Risk Prediction of Pneumonia in Maintenance Hemodialysis Patients with COVID-19: A Single-center Retrospective Study in China (preprint)

Objective:  The infection rate and mortality of COVID-19 in hemodialysis patients are extremely high. In this study, we analyzed the risk prediction of pneumonia in Chinese’s hemodialysis patients with COVID-19.  Method: We conducted a retrospective analysis of maintenance hemodialysis patients with COVID-19 admitted to Peking University Third Hospital from December 1, 2022 to January 31, 2023. We collected demographic data, underlying diseases, dialysis treatment data, and laboratory test results of these patients; logistic regression and ROC curve were used to analyze the risk factors of pneumonia.  Results:  A total of 209 hemodialysis patients with COVID-19 were enrolled in this study, of whom 80(38.3%) had pneumonia and 129(61.7%) normal. Multivariate logistic analysis revealed that older age (OR=1.030, 95%CI 1.002~1.059, p=0.036), lower hemoglobin (OR=0.968, 95%CI 0.942~0.995, p=0.019), lower albumin (OR=0.834, 95%CI 0.738-0.943, p=0.004) were risk factors for pneumonia. Patients with age >65 years old, hemoglobin <115g/L or albumin <36.8g/L had a higher risk of pneumonia, and we combined the three indexes to predict the risk of pneumonia (P= elogit(P)    / 1+  elogit(P) , logit(P)=9.593 +0.031×Age (years old) -0.038×Hemoglobin (g/L) -0.210×Albumin (g/L)), drew the ROC curve with the risk P value (AUC=0.756, 95% CI 0.687~0.825, p<0.001), when P=0.575 was selected as the cut-off value, the sensitivity and specificity of the three indexes combined to predict pneumonia were 44.0% and 94.5% respectively.  Conclusion: Older age, anemia and hypoalbuminemia were risk factors for pneumonia in MHD patients. We could reduce the incidence of pneumonia and improve the prognosis of MHD patients by correcting anemia and hypoalbuminemia.

Pre-COVID resting-state brain activity in the fusiform gyrus prospectively predicts social anxiety alterations during the pandemic (preprint)

Persistent social anxiety (SA) has been reported to be associated with the coronavirus disease 2019 (COVID-19) pandemic, but the neurobiopsychological mechanisms underlying this relationship remain unclear. This study aimed to elucidate the neurofunctional markers for the development of SA during the pandemic and the potential roles of COVID-related posttraumatic stress symptoms (PTSS) in the brain-SA alterations link. Before the COVID-19 pandemic (T1), 100 general college students underwent baseline brain resting-state magnetic resonance imaging and behavioral tests for SA. During the period of community-level outbreaks (T2), these students were recontacted to undergo follow-up assessments of SA and COVID-related PTSS. Whole-brain correlation analyses and prediction analyses found that pre-pandemic spontaneous neural activity (measured by fractional amplitude of low-frequency fluctuations) in the right fusiform gyrus (FG) was positively linked with SA alterations (T2 – T1) during the pandemic. Moreover, mediation analyses revealed a mediating role of COVID-specific PTSS in the association of right FG activity with SA alterations. Importantly, our results persisted even after adjusting for the effects of pre-pandemic family socioeconomic status, other stressful life events, and general anxiety. Overall, our study provides fresh evidence for neurofunctional markers of COVID-induced aggravation of SA and may help individuals vulnerable to SA exacerbation benefit from targeted clinical interventions.

Intrapersonal and interpersonal level factors influencing self-care practices among Hong Kong individuals with COVID-19—A qualitative study

Background The unprecedented crisis during the fifth wave of the COVID-19 pandemic in Hong Kong placed a significant burden on the health care system. Therefore, the Hong Kong government advocated that individuals with no or mild COVID-19 symptoms should self-care at home. This study aimed to understand intrapersonal and interpersonal level factors that shaped self-care practices among home-quarantined individuals with COVID-19 during the peak of the pandemic. Methods This study used convenience and snowball sampling whereby a total of 30 semi-structured telephone interviews were conducted between March and April 2022. Inductive content analysis was used to analyze the data. Results Factors reported at the intrapersonal level included socioeconomic status and housing conditions, information and knowledge about COVID-19, long COVID, and psychological adjustments brought about by home quarantine. Factors identified at the interpersonal level included caregiving responsibilities, family relationships, and social support. Conclusions Findings from this study identified a combination of intra and interpersonal level factors influenced an individual's self-care practices as a result of pandemic-induced quarantine. It was particularly concerning for those individuals in socially and economically deprived groups, where access to services was challenging. This study also raised awareness of the ineffectual and insufficient knowledge individuals held of self-medication and overall COVID-19 management. A key recommendation is developing family-based resilience programmes to support and empower vulnerable families to better cope with the realities of self-quarantine.

A narrative review on the role of temperature and humidity in COVID-19: transmission, persistence, and epidemiological evidence

Since December 2019, the 2019 coronavirus disease (COVID-19) outbreak has become a global pandemic. Understanding the role of environmental conditions is important in impeding the spread of COVID-19. Given that airborne spread and contact transmission are considered the main pathways for the spread of COVID-19, this narrative review first summarized the role of temperature and humidity in the airborne trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Meanwhile, we reviewed the persistence of the virus in aerosols and on inert surfaces and summarized how the persistence of SARS-CoV-2 is affected by temperature and humidity. We also examined the existing epidemiological evidence and addressed the limitations of these epidemiological studies. Although uncertainty remains, more evidence may support the idea that high temperature is slightly and negatively associated with COVID-19 growth, while the conclusion for humidity is still conflicting. Nonetheless, the spread of COVID-19 appears to have been controlled primarily by government interventions rather than environmental factors.

Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection (preprint)

The ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg-1 of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-achieve membrane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19.

COVID-19 Recurrent Varies with Different Combinatorial Medical Treatments Determined by Machine Learning Approaches (preprint)

Various medical treatments for COVID-19 are attempted. After patients are discharged, SARS-CoV-2 recurring cases are reported and the recurrence could profoundly impact patient healthcare and social economics. To date, no data on the effects of medical treatments on recurrence has been published. We analyzed the treatment data of combinations of ten different drugs for the recurring cases in a single medical center, Shenzhen, China. A total of 417 patients were considered and 414 of them were included in this study (3 deaths) with mild-to-critical COVID-19. Patients were treated by 10 different drug combinations and followed up for recurrence for 28 days quarantine after being discharged from the medical center between February and May, 2020. We applied the Synthetic Minority Oversampling Technique (SMOTE) to overcome the rare recurring events in certain age groups and performed Virtual Twins (VT) analysis facilitated by random forest regression for medical treatment-recurrence classification. Among those drug combinations, Methylprednisolone/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate (0.133) as compared to the average recurring rate (0.203). For the younger group (age 20-27) or the older group (age 60-70), the optimal drug combinations are different, but the above combination is still the second best. For obese patients, the combination of Ribavirin/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate for age group of 20-50, whereas the combination of Interferon/Lopinavir/Ritonavir/Arbidol led to lowest recurring rate for age group of 50-70. The insights into combinatorial therapy we provided here shed lights on the use of a combination of (biological and chemical) anti-virus therapy and/or anti-cytokine storm as a potentially effective therapeutic treatment for COVID-19.

Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications (preprint)

IMPORTANCE How to appropriately care for patients who become PCR-negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still not known. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system if a subset were to be PCR-positive again with reactivated SARS-CoV-2. OBJECTIVE To characterize a single center COVID-19 cohort with and without recurrence of PCR positivity, and develop an algorithm to identify patients at high risk of retest positivity after discharge to inform health care policy and case management decision-making. DESIGN, SETTING, AND PARTICIPANTS A cohort of 414 patients with confirmed SARS-CoV-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. EXPOSURES Polymerase chain reaction (PCR) and IgM-IgG antibody confirmed SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Univariable and multivariable statistical analysis of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data to develop an algorithm to predict patients at risk of recurrence of PCR positivity. RESULTS 16.7% (95CI: 13.0%-20.3%) patients retest PCR positive 1 to 3 times after discharge, despite being in strict quarantine. The driving factors in the recurrence prediction model included: age, BMI; lowest levels of the blood laboratory tests during hospitalization for cholinesterase, fibrinogen, albumin, prealbumin, calcium, eGFR, creatinine; highest levels of the blood laboratory tests during hospitalization for total bilirubin, lactate dehydrogenase, alkaline phosphatase; the first test results during hospitalization for partial pressure of oxygen, white blood cell and lymphocyte counts, blood procalcitonin; and the first test episodic Ct value and the lowest Ct value of the nasopharyngeal swab RT PCR results. Area under the ROC curve is 0.786. CONCLUSIONS AND RELEVANCE This case series provides clinical characteristics of COVID-19 patients with recurrent PCR positivity, despite strict quarantine, at a 16.7% rate. Use of a recurrence prediction algorithm may identify patients at high risk of PCR retest positivity of SARS-CoV-2 and help modify COVID-19 case management and health policy approaches.

Knowledge, beliefs/attitudes and practices of rural residents in the prevention and control of COVID-19: An online questionnaire survey (preprint)

Background: The outbreak of COVID-19 in Wuhan quickly spread to 34 provinces, municipalities and autonomous regions in the country and 184 countries and regions around the world. It has drawn great attention from the International Health Organization and was declared an international public health emergency on January 31, 2020. Because the population is generally susceptible to the virus, there are no effective drugs and vaccines, and active participation of the entire population in self-protection and self-isolation has become the key to cutting off transmission routes and effectively controlling the epidemic. China has vast land and a vast area with a large population. Although the agricultural population has decreased this year with the acceleration of urbanization, according to national demographics, 40% of China's rural population is still living in remote areas. This population is relatively lacking in material and economic conditions and has limited access to medical services and education. Influencing factors such as traditional health habits and consciousness should not be underestimated in rural areas. In addition, the COVID-19 outbreak coincided with the Chinese New Year, and people’s return and post-holiday resumption of work greatly increased the chance of transmission of the virus. Rural residents accounted for 60% of the people returning to the Spring Festival. They are the most mobile and susceptible group and are at high risk of viral transmission. The knowledge, consciousness, attitude and behavior of rural residents with regard to COVID-19 control are related to the success or failure of epidemic prevention and control. To investigate the knowledge, attitudes and behaviors related to the prevention and control of COVID-19 among rural residents, to analyze the influencing factors, difficulties and challenges of prevention and control in this population, and to develop a plan to improve rural residents' awareness of COVID-19 prevention and control. Targeted interventions for prevention and control capabilities provide scientific evidence.Methods: A self-designed questionnaire to assess residents’ knowledge, attitudes and behaviors related to COVID-19 prevention and control was borrowed from the Questionnaire Star service platform, and snowball sampling was used to invite rural residents to complete the questionnaire on WeChat. Data analysis was performed with SPSS 22.0 statistical software.Results: A total of 554 valid questionnaires were collected. Rural residents’ average score of knowledge about the prevention and control of new coronary pneumonia was 39.75 ± 6.703, the average score of prevention and control attitude was 45.40 ± 3.341, and the average score of prevention and control behavior was 104.69 ± 12.167. Multiple linear regression analysis showed that male residents’ scores for knowledge, attitudes and behaviors related to SARS were significantly higher than those of women who had not experienced SARS (P <0.01); the scores of attitudes and behaviors of rural residents aged 30 and under were significantly higher than those of other age groups (P <0.01) 0.01); residents with an education level of junior high school or below and those who worked as farmers had significantly lower scores in knowledge, attitude, and behavior than those with other education levels (P <0.05); the knowledge and behavior scores of respondents with poor family economic conditions were significantly lower than those with good and moderate family economic conditions (P <0.05); and residents with chronic diseases and those living in areas with confirmed cases had significantly higher knowledge and behavior scores than those without chronic diseases and no or unknown living cases (P <0.05). Rural residents’ scores for knowledge and attitudes, attitudes and behaviors, and knowledge and behavior were positively correlated with new coronary pneumonia control (P <0.05). The difficulties and challenges they perceived during the epidemic were a lack of protective equipment and travel difficulties (lack of transportation) and weak awareness of prevention and control.Conclusions: Rural residents have a good grasp of COVID-19 and a positive attitude toward the need for prevention and control by individuals, communities, and the government during the epidemic. They use common chopsticks or split meals and take Chinese herbal medicines that nourish yin, invigorate the spleen, and nourish the lungs. Protective measures such as cleaning furniture with alcohol or chlorine disinfectant, returning home, and handwashing with soap before and after meals and after contact with pollutants need to be further strengthened. A lack of protective materials and weak awareness of prevention and control are the greatest difficulties and challenges experienced by rural residents during the epidemic.Trial registration:“Not applicable” in this section

Comparison of pulmonary availability and anti-inflammatory effect of dehydroandrographolide succinate via intratracheal and intravenous administration.

Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being <5 µm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.