Inactivated Vaccine Dosage and Serum IgG Levels Correlate with Persistent COVID-19 Infection in Hematologic Malignancy Patients During the Omicron Surge in China (preprint)

In hematologic malignancies (HM) patients, COVID-19 infections carry a significant risk of mortality due to disease status, treatment, and other factors.The risk factors of the severity and persistence of COVID-19 infections remains unclear. A study observed adults with HM diagnosed with COVID-19 from November 2022 to February 2023. Patient blood samples yielded biochemical data, with COVID-19 confirmed via RNA or antigen testing. In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Using advanced multivariate logistic regression, high C-reactive protein levels (≥100mg/L) significantly increased the risk of severe/critical conditions in HM patients with COVID-19 (OR: 3.415, 95% CI: 1.294-9.012; p=0.013). Patients enduring Omicron infection beyond 30 days were deemed persistent, in contrast to those achieving infection control within this duration. The research indicated that taking ＜2 vaccine doses (OR: 0.202, 95% CI: 0.048-0.857; p=0.030), having low IgG levels (＜1000 mg/dl) (OR: 0.129, 95% CI: 0.027-0.607; p=0.010), and increased interleukin-6 levels (≥12pg/ml) (OR: 5.098, 95% CI: 1.118-23.243; p=0.035) were key indicators of ongoing infection. A significant difference in survival rates was observed between patients with persistent and non-persistent infections, with the latter showing better survival outcomes (P<0.001). In conclusion, increased C-reactive protein levels had a higher likelihood of severe health outcomes for HM patients with COVID-19 infection. Persistent infections tended to be more prevalent in those with lower vaccine dosages, diminished IgG levels, and escalated interleukin-6 levels.

The prevalence and influencing factors of COVID-19 in pregnant women in Hunan Province, China, immediately following the relaxation of epidemic control measures (preprint)

Objective: To investigate the prevalence and influencing factors of COVID-19 in pregnant women in Hunan Province immediately following the relaxation of epidemic control measures. Methods: This was a cross-sectional study with a multistage stratified sampling method. The questionnaire collected basic maternal information, data on COVID-19 infection status, and pregnancy-related information. The survey was conducted by trained investigators, and data quality checks were carried out twice per week. Results: Among the 7761 included pregnant women, 5191 (66.9%) had a positive SARS-CoV-2 test result or related symptoms. The majority of maternal infections were mild (90.0%), and very few were severe and critical (0.4% and 0.1%), and headache and body aches (65.3%) were the most common symptoms. A total of 2711 (52.2%) women gave birth, and 449 (16.6%) newborns had infections. Logistic multivariable regression analysis showedthatpregnant women with an education level of junior college and above (OR=1.392, 95% CI: 1.182, 1.639), those with a monthly household income ≥3000 yuan and above (OR=1.175, 95% CI: 1.027, 1.344), those who lived with their family during family member infection (OR=1.476, 95% CI: 1.316, 1.655), and those with pulmonary (OR=1.408, 95% CI: 1.070, 1.854) or other (OR=1.398, 95% CI: 1.188, 1.645) underlying diseases were more likely to have COVID-19. A farmer/worker occupation type (OR=0.617, 95% CI: 0.484, 0.786) was a protective factor. Conclusions: Many pregnantwomen had COVID-19 immediately following the relaxation of epidemic control measures, but most had mild cases, and few effects on newborns were observed. Mobility is the most critical factor influencing infection. The continued utilization of masks and adherence to social distancing measures remain crucial in mitigating COVID-19 transmission.

Deep Learning for Predicting Winter Temperature in North China

It is difficult to improve the seasonal prediction skill of winter temperature over North China, owing to the complex dynamics of East Asian winter and the relatively low prediction skill level of current climate models. Deep learning (DL) may be an informative and promising tool to enhance seasonal prediction, particularly in regions where the underlying mechanisms are not clear. Here, using a DL model based on the Convolutional Neural Network (CNN), we have found that the prediction skill for North China winter temperature (NCWT) can be extended up to five months by considering the remote impact of the Northeast Pacific sea-surface temperature (SST) on North China. Based on historical simulations of winter temperatures in North China, we selected six CMIP5 models with relatively small deviations for training the CNN, and the period chosen for training was 1852–1991. The N1 -https://media.proquest.com/media/hms/PFT/1/Ruo5N?_a=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%3D%3D&_s=2fC0CTd0WocPaF%2FXuQegxUXRgWY%3D ERA5 data during 1995–2017 were utilized to evaluate the performance of the CNN. Our CNN shows the best performance in a recent 10-year period (2008–2017), showing a significantly improved level of NCWT prediction skill with a correlation skill of 0.65 at a 5-month lead time, which is much better than the forecast skill of the state-of-the-art dynamic seasonal prediction system. Heat map analysis was used to explore the possible physical mechanisms associated with the NCWT anomaly from the perspective of the CNN;the results showed that the SST over the Northeast Pacific is highly relevant to NCWT prediction. The Northeast Pacific warming in the boreal summer is related to the development of the El Niño event in the coming winter, which may induce NCWT anomalies by atmospheric teleconnection. Climate model experiments support the role of Northeast Pacific warming in the boreal summer on NCWT. The improved capability for prediction from using the CNN may help to establish the energy policy for the coming winter and reduce the economic losses from extremely cold in North China.

In the Seeking of Association between Air Pollutant and COVID-19 Confirmed Cases Using Deep Learning

The COVID-19 pandemic raises awareness of how the fatal spreading of infectious disease impacts economic, political, and cultural sectors, which causes social implications. Across the world, strategies aimed at quickly recognizing risk factors have also helped shape public health guidelines and direct resources;however, they are challenging to analyze and predict since those events still happen. This paper intends to invesitgate the association between air pollutants and COVID-19 confirmed cases using Deep Learning. We used Delhi, India, for daily confirmed cases and air pollutant data for the dataset. We used LSTM deep learning for training the combination of COVID-19 Confirmed Case and AQI parameters over the four different lag times of 1, 3, 7, and 14 days. The finding indicates that CO is the most excellent model compared with the others, having on average, 13 RMSE values. This was followed by pressure at 15, PM2.5 at 20, NO2 at 20, and O3 at 22 error rates.

The TCM Preparation Feilike Mixture for the Treatment of Pneumonia: Network Analysis, Pharmacological Assessment and Silico Simulation

The Feilike mixture (FLKM) is a valid prescription that is frequently used to assist in the clinical treatment of pneumonia. However, the mechanisms of its effects remain unclear. First, through literature evaluation, it was preliminarily determined that FLKM improved clinical symptoms, regulated immune inflammation response and ameliorated pulmonary function. Then, via database search and literature mining, 759 targets of the 104 active compounds of FLKM were identified. The component-target (CT) network showed that the key active compositions were resveratrol, stigmasterol, beta-sitosterol, sesamin, and quercetin. 115 targets overlapped with pneumonia-related targets. The protein-protein interaction (PPI) network identified TNF, AKT1, IL6, JUN, VEGFA and MAPK3 as hub targets. KEGG analyses found that they were mainly enriched in immune related pathway. Next, in vivo experiment, we observed that FLKM ameliorated pathological injury of lung tissue and reduced neutrophil infiltration in rats with LPS-induced pneumonia. And FLKM decreased the concentration of TNF-α and IL-6 in BALF and downregulated the expression of p38MAPK, AKT and VEGFA in lung tissue. Finally, Molecular docking tests showed tight docking of these predicted targeted proteins with key active compounds. Molecular dynamics simulation was employed to assess stability and flexibility of receptor-ligand. Among them, AKT1- stigmasterol bound more stably, and their binding free energies were −47.91 ± 1.62 kcal/mol. This study revealed core compositions and targets for FLKM treating pneumonia and provided integrated pharmacological evidence to support its clinical efficacy.

Nursing Management of Adult Ostomy Patients During the COVID-19 Pandemic.

The continuation of the COVID-19 epidemic poses novel challenges for adult ostomy patients care. It is essential to explore nursing management for ostomy patients to ensure patients receive standardized care while minimizing exposure to COVID-19. This article reviews the perioperative nursing of Chinese adult ostomy patients in the post-epidemic era, as well as outpatient review after discharge and home care, to provide reference and basis for medical staff and patients in the post-pandemic era.

Analysis on utilization of anti-new Coronavirus disease 2019 (COVID-19) drugs of inpatients in the third people's hospital of Hubei province

Objective: To analyze the utilization of anti-new coronavirus disease 2019 (COVID-19) drugs of inpatients in Hubei N0.3 People's Hospital.

An overview of COVID-19

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China in December 2019. By Feb. 11, 2020, the World Health Organization (WHO) officially named the disease resulting from infection with SARS-CoV-2 as coronavirus disease 2019 (COVID-19). COVID-19 represents a spectrum of clinical manifestations that typically include fever, dry cough, and fatigue, often with pulmonary involvement. SARS-CoV-2 is highly contagious and most individuals within the population at large are susceptible to infection. Wild animal hosts and infected patients are currently the main sources of disease which is transmitted via respiratory droplets and direct contact. Since the outbreak, the Chinese government and scientific community have acted rapidly to identify the causative agent and promptly shared the viral gene sequence, and have carried out measures to contain the epidemic. Meanwhile, recent research has revealed critical aspects of SARS-CoV-2 biology and disease pathogenesis;other studies have focused on epidemiology, clinical features, diagnosis, management, as well as drug and vaccine development. This review aims to summarize the latest research findings and to provide expert consensus. We will also share ongoing efforts and experience in China, which may provide insight on how to contain the epidemic and improve our understanding of this emerging infectious disease, together with updated guidance for prevention, control, and critical management of this pandemic.

Lifestyle Behaviors and Quality of Life among Older Adults after the First Wave of the COVID-19 Pandemic in Hubei China (preprint)

BackgroundOlder adults’ quality of life (QoL) is facing huge challenges during the COVID-19 pandemic. New normal lifestyle behaviors, including getting adequate physical activity (PA), consuming sufficient fruits and vegetables (FV) and enacting individual preventive behaviors (frequent hand washing, facemask wearing, and social distancing), as a significant determinant for QoL, have not been adequately addressed in older adults during the pandemic. This study aimed to investigate the characteristics of QoL in Chinese older adults after the first wave of the COVID-19 pandemic in Hubei China, to examine the associations of lifestyle behaviors with QoL, and to identify the moderating role of socioeconomic indicators in the associations. MethodsA cross-sectional study was conducted in Hubei, China, from June 15, 2020, to July 10, 2020. 516 older adults completed an online survey (mean age = 67.6 ± 6.6; 57.9% women). The questionnaire consisted of demographic information, covariates (chronic diseases and infected cases of acquaintances), lifestyle behaviors (PA stage, FV intake (FVI) stage and three preventive behaviors) and QoL. T-tests, ANOVA tests, hierarchical multiple linear regression models with simple slope analyses were used to test the hypotheses. ResultsQoL significantly differed in relation to economic situation, chronic diseases, marital status, education, living situation, age group and professional status. Participants’ economic situation (β average vs. below average = 0.17, p < 0.01; β above average vs. below average = 0.15, p < 0.01), chronic diseases (β yes vs. no = 0.19, p < 0.001), FVI stage (β = 0.21, p < 0.001) and preventive behaviors (β = 0.10, p < 0.05) indicated a significant association with QoL. Education level and economic situation significantly interacted with preventive behaviors on QoL respectively (β preventive behaviors x educational level = -1.3, p < 0.01; β preventive behaviors x economic situation = -0.97, p < 0.05). ConclusionsFindings emphasize the importance of enhancing FVI and preventive behaviors on QoL improvement in older adults during the COVID-19 pandemic. Older adults who are in a lower economic situation with lower education levels should be given priority when implementing interventions to improve preventive behaviors and QoL in older adults.

Mental Health of School Aged Children Before and During the COVID-19 Pandemic: A Longitudinal Study (preprint)

Background: Mental health of children has been a major concern during the COVID-19 pandemic. This study aimed to investigate suicide, self-harm and general mental health of children before and during the COVID-19 pandemic. Methods: In this longitudinal study, we used data from the Sichuan Positive Youth Development Cohort (SPYD) in Chengdu China. Children aged 6-15 years from 5 schools in urban and suburb Chengdu completed questionnaires at January 2019 before the COVID-19 outbreak, and were followed at June 2020 when schools’ resumption, after months of school closure and social distancing measures during the COVID-19 pandemic. Questionnaires were used to collect data on suicide, self-harm, anxiety, depression, internet addiction and family function from children and demographics, socio-economic status and mental health status from parents. Mental health outcomes of children were compared before and after the pandemic. Stratified analyses were conducted by demographics and socio-family contextual factors including children’s grade, parent’s mental health and family function status. Findings: Overall 8,124 children (mean age 11·0±2·2, female 48·3%) completed questionnaires both at the wave 1 and wave 2 survey were included in this study. Suicidal thoughts, plans and attempts (Odds ratio 1·65, 95%CI1·38-1·98) and internet addiction (1·13, 1·01-1·26) of children increased significantly during the pandemic period, while self-harm (0·90, 0·83-0·99) and anxiety (0·69, 0·63-0·76) decreased, with no significant change of depression (0·98, 0·89-1·07). However, children of higher grades, with parents of worsened depression or anxiety symptoms were more likely to have worse mental health outcomes mentioned above (p<0·05), while children with improved family function were all better off (p=0·000). Interpretation: There are notable impacts of the COVID-19 pandemic on children’s mental health, and children beyond 9 years old with parents of mental health problems are especially vulnerable. Measures to screen and identify these children, support their parents and improve family function are important to protect children’s mental health during the pandemic. Further investigations on risk and protective factors, mediators of mental health of children during the pandemic are warranted to identify vulnerable individuals and inform targeted interventions.Funding Statement: This study was supported by the Hong Kong Polytechnic University (Longitudinal study of positive youth development 19H0642), the Sichuan University (Research on supportive strategies to promote positive development of primary school students in the anti-epidemic period,YQZX903). And KZ was supported by the China Medical Board Fund (CMB 16-252)Declaration of Interests: Authors declared no conflicts of interest.Ethics Approval Statement: The study protocol was approved by the Ethics Committee of Sichuan University (K2020025).

Discovery of rhodomyrtone as a broad-spectrum antiviral inhibitor with anti-SARS-CoV-2 activity (preprint)

The outbreak of new viruses, such as serve acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the emerging of drug-resistance viruses highlight the urgent need for the development of broad-spectrum antiviral drugs. Herein, we report the discovery of a plant-derived small molecule, 6,8-dihydroxy-9-isobutyl-2,2,4,4-tetramethyl-7-(3-methylbutanoyl)-4,9-dihydro-1H- xanthene-1,3(2H)-dione (rhodomyrtone, RDT), which exhibited potent broad-spectrum antiviral activities against several RNA and DNA viruses, including SARS-CoV-2, respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and Kaposi's sarcoma-associated herpesvirus (KSHV). RDT can significantly suppress viral gene expression and show the low possibility to elicit drug-resistant variants. Mechanistic study implied that RDT inhibited viral infection by disturbing the cellular factors that essential for viral gene expression. Our results suggested that RDT might be a promising lead compound for the development of broad-spectrum antiviral drugs.

Overall Reduced Baseline Lymphocyte Subsets Closely Related to the Poor Prognosis and the Disease Severity in Patients With COVID-19 and Diabetes Mellitus (preprint)

Introduction: Dysregulated host immune response was common in COVID-19. In this study we aimed at the characteristics of lymphocyte subsets and its relationship with the disease progression in COVID-19 patients with or without DM.MethodsThe baseline peripheral lymphocyte and subsets were compared between 55 healthy cases (control group) and 95 confirmed cases with COVID-19 (COVID-19 group), and between COVID-19 patients with and without DM.ResultsThe prevalence of DM in COVID-19 group was 20%, and severe cases had higher the prevalence of DM than non-severe cases (P=0.006), moreover significantly poor prognosis and higher severe rate were found in those with DM relative to those without DM (P=0.001,0.003, respectively). In COVID-19 group overall and significant reduced lymphocyte and subsets, especially B and T lymphocytes were found, especially in those with DM. Partial decreased lymphocyte subsets, age and DM closely related with the disease progression and the prognosis.ConclusionsThese findings provide a reference for clinicians that immunomodulatory treatment maybe improve disease progression and prognosis of COVID-19 patients, especially those with DM.

Epidemiological Characteristics of COVID-19 under Government-mandated Control Measures in Inner Mongolia, China (preprint)

BackgroundThere were 75 local confirmed cases during the COVID-19 epidemic followed by an outbreak of Wuhan in Inner Mongolia. The aims of our study were to provide reference to control measures of COVID-19 and scientific information for supporting government decision-making for serious infectious disease, in remote regions with relatively insufficient medical resources like Inner Mongolia.MethodsThe data published by Internet were summarized in order to describe the epidemiological and clinical characteristics of patients with COVID-19. The basic reproductive number (R 0 ), incubation period, time from illness onset to confirmed and the duration of hospitalization were analyzed. The composition of imported and local secondary cases and the mild/common and severe/critical cases among different ages, genders and major clinical symptoms were compared.ResultsIn 2020, from January 23 to February 19 (less than 1 month), 75 local cases of COVID-19 were confirmed in Inner Mongolia. Among them, the median age was 45 years old (34.0, 57.0), and 61.1% were male and 33 were imported (44.0%). 29 (38.7%) were detected through close contact tracking, more than 80.0% were mild/common cases. The fatality rate was 1.3% and the basic reproductive number (R 0 ) was estimated to be 2.3. The median incubation period was 8.5 days (6.0~12.0) and the maximum incubation period reached 28 days. There was a statistically difference in the incubation period between imported and local secondary cases ( P <0.001). The duration of hospitalization of patients with incubation period <8.5 days was higher than that of patients with incubation period ≥8.5 days (30.0 vs. 24.0 days).ConclusionIn Inner Mongolia, an early and mandatory control strategy by government associated with the rapidly reduced incidence of COVID-19, by which the epidemic growth was controlled completely. And the fatality rate of COVID-19 was relatively low.

Disrupted Rhythms of Life, Work and Entertainment Behaviours and Their Associations with Mental Health Problems under the Stress of COVID-19 Epidemic: A Survey in 5854 Chinese People with Different Backgrounds (preprint)

BACKGROUND and OBJECTIVE The rhythms of life, work and entertainment behaviours are considered as the external behavioural manifestations of biological rhythm.To evaluate the distinctive disrupted rhythms of behaviours and their associations with mental health problems in people with different backgrounds under the stress of COVID-19 epidemic.SUBJECTS AND METHODS A cross-sectional study was conducted from 10-17 March 2020 under the stress of COVID-19 epidemic.A structured e-questionnaire containing general information,rhythm scale(subscale1 for life-work rhythms and subscale2 for entertainment rhythm) and Zung's self-rating depression and anxiety scale(SDS and SAS) were filled and the data were analysed.RESULTS Overall 5854 participants were included.Significant differences were found in rhythm, SDS and SAS scores among people with different backgrounds (all P<0.05). Subjects with female gender and poor health status were mostly suffered from disrupted rhythms of life- work-entertainment behaviours, combined with depression and anxiety. Nurses and subjects being divorced or with chronic disease with psychosomatic diseases were mostly suffered from disrupted rhythms of life-work behaviours, combined with depression and anxiety. Subjects with aged 26-30 years, or annual income of 50,000-100,000CY were mostly suffered from disrupted rhythms of life-work combined with depression. Subjects with income over 300,000CY were mostly suffered from disrupted rhythm of entertainment combined with anxiety.The prevalence rates of depression and anxiety in people with the high-scores of rhythm disruption increased by 34.50% and 47.16%, respectively, compared with those with low-scores.People with the high-scores of rhythm disruption had higher SDS and SAS scores, compared to those with low scores (all P<0.001). The independent related factors of disrupted rhythms included gender,age,marital status, health status,annual income and chronic diseases with psychosomatic diseases using logistic regression.The disrupted rhythms of life and work behaviours was positively correlated with both SDS and SAS scores.CONCLUSIONS The disrupted rhythms of life, work and entertainment behaviours were closely associated with mental health problems.The disrupted rhythms of behaviours are frequent and fluxible,triggering more severe mental health problems under the stress of COVID-19 epidemic.The physicians should be aware of their importance when evaluating their interviewees or patients’ mental health and achieving maximization of therapeutic efficacy by integrating the intervention of circadian rhythm and its behaviour.

Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension (preprint)

With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.

Overall reduced lymphocyte subsets worsening disease severity and prognosis in COVID-19 severe cases with diabetes mellitus in Chengdu, China (preprint)

Background The outbreak of coronavirus disease 2019 (COVID-19) is widespread throughout China and the world. Methods Demographic, clinical data of 95 confirmed cases with COVID-19 on admission at the Public and Health Clinic Centre of Chengdu from January 16 to March 16, 2020, were retrospectively collected and analyzed. Of them 76, 19 cases were enrolled in non-DM group (without DM), DM group (with DM), respectively; according to the disease severity 57, 19, 8, 11 cases were further divided into non-severe non-DM subgroup (light and common type and without DM), severe non-DM subgroup (severe and critical illness type and without DM), non-severe DM subgroup (light and common type and with DM), severe DM subgroup (severe and critical illness type and with DM), respectively. The severe rate and the prognosis was compared between two groups. The data of peripheral lymphocyte and subsets, age, glucose metabolism parameters were compared between four subgroups, and its relationship to the disease severity, the viral negative conversion time, and the prognosis were analyzed.Results In this COVID-19 cohort the proportion of DM was 20%. Patients with DM had significantly higher severe rate and worse prognosis than those without DM, the difference was significant (severe rate ,cured, unhealed and death in DM and non-DM groups:61.11%vs.25.00%,26.32%,68.42%;5.26%vs.71.05%,26.32%,2.68%,х2=2.940, 3.394,P=0.003,0.001,respectively),simultaneously the proportion of DM in severe cases was higher than that in non-severe cases, the obvious difference was found (36.67% vs.12.31%,х2=2.744,P=0.006).Severe cases with DM tended to have the lowest lymphocytes count levels and percentage values, as well as the lowest T cells count levels and percentage values, helper T cells count levels and percentage values, suppressor T cells count levels, B cells count levels and percentage values compared with those severe cases without DM and non-severe cases with or without DM. The important influencing factors were that age, DM, lymphocyte percentage values and helper T cells percentage values for the disease severity, lymphocyte percentage values and B cell percentage values for the viral negative conversion time, and age, the disease severity and the viral negative conversion time for the prognosis.Conclusions The COVID-19 severe cases with DM had the lowest lymphocytes count level and percentage value, especially T and B lymphocytes count levels and percentage value. Overall decreased lymphocytes subsets and DM maybe worsen prognosis by worsening the disease severity and prolonging the viral negative conversion time. Combination immunomodulatory therapy based on comprehensive treatment might improve prognosis of the COVID-19 severe cases with DM.

Critical Care for Patients with Severe Covid-2019 in Sichuan Province, China: Provincial Cohort Study (preprint)

Background Data regarding critical care for patients with severe COVID-19 are limited. We aimed to describe the clinical course, multi-strategy management, and respiratory support usage for the severe COVID-19 at the provincial level. Methods Using data from Sichuan Provincial Department of Health and the multicentre cohort study, all microbiologically confirmed COVID-19 patients in Sichuan who met the national severe criteria were included and followed-up from the day of inclusion (D1), until discharge, death, or the end of the study. Findings Out of 539 COVID-19 patients, 81 severe cases (15.0%) were identified. The median (IQR) age was 50 (39-65) years, 37% were female, and 53.1% had chronic comorbidities. All severe cases were identified before requiring mechanical ventilation and treated in the intensive care units (ICUs), among whom 51 (63.0%) were treated in provisional ICUs and 77 patients (95.1%) were admitted by D1. On D1, 76 (93.8%) were administered by respiratory support, including 55 (67.9%) by conventional oxygen therapy (COT), 8 (9.9%) by high-flow nasal cannula (HFNC) and 13 (16.0%) by non-invasive ventilation (NIV). By D28, 53 (65.4%) were discharged, three (3.7%) were deceased, and 25 (30.9%) were still hospitalized. COT, administered to 95.1% of the patients, was the most commonly used respiratory support and met 62.7% of the respiratory support needed, followed by HFNC (19.3%), NIV ventilation (9.4%) and IV 8.5%. Interpretation The multi-strategy management for severe COVID-19 patients including early identification and timely critical care may contribute to the low case-fatailty. Preparation of sufficient conventional oxygen equipment should be prioritized.

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial (preprint)

Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein (preprint)

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85x10-7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.