Biogenesis aberration: One of the mechanisms of thrombocytopenia in COVID-19.

Background: The pathogenesis of COVID-19, including thrombocytopenia, has not been fully clarified. The lungs are a major organ of platelet production and thrombocytopenia induced by severe COVID-19 was proposed. Methods: the change of platelet level was analysed with clinical parameters in 95 hospitalized COVID-19 patients in Wuhan Third Hospital. The production of platelets in the lungs was explored in an ARDS rat model. Results: The level of platelets was negatively correlated with disease severity and was recovered with disease improvement. The non-survivors were accompanied by lower levels of platelet. The odds ratio (OR) of the valley level of the platelet count (PLTlow) was greater than 1, suggesting that PLTlow could be a death exposure factor. The platelet/lymphocyte ratio (PLR) was positively associated with severity of COVID-19, and the platelet/lymphocyte ratio threshold of 248.5 was best correlated with death risk (sensitivity 0.641 and specificity 0.815). To demonstrate the possible biogenesis aberration of platelet in lungs, an LPS-induced ARDS rat model was applied. Lower level of platelet in peripheral and less production of platelet from lungs in ARDS were demonstrated. Though megakaryocyte (MK) number in ARDS lungs is higher than controls, the immature platelet fraction (IPF) in postpulmonary blood is still at the same level as prepulmonary in ARDS rat, indicating that ARDS rats generated fewer platelets in lungs. Conclusion: Our data suggested that COVID-19-induced severe lung inflammation may impair platelet production in the lung. Thrombocytopenia may be mainly caused by platelet consumption for multiorgan thrombosis; however, biogenesis aberration of platelet in the lung induced by diffuse interstitial pulmonary damage cannot be ruled out.

Early Renal-Replacement Therapy May Reduce the All-Cause Mortality of Severe COVID-19: An Observational Cohort Study.

INTRODUCTION: The efficacy of renal-replacement treatment (RRT) remains to be validated in COVID-19. In this retrospective cohort study, we aimed to assess the efficacy of early initiation of RRT in intensive care unit (ICU) adults with severe COVID-19. METHODS: Fifty-eight adult patients in ICU with critically ill or severe COVID-19 with a tendency of critical illness were recruited from February 9, 2020, to March 30, 2020. Early RRT were determined by the ICU medical team based on boom in cytokines levels, increased organs injury/failure, and rapid aggravation of condition. All participants were followed up from the first day of ICU admission to March 30, 2020. The primary outcome was all-cause mortality in ICU. RESULTS: The mean age of the cohort was 68.4 ± 14.6 years, with 81.0% having at least one comorbidity before hospitalization. Twenty patients (34.5%) initiated early RRT after 24.1 ± 10.4 days from the onset and 6.4 ± 3.6 days from ICU admission. Thirty-four of 58 participants (58.6%) died during ICU follow-up. Univariate and multivariate Cox proportional-hazards model showed that early RRT was associated with a lower risk of all-cause mortality in ICU with an adjusted HR of 0.280 (95% CI: 0.106-0.738, p = 0.010). Sudden unexpected death (SUD) was remarkably reduced in the early RRT group, compared with the control group (0.2 vs. 2.9 per 100 person-day, p = 0.02). CONCLUSION: Early RRT can reduce the all-cause in-hospital mortality, especially SUD in patients with severe COVID-19, but not improve multi-organ impairment or increase the risk of AKI. Early initiation of RRT merits an optional strategy in critically ill patients with COVID-19 (ChiCTR2000030773).

Factors Associated With Psychological Outcomes Among Vaccinated and Unvaccinated Health Care Workers Against COVID-19 Infection in Bangladesh.

Background: Vaccination of healthcare workers (HCWs) is recommended during the COVID-19 pandemic to reduce the risk of infection for themselves and their patients, as well as to encourage their patients to get immunized. The present study aimed to investigate the psychological outcomes and associated factors among vaccinated and unvaccinated HCWs against COVID-19 infection in Bangladesh. Methods: From March to August 2021, an online nationwide survey was conducted with a total of 2,038 Bangladeshi HCWs. The frequency of symptoms of general health problems, depression, anxiety, stress, post-traumatic stress disorder, insomnia, and loneliness was assessed using the Bangla versions of the GHQ-12, PHQ-2, GAD-2, PSS-4, PC-PTSD-5, ISI, and UCLA-LS scales, respectively. Results: Compared with unvaccinated HCWs (n = 1,058), vaccinated HCWs (n = 980) had a statistically significant lower prevalence of general health problems (16.7 vs. 59.1%), depression (15.6 vs. 31.9%), post-traumatic stress disorder (22.3 vs. 30.8%), insomnia (23.8 vs. 64.9%), and loneliness symptoms (13.9 vs. 21.8%). Among vaccinated HCWs, females were significantly associated with a higher risk of symptoms of general health problems (AOR, 2.71; 95% CI, 0.97-7.60), anxiety (AOR, 2.17; 95% CI, 1.14-4.13), and loneliness (AOR, 2.52; 95% CI, 1.11-5.73). Except for anxiety and post-traumatic stress disorder symptoms, participants living in urban areas had a significantly lower risk of all psychological outcomes (e.g., depression: AOR, 0.43; 95% CI, 0.27-0.67; stress: AOR, 0.64; 95% CI, 0.47-0.88). Respondents who were married were significantly less likely to experience symptoms of general health problems (AOR, 0.10; 95% CI, 0.02-0.39), depression (AOR, 0.31; 95% CI, 0.22-0.82), insomnia (AOR, 0.46; 95% CI, 0.20-1.03), and loneliness (AOR, 0.31; 95% CI, 0.10-0.92). Participants who worked as doctors were significantly less chance of experiencing symptoms of general health problems (AOR, 0.18; 95% CI, 0.08-0.37), depression (AOR, 0.51; 95% CI, 0.30-0.87), and anxiety (AOR, 0.54; 95% CI, 0.37-0.78). On the other hand, unvaccinated HCWs who were 18-29 years old and had <5 years of work experience were significantly associated with a higher risk of all psychological outcomes except anxiety and insomnia symptoms (e.g., depression among 18-29 years old: AOR, 1.83; 95% CI, 0.27-2.60; stress among those with <5 years of work experience: AOR, 2.37; 95% CI, 0.93-6.07). Participants who worked as nurses were significantly more likely to suffer from depression (AOR, 1.44; 95% CI, 0.84-2.46), anxiety (AOR, 1.42; 95% CI, 0.24-1.73), and stress (AOR, 1.55; 95% CI, 0.31-0.89) symptoms. Except for anxiety and stress symptoms, respondents who worked as frontline workers and provided direct care to infected patients were the significantly higher chance of experiencing all psychological outcomes (e.g., depression among who worked as frontline workers: AOR, 2.41; 95% CI, 0.23-3.73; insomnia among those who provide direct care to infected patients: AOR, 2.60; 95% CI, 0.34-3.06). Participants who were infected with COVID-19 had a significantly less chance of experiencing symptoms of general health problems (AOR, 0.89; 95% CI, 0.65-1.22), depression (AOR, 0.66; 95% CI, 0.48-0.92), and anxiety (AOR, 0.63; 95% CI, 0.46-0.87). Conclusions: To control the infection and improve psychological outcomes, this study suggests emphasizing the vaccinated to unvaccinated HCWs as soon as possible. They also required special attention, health-related education, and psychological support.

Psychological Outcomes and Associated Factors Among the International Students Living in China During the COVID-19 Pandemic.

Background: The emergence of coronavirus disease 2019 (COVID-19) has created a severe mental health problem for international students living in China. Despite the little information on the psychological impact on international students, we aimed to assess the psychological outcomes and associated factors among international students currently living in China during the COVID-19 pandemic. Methods: An online cross-sectional survey was conducted from May 28, 2020 to June 12, 2020 on 402 full-time international students across 26 provinces in China. The frequency of symptoms of depression, anxiety, stress, insomnia, psychological distress, loneliness, and fear was assessed with the English versions of the Depression Anxiety Stress Scale (DASS-21), Insomnia Severity Index (ISI), Kessler Psychological Distress Scale (K6), University of California, Los Angeles, Loneliness Scale (UCLA-LS), and Fear of COVID-19 scale (FCV-19S) scales, respectively. Results: The prevalence of symptoms of depression (73.4%), anxiety (76.6%), stress (58.5%), insomnia (77.6%), psychological distress (71.4%), loneliness (62.4%), and fear (73.1%) among international students during the COVID-19 pandemic was shown. The prevalence of moderate to extremely severe symptoms of all psychological outcomes was significantly associated with 26-30-year-old students, students who lived with roommates, and students who stayed in China shorter than 2 years. Participants in the central region reported significantly moderate to extremely severe symptom levels of all the psychological outcomes except fear symptoms. Univariate analysis indicated that a significant association of all psychological outcomes was found among 26-30-year-old students and students who stayed in China shorter than 2 years. Multivariate analysis showed that Engineering, Business, Social Sciences and Law, and Language students were significantly associated with the symptoms of depression, anxiety, insomnia, and fear. Participants staying in China for shorter than 2 years were associated with a higher risk of all psychological outcomes except psychological distress and loneliness symptoms. Conclusions: We found a higher prevalence of psychological outcomes and risk factors among international students during the COVID-19 pandemic. We immediately appealed to university authorities, mental health professionals, and government officials to provide mental health interventions and strategies for their international students, particularly young, central region students, living with roommates, different study backgrounds, and short time staying during the pandemic.

Correlation between anxiety-depression symptoms and immune characteristics in inpatients with 2019 novel coronavirus in Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is widely acknowledged as a severe traumatic event, and depression, anxiety, and psychological distress are common in diagnosed patients. However, the correlations of biological indicators with emotion are rarely reported. The primary objective of this study was to explore the dysfunction of immune-inflammatory characteristics in patients with depression-anxiety symptoms. METHODS: We investigated the mental status of inpatients with COVID-19 in Wuhan and compared the differences in cytokines and lymphocytes between patients with and without depression-anxiety symptoms at admission. After two weeks of treatment, we evaluated the mental conditions and measured the cytokines and lymphocytes of the patients with depression and anxiety symptoms and explored the changes and their associations. RESULTS: Approximately half of the patients with COVID-19 had depression and anxiety symptoms, and the symptoms were related to the ratio of CD4+/CD8+ and the level of CD4+T lymphocytes. When compared with patients without depression-anxiety symptoms, CD4+T lymphocytes level was significantly higher in COVID-19 patients with depression-anxiety symptoms. CONCLUSION: This study provided novel evidence regarding the association between depression and anxiety symptoms and immune characteristics, especially CD4+T lymphocyte levels, in COVID-19 patients. We emphasized the importance of paying attention to the dynamic immune process of patients diagnosed with COVID-19 with depression/anxiety.

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

Management perspectives from the 2019 Wuhan international workshop on fulminant myocarditis.

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients.

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases.

Coronavirus disease 2019 (COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients (>18 years old) between January 29, 2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups-non-critically ill, critically ill, and death groups-in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol (LDL-C), and high-density lipoproteins cholesterol (HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old (interquartile range (IQR), 52-71). Among the patients enrolled in the study, 2,008 (76.6%) were diagnosed as non-critically ill and 615 (23.4%) were critically ill patients, including 383 (14.6%) critically ill survivors and 232 (8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein (LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time (APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately leads to death for some critically ill patients.

Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19.

In December 2019, an outbreak of novel coronavirus (2019-nCoV) occurred in Wuhan, Hubei Province, China. By February 14, 2020, it has led to 66 492 confirmed patients in China and high mortality up to ~2.96% (1123/37 914) in Wuhan. Here we report the first family case of coronavirus disease 2019 (COVID-19) confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid (SHL). This report describes the identification, diagnosis, clinical course, and management of three cases from a family, suggests the expected therapeutic effects of SHL on COVID-19, and warrants further clinical trials.

Strategies of strengthening the supporting role of science and technology in public health emergency: A case study on the COVID-19 / 中华医学科研管理杂志

Objective@#The research was aimed to discuss the role of science and technology research in the public health emergency response, and to provide theoretical support for building Healthy China, implementing the National Strategy of Innovation-Driven Development.@*Methods@#Take COVID-19 as an example, to sum up the characteristics and the function of science and technology research in the public health emergency prevention and control system.@*Results@#In order to make the scientific and technological research as the supporting system in public health emergency, we need to strengthen the basic research, to improve the research and development for controlling product with the independent intellectual property, to optimize the training system and evaluating system in public health technology, to deepen the international collaboration and to popularize the basic scientific knowledge.@*Conclusions@#Through systematically arrangement for disease controlling and prevention, for the industrial supporting, for the health improvement, for the talent training system and for the cooperation and the communication, we need to fasten the technological innovation for better preparation and responding to public health emergencies.

A familial cluster, including a kidney transplant recipient, of Coronavirus Disease 2019 (COVID-19) in Wuhan, China.

In December 2019, an outbreak of COVID-19 occurred in Wuhan, China, and spread to the whole of China and to multiple countries worldwide. Unlike SARS and MERS, where secondary transmission mostly occurred in hospital settings, COVID-19 transmission occurs in large numbers within families. Herein we report three cases of a familial cluster with one family member being a kidney transplant recipient. The initial clinical symptoms of COVID-19 in these three patients were the same, but their progression was different. Based on the severity of clinical symptoms, chest computer tomography findings and SARS-Cov-2 RNA test results, we admitted the husband to the respiratory intensive care unit (RICU) and used a treatment consisting of immunosuppressant reduction/cessation and low dose methylprednisolone-based therapy, and his wife to the respiratory isolation ward. In contrast, the son received in-home isolation and home-based care. All three family members made a full recovery.