Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.

Multisystem inflammatory syndrome (MIS-C) with SARS-CoV-2 omicron variant BA.2.38 in a four-year-old Chinese girl: A case report.

We report a severe COVID-19 complicated with MIS-C in a girl treated by the author in China, and discuss the current research status and progress in the diagnosis and therapy of MIS-C in children. The patient was a 4-year-old child previously healthy who was referred to the hospital with a complaint of fever, finally, Multisystem inflammatory syndrome was diagnosed with COVID-19.

Risk factors for pulmonary embolism in patients with COVID-19: a systemic review and meta-analysis.

PURPOSE: To detect the risk factors for pulmonary embolism (PE) in patients with COVID-19. METHODS: Studies were searched for in PubMed, Cochrane Library, Web of Science, and EMBASE. Two authors independently screened articles and extracted data. The data were pooled by meta-analysis and three subgroup analyses were performed. RESULTS: Of the 2210 articles identified, 27 studies were included. Pooled analysis suggested that males (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.26-1.75, P = 0.000), obesity (OR 1.37, 95% CI 1.03-1.82, P = 0.033), mechanical ventilation (OR 3.34, 95% CI 1.90-5.86, P = 0.000), severe parenchymal abnormalities (OR 1.92, 95% CI 1.43-2.58, P = 0.000), ICU admission (OR 2.44, 95% CI 1.48-4.03, P = 0.000), and elevated D-dimer and white blood cell values (at two time points: hospital admission or closest to computed tomography pulmonary angiography) (P = 0.000) correlated with a risk for PE occurrence in COVID-19 patients. However, age and common comorbidities had no association with PE occurrence. Computed tomography pulmonary angiography, unclear-ratio/low-ratio, and hospitalization subgroups had consistent risk factors with all studies; however, other subgroups had fewer risk factors for PE. CONCLUSIONS: Risk factors for PE in COVID-19 were different from the classic risk factors for PE and are likely to differ in diverse study populations.

Development of a Genetically Engineered Bivalent Vaccine against Porcine Epidemic Diarrhea Virus and Porcine Rotavirus.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute diarrhea, vomiting, dehydration, and a high mortality rate in neonatal piglets. In recent years, PEDV has been associated with co-infections with other swine enteric viruses, including porcine rotavirus (PoRV), resulting in increased mortality among newborn piglets. In this paper, we developed a bivalent vaccine against PEDV and PoRV by constructing a recombinant PEDV encoding PoRV VP7 (rPEDV-PoRV-VP7). The recombinant virus was constructed by replacing the entire open reading frame 3 (ORF3) in the genome of an attenuated PEDV strain YN150 with the PoRV VP7 gene using reverse genetic systems. Similar plaque morphology and replication kinetics were observed in Vero cells with the recombinant PEDV compared to the wild-type PEDV. It is noteworthy that the VP7 protein could be expressed stably in rPEDV-PoRV-VP7-infected cells. To evaluate the immunogenicity and safety of rPEDV-PoRV-VP7, 10-day-old piglets were vaccinated with the recombinant virus. After inoculation, no piglet displayed clinical symptoms such as vomiting, diarrhea, or anorexia. The PoRV VP7- and PEDV spike-specific IgG in serum and IgA in saliva were detected in piglets after rPEDV-PoRV-VP7 vaccination. Moreover, both PoRV and PEDV neutralizing antibodies were produced simultaneously in the inoculated piglets. Collectively, we engineered a recombinant PEDV expressing PoRV VP7 that could be used as an effective bivalent vaccine against PEDV and PoRV.

The Impact of China's Paired Assistance Policy on the COVID-19 Crisis-An Empirical Case Study of Hubei Province.

To control the coronavirus pandemic (COVID-19), China implemented the Paired Assistance Policy (PAP). Local responders in 16 cities in Hubei Province were paired with expert teams from 19 provinces and municipalities. Fully supported by the country's top-down political system, PAP played a significant role in alleviating the COVID-19 pandemic in Hubei Province and China as a whole. In this study, we examined PAP using a two-way fixed effects model with the cumulative number of medical support personnel and cumulative duration as measurements. The results show personnel and material support played an active role in the nation's response to the COVID-19 public health crisis.

Mammalian viral suppressors of RNA interference.

The antiviral defense directed by the RNAi pathway employs distinct specificity and effector mechanisms compared with other immune responses. The specificity of antiviral RNAi is programmed by siRNAs processed from virus-derived double-stranded RNA by Dicer endonuclease. Argonaute-containing RNA-induced silencing complex loaded with the viral siRNAs acts as the effector to mediate specific virus clearance by RNAi. Recent studies have provided evidence for the production and antiviral function of virus-derived siRNAs in both undifferentiated and differentiated mammalian cells infected with a range of RNA viruses when the cognate virus-encoded suppressor of RNAi (VSR) is rendered nonfunctional. In this review, we discuss the function, mechanism, and evolutionary origin of the validated mammalian VSRs and cell culture assays for their identification.

Analysis of 256 pediatric oral and maxillofacial emergency in-patients during the outbreak of COVID-19.

BACKGROUND/AIMS: Pediatric oral and maxillofacial surgeons have faced severe challenges in ward management due to their high risk of exposure during the COVID-19 epidemic. The aim of this study was to analyze and summarize the treatment methods and infection prevention and control measures applied in emergency cases in the Department of Pediatric Oral and Maxillofacial Surgery, Children's Hospital of Chongqing Medical University, during the COVID-19 epidemic. METHODS: In this retrospective study, information was collected from 256 pediatric emergency patients who were treated from January 23, 2020 to August 9, 2021. The patients' data were statistically analyzed according to age, gender, disease and pathogenesis, operation time, and the main treatment applied in pediatric oral and maxillofacial emergency cases during the COVID-19 epidemic. RESULTS: During the epidemic period, 256 pediatric emergency patients were successfully treated. Among them, there were 170 boys and 86 girls. In all, 182 patients were diagnosed with oral or facial lacerations; 43 had jaw fractures; 26 had maxillofacial infections; and five had dento-alveolar fractures. A total of 246 patients underwent surgery under negative pressure with level 3 protection standards. No doctors or patients infected with COVID-19 were found throughout the stury period. CONCLUSIONS: Pediatric oral and maxillofacial emergency in-patients mainly experienced maxillofacial trauma during the COVID-19 epidemic, followed by infection. Effective diagnosis and treatment, and avoidance of COVID-19 infection can be achieved by strictly following epidemic prevention and treatment procedures.

Mobility restrictions and their implications on the rental housing market during the COVID-19 pandemic in China's large cities.

The COVID-19 pandemic has caused significant mobility restrictions and generated profound impacts on global socio-economic development. Mobility restrictions can generate significant impacts on the demand and supply sides of the rental housing market. By taking 77 large Chinese cities as cases, this research establishes a stepwise mediation effect test to evaluate the impacts of the pandemic on the rental housing market during Q1 2020. The results show that the confirmed cases were negatively associated with rental unit transactions, and the inter-city and intra-city movement played a significant role of mediating effects. Meanwhile, the impact of pandemic on rents lagged behind rental transaction in China's large cities, and the strict mobility controls caused the high vacancy rate of rental housing, leading to the bankruptcy of many housing rental agencies. Our research add to the burgeoning literature examining the mediating effect of mobility control between confirmed case and housing rental market. It demonstrates that the change of housing rental market induced by pandemic in China is the short-term influence on rental unit transaction, which is different from western countries. In China, a country with the most strict mobility control, the challenges come from the impact of pandemic on housing rental agencies.

Workplace and lifestyle heterogeneity in subjective wellbeing: Latent Class Analysis of UK Time Use Survey before and during COVID-19 (preprint)

Background: Mental health in the UK had deteriorated compared with pre-pandemic trends. The impact of COVID-19 on the subjective wellbeing of working populations with distinct lifestyles is not yet studied. Methods: Combining time use surveys collected pre- and during COVID-19, latent class analysis was used to identify distinct lifestyles based on aggregated daily activity patterns and reported working modes. We provide qualitative pen portraits alongside pre-versus-during pandemic comparisons of intraday time use and wellbeing patterns. Lifestyle heterogeneity in wellbeing was quantified in relation to aggregated activity types. Results: COVID-19 impact on wellbeing varied significantly between usual working hours (6am-6pm) and rest of the day. The decline in wellbeing outside of usual working hours was significant and consistent across lifestyles. During usual working hours, the direction of impact varied in line with working modes: wellbeing of homeworkers decreased, remained relatively stable for commuters, and increased for certain hybrid workers. Magnitude of impact correlates strongly with lifestyle: those working long and dispersed hours are more sensitive, whereas non-work dominated lifestyles are more resilient. Conclusion: The direction and magnitude of impact from COVID-19 were not uniformly manifested across activity types, time of day, and latent lifestyles. Blurring work-life boundaries and general anxiety about the pandemic may be key determinants of the decline outside of usual working hours. During usual working hours, strong yet complex correlations between wellbeing and time-use changes suggested that policies aiming to enhance wellbeing of workers need to consider not only spatial flexibility but also provide wider support for temporal flexibility.

Identification of potential target endoribonuclease NSP15 inhibitors of SARS-COV-2 from natural products through high-throughput virtual screening and molecular dynamics simulation.

SARS-CoV-2 wreaks havoc around the world, triggering the COVID-19 pandemic. It has been confirmed that the endoribonuclease NSP15 is crucial to the viral replication, and thus identified as a potential drug target against COVID-19. The NSP15 protein was used as the target to conduct high-throughput virtual screening on 30,926 natural products from the NPASS database to identify potential NSP15 inhibitors. And 100 ns molecular dynamics simulations were performed on the NSP15 and NSP15-NPC198199 system. In all, 10 natural products with high docking scores with NSP15 protein were obtained, among which compound NPC198199 scored the highest. The analysis of the binding mode between NPC198199 and NSP15 found that NPC198199 would form H-bond interactions with multiple key residues at the catalytic site. Subsequently, a series of post-dynamics simulation analyses (including RMSD, RMSF, PCA, DCCM, RIN, binding free energy, and H-bond occupancy) were performed to further explore inhibitory mechanism of compound NPC198199 on NSP15 protein at the molecular level. The research strongly indicates that the 10 natural compounds screened can be used as potential inhibitors of NSP15, and provides valuable information for the subsequent drug discovery of anti-SARS-CoV-2. PRACTICAL APPLICATIONS: Natural products play an important role in the treatment of many difficult diseases. In this study, high-throughput virtual screening technology was used to screen the natural product database to obtain potential inhibitors against endoribonuclease NSP15. The binding mechanism between natural products and NSP15 was investigated at the molecular level by molecular dynamics technology so that it is expected to become candidate drugs for the treatment of SARS-CoV-2. We hope that our research can provide new clue to combat COVID-19 and overcome the epidemic situation as soon as possible.

Omicron variant as nature's solution to the COVID-19 pandemic.

WHAT IS KNOWN AND OBJECTIVE: Omicron is a variant of the COVID-19 virus that is causing considerable concern worldwide, with an increasing number of countries re-imposing national lockdowns. Our objective is to comment on its impact and to suggest that, threatening as it is, Omicron may well contribute to a resolution of the current pandemic. COMMENT: On 31 December 2019, the World Health Organization (WHO) reported on a cluster of cases of pneumonia in Wuhan, China. Soon after, Chinese investigators who made the discovery identified the causative virus as a new coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An effective vaccine was licenced for emergency use within a year of its first sequencing. SARS-CoV-2, in common with many respiratory viruses, mutates rapidly, and the challenge for vaccine developers is to obtain vaccines that are effective against the new variants. The licenced first-generation vaccines were fortunately all highly effective against the variant known as Delta. The variant of greatest current concern is the Omicron variant, a highly infectious agent, which seems to show a significant vaccine escape with existing vaccines. Infection protects against further infection. If Omicron turns out to cause less severe disease, it may well be a contributor to ending the pandemic. WHAT IS NEW AND CONCLUSION: It is unlikely that the available vaccines will bring rapid control of the current pandemic, given their patchy availability worldwide and the residual pool of unvaccinated people. New vaccines take time to develop and to deploy even in the age of mRNA vaccines. If Omicron turns out to be relatively mild, it may well be that when we look back at the history of the current pandemic, the variant would be seen as a contributor to its solution. The hand of nature may well show more largesse than the developed nations in immunizing the world.

SARS-CoV-2 pseudovirus infectivity and expression of viral entry-related factors ACE2, TMPRSS2, Kim-1, and NRP-1 in human cells from the respiratory, urinary, digestive, reproductive, and immune systems.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of syndromes involving multiple organ systems and is primarily mediated by viral spike (S) glycoprotein through the receptor-binding domain (RBD) and numerous cellular proteins including ACE2, transmembrane serine protease 2 (TMPRSS2), kidney injury molecule-1 (Kim-1), and neuropilin-1 (NRP-1). In this study, we examined the entry tropism of SARS-CoV-2 and SARS-CoV using S protein-based pseudoviruses to infect 22 cell lines and 3 types of primary cells isolated from respiratory, urinary, digestive, reproductive, and immune systems. At least one cell line or type of primary cell from each organ system was infected by both pseudoviruses. Infection by pseudoviruses is effectively blocked by S1, RBD, and ACE2 recombinant proteins, and more weakly by Kim-1 and NRP-1 recombinant proteins. Furthermore, cells with robust SARS-CoV-2 pseudovirus infection had strong expression of either ACE2 or Kim-1 and NRP-1 proteins. ACE2 glycosylation appeared to be critical for the infections of both viruses as there was a positive correlation between infectivity of either SARS-CoV-2 or SARS-CoV pseudovirus with the level of glycosylated ACE2 (gly-ACE2). These results reveal that SARS-CoV-2 cell entry could be mediated by either an ACE2-dependent or -independent mechanism, thus providing a likely molecular basis for its broad tropism for a wide variety of cell types.

Understanding the Spatial Impact of COVID-19: New Insights from Beijing after One Year into Post-Lockdown Recovery (preprint)

This paper studies the spatial impact of COVID-19 pandemic through the lens of intra-city population and house rent changes in Beijing, China. Drawing on multiple geospatial data sets, we find that the pandemic has flattened the housing bid-rent curve in Beijing, which corroborates existing literature mainly based on cities in developed countries. Through regression analysis and spatial equilibrium modelling, we identify key mechanisms of the flattened bid-rent curve and the accompanying decentralisation of residents. First, workplace population change, particularly in central Beijing, seems to be the main factor contributing to the resident population and house rent changes. Second, we find no significant evidence on the spatial impact from remote working, as the share of remote working in Beijing appears low after about one year recovery. This finding contrasts to existing studies where remote working has been perceived as the main driver for urban spatial structure change in a developed country context. Third, through a novel method for quantifying locational preference changes, it is found that the observed decentralisation trend in Beijing, ceteris paribus, may also be associated with increased (decreased) preference for living in suburban (central) locations. However, the preference change for central locations is marginal, hence providing an early rebuttal of the ‘demise of centres’ proposition.

D-Limonene Is a Potential Monoterpene to Inhibit PI3K/Akt/IKK-α/NF-κB p65 Signaling Pathway in Coronavirus Disease 2019 Pulmonary Fibrosis.

At the time of the prevalence of coronavirus disease 2019 (COVID-19), pulmonary fibrosis (PF) related to COVID-19 has become the main sequela. However, the mechanism of PF related to COVID (COVID-PF) is unknown. This study aimed to explore the key targets in the development of COVID-PF and the mechanism of d-limonene in the COVID-PF treatment. The differentially expressed genes of COVID-PF were downloaded from the GeneCards database, and their pathways were analyzed. d-Limonene was molecularly docked with related proteins to screen its pharmacological targets, and a rat lung fibrosis model was established to verify d-limonene's effect on COVID-PF-related targets. The results showed that the imbalance between collagen breakdown and metabolism, inflammatory response, and angiogenesis are the core processes of COVID-PF; and PI3K/AKT signaling pathways are the key targets of the treatment of COVID-PF. The ability of d-limonene to protect against PF induced by bleomycin in rats was reported. The mechanism is related to the binding of PI3K and NF-κB p65, and the inhibition of PI3K/Akt/IKK-α/NF-κB p65 signaling pathway expression and phosphorylation. These results confirmed the relationship between the PI3K-Akt signaling pathway and COVID-PF, showing that d-limonene has a potential therapeutic value for COVID-PF.

Public health risks of regional assessment of the coronavirus diseases 2019 in Wenzhou, Zhejiang

Objective To establish an index system for comprehensive evaluation of public health risks of the coronavirus diseases 2019(COVID-19),and to evaluate the COVID-19 in different counties(districts) of Wenzhou, so as to provide scientific evidence for the implementation of targeted prevention and control measures. Methods Rank-sum ratio(RSR) was used to evaluate 12 quality indicators of 5 categories by brain storming method with data including the incidence of COVID-19 and public health risks of COVID-19 epidemic in Wenzhou during January and February, 2020.The regional public health risks of COVID-19 were ranked according to rank-sum ratio size. Results The top three counties(districts) with most reported cases were Yueqing,Rui′an and Lucheng,accounting for 61.90%(312/504) of the total number in Wenzhou.The ratio of import cases to indigenous cases was 1∶1.39.The top three counties(districts) reported most clustering epidemics were Yueqing,Rui′an and Lucheng,accounting for 62.03%(49/79) of the total number in Wenzhou.About 70.63%(356/504)of the cases were found before the medical visit.The time from onset to first medical visit was 2.39 d, and the time from medical visit to diagnosis was 4.49 d.The average number of close contacts for confirmed cases was 29,and the top three counties(districts)with most reported average number of close contacts were Jingkai(135 cases),Dongtou(59 cases)and Cangnan(50 cases).Among all13 counties(districts),Longgang,Wencheng and Jingkai were at lower level,Yueqing and Lucheng were at higher level,and the other counties(districts)were at the middle level of public health risks of COVID-19. Conclusions RSR method is flexible and simple.It has no specific requirements on samples,and can eliminate the effects of comprehensive assessment indexes of different dimension.It has high value in evaluating public health risks of the COVID-19.The evaluating of public health risks of COVID-19 should be strengthened.Targeted prevention and control measures should be taken to positively prevent the outbreak of COVID-19.

Mental health status among Chinese healthcare-associated infection control professionals during the outbreak of coronavirus disease 2019: A national cross-sectional survey.

ABSTRACT: Recently, the coronavirus disease 2019 (COVID-19) epidemic has greatly threatened global public health. The responsibility of healthcare-associated infection control professionals (ICPs) is to prevent and control the nosocomial infections. The mental health status of ICPs deserves more attention, however, the correlational research is still lacking. This study aims to investigate the incidence and risk factors of mental health status among ICPs in China during the outbreak of COVID-19.A national cross-sectional survey was performed. The online questionnaire was completed by 9228 ICPs from 3776 hospitals throughout China. Data collection tools were used, including demographics data questionnaire, the Chinese version of the 12-item general health questionnaire (GHQ-12) and the Chinese version of the psychological capital questionnaire (PCQ) for medical staff. Univariate and multivariable analyses were conducted.The total score of mental health of Chinese ICPs was 3.45 ±â€Š2.57. 5608 (60.77%) ICPs might have mental health problems. The psychological capital was in the upper-middle level with an average score of 3.72 ±â€Š0.38. An increased mental health problem risk was associated with the greater self-efficacy and working in the public hospital; a significantly lower risk was obtained by working in the second-class hospital rather than in the third-class hospitals. Besides, mental health problem risk of ICPs working in hospitals of the western economic region or northeast economic region was more significant than that in hospitals of the central economic region. However, a lower risk was caused by the unmarried than married, and working years in department ≤1 year contributed to the lower risk than that >20 years. Moreover, fewer working hours per week, higher values of hope, and optimism each were contributed to a lower risk.Chinese healthcare-associated ICPs were under different levels of mental health problems in fighting against COVID-19. More importantly, we should actively deal with the mental health problem of ICPs and help them get rid of psychological disorders.

Questionnaire survey on occupational exposure of health care workers working in COVID-19 isolation wards of designated hospitals in 2020

OBJECTIVE: To investigate the status of occupational exposure of health care workers working in the COVID-19 isolation wards of designated hospitals so as to take targeted measures for occupational protection. METHODS By means of convenient sampling method, a self-designed questionnaire was applied to investigate the status of occupational exposure of health care workers who supported or worked in the designated hospitals for patients with COVID-19 from Mar. 1, to Mar. 5, 2020. RESULTS: Among the 293 health care workers working in the COVID-19 isolation wards, 28.00% had occupational exposure. The skin or hair' contacting with contaminated outer surface of personal protective equipment(PPE)(65.85%) was the most common type of occupational exposure. The removal of PPE(60.98%) and the operations that may generate aerosol(47.56%) were the major links where the occupational exposure took place. After the occupational exposure occurred, 68.29% of the health care workers carried out emergency treatment, and 71.95% of the health care workers were able to report the exposure according to standard procedures. The top 3 medical operations that were most likely to cause exposure were tracheotomy, bronchoscopy and endotracheal intubation. The top 3 nursing operations that were most likely to cause occupational exposure were artificial airway nursing, sputum suction and throat swab collection. The top 3 risk factors that were most likely to cause occupational exposure of health care workers were the implementation of operations that may generate aerosol, failure to comply with disinfection and isolation system, and sudden changes in the patients' condition for emergency rescue. CONCLUSION: There are varying degrees of occupational exposure among the health care workers working in the COVID-19 isolation wards of designated hospitals. It is necessary for the management department of medical institutions to formulate practical prevention and control measures according to the high frequency types, operation links and risk factors of the occupational exposure so as to reduce the risk of occupational exposure among the health care workers.

Protective Factors and Risk Factors in Patients with COVID-19 Pneumonia and/or Infection (preprint)

This study examined 50 COVID-19 patients who have been cured in Anhui Province, China. The protective factors and risk factors for these patients were investigated. By comparing CT-negative and CT-positive patients, we found protective factors in blood: lymphocytes, eosinophils number and %, basophils%, reticulocyte%, high fluorescence reticulocyte ratio, and reticulocyte absolute value. Comparing patients with underlying disease and without underlying disease, we found protective factors in blood: lymphocytes%, basophils%, large platelets, and low-fluorescent reticulocyte ratio. Regarding the biochemistry indicators, albumin/globulin, apolipoprotein and prealbumin can be considered as protective factors for patients without lung symptoms. Urea, glucose, total bile aicd, creatinine and hypersensitivity CRP can be considered as risk factors for patients with underlying diseases. For patients with repeatedly negative and positive results in nucleic acid tests, they were at a medium level in terms of both protective and risk factors, explaining the mild symptoms and repeatedly results in nucleic acid tests.

Development a Nomogram to Predict Prognosis in Severe and Critically Ill Patients with COVID-19 (preprint)

Background: The number of deaths caused by COVID-19 are on the rising worldwide. This study focused on severe and critically ill COVID-19, aim to explore independent risk factors associated with disease severity and to build a nomogram to predict patients’ prognosis.Methods: Patients with laboratory-confirmed COVID-19 admitted to the Union Hospital, Tongji Medical College and Hankou Hospital of Wuhan, China, from February 8th to April 6th, 2020. LASSO Regression and Multivariate Analysis were applied to screen independent factors. COX Nomogram was built to predict the 7-day, 14-day and 1-month survival probability.Results: A total of 115 severe [73 (63.5%)] and critically ill [42 (36.5%)] patients were included in this study, containing 93 (80.9%) survivors and 22 (19.1%) non-survivors. For disease severity, D-dimer [OR 6.33 (95%CI, 1.27-45.57], eosinophil percentage [OR 8.02 (95%CI, 1.82-45.04)], total bilirubin [OR 12.38 (95%CI, 1.24-223.65)] and lung involvement score [OR 1.22 (95%CI, 1.08-1.40)] were the independent factors associated with critical illness. Troponin [HR 9.02 (95%CI, 3.02, 26.97)] and total bilirubin [HR 3.16 (95%CI, 1.13, 8.85)] were the independent predictors for patients’ prognosis. Troponin≥26.2 ng/L and total bilirubin＞20 μmol/L were associated with poor prognosis. The nomogram based on the independent risk factors had a C-index of 0.92 (95%CI, 0.87, 0.98) for predicting survival probability. The survival nomogram validated in the critically ill patients had a C-index of 0.83 (95%CI: 0.75, 0.94).Conclusions: In conclusion, in severe and critically ill patients with COVID-19, D-dimer, eosinophil percentage, total bilirubin and lung involvement score were the independent risk factors associated with disease severity. The proposed survival nomogram accurately predicted prognosis. The survival analysis may suggest that early incidence of multiple organ dysfunction may be an important predictor of poor prognosis.