Changes in the Facial Microbiome in Healthy Women After Wearing Masks during COVID-2019 (preprint)

Wearing masks has become a new normal in our daily lives because of the global outbreak of COVID-2019 (COVID-19). To compare the differences in the facial microbiota of healthy women before and after wearing masks and to further explore the probable effect of the habits of regularly wearing masks on the facial microbiome, we re-enrolled the same 19 healthy female participants in our previous study and detected the microbial composition of facial DNA samples using 16S rRNA gene amplicon sequencing. Both alpha and beta diversity, and the abundance and function of facial microflora of recruited healthy women changed remarkably before and after wearing masks. The destination with different air quality indices, which ever was the strongest factor on microbial composition before wearing masks, no longer contributed to both microbiota composition and pathway after wearing masks. Sufficient sleep protected skin from sensitivity and apoptosis, which might be related to Prevotella expression and the function of cytochrome c. Maskne was the common complication of wearing masks. Suitable mask-wearing habits should be recommended to avoid facial skin problems.

Health-seeking behavior of COVID-19 cases during the first eight weeks of the outbreak in Singapore: differences between local community and imported cases and having visits to single or multiple healthcare providers.

BACKGROUND: COVID-19 is a novel pandemic affecting almost all countries leading to lockdowns worldwide. In Singapore, locally-acquired cases emerged after the first wave of imported cases, and these two groups of cases may have different health-seeking behavior affecting disease transmission. We investigated differences in health-seeking behavior between locally-acquired cases and imported cases, and within the locally-acquired cases, those who saw single versus multiple healthcare providers. METHODS: We conducted a retrospective study of 258 patients who were diagnosed with COVID-19 from 23 January to 17 March 2020. Variables related to health-seeking behavior included number of visits prior to hospitalization, timing of the first visit, duration from symptom onset to admission, and places where the cases had at least one visit. RESULTS: Locally-acquired cases had longer duration from onset of symptoms to hospital admission (median 6 days, interquartile range [IQR] 4-9) than imported cases (median 4 days, IQR 2-7) (p < 0.001). Singapore residents were more likely to have at least one visit to private clinics and/or government-subsidized public clinics than non-residents (84.0% vs. 58.7%, p < 0.001). Among locally-acquired cases, those who sought care from a single healthcare provider had fewer visits before their hospital admissions compared with those who went to multiple providers (median 2 vs. 3, p = 0.001). CONCLUSION: Our study indicates the need to encourage individuals to seek medical attention early on in their patient journey, particularly from the same healthcare provider. This in turn, would facilitate early detection and isolation, hence limiting local transmission and enabling better control of the COVID-19 outbreak.

The Effect of Online Support of an Internet Plus Shared Care Diabetes Management Model on Metabolic Indicators for Patients With Type 2 Diabetes During the COVID-19 Pandemic (preprint)

Purpose: This study aimed to explore the influences of online support of an Internet plus Shared Care diabetes management model on metabolic indicators and the differences before and after the coronavirus disease 2019 (COVID-19) pandemic. Method: Type 2 diabetes patients who visited the Peking University First Hospital Internet plus Shared Care clinic from May 18, 2020 to June 20, 2020 (after the COVID-19 pandemic subsided) were enrolled in the study. The age, gender, usage of insulin, and duration of diabetes of the patients were collected. The glycosylated hemoglobin (HbA1c), interval between two consecutive visits, communication frequencies with online diabetes educators through an app, online self-monitoring of blood glucose (SMBG) and upload count and SMBG pairing count (before–after meal) were collected before (prior to January 20, 2020) and after (from May 18, 2020 to June 20, 2020) the COVID-19 pandemic for logistic regression analysis. The R-3.4.4 and TWANG programs were used for analysis. The group of patients whose HbA1c did not change during the pandemic was the control group, while the group of patients with improved HbA1c was the dependent variable. Independent variables included age, gender, duration of disease, insulin usage, online communication amount, SMBG count, and SMBG pairing count. Propensity score matching (PSM) was applied with age, duration, gender, body mass index (BMI), HbA1c, low density lipoprotein- cholesterol (LDL-C), and blood pressure (BP) at baseline as the concomitant variable. After the PSM weighting, the average treatment effect (ATE) of post-pandemic BMI, HbA1c, LDL-C, and BP was compared with the baseline. Results: A total of 387 patients were enrolled in the study including 184 female (47.5%). The baseline values were the following: age, 61.7±9.4 year;, duration of diabetes, 11.7±8.2 years; BMI, 25.9±3.8Kg/m 2 ; HbA1c, 7.2±1.3%; LDL-C, 2.49±0.85mmol/L; systolic BP, 130.8±14.9 mmHg; and diastolic BP, 81.1±40.9 mmHg. Among variables, online communication amounted to a statistically significant contribution to the HbA1c improvement after the COVID-19 pandemic (OR=2.178, p=0.003). During the pandemic, each patient received 18 (3, 56) times online communication support per quarter. Patients were divided into four groups by quartiles: Q1 (more than 56 times/quarter, n=95), Q2 (18–56 times/quarter, n=97), Q3 (3–18 times/quarter, n=93), and Q4 (0–3 times/quarter, n=102). After PSM, post-pandemic data showed significant differences. Between-group variance was found in HbA1c (Q1 vs. Q3, -0.42±0.16%, p=0.009; Q1 vs. Q4, -0.53±0.15%, p=0.0009) and BMI (Q1 vs. Q3, -1.2±0.5, p=0.02; Q1 vs. Q4 -1.5±0.7, p=0.01) of patients. Conclusion: During the COVID-19 pandemic, high-quality online support of the Internet plus Shared Care diabetes management model can significantly improve the HbA1c and BMI of type 2 diabetes patients.

Characterizing User Susceptibility to COVID-19 Misinformation on Twitter (preprint)

Though significant efforts such as removing false claims and promoting reliable sources have been increased to combat COVID-19 "misinfodemic", it remains an unsolved societal challenge if lacking a proper understanding of susceptible online users, i.e., those who are likely to be attracted by, believe and spread misinformation. This study attempts to answer {\it who} constitutes the population vulnerable to the online misinformation in the pandemic, and what are the robust features and short-term behavior signals that distinguish susceptible users from others. Using a 6-month longitudinal user panel on Twitter collected from a geopolitically diverse network-stratified samples in the US, we distinguish different types of users, ranging from social bots to humans with various level of engagement with COVID-related misinformation. We then identify users' online features and situational predictors that correlate with their susceptibility to COVID-19 misinformation. This work brings unique contributions: First, contrary to the prior studies on bot influence, our analysis shows that social bots' contribution to misinformation sharing was surprisingly low, and human-like users' misinformation behaviors exhibit heterogeneity and temporal variability. While the sharing of misinformation was highly concentrated, the risk of occasionally sharing misinformation for average users remained alarmingly high. Second, our findings highlight the political sensitivity activeness and responsiveness to emotionally-charged content among susceptible users. Third, we demonstrate a feasible solution to efficiently predict users' transient susceptibility solely based on their short-term news consumption and exposure from their networks. Our work has an implication in designing effective intervention mechanism to mitigate the misinformation dissipation.

Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor (preprint)

Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.

Diagnostic performance of COVID-19 serological assays during early infection: A systematic review and meta-analysis of 11 516 samples.

OBJECTIVE: The use of coronavirus disease 2019 (COVID-19) serological testing to diagnose acute infection or determine population seroprevalence relies on understanding assay accuracy during early infection. We aimed to evaluate the diagnostic performance of serological testing in COVID-19 by providing summary sensitivity and specificity estimates with time from symptom onset. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed was performed up to May 13, 2020. All English language, original peer-reviewed publications reporting the diagnostic performance of serological testing vis-à-vis virologically confirmed SARS-CoV-2 infection were included. RESULTS: Our search yielded 599 unique publications. A total of 39 publications reporting 11 516 samples from 8872 human participants met eligibility criteria for inclusion in our study. Pooled percentages of IgM and IgG seroconversion by Day 7, 14, 21, 28 and after Day 28 were 37.5%, 73.3%, 81.3%, 72.3% and 73.3%, and 35.4%, 80.6%, 93.3%, 84.4% and 98.9%, respectively. By Day 21, summary estimate of IgM sensitivity was 0.872 (95% CI: 0.784-0.928) and specificity 0.973 (95% CI: 0.938-0.988), while IgG sensitivity was 0.913 (95% CI: 0.823-0.959) and specificity 0.960 (95% CI: 0.919-0.980). On meta-regression, IgM and IgG test accuracy was significantly higher at Day 14 using enzyme-linked immunosorbent assay (ELISA) compared to other methods. CONCLUSIONS: Serological assays offer imperfect sensitivity for the diagnosis of acute SARS-CoV-2 infection. Estimates of population seroprevalence during or shortly after an outbreak will need to adjust for the delay between infection, symptom onset and seroconversion.

Clinical Course and Risk Factors for Liver Injury of Severe and Critical Patients With COVID-19 (preprint)

Background: Information regarding the clinical course of COVID-19 patients with liver injury is very limited, especially in severe and critical patients. The objective of this study was to describe the characteristics and clinical course of liver function in patients admitted with severe and/or critical SARS-CoV-2 infection, as well as explore the risk factors that affect liver function in the enrolled COVID-19 patients.Methods: Information on clinical characteristics of 63 severe and critical patients with confirmed COVID-19 were collected and analyzed.Results: The incidence of abnormal aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the critical group was significantly higher than in the severe group (respectively 81.48%, 81.49%, 62.67%, and 45.71%, 63.88%, 22.86%, p＜0.05). The time for liver function parameters to reach their extremes was approximately 2-3 weeks after admission. The independent factors associated with liver injury were patients with invasive ventilators, decreased percentages of neutrophils, lymphocytes and monocytes, and sequential organ failure assessment (SOFA) score ≥ 2 (p＜0.05).Conclusions: Abnormal liver tests are commonly observed in severe and critical patients with COVID-19. The patients with severe illness should be closely observed to monitor liver function parameters, particularly when they present with independent risk factors of liver injury.

Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network (preprint)

The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2 RNA directly binds to the targeted loci in human genome and further interacts with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.

How fear and collectivism influence public's preventive intention towards COVID-19 infection: A study based on big data from the social media (preprint)

Background: Despite worldwide calls for precautionary measures to combat COVID-19, the public's preventive intention still varies significantly among different regions. Exploring the influencing factors of the public's preventive intention is very important to curtail the spread of COVID-19. Previous studies have found that fear can effectively improve the public's preventive intention, but they ignore the impact of differences in cultural values. The present study examines the combined effect of fear and collectivism on the public's preventive intention towards COVID-19 through the analysis of social media big data. Methods: : The Sina microblog posts of 108,914 active users from Chinese mainland 31 provinces were downloaded. The data was retrieved from January 11 to February 21 2020. Afterwards, we conducted a province-level analysis of the contents of downloaded posts. Three lexicons were applied to automatically recognise the scores of fear, collectivism, and preventive intention of 31 provinces. After that, a multiple regression model was established to examine the combined effect of fear and collectivism on the public's preventive intention towards COVID-19. The simple slope test and the Johnson-Neyman technique were used to test the interaction of fear and collectivism on preventive intention. Results: : The study reveals that: (a) both fear and collectivism can positively predict people's preventive intention and (b) there is an interaction of fear and collectivism on people's preventive intention, where fear and collectivism reduce each other's positive influence on people's preventive intention. Conclusion: The promotion of fear on people's preventive intention may be limited and conditional, and values of collectivism can well compensate for the promotion of fear on preventive intention. These results provide scientific inspiration on how to enhance the public's preventive intention towards COVID-19 effectively.

Differences in COVID-19 Related Testing and Healthcare Utilization by Race and Ethnicity in the Veterans Health Administration (preprint)

Importance: Recent reports indicate differences in COVID-19 related care and outcomes between Black and White Americans.Objective: We examine the COVID-19 related healthcare utilization and mortality by race and ethnicity of patients tested for SARS-CoV-2 in the Veterans Health Administration (VHA).Design: A retrospective cohort study.Setting: We used the VHA COVID-19 shared data resources between February 1 and June 30, 2020.Participants: Veterans tested for SARS-CoV-2 virus by VHA.Exposure(s): Three racial-ethnicity groups of Black, Hispanic, and White (as reference).Main Outcome(s) and Measure(s): Main outcomes are testing rate, positivity rate, hospitalization rate, ICU admission rate, and in-hospital mortality. Controlling for sex, age and Elixhauser comorbidity index, we report adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) from logistic regression models.Results: Of 8,667,996 active veteran enrollees, 252,702 were tested by VHA from February to June, 2020, with 20,500 positive results and 4,790 hospitalizations. The testing rate was 4.4% among Black and 4.7% among Hispanic veterans compared to White veterans, 2.8%. The testing positivity rate was similarly elevated among Black and Hispanic veterans compared to White veterans. The aORs of hospitalization in Black veterans (1.88; 95% CI 1.74, 2.03) and Hispanic veterans (1.41; 95% CI 1.25, 1.60) were higher compared to White veterans. No significant differences by race and ethnicity were observed in OR or aOR of ICU admission and in-hospital death among hospitalized patients.Conclusions and Relevance: On a national level, the VHA was more likely to test and hospitalize Black and Hispanic veterans compared to White veterans, but there were no significant differences in ICU admission or in-hospital mortality among those hospitalized. This pattern of differences may relate to social determinants of health, implicit biases, or preferences for VHA care affecting initial care seeking, but not in-hospital outcomes.Funding Statement: The study is funded by seed funding from Baylor College of Medicine,Houston, Texas, United States, and the Center for Innovations in Quality, Effectiveness and Safety (VA HSRD CIN 13-413), Michael E. DeBakey VA Medical Center, Houston, Texas, United States. Declaration of Interests: None to declareEthics Approval Statement: The study was approved by the institutional review board (IRB) of Baylor College of Medicine and the Research and Development Committee of the Michael E. DeBakey VA Medical Center.

Stigma towards Wuhan people during the COVID-19 epidemic: An exploratory study based on social media (preprint)

Background: Stigma associated with infectious diseases is common and causes various negative effects on stigmatized people. With Wuhan as the center of the COVID-19 outbreak in China, its people have become an object of stigmatization. To provide necessary information for stigma mitigation, this study aims to identify the stigmatizing attitudes towards Wuhan people and trace their changes as the COVID-19 progressed in China by analyzing related posts on social media. Methods: We collected a total of 19,780 Weibo posts containing the keyword ‘Wuhan people’ and performed a content analysis to identify stigmatizing attitudes in the posts. Then we divided our observation time into three periods and performed Repeated Measures ANOVA to compare the differences in attitudes in three periods. Results: Results show that stigma was mild with 2.46% of related posts being stigmatizing. The percentages of stigmatizing posts differed significantly in 3 periods (F (2,66) = 5.60, p <.01, η2= 0.15). The percentages of ‘Infectious’ posts (F (2,66) = 3.69, p <.05, η2 = 0.10) and ‘Stupid’ posts (F (2,66) = 3.65, p <.05, η2 = 0.10) are significantly different in 3 periods. The percentages of ‘Irresponsible’ posts is not significant different in 3 periods (F (2,66) = 0.63, p =.53, η2 = 0.02). After government interventions, stigma didn’t reduce significantly, and stigma with ‘Infectious’ attitude even increased. It was until the government interventions took effect that stigma significantly reduced. Conclusions: This study found that stigma towards Wuhan people included diverse attitudes and changed at different periods. After government interventions but before they took effect, stigma with ‘Infectious’ attitude increased. After government interventions took effect, general stigma, and stigma with ‘Infectious’ and ‘Stupid’ attitudes decreased. This study constitutes an important endeavor to understand the stigma towards Wuhan people in China during the COVID-19 epidemic. Implications for stigma reduction and improvement of the public’s perception in different periods of epidemic control are discussed.

Stigma Towards Wuhan People During the COVID-19 Epidemic: An Exploratory Study Based on Social Media (preprint)

Background: Stigma associated with infectious diseases is common and causes various negative effects on stigmatized people. With Wuhan as the center of the COVID-19 outbreak in China, its people have become an object of stigmatization. To provide necessary information for stigma mitigation, this study aims to identify the stigmatizing attitudes towards Wuhan people and trace their changes as the COVID-19 progressed in China by analyzing related posts on social media.Methods: We collected a total of 19,780 Weibo posts containing the keyword ‘Wuhan people’ and performed a content analysis to identify stigmatizing attitudes in the posts. Then we divided our observation time into three periods and performed Repeated Measures ANOVA to compare the differences in attitudes in three periods. Results: Results show that stigma was mild with 2.46% of related posts being stigmatizing. The percentages of stigmatizing posts differed significantly in 3 periods (F (2,66) = 5.60, p <.01, η2= 0.15). The percentages of ‘Infectious’ posts (F (2,66) = 3.69, p <.05, η2 = 0.10) and ‘Stupid’ posts (F (2,66) = 3.65, p <.05, η2 = 0.10) are significantly different in 3 periods. The percentages of ‘Irresponsible’ posts is not significant different in 3 periods (F (2,66) = 0.63, p =.53, η2 = 0.02). After government interventions, stigma didn’t reduce significantly, and stigma with ‘Infectious’ attitude even increased. It was until the government interventions took effect that stigma significantly reduced. Conclusions: This study found that stigma towards Wuhan people included diverse attitudes and changed at different periods. After government interventions but before they took effect, stigma with ‘Infectious’ attitude increased. After government interventions took effect, general stigma, and stigma with ‘Infectious’ and ‘Stupid’ attitudes decreased. This study constitutes an important endeavor to understand the stigma towards Wuhan people in China during the COVID-19 epidemic. Implications for stigma reduction and improvement of the public’s perception in different periods of epidemic control are discussed.

Carboxypeptidase B Inhibits Over-activation of Anaphylatoxin-neutrophil Extracellular Trap Axis in COVID-19 Patients (preprint)

Background: Thrombosis and coagulopathy are highly prevalent in severe patients with COVID-19 and increase the risk of death. Immunothrombosis has recently been demonstrated to contribute to the thrombotic events in COVID-19 patients with coagulopathy. Neutrophil extracellular traps (NETs) are primary components of immunothrombosis, whereas the mechanism of NET formation remains unclear. We aim to explore the clinical roles of NETs and the regulation of complement on the NET formation in COVID-19. Methods: : We recruited 135 COVID-19 patients and measured plasma levels of C5, C3, cell-free DNA and myeloperoxidase-DNA. We detected complement-induced NET formation by immunofluorescent staining and evaluated the cytotoxicity to vascular endothelial HUVEC cells by CCK-8 assay. Results: : We found that the plasma levels of complements (C3 and C5) and NETs were closely related to coagulopathy and multiple organ dysfunction in patients with COVID-19. By using anti-C3a and anti-C5a antibodies, we revealed that the complement component anaphylatoxins in the plasma of COVID-19 patients strongly induced NET formation. The pathological effect of the anaphylatoxin-NET axis on the damage of vascular endothelial cells could be relieved by recombinant carboxypeptidase B (CPB), a stable homolog of enzyme CPB2 which can degrade anaphylatoxins to inactive products. Conclusions: : Over-activation in anaphylatoxin-NET axis plays a pathological role in COVID-19. Early intervention in anaphylatoxins might help prevent thrombosis and disease progression in COVID-19 patients.

Clinical Course and Risk Factors for Liver Injury of Severe and Critical Patients With COVID-19: A Single-centered, Retrospective, Observational Study (preprint)

Background: The information regarding the clinical course of COVID-19 patients with liver injury is very limited, especially in severe and critical patients. The objective of this study was to describe the characteristics and clinical course of patients admitted with severe and/or critical SARS-CoV-2 infection in liver function, as well as explore the risk factors that affect liver function in the enrolled COVID-19 patients.Methods: Information on clinical characteristics of 63 severe and critical patients with confirmed COVID-19 were collected and analyzed.Results: The incidence of abnormal aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the critical group was obviously higher than in the severe group (81.48%, 81.49%, 62.67%, and 45.71%, 63.88%, 22.86%, respectively, p＜0.05). The time for liver parameters to reach their peak or trough was approximately 2-3 weeks. No significant difference was observed in cycle threshold values of open reading frame 1ab and nucleocapsid protein gene on admission or at the peak among liver injury group, abnormal group and normal group (p＞0.05). Patients with invasive ventilator, decreased percentage of neutrophil, lymphocyte and monocyte, and SOFA score ≥ 2 (p＜0.05) were the independent factors associated with liver injury.Conclusions: Abnormal liver tests are commonly observed in severe and critical patients with COVID-19. The time of 2-3 weeks after admission should be paid attention to patients with critical COVID-19 in case of the occurrence of liver injury. As independent risk factors for the occurrence of liver injury, regarding decreased ratio of neutrophils, lymphocytes and monocytes, the requirement of invasive ventilator, and SOFA score ≥2 , patients with these abnormal parameters should be of particular concerned during hospitalization.

Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. METHODS: We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study-a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed. FINDINGS: Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14-28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00-0·48]) compared with infection with wild-type virus only. INTERPRETATION: The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines. FUNDING: National Medical Research Council Singapore.

Comparative therapeutic efficacy of interferon and combination Kaletra plus interferon alpha-2b against SARS-CoV-2 (preprint)

Background: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people’s attentions. Whether interferon alfa-2b or Kaletra plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown.Methods: This is a retrospective cohort study of 123 laboratory-confirmed COVID-19 patients between Jan.13 2020 and Apr. 23. All patients received standard supportive care and regular clinical monitoring, patients were assigned to standard care group (n=12), interferon alfa-2b group (n=44), and combination Kaletra plus interferon alfa-2b group (n=67) according to their therapies. The primary endpoint for this study was the duration of oxygen-support requirement and virus clearance time. The associations of therapies with these outcomes were assessed by Cox proportional hazards regression. Results: Baseline clinical and laboratory characteristics were similar among 3 groups (p＞0.05). There was no significant association of Kaletra /interferon alfa-2b with faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% CI, 0.45–1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI, 0.32–1.11]; P = 0.10 in Kaletra plus interferon alfa-2b group). The duration of oxygen-support requirement in therapy groups similarly showed no significant association. There were no differences among 3 groups in the incidence of adverse events (p＞0.05).Conclusions: In patients with confirmed SARS-CoV-2 infection, no benefit was observed with interferon alfa-2b and Kaletra plus interferon alfa-2b treatment beyond standard care. Further trials in appropriately randomized design may contribute to validate the effective role and safety profile of the test drugs. 

COVID-19 management in a UK NHS Foundation Trust with a High Consequence Infectious Diseases centre: a detailed descriptive analysis (preprint)

BackgroundRecent large national and international cohorts describe the baseline characteristics and outcome of hospitalised patients with COVID-19, however there is little granularity to these reports. We aimed to provide a detailed description of a UK COVID-19 cohort, focusing on clinical decisions and patient journeys. MethodsWe retrospectively analysed the management and 28-day outcomes of 316 consecutive adult patients with SARS-CoV-2 PCR-confirmed COVID-19 admitted to a large NHS Foundation Trust with a tertiary High Consequence Infectious Diseases centre in the North of England. FindingsMost patients were elderly (median age 75) with multiple comorbidities. One quarter were admitted from residential or nursing care. Symptoms were consistent with COVID-19, with cough, fever and/or breathlessness in 90.5% of patients. Two thirds of patients had severe disease on admission. Mortality was 81/291 (27.8%). Most deaths were anticipated; decisions to initiate respiratory support were individualised after consideration of patient wishes, premorbid frailty and comorbidities, with specialist palliative care input where appropriate. 22/291 (7.6%) patients were intubated and 11/22 (50%) survived beyond discharge. Multiple logistic regression identified age as the most significant risk factor for death (OR 1.09 [95% CI 1.06 - 1.12] per year increase, p < 0.001). InterpretationThese findings provide important clinical context to outcome data. Deaths were anticipated, occurring in patients with advance decisions on ceilings of treatment. Age was the most significant risk factor for death, confirming that demographic factors in the population are a major influence on hospital mortality rates. FundingFunding was not required.

Clinical features of 162 fatal cases of COVID-19: a multi-center, retrospective study (preprint)

Understanding the epidemiological and clinical characteristics of fatal cases infected with SARS-CoV-2 is import to develop appropriate preventable intervention programs in hospitals. Demographic data, clinical symptoms, clinical course, co-morbidities, laboratory findings, CT scans, treatments and complications of 162 fatal cases were retrieved from electric medical records in 5 hospitals of Wuhan, China. The median age was 69.5 years old (IQR: 63.0-77.25; range: 29-96). 112 (69.1%) cases were men. Hypertension (45.1%) was the most common co-morbidity, but 59 (36.4%) cases had no co-morbidity. At admission, 131 (81.9%) cases were assessed as severe or critical. However, 39 (18.1%) were assessed as moderate. Moderate cases had a higher prevalence of hypertension and chronic lung disease comparing with severe or critical cases (P<0.05, respectively). 126 (77.8%) and 132 (81.5%) cases received antiviral treatment and glucocorticoids, respectively. 116 (71.6%) cases were admitted to ICU and 137 (85.1%) cases received mechanical ventilation. Respiratory failure or acute respiratory distress syndrome (93.2%) was the most common complication. The young cases of COVID-19, without co-morbidity and in a moderate condition at admission could develop fatal outcome. We need to be more cautious in case management of COVID-19 for preventing the fatal outcomes.

Evaluation the auxiliary diagnosis value of antibodies assays for detection of novel coronavirus (SARS-Cov-2) causing an outbreak of pneumonia (COVID-19) (preprint)

Background: The spread of an novel coronavirus (SARS-CoV-2, previously named 2019-nCoV) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. Elucidating the diagnostic value of different methods, especially the auxiliary diagnosis value of antibodies assays for SARS-CoV-2 infection is helpful for improving the sensitivities of pathogenic-diagnosis, providing timely treatment, and differentiating the infected cases from the healthy, thus preventing further epidemics. Methods: Medical records from 38 patients with confirmed SARS-CoV-2 infection in the Second People's Hospital of Fuyang from January 22, 2020 to February 28, 2020 were collected and retrospectively analyzed. Specimens including throat swabs, sputum and serum were collected during the hospitalization period, viral RNAs and serum IgM-IgG antibodies to SARS-CoV-2 were measured respectively. The detectability of different methods as well as the auxiliary diagnosis value of antibodies test for SARS-CoV-2 infection were analyzed. Results: Among 38 patients, the total seropositive rate for IgM and IgG was 50.0% and 92.1%, respectively. Two patients remained seronegative throughout the course of illness. In the early phase of illness, the RNA test for sputum specimens possessed the highest detectability(92.3%), followed by the the RNA test for throat swabs (69.2%), and the antibodies assays presented lower positive rates(IgM, 23.0%, IgG, 53.8%). While, the sensitivity of antibodies assays overtook that of RNA test since day 8 after onset (IgM, 50.0%; IgG, 87.5%). Of note, the positive rate of throat swabs was only 13.0% for cases in later phase([≥]15 d.a.o), and the sensitivities of IgM and IgG rose to 52.2% and 91.3%, respectively. Combined use of antibodies assay and qRT-PCR at the same time was able to improve the sensitivities of pathogenic-diagnosis, especially for the throat swabs group at the later stage of illness. Moreover, most of these cases with undetectable viral RNA in throat swabs specimens at the early stage of illness were able to be IgM/IgG seropositive after 7 days. Conclusions: The antibodies detection against SARS-CoV-2 offers vital clinical information for physicians, and could be used as an effective supplementary indicator for suspected cases of negative viral nucleic acid detection or in conjunction with nucleic acid detection in the diagnosis of suspected cases.

Clinical Data on Hospital Environmental Hygiene Monitoring and Medical Staffs Protection during the Coronavirus Disease 2019 Outbreak (preprint)

Background: The outbreak of coronavirus disease 2019 (COVID-19) has placed unprecedented challenges on hospital environmental hygiene and medical staff protection. It is crucial to assess hospital environmental hygiene to understand the most important environmental issues for controlling the spread of COVID-19 in hospitals. Objective: To detect the presence of COVID-19 in the samples from the area at risk of contamination in the First Hospital of Jilin University. Methods: Viruses in the air were collected by natural sedimentation and air particle sampler methods. Predetermined environmental surfaces were sampled using swabs at seven o'clock in the morning before disinfection. The real-time reverse-transcription PCR method was used to detect the existence of COVID-19 pathogens. Results: Viruses could be detected on the surfaces of the nurse station in the isolation area with suspected patients and in the air of the isolation ward with an intensive care patient. Conclusion: Comprehensive monitoring of hospital environmental hygiene during pandemic outbreaks is conducive to the refinement of hospital infection control. It is of great significance to ensure the safety of medical treatment and the quality of hospital infection control through the monitoring of environmental hygiene.