Filopodial Mechanotransduction is regulated by Angiotensin-Converting Enzyme 2 (ACE2) and by SARS-CoV-2 spike protein (preprint)

Filopodia are dynamic, actin-rich cellular protrusions, increasingly linked to cellular mechanotransduction. However, how dynamic filopodia translate external mechanical cues remains poorly understood. Recent studies show that the SARS-CoV-2 spike (S) protein binds the ACE2 receptor on airway multicilia and that cilia are required for viral infection(1) and sufficient to induce filopodial extension and viral binding. To test if spike protein is sufficient to induce filopodial expansion, we employed live-cell single-particle tracking with quantum dots targeting ACE2, to reveal a robust filopodia extension and virus binding mechanism requiring the enzymatic activity of ACE2. Using time-lapse imaging, we reveal that spike protein binding to filopodia is associated with intracellular actin remodeling, alterations in bulk cell stiffness, and an elevation in intracellular calcium levels linked to actin-rearrangement, filopodia initiation, and persistence. We propose the activation of ACE2 creates an active signaling and mechanosensory environment within adherent cells and airway epithelial cells that allows the remodeling of actin in filopodia to trap virus and potentially organize viral exit from cells.

Anxiety, depression and post-traumatic stress disorder and related factors among Chinese population during the COVID-19 pandemic: A cross-sectional study

The sudden outbreak of coronavirus disease 2019 (COVID-19) has deep and wide negative mental impacts on the public, and studies on the impact of COVID-19 on social and mental well-being are necessary. This study aimed to evaluate mental distress, including anxiety, depression, and post-traumatic stress disorder (PTSD), and its related risk factors in Chinese adults in the early stages of the COVID-19 pandemic. This study used a large-scale cross-sectional design. A total of 2067 adult participants completed the online survey via REDcap from 1st to 15th of March 2020 during the COVID-19 outbreak in China. Anxiety, depression, PTSD, and related risk factors, including self-efficacy, coping style, and social support, were measured using valid and reliable instruments. The data were analyzed using multiple linear regression. We found that 201 (9.7%) participants reported moderate-to-severe anxiety, 669 (33.8%) reported depression, and 368 (17.8%) reported symptoms of PTSD. Self-efficacy, coping style, and social support significantly affected anxiety, depression, and PTSD symptoms. Participants' sociodemographic characteristics, COVID-19 pandemic-related factors, low self-efficacy, low social support, and negative coping were predictors of mental distress during the COVID-19 pandemic. Our study will help healthcare professionals carry out early predictions and identification of high-risk groups and provide appropriate interventions to target groups during public health emergencies that plague the world.

Insomnia plays a key role in mental health problems of COVID-19 patients in Square Cabin Hospitals: a network analysis (preprint)

Background: While the emergence of the Coronavirus Disease 2019 (COVID-19) has greatly affected the mental health and wellbeing of people everywhere, the core symptoms of common syndromes of psychological distress remain unclear, especially among COVID-19 patients who have been quarantined in Square Cabin Hospitals. Using the method of network analysis, the current study explored the relations between stress, depression, anxiety and insomnia symptoms among COVID-19 patients in Shanghai Four-Leaf Clover Cabin Hospital. Method: The study used an online survey to gauge the mental health issues of COVID-19 patients at Shanghai Four-Leaf Clover Cabin Hospital from April 18 to May 19, 2022. The Perceived Stress Scale, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Insomnia Severity Index were used to assess perceived stress symptoms, depressive symptoms, anxiety symptoms, and insomnia symptoms, respectively. The central symptoms and bridge symptoms were determined using a regularized partial correlation network. Results: A total of 1014 patients was included in this study. Overall, 61.5%, 49.2% , and 56.1% of all patients reported symptoms of depressive, anxiety, and insomnia, respectively. “Distress caused by the sleep difficulties” had the highest expected influence, followed by “Excessive worry”, “Severity of sleep onset”, “Overburden”, “Uncontrollable worry”, “Trouble relaxing”, “Restlessness”. Seven bridge symptoms were identified: “Sad Mood”, “Severity of sleep onset”, “Sleep”, “Motor”, “Feeling afraid”, “Nervousness”, “Appetite”. In addition, significant differences in network global strength were found between women and men. Conclusions: Psychological distress was prevalent among COVID-19 patients and insomnia symptoms played a key role in the network of psychological distress symptoms. As a result, specific insomnia symptoms should be closely monitored as potential intervention targets in alleviating or preventing common, frequently co-occurring psychiatric syndromes.

The value of ROX index in evaluating the efficacy of high-flow nasal cannula oxygen therapy in patients with COVID-19

Objective: To assess the value of the ROX index in evaluating the efficacy of highflow nasal cannula oxygen therapy (HFNC) in patients with coronavirus infected disease (COVID-19).

Circulating Mid-regional Proadrenomedullin is a predictor of mortality in patients with COVID-19: a systematic review and meta-analysis (preprint)

Background Although there is increasing understanding of the changes in the laboratory parameters of coronavirus disease 2019 (COVID-19), the correlation between circulating Mid-regional Proadrenomedullin (MR-proADM) and clinical outcomes of patients with COVID-19 is not fully understood. In this study, we aimed to evaluate the prognostic value of MR-proADM in patients with COVID-19.Methods The PubMed, Embase, Web of Science, Cochrane Library, Wanfang, SinoMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched from 1 January 2020 to 20 March 2022 for relevant literature. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess quality bias, STATA was employed to pool the effect size by a random effects model, and potential publication bias and sensitivity analyses were performed.Results 14 studies comprising 1822 patients with COVID-19 met the inclusion criteria, there were 1145 males and 677 females, and the mean age was 64.8 years. The concentration of MR- proADM was compared between the survivors and nonsurvivors in 9 studies and the difference was significant (P < 0.01), I2 = 46%. The combined sensitivity was 0.88 [0.81–0.93], and the combined specificity was 0.77 [0.65–0.86]. We drew the SROC curve and calculated the AUC = 0.90 [0.87–0.93]. An increase of 1 nmol/L of MR-proADM was independently associated with a more than threefold increase in mortality (odds ratio 3.03, 95% confidence interval 2.26–4.06, I2 = 0.0%, P = 0.633). The predictive value of MR-proADM for death was better than many other biomarkers.Conclusion MR- proADM had a very good predictive value for the poor prognosis of COVID-19 patients. Increased levels of MR-proADM were independently associated with mortality in COVID-19 patients and may allow a better risk stratification.

Epidemiological and virological surveillance of influenza viruses in China during 2020-2021.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza activity declined globally and remained below previous seasonal levels, but intensified in China since 2021. Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world. To better respond to influenza outbreaks under the COVID-19 pandemic, we analyzed the epidemiology, antigenic and genetic characteristics, and antiviral susceptibility of influenza viruses in the mainland of China during 2020-2021. METHODS: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network. Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses. Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods. RESULTS: In the mainland of China, influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season, but it did not exceed the peak in previous years. Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity, with the subgroup 1A.3a.2 viruses currently predominated. 37.8% viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020-2021 and 2021-2022 Northern Hemisphere influenza seasons. In addition, China has a unique subgroup of 1A.3a.1 viruses. All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors, except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors. CONCLUSIONS: Influenza activity increased in the mainland of China in 2021, and caused flu season in the winter of 2021-2022. Although the diversity of influenza (sub)type decreases, B/Victoria lineage viruses show increased genetic and antigenic diversity. The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus globally.

Changes in lifestyles and depressive symptom among patients with chronic diseases during COVID-19 lockdown (preprint)

This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs.We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8–16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown.A total of 3,327 participants were included in the COVID-19 survey, including 2,098 (63.1%) reported having NCDs at baseline and 1,457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9–13.5%, and poor sleepers from 23.9–15.3%, while low physical activity increased from 13.4–25.2%, among participants with NCDs. Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI, 1.05–1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI, 1.15–2.02).Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown, which is highly likely to happen in the near future.

A New COVID-19 Quarantine Directive: QDex Evaluated Dynamic Geofencing

COVID-19 is a highly contagious coronavirus that has caused traumatic global havoc. By September 14, 2021, there were 224+ million confirmed cases and 4.6+ million fatalities world-wide [1]. Internet of Things (IoT)-based quarantine strategies effectively slow down and prevent COVID-19 transmission [2]. However, the unstan-dardized quarantine strategy may cause negative consequences. Typically, quarantine deactivates normal economic interactions, thus causing huge economic loss [3]. Moreover, the lack of versatility and resiliency also brings safety challenges on some occasions. In this investigation, a performance scoring quarantine index, referred to as QDex, is developed to provide guidance for a new concept of dynamic geofencing quarantine directive. QDex evaluation features adaptive dynamic geofencing (QEDG) for quarantine. In QEDG, QDex is newly defined to evaluate the dynamic geofencing in relation to epidemic control and economic loss. They are represented by two formulated indicators, namely the transmission risk (TR) and the active profit (AP), which are related to the isolator bio status (e.g., body temperature). Based on the evaluation results of TR and AP, QEDG provides a proper geofencing indication for quarantine, which decreases epidemic transmission and restores economic recovery. The requirement-based applicable communication technologies for QEDG are discussed and analyzed, and two typical use cases are included. Finally, the limitations and challenges of QEDG are discussed.

Usage of Compromised Lung Volume in Monitoring Steroid Therapy on Severe COVID-19 (preprint)

Background: Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19)and for monitoringits progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. Methods: Between February 7 and February 17, 2020, 300 chest CT scans from 72 patients with severe COVID-19 were retrospectively collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3–7 days); Stage 3 (8–14 days); Stage 4 (15–21 days); and Stage 5 (22–31 days). QCT was performed using a threshold-based quantitative analysis to segment the lungaccording to different Hounsfield unit (HU) intervals. The primary outcomeswerechanges in percentage of compromised lung volume (%CL, –500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. Results: Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (-3.27% [95%CI, -5.86 to -0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P <0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P <0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group ( P <0.05), but not inthe low CL group. Conclusions: Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247

Changes in Lifestyles and Depressive Symptom Among Patients with Chronic Diseases During COVID-19 Lockdown (preprint)

Background: During the COVID-19 pandemic, patients with non-communicable diseases (NCDs), even without symptoms or a diagnosis of COVID-19, may be affected more than the general population due to the lockdown and healthcare service redistribution. This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs.Methods: We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8-16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown.Findings: A total of 3,327 participants were included in the COVID-19 survey, including 2,098 (63.1%) reported having NCDs at baseline and 1,457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9% to 13.5%, and poor sleepers from 23.9% to 15.3%, while low physical activity increased from 13.4% to 25.2%, among participants with NCDs. Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI, 1.05-1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI, 1.15-2.02).Interpretation: Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown, which is highly likely to happen in the near future.Funding: Initial foundational funding for the Stanford Wellness Living laboratory (WELL) was provided by Amway via an unrestricted gift through the Nutrilite Health Institute Wellness Fund to Stanford University. Through Zhejiang University, the Cyrus Tang Foundation and Zhejiang University Education Foundation also provided important financial support for the study. The follow-up survey was supported by Hsun K. Chou Fund of Zhejiang University Education Foundation.Declaration of Interest: The authors declare no conflict of interest.Ethical Approval: The WELL-China project was approved by the ethics review board at both Zhejiang University (No. ZGL201507-3) in China and Stanford University (IRB- 35020) in USA. All participants provided written informed consent. The follow-up telephone interview was further approved by the ethics review board at Zhejiang University (No. ZGL202004-01).

The Severity of COVID-19 and Its Determinants: A Systematic Review and Meta-Analysis in China

To analyse the prevalence of severe and critical COVID-19 cases and its determinants, a systematic review and meta-analysis were conducted using Review Manager. Four English and two Chinese databases were used to identify and explore the relationships between the severity of COVID-19 and its determinants, with no restrictions on publication date. The odds ratio and 95% CI were combined to assess the influencing level of all factors. Twenty-three articles containing a total of 15,828 cases of COVID-19 were included in this systematic review. The prevalence of severe and critical COVID-19 cases was 17.84% and 4.9%, respectively. A total of 148 factors were identified, which included behavioural, symptom, comorbidity, laboratory, radiographic, exposure, and other factors. Among them, 35 factors could be included in the meta-analysis. Specifically, for example, the male (OR 1.55, 95% CI 1.42–1.69) and elderly (OR 1.06, 95% CI 1.03–1.10) populations tended to experience severe and critical illness. Patients with cough, dyspnea, fatigue, fever, and gastrointestinal symptoms could have severe and critical diseases. Regarding laboratory results, albumin, aspartate aminotransferase, creatinine, D-dimer, fibrinogen, neutrophils, procalcitonin, platelets, and respiratory rate were potential factors that could be used to predict the severity of COVID.

Comparative Efficacy and Safety of Current Drugs against COVID-19: a Systematic Review and Net-work Meta Analysis (preprint)

The rapid spread of coronavirus disease (COVID-19) has greatly disrupted the livelihood of many people around the world. To date, more than 35.16 million COVID-19 cases with 1.037million total deaths have been reported worldwide. Compared with China, where the disease was first reported, cases of COVID-19, the number of confirmed cases for the disease in the rest of the world have been incredibly high. Even though several dugs have been suggested to be used against the disease, the said interventions should be backed by empirical clinical evidence. Therefore, this paper provides a systematic review and a meta-analysis of efficacy and safety of different COVID-19 drugs. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCurrently, Covid-19 is one of the most urgent and significant health challenge, globally. However, so far there is no specific and effective treatment strategy against the disease. Nonetheless, there are numerous debates over the effectiveness and potential adverse effects of different COVID-19 antivirals. In general, there is invaluable need to continually report on new advances and successes against COVID-19, apparently to aid in managing the pandemic. Added value of this studyThis study provides a comprehensive, evidence-based guide on the management of multiple COVID-19 symptoms. In particular, we provide a review of 14 drugs, placebos and standard treatments against COVID 19. Meanwhile, we also performed a meta-analysis based on four clinical outcome indicators, to measure and compare the efficacy and safety of current interventions. Implications of all the available evidenceFindings of this research will guide clinical decision in COVID-19 patients. It will also provide a basis for predicting clinical outcomes such as efficacy, mortality and safety of interventions against the disease.

Massachusetts General Hospital Covid-19 Registry reveals two distinct populations of hospitalized patients by race and ethnicity (preprint)

ObjectiveTo evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH). MethodsThe MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N=866 patients hospitalized with Covid-19 from March 11, 2020 - May 4, 2020. ResultsOverall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR=(48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR=(40.6, 61.6) versus 72y; (58.0, 81.7) (p< 0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p=0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p< 0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p< 0.001; OR=1.99, p=0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p< 0.001). ConclusionsHospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.

Nomogram for Prediction of fatal outcome in Patients with Severe COVID-19: A Multicenter Study (preprint)

Background & Aims: To develop an effective model of predicting fatalOutcome in the severe coronavirus disease 2019 (COVID-19) patients.Methods: Between February 20, 2020 and April 4, 2020, consecutive COVID-19 patients from three designated hospitals were enrolled in this study. Independent high- risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients.Results: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR 1.184, 95% CI 1.061-1.321), Panting(breathing rate ≥ 30/min) (HR 3.300, 95% CI 2.509-6.286), lymphocyte count < 1.0 × 109/L (HR 2.283, 95% CI 1.779-3.267), and IL-6 >10pg/mL (HR 3.029, 95% CI 1.567-7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC 0.900, [95% CI 0.841-0.960], sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC 0.811, [95% CI 0.763-0.961], sensitivity 77.3%, specificity 73.5); in validation cohort 2 (AUC 0.862, [95% CI 0.698-0.924], sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of interleukin-6 (IL-6) receiving tocilizumab was better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference (p = 0.105 for training cohort, p = 0.133 for validation cohort 1, and p = 0.210 for validation cohort 2).Conclusions: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.

Nomogram for Prediction of fatal outcome in Patients with Severe COVID-19 Pneumonia: A Multicenter Study (preprint)

Background & Aims: To develop an effective model of predicting fatal Outcome in the severe coronavirus disease 2019 (COVID-19) patients.Methods: Between February 20, 2020 and April 4, 2020, consecutive COVID-19 patients from three designated hospitals were enrolled in this study. Independent high- risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients.Results: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR 1.184, 95% CI 1.061-1.321), Panting(breathing rate ≥ 30/min) (HR 3.300, 95% CI 2.509-6.286), lymphocyte count < 1.0 × 109/L (HR 2.283, 95% CI 1.779-3.267), and IL-6 >10pg/mL (HR 3.029, 95% CI 1.567-7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC 0.900, [95% CI 0.841-0.960], sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC 0.862, [95% CI 0.763-0.961], sensitivity 92.9%, specificity 64.5%); in validation cohort 2 (AUC 0.811, [95% CI 0.698-0.924], sensitivity 77.3%, specificity 73.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. Conclusions: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients.

Structure of SARS-CoV-2 main protease in the apo state reveals the inactive conformation (preprint)

Mpro is of considerable interest as a drug target in the treatment of COVID-19 since the proteolytic activity of this viral protease is essential for viral replication. Here we report the first insight of the structure Mpro for SARS-CoV-2 in the inactive conformation under conditions close to the physiological state (pH 7.5) to an overall resolution of 1.9 [A]. The comparisons of Mpro in different states reveal that substrate binding site and the active site are more flexible in the inactive conformation than that in the active conformations. Notably, compared with the active conformation of the apo state structure in pH7.6 of SARS, the SARS-CoV-2 apo state is in the inactive conformation under condition close to physiological state (pH7.5). Two water molecules are present in the oxyanion hole in our apo state structure, whereas in the ligand-bound structure, water molecular is absence in the same region. This structure provides novel and important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational, structure-based, approaches for the design of specific SARS-CoV-2 ligands as new therapeutic agents.

Blood glucose is a representative of the clustered indicators of multi-organ injury for predicting mortality of COVID-19 in Wuhan, China (preprint)

Background Concomitance with diabetes is associated with high mortality in critical conditions. Patients with previous diabetes are more vulnerable to COVID-19. However, new-onset COVID-19-related diabetes (CRD) and its relevance have scarcely been reported. This study investigates new-onset CRD and its correlation with poor outcomes or death in patients with COVID-19. Methods We performed a single center, retrospective case series study in 120 patients with laboratory confirmed COVID-19 at a university hospital. Fasting blood glucose (FBG) [≥]7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as CRD. The Critical status was defined as admitted to intensive care unit (ICU) or death. Results After excluding patients with a history of diabetes, chronic heart, kidney, and liver disease, 69 patients with COVID-19 were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). The prevalence of CRD in Critical and Moderate+Severe patients was 53.85% and 13.95%, respectively. Kaplan-Meier survival analysis revealed a significantly higher mortality rate in patients with CRD (P=0.0019). Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Cluster analysis suggested that indicators for multi-organ injury were interdependent, and more proximities of FBG with indicators for multi-organ injury was present. Conclusion Our results suggest that new onset COVID-19-related diabetes is an indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and even self-monitoring, glucose testing will be much helpful for predicting poor outcomes to facilitate appropriate intensive care in patients with COVID-19.

Clinical characteristics of 28 patients with novel coronavirus pneumonia / 中华传染病杂志

Objective@#To analysis the clinical characteristics and experiences in diagnosis and treatment of the patients with novel coronavirus pneumonia (NCP).@*Methods@#Clinical data of 28 patients with NCP in Nanning Fourth People's Hospital from January 22 to February 5 in 2020 were collected. The clinical manifestations, epidemiological history, laboratory tests, imaging examinations and treatments of patients were analyzed retrospectively.@*Results@#The 28 patients with confirmed viral pneumonia included 11 males and 17 females, ranging from 11 to 68 years. They all had history of epidemiological exposure and were all positive for 2019-nCoV nucleic acid in throat swabs. There were one mild case, 25 ordinary cases and two severe cases. There were four groups of family clusters. The illness onset ranged from 1 to 12 days after exposure, and the time from the symptom onset to the positive result of the nucleic acid test was 0 to 13 days. The clinical symptoms were mainly fever and cough, which progressed rapidly in a short period of time. Since the onset of illness, the peak values of axillary temperature of the 28 patients were 36.6~39.5 ℃, while five patients had no fever throughout the course of the disease with the peak temperature of ≤37 ℃. There were two patients presented with decreased white blood cell counts, five patients with elevated C reactive protein, six patients with abnormal alanine aminotransferase, three patients with abnormal aspartate aminotransferase,10 patients with elevated creatine kinase, three patients with elevated creatine kinase isoenzyme, four patients with elevated lactate dehydrogenase, and all with normal procalcitonin levels. The chest computed tomography examinations showed that the common features were ground glass shadows (21 cases), blurred edges (18 cases), speckles and patchy shadows (17 cases), thickening and disorder of some lung textures (7 cases), and visible band shadows (7 cases). Pulmonary lesions often progressed rapidly. One 11-year-old child was treated with alpha-interferon alone, and 27 patients were treated with alpha-interferon inhalation plus lopinavir/ritonavir with 4 withdrawal due to adverse reactions. Up to February 12, nine patients had been discharged from the hospital, who were ordinary cases, without death cases.@*Conclusions@#The NCP patients mostly present with fever and cough. Pulmonary lesions often progress rapidly. Respiratory pathogen testing should be conducted as early as possible and repeatedly. Disisolation should be cautious for suspected people who are negative for 2019-nCoV nucleic acid in pharynx swabs.