An integrated strategy to identify COVID-19 causal genes and characteristics represented by LRRC37A2.

Genome-wide association study (GWAS) could identify host genetic factors associated with coronavirus disease 2019 (COVID-19). The genes or functional DNA elements through which genetic factors affect COVID-19 remain uncharted. The expression quantitative trait locus (eQTL) provides a path to assess the correlation between genetic variations and gene expression. Here, we firstly annotated GWAS data to describe genetic effects, obtaining genome-wide mapped genes. Subsequently, the genetic mechanisms and characteristics of COVID-19 were investigated by an integrated strategy that included three GWAS-eQTL analysis approaches. It was found that 20 genes were significantly associated with immunity and neurological disorders, including prior and novel genes such as OAS3 and LRRC37A2. The findings were then replicated in single-cell datasets to explore the cell-specific expression of causal genes. Furthermore, associations between COVID-19 and neurological disorders were assessed as a causal relationship. Finally, the effects of causal protein-coding genes of COVID-19 were discussed using cell experiments. The results revealed some novel COVID-19-related genes to emphasize disease characteristics, offering a broader insight into the genetic architecture underlying the pathophysiology of COVID-19.

Genome-wide Mendelian randomization and single-cell RNA sequencing analyses identify the causal effects of COVID-19 on 41 cytokines.

The elevated levels of inflammatory cytokines have attracted much attention during the treatment of COVID-19 patients. The conclusions of current observational studies are often controversial in terms of the causal effects of COVID-19 on various cytokines because of the confounding factors involving underlying diseases. To resolve this problem, we conducted a Mendelian randomization analysis by integrating the GWAS data of COVID-19 and 41 cytokines. As a result, the levels of 2 cytokines were identified to be promoted by COVID-19 and had unsignificant pleiotropy. In comparison, the levels of 10 cytokines were found to be inhibited and had unsignificant pleiotropy. Among down-regulated cytokines, CCL2, CCL3 and CCL7 were members of CC chemokine family. We then explored the potential molecular mechanism for a significant causal association at a single cell resolution based on single-cell RNA data, and discovered the suppression of CCL3 and the inhibition of CCL3-CCR1 interaction in classical monocytes (CMs) of COVID-19 patients. Our findings may indicate that the capability of COVID-19 in decreasing the chemotaxis of lymphocytes by inhibiting the CCL3-CCR1 interaction in CMs.

Telehealth-Based Family Conferences with Implementation of Shared Decision Making Concepts and Humanistic Communication Approach: A Mixed-Methods Prospective Cohort Study.

Smartphone-enabled, telehealth-based family conferences represent an attractive and safe alternative to deliver communication during the COVID-19 pandemic. However, some may fear that the therapeutic relationship might be filtered due to a lack of direct human contact. The study aims to explore whether shared decision-making model combining VALUE (Value family statements, Acknowledge emotions, Listen, Understand the patient as a person, Elicit questions) and PLACE (Prepare with intention, Listen intently and completely, Agree on what matters most, Connect with the patient's story, Explore emotional cues) framework can help physicians respond empathetically to emotional cues and foster human connectedness in a virtual context. Twenty-five virtual family conferences were conducted in a national medical center in Taiwan. The expression of verbal emotional distress was noted in 20% of patients and 20% of family members, while nonverbal distress was observed in 24% and 28%, respectively. On 10-point Likert scale, the satisfaction score was 8.7 ± 1.5 toward overall communication and 9.0 ± 1.1 on meeting the family's needs. Adopting SDM concepts with VALUE and PLACE approaches helps physicians foster connectedness in telehealth family conferences. The model has high participant satisfaction scores and may improve healthcare quality among the pandemic.

The change of atmospheric ozone formation sensitivity in Fujian Province based on OMI satellite data during the period of COVID-19

Based on the OMI satellite data, the characteristics of atmospheric ozone sensitivity in Fujian province and its nice municipalities during the period of COVID-19 epidemic were assessed with HCHO and NO2 vertical column densities as proxies for ozone sensitivity. The results showed that Fujian Province was dominated by VOCs-limited regime before the pandemic with the controlled area proportion of 46.5%. The other two regimes: NOx-VOCs-limited regime and NOx-limited regime, controlled 25.0% and 28.5% of the area, respectively. The area proportion controlled by VOXs-limited regime was highest in Xiamen and lowest in Nanping. During the period with strict pandemic control policies, VOXs-limited regime, NOx-VOCs-limited regime and NOx-limited regime controlled 29.5%, 21.1%, and 49.4% of the area, respectively. The area proportion controlled by NOx-limited regime was highest in Ningde and lowest in Putian. During the stable period, VOXs-limited regime, NOx-VOCs-limited regime and NOx-limited regime controlled 23.1%, 29.1%, and 47.8% of the area, respectively. NOx-limited regime was the dominant regime with highest area proportion controlled in Nanping and lowest area proportion in Xiamen. Compared with the before pandemic period, the area proportion of Xiamen controlled by VOCs-limited regime was obviously reduced（38.1% less） during the period with strict control policies, and the lowest reduction was in Sanming with a moderate decrease of 7.9%. According to the conversion results, Putian, Quanzhou, and Xiamen were categorized into the first city group where changes in ozone sensitivity were jointly influenced by its precursors including formaldehyde（HCHO） and nitrogen dioxide（NO2）, while other cities could be categorized into the second group where ozone sensitivities were mainly affected by NO2 column concentrations. Therefore, effective strategies for ozone reduction would be more complex in the first group of cities.

Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection.

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30-32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tß4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tß4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tß4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tß4 (rhTß4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTß4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host's immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTß4 to the treatment of human CoV diseases such as COVID-19.

Smartphone-Enabled, Telehealth-Based Family Conferences in Palliative Care During the COVID-19 Pandemic: Pilot Observational Study.

BACKGROUND: In the palliative care setting, infection control measures implemented due to COVID-19 have become barriers to end-of-life care discussions (eg, discharge planning and withdrawal of life-sustaining treatments) between patients, their families, and multidisciplinary medical teams. Strict restrictions in terms of visiting hours and the number of visitors have made it difficult to arrange in-person family conferences. Phone-based telehealth consultations may be a solution, but the lack of nonverbal cues may diminish the clinician-patient relationship. In this context, video-based, smartphone-enabled family conferences have become important. OBJECTIVE: We aimed to establish a smartphone-enabled telehealth model for palliative care family conferences. Our model integrates principles from the concept of shared decision making (SDM) and the value, acknowledge, listen, understand, and elicit (VALUE) approach. METHODS: Family conferences comprised three phases designed according to telehealth implementation guidelines-the previsit, during-visit, and postvisit phases. We incorporated the following SDM elements into the model: "team talk," "option talk," and "decision talk." The model has been implemented at a national cancer treatment center in Taiwan since February 2020. RESULTS: From February to April 2020, 14 telehealth family conferences in the palliative care unit were analyzed. The patients' mean age was 73 (SD 10.1) years; 6 out of 14 patients (43%) were female and 12 (86%) were married. The primary caregiver joining the conference virtually comprised mostly of spouses and children (n=10, 71%). The majority of participants were terminally ill patients with cancer (n=13, 93%), with the exception of 1 patient with stroke. Consensus on care goals related to discharge planning and withdrawal of life-sustaining treatments was reached in 93% (n=13) of cases during the family conferences. In total, 5 families rated the family conferences as good or very good (36%), whereas 9 were neutral (64%). CONCLUSIONS: Smartphone-enabled telehealth for palliative care family conferences with SDM and VALUE integration demonstrated high satisfaction for families. In most cases, it was effective in reaching consensus on care decisions. The model may be applied to other countries to promote quality in end-of-life care in the midst of the COVID-19 pandemic.

Machine learning based early warning system enables accurate mortality risk prediction for COVID-19.

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.

Clinical retrospective study on the efficacy of Qingfei Paidu decoction combined with Western medicine for COVID-19 treatment.

BACKGROUND: Coronavirus disease 2019 (COVID-19)2 has emerged as a global pandemic. However, as effective treatments for this disease are still unclear, safe and efficient therapies are urgently needed. Qingfei Paidu decoction (QPD)3 is strongly recommended in the Chinese Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 6th Edition). However, clinical research data on the effects of QPD on COVID-19 are scarce. Our study aimed to explore the effects of combined treatment with QPD and Western medicine on COVID-19. METHODS: In this study, 63 patients with confirmed COVID-19 were analyzed. During the first 14 days of hospitalization, patients with deteriorating symptoms were administered QPD along with Western medicine therapy (the antiviral medicine selected from interferon, lopinavir, or arbidol). The clinical characteristics and blood laboratory indices (blood routine, inflammatory factors, and multi-organ biochemical indices) were examined, and the total lung severity scores were evaluated in each patient by reviewing chest computed tomography before treatment and at the end of treatment. RESULTS: Before QPD treatment, the combined treatment group showed higher blood C-reactive protein levels and more severe pulmonary inflammation and clinical symptoms than the Western medicine treatment group. Both groups met the discharge criteria after a similar length of hospitalization. At the end of treatment, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in both groups (P <  0.05). In contrast, C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels were improved only in the combined treatment group (P <  0.05), and C-reactive protein and creatine kinase were the most pronounced (P <  0.01). Compared with baseline, at the end of treatment, the proportion of patients with normal values of C-reactive protein, total lymphocyte count, and lactate dehydrogenase were increased in the combined treatment group (P < 0.05), whereas no significant difference was observed in the Western medicine treatment group (P >  0.05). CONCLUSION: The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended to mitigate the extent of multi-organ impairment. Long-term randomized controlled trials with follow-up evaluations are required to confirm the results presented here.

Mechanism of apoptosis regulation induced by coronavirus in infected cells

Coronaviruses are the common pathogenic microorganisms that infect human and animals and cause health hazards. Cell immune responses are induced to fight against coronavirus infection in infected cells. In order to initiate transcription and translation and to assemble the next generation in infected cells, viruses respond to cellular immune response and participate in many cellular activities. When specific receptors such as death receptors are bound by viral proteins, cells initiate apoptotic processes. Some viral proteins play critical roles in promoting or inhibiting apoptosis in the apoptotic process. For example, S protein induces external apoptotic pathway by binding to death receptor in cell membrane, M and S proteins induce internal apoptotic pathway by causing endoplasmic reticulum stress and Ca2+ imbalance. On the other hand, E protein inhibits apoptosis in infected cells. This article reviews the mechanism of pro-apoptotic or anti-apoptotic effects of coronavirus on infected cells. By understanding the different roles of different viral proteins in extrinsic and intrinsic apoptotic pathways, it is expected to provide ideas for artificial intervention in cell regulation for prevention and control of coronavirus infection.