)in Zibo, so as to analyze the characteristics of the epidemic.

Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease.

Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Our investigation on the quantity and distribution patterns of angiotensin-converting enzyme 2 (ACE2) in airway epithelium via immunofluorescence staining revealed that the mean fluorescence intensity of the ACE2-positive epithelial cells was significantly higher in club cells than those in other epithelial cells (including ciliated cells, basal cells, goblet cells, neuroendocrine cells, and alveolar type 2 cells). Compared with nonsmokers, the median percentage of club cells in bronchiolar epithelium and ACE2-positive club cells was significantly higher in COPD patients. In vitro, SARS-CoV-2 infection (at a multiplicity of infection of 1.0) of primary small airway epithelial cells, cultured on air-liquid interface, confirmed a higher percentage of infected ACE2-positive club cells in COPD patients than in nonsmokers. Our findings have indicated the role of club cells in modulating the pathogenesis of SARS-CoV-2-related severe pneumonia and the poor clinical outcomes, which may help physicians to formulate a novel therapeutic strategy for COVID-19 patients with coexisting COPD.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma.

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

The Gut Viral Metagenome Analysis of Domestic Dogs Captures Snapshot of Viral Diversity and Potential Risk of Coronavirus.

The close relations between dogs (Canis lupus familiaris) and humans lay a foundation for cross species transmissions of viruses. The co-existence of multiplex viruses in the host accelerate viral variations. For effective prediction and prevention of potential epidemic or even pandemic, the metagenomics method was used to investigate the gut virome status of 45 domestic healthy dogs which have extensive contact with human beings. A total of 248.6 GB data (505, 203, 006 valid reads, 150 bp in length) were generated and 325, 339 contigs, which were best matched with viral genes, were assembled from 46, 832, 838 reads. In the aggregate, 9,834 contigs (3.02%) were confirmed for viruses. The top 30 contigs with the most reads abundance were mapped to DNA virus families Circoviridae, Parvoviridae and Herpesviridae; and RNA virus families Astroviridae, Coronaviridae and Picornaviridae, respectively. Numerous sequences were assigned to animal virus families of Astroviridae, Coronaviridae, Circoviridae, etc.; and phage families of Microviridae, Siphoviridae, Ackermannviridae, Podoviridae, Myoviridae and the unclassified phages. Further, several sequences were homologous with the insect and plant viruses, which reflects the diet and habitation of dogs. Significantly, canine coronavirus was uniquely identified in all the samples with high abundance, and the phylogenetic analysis therefore showed close relationship with the human coronavirus strain 229E and NL63, indicating the potential risk of canine coronavirus to infect humans by obtaining the ability of cross-species transmission. This study emphasizes the high detection frequency of virus harbored in the enteric tract of healthy contacted animal, and expands the knowledge of the viral diversity and the spectrum for further disease-association studies, which is meaningful for elucidating the epidemiological and biological role of companion animals in public health.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Clinical course and management of 73 hospitalized moderate patients with COVID-19 outside Wuhan.

Moderate cases account for the majority in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and can also progress to severe/critical condition. Here, we investigated the clinical course and management of hospitalized moderate SARS-CoV-2 patients. The medical records and follow-up data were analyzed from the SARS-CoV-2 patients outside Wuhan. A total of 73 moderate patients (38 men, 35 women) were included, with median age of 47.0 (38.5-57.5) years. Among them, only one patient (1.4%) died using active treatment to improve symptoms. The median duration of the four main symptoms cough, fever, chest tightness, and fatigue were 11.0, 8.0, 11.0, and 7.0 days, respectively; the median duration of the positive nucleic acid test (NAT) results for SARS-CoV-2 was 16.5 days; the median hospitalization time was 25.0 days in 72 moderate survivors. The duration of cough and fever was positively correlated with the duration of the positive NAT results. On admission, 50% had lymphopenia; less than 30% had abnormal blood biochemistry findings involving hyperglycemia, liver function and myocardial enzymes. At discharge, the laboratory indexes were substantially improved. Two weeks after discharge, 5.6% survivors experienced a recurrence of the positive NAT results. Moderate SARS-CoV-2 patients have a good prognosis by the active treatment. A small proportion of the recovered moderate patients still may be virus carriers and require an additional round of viral detection.

The precision of epidemiological investigation of COVID-19 transmission in Shanghai, China.

BACKGROUND: Shanghai had a local outbreak of COVID-19 from January 21 to 24. Timely and precise strategies were taken to prevent further spread of the disease. We discussed and shared the experience of COVID-19 containment in Shanghai. PROCESS: The first two patients worked at two hospitals but no staff from the two hospitals were infected. The suspected case and his two close contacts were confirmed to be infected within 12 h. The testing rate of individuals was low. The scope of screening was minimized to two related districts and the close contact tracing was completed within 12 h, which were precise and cost-effective. CONCLUSIONS: Active monitoring, precise epidemiological investigation and timely nucleic acid testing help discover new cases, minimize the scope of screening, and interrupt the transmission.

Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19.

BACKGROUND: The World Health Organization characterizes novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic. Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expression occurring in patients with COVID-19 on admission and after initial treatment. METHODS: Eleven patients diagnosed with COVID-19 with similar initial treatment regimens were enrolled in the hospital. Plasma cytokine, peripheral T cell proportions, and microfluidic quantitative polymerase chain reaction analyses for gene expression were conducted. RESULTS: Five patients with mild and 6 with severe disease were included. Cough and fever were the primary symptoms in the 11 COVID-19 cases. Older age, higher neutrophil count, and higher C-reactive protein levels were found in severe cases. IL-10 level significantly varied with disease progression and treatment. Decreased T-cell proportions were observed in patients with COVID-19, especially in severe cases, and all were returned to normal in patients with mild disease after initial treatment, but only CD4+ T cells returned to normal in severe cases. The number of differentially expressed genes (DEGs) increased with the disease progression, and decreased after initial treatment. All downregulated DEGs in severe cases mainly involved Th17-cell differentiation, cytokine-mediated signaling pathways, and T-cell activation. After initial treatment in severe cases, MAP2K7 and SOS1 were upregulated relative to that on admission. CONCLUSIONS: Our findings show that a decreased T-cell proportion with downregulated gene expression related to T-cell activation and differentiation occurred in patients with severe COVID-19, which may help to provide effective treatment strategies for COVID-19.

Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking.

Chlorogenic acid (CGA) is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. Here, network pharmacology was used to investigate the mechanism by which CGA affected COVID-19. A total of 70 potential targets related to the treatment of COVID-19 were obtained, among which NFE2L2, PPARG, ESR1, ACE, IL6, and HMOX1 might be the main potential targets. Finally, CGA and potential target proteins were scored by molecular docking, and the prediction results of network pharmacology were preliminarily verified. Moreover, CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking. The mechanism of CGA against COVID-19 was initially investigated using network pharmacology, followed by molecular docking.

Analysis of Risk Factors for Thromboembolic Events in 88 Patients with COVID-19 Pneumonia in Wuhan, China: A Retrospective Descriptive Report.

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.

Chronic Respiratory Diseases and the Outcomes of COVID-19: A Nationwide Retrospective Cohort Study of 39,420 Cases.

BACKGROUND: Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19). OBJECTIVES: We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19. METHODS: Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system. CRD was diagnosed based on International Classification of Diseases-10 codes. The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization. The secondary endpoint was death within 30 days after hospitalization. RESULTS: We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020. Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively. Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%). COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%). After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization. Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without. Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without. CONCLUSION: CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19.

Association between use of Qingfei Paidu Tang and mortality in hospitalized patients with COVID-19: A national retrospective registry study.

BACKGROUND: Qingfei Paidu Tang (QPT), a formula of traditional Chinese medicine, which was suggested to be able to ease symptoms in patients with Coronavirus Disease 2019 (COVID-19), has been recommended by clinical guidelines and widely used to treat COVID-19 in China. However, whether it decreases mortality remains unknown. PURPOSE: We aimed to explore the association between QPT use and in-hospital mortality among patients hospitalized for COVID-19. STUDY DESIGN: A retrospective study based on a real-world database was conducted. METHODS: We identified patients consecutively hospitalized with COVID-19 in 15 hospitals from a national retrospective registry in China, from January through May 2020. Data on patients' characteristics, treatments, and outcomes were extracted from the electronic medical records. The association of QPT use with COVID-19 related mortality was evaluated using Cox proportional hazards models based on propensity score analysis. RESULTS: Of the 8939 patients included, 28.7% received QPT. The COVID-19 related mortality was 1.2% (95% confidence interval [CI] 0.8% to 1.7%) among the patients receiving QPT and 4.8% (95% CI 4.3% to 5.3%) among those not receiving QPT. After adjustment for patient characteristics and concomitant treatments, QPT use was associated with a relative reduction of 50% in-hospital COVID-19 related mortality (hazard ratio, 0.50; 95% CI, 0.37 to 0.66 p < 0.001). This association was consistent across subgroups by sex and age. Meanwhile, the incidences of acute liver injury (8.9% [95% CI, 7.8% to 10.1%] vs. 9.9% [95% CI, 9.2% to 10.7%]; odds ratio, 0.96 [95% CI, 0.81% to 1.14%], p = 0.658) and acute kidney injury (1.6% [95% CI, 1.2% to 2.2%] vs. 3.0% [95% CI, 2.6% to 3.5%]; odds ratio, 0.85 [95% CI, 0.62 to 1.17], p = 0.318) were comparable between patients receiving QPT and those not receiving QPT. The major study limitations included that the study was an observational study based on real-world data rather than a randomized control trial, and the quality of data could be affected by the accuracy and completeness of medical records. CONCLUSIONS: QPT was associated with a substantially lower risk of in-hospital mortality, without extra risk of acute liver injury or acute kidney injury among patients hospitalized with COVID-19.

Clinical features of critically ill patients infected with SARS-CoV-2 outside Wuhan with and without diabetes.

Aim: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rapidly develop to critical condition. Here, we investigated the clinical features of critically ill SARS-CoV-2 patients with and without diabetes and identified risk factors for death of these patients. Methods: The medical records including epidemiological, demographic, clinical, and laboratory data from 49 critically ill SARS-CoV-2 patients were collected and analyzed in Huanggang City and Xiaogan City, Hubei Province, outside Wuhan. Results: Sixty-seven percent (33) of patients survived and 33% (16) of patients died in 49 critically ill patients (32 men, 17 women), with a median age of 63 years (IQR 53-73). Univariate analyses indicated that the deceased patients were more often associated with two or more comorbidities, one or more gastrointestinal symptoms, high neutrophil percentage, low lymphocytes and lymphocyte percentage, high C-reactive protein, high procalcitonin, high fasting blood glucose (FBG), and high lactate dehydrogenase (LDH) compared with the survivors; moreover, the patients with T2DM had the higher neutrophil percentage, the lower lymphocyte percentage, and the higher levels of FBG and LDH compared with the patients without T2DM. Multivariable logistic regression analyses indicated that gastrointestinal symptoms (≥ 1 symptoms), decreased lymphocytes (< 1.1 × 109/L), and increased FBG (≥ 7.0 mmol/L) were the independent risk factors for death of critically ill patients. Conclusions: Critically ill COVID patients with T2DM had more severe damages of the lymphocytes, islet cells, and heart function, and gastrointestinal symptoms, lymphopenia, and increased FBG may be early predictors for poor prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13410-020-00888-3.

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.