Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants (preprint)

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked with en-hanced immunity, regeneration, improved cognitive function, maintenance of gut mi-crobiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because the respiratory and gastrointestinal tracts are rich in microbial diversity and contain high ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity and the potential use of functional foods as a strategy to combat these effects.

Research progress on adenovirus vector vaccines

Adenovirus（Ad） vectors have been widely used as gene delivery vehicles in gene therapy studies since Ad does not integrate into the host genome, thus the risk of insertion mutation is very low.Ad vectors induce immune responses and have relatively high thermal stability, which make them potential vaccine vectors.The outbreak of coronavirus disease 2019（COVID-19） has drawn more attention to the application of Ad vector vaccines.Vaccination is still the most economical and effective means to prevent and control infectious diseases, including COVID-19, and a variety of Ad vector vaccines have been developed.In this review, we describe the basic characteristics, immune mechanism, clinical application and research progress of Ad vectors.

Clinical characteristics and outcomes in COVID-19 patients with chronic kidney disease in the SARS-CoV-2 Omicron wave: a case-control study (preprint)

Background Since March 2022, the SARS-CoV-2 Omicron variant, mainly the BA.2 sub-lineage, has swept throughout Shanghai, China and caused a wide range of infections. Patients with chronic kidney disease (CKD) are particularly vulnerable to the subvariant and have unique clinical manifestations and outcomes, which have not been studied yet.Methods We retrospective collected data from 2140 hospitalized patients with SARS-CoV-2 Omicron infection from March 29, 2022, to May 17, 2022. Demographic characteristics, clinical symptoms, ancillary examination results, and treatments were described respectively. Presence of COVID-19 pneumonia, disease severity (according to WHO), composite outcome (critical COVID-19 and death), and negative conversion time were defined as primary outcomes. Multivariate analyses were used to evaluate risk factors affecting the primary outcomes.Results The main clinical types of CKD group were severe and critical. Negative conversion time varies according to the stage of CKD patients. The CKD group was more likely to have pneumonia, respiratory and circulatory support, severe disease and death, as compared to the non-CKD group. CKD and the number of comorbidities were found to be risk factors for pneumonia, critical COVID-19and composite outcome among Omicron patients.Conclusion We provided the first snapshot of clinical characteristics and outcomes of CKD patients in the Omicron wave, highlighting the vulnerability of CKD population and providing clues for future studies in special or immunocompromised populations.

COVID-19 could cause long term peripheral nerve demyelination and axonal loss: A One Year Prospective Cohort Study (preprint)

Background: There is a lack of studies on large-sample, medium-, or long-term follow-up data of peripheral neuropathy (PNP) in the COVID-19 survivors. This study evaluated the characteristics and related risk factors of PNP in the medium- and long-term rehabilitation,which provided real-world study data for the complete recovery of COVID-19 patients. Methods: This study was a prospective cohort study of the COVID-19 survivors. We collected data on baseline characteristics, symptoms at onset and after discharge during the 6-month and 12-month follow-up. Peripheral nerves were measured by electromyography and inducible potentiometer. We used multivariable logistic regression to analyze the influencing factors of PNP. Additionally, we compared the difference between the two measurements among the population who completed both measurements. Results: 313 patients were included in the study and all of them underwent nerve conduction study. 67 patients completed two measurements at 6-month and 12-month follow-up. Commonly reported symptoms contained memory loss (86%), hair loss (28%), anxiety (24%), and sleep difficulties (24%). 232 patients (74%) were found with PNP, including 51 (16%) with mononeuropathy and 181 (58%) with generalized PNP. Patients with measurement at 12-month follow-up had a higher prevalence of generalized PNP (p=0.006). For pathological types, 64 (20%) patients had only axonal loss, 67 (21%) had only demyelination, and 101 (32%) had a mixed type. There was no significant difference in the prevalence of accompanying symptoms after discharge between the two groups with or without PNP. After adjustment, age was positively associated with PNP (OR=1.22 per 10-year increase of age, 95% CI, 1.05-1.41). Compared with less than the median amount of IgG at discharge, higher amount of IgG was associated with decreased risk of F-wave abnormality (OR=0.32, 95%CI, 0.11-0.82), but no significant difference in other types of PNP. Conclusions and Relevance: SARS-CoV-2 could cause PNP in hospital survivors with COVID-19, which persisted and was associated with age, education, and IgG antibody at discharge, but had no significant correlation with symptoms after discharge.

Construction of SCUIR Propagation Model Based on Time-Varying Parameters

The novel coronavirus is a new type of virus, and its transmission characteristics are different from the previous virus. Based on the SEIR transmission model, this paper redefines the latent state as close contacts state, introduces an asymptomatic infection state, and considers the influence of time on the state transition parameters in the model, proposing a new transmission model. The experimental results show that the fitting accuracy of the model has significantly improved. Compared with the traditional model, the fitting error was reduced by 8.3%-47.6%. Also, this study uses the US epidemic data as the training set to predict the development of the US epidemic, and the forecast results show that the US epidemic cannot be quickly controlled in a short time. However, the number of active cases will usher in a rapid decline after August 2021.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis (preprint)

BackgroundIt was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC. MethodsPublished and preprinted randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, or Delta) were searched until 31 August 2021. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1- estimate). ResultsSeven RCTs (51,169 participants), 10 cohort studies (14,385,909 participants) and 16 case-control studies (734,607 cases) were included. Eight COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, and BBIBP-CorV) were included in this analysis. Full vaccination was effective against Alpha, Beta/Gamma, and Delta variants, with VE of 88.3% (95% CI, 82.4-92.2), 70.7% (95% CI, 59.9-78.5), and 71.6% (95% CI, 64.1-77.4), respectively. But partial vaccination was less effective, with VE of 59.0% (95% CI, 51.3-65.5), 49.3% (95% CI, 33.0-61.6), and 52.6% (95% CI, 43.3-60.4), respectively. mRNA vaccines seemed to have higher VE against VOC over others, significant interactions (pinteraction < 0.10) were observed between VE and vaccine type (mRNA vaccines vs. non-mRNA vaccines). ConclusionsFull vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta/Gamma and Delta variants. Partial vaccination has less VE against VOC. mRNA vaccines seem to have higher VE against Alpha, Beta/Gamma, and Delta variants over others.

Understanding and Strengthening the Emergency Management and Comprehensive Disaster Reduction in China’s Rural Areas: Lessons from Coping with the COVID-19 Epidemic

Community based bottom-up design is the foundation of national emergency management system. The outbreak of COVID-19 epidemic in early 2020 is a major test of emergency management capability in rural China. This paper first describes the necessity of strengthening the emergency management design in rural areas of China. Then this paper introduces the fundamental role of emergency management design based on bottom-up for the security of rural areas in China, especially in improving the level of comprehensive disaster reduction at the grassroots level, which plays an important role in improving the emergency management ability of China’s rural areas. Based on the above analysis, this paper takes the COVID-19 epidemic prevention and control of epidemic in rural areas of China as an example, and find out many problems in China’s rural emergency management system, such as the grass-roots government’s emergency needs cannot be met, the existing mode of systematic lack, the lack of psychological intervention and so on. Finally, this paper proposes to strengthen the emergency management design in China’s rural areas from expanding the scope of emergency management subjects, strengthening the systematic design of rural emergency management system and strengthening the psychological intervention in rural areas.

Comparative Effectiveness and Safety of 32 Pharmacological Interventions Recommended by Guidelines for COVID-19: A Systematic Review and Network Meta-Analysis Combining 66 Trials (preprint)

Background: To evaluate comparative efficacy and safety of pharmacological interventions in patients with coronavirus disease 2019. Methods: Medline, Embase, the Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with SARS-COV-2/SARS-COV. Random-effects network meta-analysis within Bayesian framework was performed, followed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessing quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion (VNC) and overall adverse events (OAE). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.Results: 66 RCTs with 19,095 patients were included, involving standard care (SOC), 8 different antiviral agents, 6 different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids and other treatments. Compared with SOC, significant reduction of mortality was observed for TCM (OR=0.34, 95%CI: 0.20-0.56, moderate quality) and corticosteroids (OR=0.84, 0.75-0.96, low quality) with improved cure rate (OR=2.16, 1.60-2.91, low quality for TCM; OR=1.17, 1.05-1.30, low quality for corticosteroids). However, increased risk of mortality was found for CQ_HD versus SOC (OR=3.20, 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR=0.52, 0.38-0.70, very low quality) but CQ_HD (OR=2.51, 1.20-5.24) and IFN (OR=2.69, 1.02-7.08) versus SOC with very low quality) were associated with an increased risk. Conclusions: Corticosteroids and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low quality and further high-quality trials are needed.

Establishing emergency medical system of classified treatment to alleviate the overload medical needs after the community outbreak of corona virus disease 2019 in Wuhan City / 中华传染病杂志

Wuhan is the city with the most serious outbreak of corona virus disease 2019 (COVID-19) in China. The outbreak of community has exhausted the current medical resources. With integrating local and support medical resources from other province, Wuhan City has rapidly rebuilt a new emergency medical system of classified treatment, and effectively responded to the overload medical demand after the outbreak in the community.

Characteristics of confirmed coronavirus disease cases at the south campus of Shanghai East Hospital: A retrospective study (preprint)

Background: A fever outpatient clinic at the south campus of Shanghai East Hospital (SEH) openedin response to the coronavirus disease (COVID-19) outbreak. We analyzed the data of all 11,972patients who visited the fever clinic and the 29 confirmed COVID-19 cases to determine the clinical and epidemiological characteristics of confirmed COVID-19 cases diagnosed at SEH.Methods: Data were collected from all fever outpatient clinic patients between January 23 and September 30, 2020. We compared the characteristics of confirmed patients, including age, occupation, area, symptoms, laboratory results, and computed tomography (CT) findings, according to month.Results: By September 30, 2020, 11,972 patients, including 29 (0.24%) confirmed COVID-19 cases, visited the clinic. Four of five confirmed domestic cases identified during January–February 2020 were from Wuhan (mainly elderly retirees and local employees), Hubei. After the epidemic spread internationally, all 22 confirmed cases identified during March–April 2020 were individuals who returned from abroad. They were predominantly young Chinese international students. The sporadic two confirmed cases during May–September 2020 included an employee returning to work from Hubei and an Indian servant from abroad. Symptoms, laboratory tests, and CT findings were consistent with previous reports of COVID-19-positive cases.Conclusions: The characteristics of confirmed COVID-19 cases at SEH varied among different periods in response to the spread of the pandemic. However, due to the effective early isolation and quarantine measures, no outbreak occurred in SEH, which contributed to the prevention and control of the epidemic in Shanghai. 

Add-On Semi-Individualized Chinese Medicine for Coronavirus Disease 2019 (ACCORD): A Retrospective Cohort Study of Hospital Registries (preprint)

Background: Previous studies showed that the effect of antivirals for COVID-19 was promising but varied across patient population, and was modest among severe cases. Chinese Medicine (CM) was extensively used and reported effective in China, awaiting further evidence support. We aimed to evaluate the real-world effectiveness of add-on semi-individualized.Methods: A retrospective total sampling cohort of 1788 adult confirmed COVID-19 patients were recruited from all 2235 consecutive records retrieved from 5 hospitals in Wuhan during15 January to 13 March 2020. Consultation notes, laboratory/imaging investigations, pharmacy and prognosis records were linked by an electronic medical record system and verified by at least 2 researchers independently. The mortality of add-on semi-individualized CM users and non-users was compared by weighted hazard ratios of multivariable Cox regression and by propensity score matching. Change of biomarkers was compared between groups and the frequency of CMs used was analysed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. Sensitivity analyses were conducted to test the robustness.Findings: The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a significant mortality reduction of 58% (HR=0.42, 95%CI: 0.23 to 0.77, p=0.005) and 66% (HR=0.34, 95%CI: 0.15 to 0.76, p=0.009) among all and severe/critical COVID-19 cases with dose-dependent response, after inversely weighted with propensity score calculated by age, gender, history of hypertension, diabetes, coronary artery disease and disease severity. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission compared to baseline.Interpretation: Add-on semi-individualized CM was associated with reduced mortality demonstrating dose-dependent response, especially among severe/critical COVID-19 patients. Chinese medicine could be considered as an add-on regimen for trial use.Funding Statement: This work is partially supported by the National Key Research and Development Program (2017YFC1703506 and 2020YFC0841600). Declaration of Interests: No financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: This study was approved by the ethics review board of Hubei Provincial Hospital of Traditional Chinese Medicine (HBZY2020-C01-01). Written consent was waived due to the retrospective nature.

Characteristics of Confirmed Novel Coronavirus Disease Cases at Shanghai East Hospital: A Retrospective Single-Center Study (preprint)

Background: Since the outbreak of the novel coronavirus disease (COVID-19), the fever outpatient clinic has been open in Shanghai East Hospital (SEH). We analyzed the data for all 4,699 patients from SEH and the 27 confirmed COVID-19 cases among them to determine the clinical and epidemiological characteristics of confirmed COVID-19 cases identified in the SEH. Methods: Data were collected for patients who visited the fever outpatient clinic in the SEH between January 23 and April 30, 2020. We compared the characteristics of confirmed cases, including age, occupation, area, symptoms, laboratory results, and computed tomography (CT) scans, by month.Results: By April 30, 4,699 patients had visited the fever outpatient clinic of the SEH; of those, 27 (0.57%) were confirmed COVID-19 cases. Among the confirmed domestic cases identified between January and February, four of five were from Wuhan, Hubei. Following the spread of the epidemic to other parts of the world, all confirmed cases identified in March–April were cases of individuals who were returning from abroad, mainly Chinese students living abroad. Further, all cases were from outside Shanghai, and no local residents were diagnosed in the clinic. Symptoms, laboratory tests, and CT scans were consistent with previous literature reports of positive COVID-19 cases. Conclusions: Given the necessity to control the spread of this epidemic domestically and abroad, the focus of COVID-19 prevention and control has shifted. In Shanghai, measures taken to prevent COVID-19 spread were very successful. Early isolation and quarantine are necessary and effective measures.