Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study.

Vitamin C, (ascorbic acid), vitamin D (cholecalciferol) and zinc (zinc sulfate monohydrate) supplements are important in immunity against coronavirus disease-2019 (COVID-19). However, a limited number of studies have been conducted on the association of vitamins and supplements with the reduced risks of COVID-19 infection. This study aims to evaluate the association of vitamins and supplements as treatment options to reduce the severity of COVID-19. Data were collected from 962 participants from 13 December 2020 to 4 February 2021. The presence of COVID-19 was confirmed by qRT-PCR. The Chi-square test and multivariate regression analyses were conducted. The ratio of uptake of vitamin C:vitamin D:zinc was 1:1:0.95. Uptake of vitamin C, vitamin D and zinc were significantly associated with the reduced risk of infection and severity of COVID-19 (OR: 0.006 (95% CI: 0.03-0.11) (p = 0.004)) and (OR: 0.03 (95% CI: 0.01-0.22) (p = 0.005)). The tendency of taking supplements was associated with the presence of infection of COVID-19 (p = 0.001), age (p = 0.02), sex (p = 0.05) and residence (p = 0.04). The duration of supplementation and medication was significantly associated with reduced hospitalization (p = 0.0001). Vitamins C, D and zinc were not significantly (p = 0.9) associated with a reduced risk of severity when taken through the diet. Hospitalization (p = 0.000001) and access to health facilities (p = 0.0097) were significantly associated with the survival period of the participants. Participants with better access to health facilities recovered early (OR: 6.21, 95% CI 1.56-24.7). This study will add knowledge in the field of treatment of COVID-19 by using vitamins and zinc supplements.

The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

The roles of inactivated vaccines in older patients with infection of Delta variant in Nanjing, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading around the world. The COVID-19 vaccines may improve concerns about the pandemic. However, the roles of inactivated vaccines in older patients (aged ≥60 years) with infection of Delta variant were less studied. METHODS: We classified the older patients with infection of Delta variant into three groups based on the vaccination status: no vaccination (group A, n = 113), one dose of vaccination (group B, n = 46), and two doses of vaccination (group C, n = 22). Two inactivated COVID-19 vaccines (BBIBP-CorV or CoronaVac) were evaluated in this study. The demographic data, laboratory parameters, and clinical severity were recorded. RESULTS: A total of 181 older patients with infection of Delta variant were enrolled. 111 (61.3%) patients had one or more co-morbidities. The days of "turn negative" and hospital stay in Group C were lower than those in the other groups (P < 0.05). The incidences of multiple organ dysfunction syndrome (MODS), septic shock, acute respiratory distress syndrome (ARDS), acute kidney injury, and cardiac injury in Group A were higher than those in the other groups (P < 0.05). The MV-free days and ICU-free days during 28 days in Group A were also lower than those in the other groups (P < 0.05). In patients with co-morbidities, vaccinated cases had lower incidences of MODS (P = 0.015), septic shock (P = 0.015), and ARDS (P = 0.008). CONCLUSIONS: The inactivated COVID-19 vaccines were effective in improving the clinical severity of older patients with infection of Delta variant.

Mechanism of Xuanbai Qingfei Jiedu decoction in the treatment of COVID-19 based on network pharmacology

Objective: To explore the pharmacological mechanism of Xuanbai Qingfei Jiedu Decoction in the treatment of coronavirus disease 2019 (COVID-19) on account of network pharmacology.

Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent response for novel coronavirus disease 2019 (COVID-19). This study aimed to explore the roles of ACE2, apelin and sodium-glucose cotransporter 2 (SGLT2) in SARS-CoV-2-mediated cardiorenal damage. METHODS AND RESULTS: The published RNA-sequencing datasets of cardiomyocytes infected with SARS-CoV-2 and COVID-19 patients were used. String, UMAP plots and single cell RNA sequencing data were analyzed to show the close relationship and distinct cardiorenal distribution patterns of ACE2, apelin and SGLT2. Intriguingly, there were decreases in ACE2 and apelin expression as well as marked increases in SGLT2 and endothelin-1 levels in SARS-CoV-2-infected cardiomyocytes, animal models with diabetes, acute kidney injury, heart failure and COVID-19 patients. These changes were linked with downregulated levels of interleukin (IL)-10, superoxide dismutase 2 and catalase as well as upregulated expression of profibrotic genes and pro-inflammatory cytokines/chemokines. Genetic ACE2 deletion resulted in upregulation of pro-inflammatory cytokines containing IL-1ß, IL-6, IL-17 and tumor necrosis factor α. More importantly, dapagliflozin strikingly alleviated cardiorenal fibrosis in diabetic db/db mice by suppressing SGLT2 levels and potentiating the apelin-ACE2 signaling. CONCLUSION: Downregulation of apelin and ACE2 and upregulation of SGLT2, endothelin-1 and pro-inflammatory cytokines contribute to SARS-CoV-2-mediated cardiorenal injury, indicating that the apelin-ACE2 signaling and SGLT2 inhibitors are potential therapeutic targets for COVID-19 patients.

Reverse Transcription Recombinase-Aided Amplification Assay With Lateral Flow Dipstick Assay for Rapid Detection of 2019 Novel Coronavirus.

Background: The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed. Methods: Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively. Results: The limit of detection was 1 copies/µl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples. Conclusion: This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.

The therapeutic efficacy of Huashi Baidu Formula combined with antiviral drugs in the treatment of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: The Corona Virus Disease 2019 (COVID-19) is a new acute respiratory infectious disease that has become a major global public health event. In China, the combination of Huashi Baidu Formula (HBF) and antiviral drugs is used in the clinical treatment of severe patients with new coronary pneumonia, but there is still a lack of evidence-based medical evaluation. METHODS: We search for research in PubMed/MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, Cochrane Library, Embase, China Biomedical Database (CBM), and Chinese Science Citation Database (CSCD). For "Huashi Baidu Formula" and "COVID-19," we screened suitable articles without language restrictions on keywords, and recorded and analyzed the screened literature with RevMan 5.3 and STATA 14.2 software. RESULTS: This systematic review and meta-analysis will evaluate the efficacy and safety of HBF combined with antiviral drugs in the treatment of COVID-19, and provide the rationality of clinical drug application. CONCLUSION: Our findings will provide references for clinical diagnosis and treatment and guidance programs for COVID-19. INPLASY REGISTRATION NUMBER: INPLASY202080098.

Cancer Patient Management Strategy in a Cancer Center of Zhejiang, China During the COVID-19 Pandemic (preprint)

Background: Due to the increased risk of viral infection and the severe shortage of medical resources during the pandemic of COVID-19, most hospitals in the epidemic areas significantly reduced non-emergency admissions and services, if not closed. As a result, it has been difficult to treat cancer patients on time, which adversely affects their prognosis. To address this problem, cancer centers must develop a strategic plan to manage both inpatients and outpatients during the pandemic, provide them with the necessary treatment, and at the same time prevent the spread of the virus among patients, visitors and medical staff. Methods: : Based upon the epidemic situation in Zhejiang Province, China, the number of running non-emergency medical wards in the Zhejiang Cancer Hospital was gradually increased in a controlled manner. All staff of the hospital received COVID-19 preventive training and was provided with three different levels of protection according to the risks of their services. Only patients without a known history of SARS-CoV-2 contact were eligible to schedule an appointment. Body temperature was measured on all patients upon their arrival at the hospital. Chest CT image, blood cell counting and travel/contact history were investigated in patients with fever. Respiratory tract samples, such as sputum and throat swabs, from all patients, including those clinically suspected of SARS-CoV-2 infection, were collected for nucleic acid detection of SARS-CoV-2 before treatment. Results: : A total of 3697 inpatients and 416 outpatients seeking cancer treatment were enrolled from February 1 to April 3, 2020, in compliance with the hospital’s infection-control interventions. The clinicopathological parameters of the patients were summarized herein. 4237 samples from 4101 patients produced negative RNA testing results. Four clinically suspected patients all presented negative RNA test results and were excluded from the SARS-CoV-2 infection through follow-up retesting and monitoring. Seven patients with only N-gene positive results were retested, followed by CT scan and SARS-CoV-2 contact history investigation. All of them were finally diagnosed as non-infected patients. There was one outpatient who was confirmed positive by virus RNA test and then followed up. She might be an asymptomatic laboratory-confirmed case. During the study period, there was no SARS-CoV-2 infection among staff, patients and escorts of patients in the Zhejiang Cancer Hospital. Conclusion: This study suggested our infection-control interventions, including viral nucleic acid test, could be used as a reliable method to screen cancer patients in the area with moderate COVID-19 prevalence. Cancer may not be a high-risk factor of SARS-CoV-2 infection.

Fangcang shelter hospitals are a One Health approach for responding to the COVID-19 outbreak in Wuhan, China.

In February 2020, the exponential growth of COVID-19 cases in Wuhan city posed a huge economic burden to local medical systems. Consequently, Wuhan established Fangcang Shelter hospitals as a One Health approach for responding to and containing the COVID-19 outbreak by isolating and caring for mild-to-moderate cases. However, it is unclear to what degree the hospitals contained COVID-19. This study performed an interrupted time series analysis to compare the number of new confirmed cases of COVID-19 before and after the operation of Fangcang Shelter hospitals. The initial number of confirmed cases in Wuhan increased significantly by 68.54 cases per day prior to February 4, 2020. Compared with the number of cases noted 20 days before the use of Fangcang Shelter hospitals, a sustained reduction in the number of confirmed cases (trend change, -125.57; P < 0.0001) was noted 41 days after the use of the hospitals. Immediate-level changes were observed for confirmed cases (level change, 725.97; P = 0.025). These changes led to an estimated 5148 fewer confirmed cases (P < 0.0001). According to the mean confirmed cases of 395.71 per day before the intervention, we estimated that Wuhan had advanced the terminal phase of COVID-19 by 13 days. Furthermore, immediately after introduction of Fangcang Shelter Hospitals on February 5, the reproduction number dropped rapidly, from a pre-introduction rate of 4.0 to 2.0. The Fangcang Shelter hospitals most likely to reversed the epidemic trend of COVID-19 while a containment strategy was implemented in Wuhan. In a One Health perspective, Fangcang Shelter hospitals, with their functions of isolation and treatment of confirmed COVID-19 patients, engaging professionals from many disciplines, such as medicine, engineering, architecture, psychology, environmental health, and social sciences. The results of this study provide a valuable reference for health policy makers in other countries.

Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study.

Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74-6·33; p<0·0001), fatigue (OR 1·56, 1·01-2·41; p=0·043), white blood cell count less than 4 × 109 per L (OR 2·44, 1·28-4·64; p=0·0066), lymphocyte count less than 0·8 × 109 per L (OR 1·82, 1·00-3·31; p=0·049), ground glass opacity (OR 1·95, 1·32-2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04-2·28; p=0·032) were independent risk factors for confirmed COVID-19. Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease. Funding: National Natural Science Foundation of China.