Azvudine reduces the mortality rate of patients with Coronavirus disease 2019: a single-center retrospective analysis study (preprint)

Background: Several therapeutic drugs have been authorized for the treatment of patients with Coronavirus disease 2019 (COVID-19). However, further research on the mechanisms of action, efficacy, and target populations of these novel therapeutic drugs are necessary. Hence, this study aimed to investigate the effectiveness of azvudine in hospitalized patients with COVID-19. Methods: We conducted a retrospective cohort study of patients with COVID-19 admitted to our hospital from December 1, 2022, to March 31, 2023. Patients were divided into retrospective cohorts receiving azvudine antiviral therapy and standard treatment, and were followed-up for up to 28 days. Results: Prior to data processing, azvudine treatment was associated with reduced mortality rates at 7 days (1.09/1000 persons vs.5.06/1000 persons, p<0.001)and 14 days (3.35/1000 persons vs. 5.65/1000 persons, p=0.001). After propensity score matching, a decrease in mortality rates at 7 days (0.08/1000 persons vs.6.29/1000 persons, p<0.001), 14 days (3.42/1000 persons vs. 7.26/1000 persons, p<0.001), and 28 days (4.33/1000 persons vs. 7.29/1000 persons, p=0.003) were observed following azvudine treatment. After inverse probability of treatment weighting adjustment, the results were consistent with propensity score matching. In the clinical subgroup analysis, for hospitalized severe and critical patients with COVID-19, azvudine treatment intervention significantly reduced patient mortality rates. Conclusions: The study suggests that in hospitalized patients with COVID-19, azvudine treatment significantly reduces patient mortality rates in hospitalized COVID-19 infections, wherein the effects are more pronounced in severe and critical patients.

Investigation on the Control of COVID-19 in Wuhan: Number of Infections Outside Hospitals and the Reproduction Number.

COVID-19 is erupting globally, and Wuhan successfully controlled it within a month. Infections arose from infectious persons outside hospitals. After data revision, data-based and model-based analyses were implemented, and the conclusions are as follows. The incubation period of most infected people may be 6-7 days. The number of infectious persons outside hospitals in Wuhan on January 20, 2020 was about 10000 and reached more than 20000 on the day of Lockdown; it exceeded 72000 on February 4. Both data-based and model-based analyses gave out the evolution of the reproduction number, which was over 2.5 in early January, went down to 1.62 in late January and 1.20 in early February, with a sudden drop to less than 0.5 due to the strict Stay-at-home management after February 11. Strategies of Stay-at-home, Safe-protective measures, and Ark hospitals were the main contributions to control COVID-19 in Wuhan. In Wuhan, 2 inflection points of COVID-19, exactly correspond to February 5 and February 15, the 2 days when Ark hospitals were introduced, and the complete implementation of Stay-at-home. Based on the expression of the reproduction number, group immunity is also discussed. It shows that only when the group immunization rate is over 75% can COVID-19 be under control; group immunity would be full infection and the total deaths will be 220000 for a city as big as Wuhan. Sensitivity analysis suggests that 30% of people staying at home in combination with better behavior changes, such as social-distancing and frequent handwashing, can effectively contain COVID-19. However, only when this proportion is over 60% can the controlled effect and efficiency like Wuhan be obtained.

Delivery and neonatal outcomes of pregnant women during the Shanghai lockdown: A retrospective analysis.

Objectives: Shanghai witnessed an unprecedented outbreak of COVID-19 and experienced a strict lockdown from March 28, 2022 to May 31, 2022. Most studies to date are on the first lockdown after the outbreak in December 2019. This study aimed to examine the impact of lockdown on delivery and neonatal outcomes among uninfected pregnant women in the new phase of the COVID-19 outbreak. Methods: A retrospective analysis was conducted in the Obstetrics and Gynecology Hospital of Fudan University. Pregnant women without COVID-19 who delivered from March 28, 2022 to May 31, 2022 (lockdown group) and the same period in 2021 (non-lockdown group) were recruited for this study. Logistic regression models and 1 : 1 propensity score matching (PSM) were used to assess the effect of lockdown on delivery outcomes. Results: A total of 2,962 patients were included in this study, 1,339 of whom were from the lockdown group. Compared with the non-lockdown group, pregnant women giving birth during lockdown had an increased risk of term prelabor rupture of membranes (TPROM) (aOR = 1.253, 95% CI: 1.026-1.530), and decreased risks of postpartum hemorrhage (PPH) (aOR = 0.362, 95% CI: 0.216-0.606) and fetal malformation (aOR = 0.309, 95% CI: 0.164-0.582). The risk of large for gestational age (LGA) (aOR = 0.802, 95% CI: 0.648-0.992) and rate of admission to the neonatal intensive care unit (NICU) (aOR = 0.722, 95% CI: 0.589-0.885) also significantly declined. After 1 : 1 PSM, the impact of lockdown on the risk of TPROM (aOR = 1.501, 95% CI: 1.083-2.080), PPH (aOR = 0.371, 95% CI: 0.211-0.654), fetal malformation (aOR = 0.332, 95% CI: 0.161-0.684), LGA (aOR = 0.749, 95% CI: 0.594-0.945) and rate of admission to the NICU (aOR = 0.700, 95% CI: 0.564-0.869) all remained. There were no other delivery or neonatal outcomes affected by the lockdown after the COVID-19 outbreak. Conclusion: This study indicated a significant increase in the risk of term PROM, significant decreases in the risk of PPH, fetal malformation and LGA, and a marked decline in the rate of admission to the NICU during Shanghai Lockdown.

A full genome tiling array enhanced the inspection and quarantine of SARS-CoV-2.

As the worldwide spreading epidemic of SARS-CoV-2, quick inspection and quarantine of passengers for SARS-CoV-2 infection are essential for controlling the spread of SARS-CoV-2, especially the cross-border transmission. This study reports a SARS-CoV-2 genome sequencing method based on a re-sequencing tiling array successfully used in border inspection and quarantine. The tiling array chip has four cores, with one core of 240,000 probes dedicated to the whole genome sequencing of the SAR-CoV-2 genome. The assay protocol has been improved to reduce the detection time to within one day and can detect 96 samples in parallel. The detection accuracy has been validated. This fast and simple procedure is also of low cost and high accuracy, and it is particularly suitable for the rapid tracking of viral genetic variants in custom inspection applications. Combining these properties means this method has significant application potential in the clinical investigation and quarantine of SARS-CoV-2. We used this SARS-CoV-2 genome re-sequencing tiling array to inspect and quarantine China's entry and exit ports in the Zhejiang Province. From November 2020 to January 2022, we observed the gradual shift of SARS-CoV-2 variants from the D614G type to the Delta Variant, and then to the dominance of the Omicron variant recently, consistently with the global emergency pattern of the new SARS-CoV-2 variant.

Performance of D-dimer to lymphocyte ratio in predicting the mortality of COVID-19 patients.

Background: Nowadays, there is still no effective treatment developed for COVID-19, and early identification and supportive therapies are essential in reducing the morbidity and mortality of COVID-19. This is the first study to evaluate D-dimer to lymphocyte ratio (DLR) as a prognostic utility in patients with COVID-19. Methods: We retrospectively analyzed 611 patients and separated them into groups of survivors and non-survivors. The area under the curve (AUC) of various predictors integrated into the prognosis of COVID-19 was compared using the receiver operating characteristic (ROC) curve. In order to ascertain the interaction between DLR and survival in COVID-19 patients, the Kaplan-Meier (KM) curve was chosen. Results: Age (OR = 1.053; 95% CI, 1.022-1.086; P = 0.001), NLR (OR = 1.045; 95% CI, 1.001-1.091; P = 0.046), CRP (OR = 1.010; 95% CI, 1.005-1.016; P < 0.001), PT (OR = 1.184; 95% CI, 1.018-1.377; P = 0.029), and DLR (OR = 1.048; 95% CI, 1.018-1.078; P = 0.001) were the independent risk factors related with the mortality of COVID-19. DLR had the highest predictive value for COVID-19 mortality with the AUC of 0.924. Patients' survival was lower when compared to those with lower DLR (Log Rank P <0.001). Conclusion: DLR might indicate a risk factor in the mortality of patients with COVID-19.

Effect of nasal irrigation in adults infected with Omicron variant of COVID-19: A quasi-experimental study.

Objective: To investigate the effect of nasal irrigation on the duration of symptoms and nucleic acid conversion in adults infected with the Omicron variant of COVID-19. Methods: This quasi-experimental study enrolled patients diagnosed with asymptomatic, mild, or moderate Omicron infection at the Shandong Public Health Clinical Center between April 1, 2022 and May 1, 2022. Patients were divided into two groups to receive Lianhua Qingwen granules and traditional Chinese medicine (TCM) prescriptions (conventional group) and 3% hypertonic saline nasal irrigation based on conventional treatment (nasal irrigation groups), respectively. Primary outcomes were symptom disappearance time and nucleic acid negative conversion time. Secondary outcomes were peripheral blood white blood cell (WBC), lymphocyte (LYM) count, neutrophil (NEU) count, C-reactive protein (CRP) level, and chest CT examination findings. Results: Eighty patients were included (40 patients/group). Multiple linear regression analysis showed that, after adjustment for comorbidities, smoking history, LYM count, and Ct values of N gene, the patients in the nasal irrigation group were more likely to get lower nucleic acid negative conversion time (ß = -11.052, 95% CI: -8.277-13.827, P < 0.001) compared with the conventional group. The symptom disappearance time showed no significant improvement (P > 0.05). Subgroup analysis for treatment-naïve patients in the nasal irrigation group showed similar nucleic acid negative conversion time improvement (P = 0.038). Conclusion: Early nasal irrigation shortens the nucleic acid negative conversion time in adults infected with the Omicron variant but without improvements in symptom disappearance time.

Effect of nasal irrigation in adults infected with Omicron variant of COVID-19: A quasi-experimental study

Objective To investigate the effect of nasal irrigation on the duration of symptoms and nucleic acid conversion in adults infected with the Omicron variant of COVID-19. Methods This quasi-experimental study enrolled patients diagnosed with asymptomatic, mild, or moderate Omicron infection at the Shandong Public Health Clinical Center between April 1, 2022 and May 1, 2022. Patients were divided into two groups to receive Lianhua Qingwen granules and traditional Chinese medicine (TCM) prescriptions (conventional group) and 3% hypertonic saline nasal irrigation based on conventional treatment (nasal irrigation groups), respectively. Primary outcomes were symptom disappearance time and nucleic acid negative conversion time. Secondary outcomes were peripheral blood white blood cell (WBC), lymphocyte (LYM) count, neutrophil (NEU) count, C-reactive protein (CRP) level, and chest CT examination findings. Results Eighty patients were included (40 patients/group). Multiple linear regression analysis showed that, after adjustment for comorbidities, smoking history, LYM count, and Ct values of N gene, the patients in the nasal irrigation group were more likely to get lower nucleic acid negative conversion time (β = −11.052, 95% CI: −8.277–13.827, P < 0.001) compared with the conventional group. The symptom disappearance time showed no significant improvement (P > 0.05). Subgroup analysis for treatment-naïve patients in the nasal irrigation group showed similar nucleic acid negative conversion time improvement (P = 0.038). Conclusion Early nasal irrigation shortens the nucleic acid negative conversion time in adults infected with the Omicron variant but without improvements in symptom disappearance time.

Alterations in smell or taste in individuals infected with SARS-CoV-2 during periods of Omicron variant dominance.

OBJECTIVES: To characterize the prevalence, severity, correlation with initial symptoms, and role of vaccination in patients with COVID-19 with smell or taste alterations (STAs). METHODS: We conducted an observational study of patients infected with SARS-CoV-2 Omicron admitted to three hospitals between May 17 and June 16, 2022. The olfactory and gustatory functions were evaluated using the taste and smell survey and the numerical visual analog scale at two time points. RESULTS: The T1 and T2 time point assessments were completed by 688 and 385 participants, respectively. The prevalence of STAs at two time points was 41.3% vs 42.6%. Furthermore, no difference existed in the severity distribution of taste and smell survey, smell, or taste visual analog scale scores between the groups. Patients with initial symptoms of headache (P = 0.03) and muscle pain (P = 0.04) were more likely to develop STAs, whereas higher education; three-dose vaccination; no symptoms yet; or initial symptoms of cough, throat discomfort, and fever demonstrated protective effects, and the results were statistically significant. CONCLUSION: The prevalence of STAs did not decrease significantly during the Omicron dominance, but the severity was reduced, and vaccination demonstrated a protective effect. In addition, the findings suggest that the presence of STAs is likely to be an important indicator of viral invasion of the nervous system.

miR-615 facilitates porcine epidemic diarrhea virus replication by targeting IRAK1 to inhibit type III interferon expression.

Porcine epidemic diarrhea virus (PEDV) in the Coronavirus family is a highly contagious enteric pathogen in the swine industry, which has evolved mechanisms to evade host innate immune responses. The PEDV-mediated inhibition of interferons (IFNs) has been linked to the nuclear factor-kappa B (NF-κB) pathway. MicroRNAs (miRNAs) are involved in virus-host interactions and IFN-I regulation. However, the mechanism by which the PEDV regulates IFN during PEDV infection has not yet been investigated in its natural target cells. We here report a novel mechanism of viral immune escape involving miR-615, which was screened from a high-throughput sequencing library of porcine intestinal epithelial cells (IECs) infected with PEDV. PEDV infection altered the profiles of miRNAs and the activities of several pathways involved in innate immunity. Overexpression of miR-615 increased PEDV replication, inhibited IFN expression, downregulated the NF-κB pathway, and blocked p65 nuclear translocation. In contrast, knockdown of miR-615 enhanced IFN expression, suppressed PEDV replication, and activated the NF-κB pathway. We further determined that IRAK1 is the target gene of miR-615 in IECs. Our findings show that miR-615 suppresses activation of the NF-κB pathway by suppressing the IRAK1 protein and reducing the generation of IFN-IIIs, which in turn facilitates PEDV infection in IECs. Moreover, miR-615 inhibited PEDV replication and NF-κB pathway activation in both IECs and MARC-145 cells. These findings support an important role for miR-615 in the innate immune regulation of PEDV infections and provide a novel perspective for developing new treatments.

Immunogenicity and protective efficacy of a DNA vaccine inducing optimal expression of the SARS-CoV-2 S gene in hACE2 mice.

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.

Identification and integrated analysis of lncRNAs and miRNAs in IPEC-J2 cells provide novel insight into the regulation of the innate immune response by PDCoV infection.

BACKGROUND: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are pivotal regulators involved in the pathogenic mechanism of multiple coronaviruses. Porcine deltacoronavirus (PDCoV) has evolved multiple strategies to escape the innate immune response of host cells, but whether ncRNAs are involved in this process during PDCoV infection is still unknown. RESULTS: In this study, the expression profiles of miRNAs, lncRNAs and mRNAs in IPEC-J2 cells infected with PDCoV at 0, 12 and 24 hours postinfection (hpi) were identified through small RNA and RNA sequencing. The differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were screened from the comparison group of IPEC-J2 cells at 0 and 12 hpi as well as the comparison group of IPEC-J2 cells at 12 and 24 hpi. The target genes of these DEncRNAs were predicted. The bioinformatics analysis of the target genes revealed multiple significantly enriched functions and pathways. Among them, the genes that were associated with innate immunity were specifically screened. The expression of innate immunity-related ncRNAs and mRNAs was validated by RT-qPCR. Competing endogenous RNA (ceRNA) regulatory networks among innate immunity-related ncRNAs and their target mRNAs were established. Moreover, we found that the replication of PDCoV was significantly inhibited by two innate immunity-related miRNAs, ssc-miR-30c-3p and ssc-miR-374b-3p, in IPEC-J2 cells. CONCLUSIONS: This study provides a data platform to conduct studies of the pathogenic mechanism of PDCoV from a new perspective and will be helpful for further elucidation of the functional role of ncRNAs involved in PDCoV escaping the innate immune response.

Analysis of the Quantitative Evaluation of the Public Medical and Health System Costs During Pandemic Governance: Investigation Based on COVID-19

It is of great reference significance for broadening the research perspective of pandemic governance, improving the efficiency of pandemic governance and the credibility of the government, to scientifically measure and analyze the public medical and health system costs. This article takes the typical case “pandemic prevention and control event of S city, China” as the research background. First, the concept of public medical and health system costs during pandemic governance is defined. Then, the public medical and health system costs are embedded into the pandemic governance system, and the generation process of the public medical and health system costs in the actual situation are investigated. Furthermore, through in-depth interview, multi-case grounded theory and fuzzy subordinate function analysis, the scientific construction of the public medical and health system cost index system are completed. Finally, based on G1 method/entropy method combined with weighting and fuzzy comprehensive evaluation method, the public medical and health system costs of the pandemic prevention and control events of S city is measured. The results show the following: (1) it is important that good single dimensions and reliable indicators are embodied in the public medical and health system costs scale. Among them, the behavioral public medical and health system costs of the masses is the largest proportion of all indicators;(2) after the pandemic prevention and control event is over, the public medical and health system cost are difficult to repair, and some lagging ideas and behaviors shown by local governments lead to a continuous expansion of the public medical and health system costs associated with pandemic governance;and (3) local governments should not conceal information asymmetry. Instead, local governments should give greater freedom to other actors to deal with pandemic governance, and governance entities should cooperate with each other. This will mitigate the effect of public medical and health system costs. Corresponding policy recommendations are proposed.

Cover Picture: Nanoantidote for repression of acidosis pH promoting COVID-19 infection (View 4/2022)

Acidosis-related pH promotes SARS-CoV-2 pseudovirus infection by increasing cell membrane ACE2 expression. A CaCO3-NPs antacid nanoantidote restored the normal blood related pH 7.4, attenuating the SARS-CoV-2 pseudovirus infection. In article number 20220004, Wenguo Cui, Cheng Li, Siguang Li and their co-workers have suggested the existence of a positive feedback loop in which SARS-CoV-2 infection-induced acidosis enhances further SARS-CoV-2 infection. CaCO3-NPs nanoantidote may become an effective antacid.

ECG Utilization Patterns of Patients With Arrhythmias During COVID-19 Epidemic and Post-SARS-CoV-2 Eras in Shanghai, China.

Background: The COVID-19 pandemic has led to concerns around its subsequent impact on global health. Objective: To investigate the health-seeking behavior, reflected by ECG utilization patterns, of patients with non-COVID-19 diseases during and after COVID-19 epidemic. Methods: Taking advantage of the remote ECG system covering 278 medical institutions throughout Shanghai, the numbers of medical visits with ECG examinations during the lockdown (between January 23 and April 7, 2020), post-lockdown (between April 8 and December 31, 2020) and post-SARS-CoV-2 (between January 23 and April 7, 2021) periods were analyzed and compared against those during the same periods of the preceding years (2018 and 2019). Results: Compared with the same period during pre-COVID years, the number of medical visits decreased during the lockdown (a 38% reduction), followed by a rebound post-lockdown (a 17% increase) and a fall to the baseline level in post-SARS-CoV-2 period. The number of new COVID-19 cases announced on a given day significantly correlated negatively with the numbers of medical visits during the following 7 days. Medical visit dynamics differed for various arrhythmias. Whereas medical visits for sinus bradycardia exhibited a typical decrease-rebound-fallback pattern, medical visits for atrial fibrillation did not fall during the lockdown but did exhibit a subsequent increase during the post-lockdown period. By comparison, the volume for ventricular tachycardia remained constant throughout this entire period. Conclusion: The ECG utilization patterns of patients with arrhythmias exhibited a decrease-rebound-fallback pattern following the COVID-19 lockdowns. Medical visits for diseases with more severe symptoms were less influenced by the lockdowns, showing a resilient demand for healthcare.

Cluster Analysis of US COVID-19 Infected States for Vaccine Distribution.

Since December 2019, COVID-19 has been raging worldwide. To prevent the spread of COVID-19 infection, many countries have proposed epidemic prevention policies and quickly administered vaccines, However, under facing a shortage of vaccines, the United States did not put forward effective epidemic prevention policies in time to prevent the infection from expanding, resulting in the epidemic in the United States becoming more and more serious. Through "The COVID Tracking Project", this study collects medical indicators for each state in the United States from 2020 to 2021, and through feature selection, each state is clustered according to the epidemic's severity. Furthermore, through the confusion matrix of the classifier to verify the accuracy of the cluster analysis, the study results show that the Cascade K-means cluster analysis has the highest accuracy. This study also labeled the three clusters of the cluster analysis results as high, medium, and low infection levels. Policymakers could more objectively decide which states should prioritize vaccine allocation in a vaccine shortage to prevent the epidemic from continuing to expand. It is hoped that if there is a similar epidemic in the future, relevant policymakers can use the analysis procedure of this study to determine the allocation of relevant medical resources for epidemic prevention according to the severity of infection in each state to prevent the spread of infection.