ACP-Dnnel: Anti-coronavirus Peptides Prediction based on Deep Neural Network Ensemble Learning (preprint)

Background The ongoing COVID-19 pandemic has caused global economic crisis and dramatic loss of human life. There is an urgent need for safe and efficient anti-coronavirus infection drugs. Anti-coronavirus peptides (ACovPs) can inhibit coronavirus infection. With high-efficiency, low-toxicity, and broad-spectrum inhibitory effects on coronaviruses, they are promising candidates to be developed into a new type of anti-coronavirus drug. Experiment is the traditional way of ACovPs identification, which is less efficient and more expensive. With the accumulation of experimental data on ACovPs, computational prediction provides a cheaper and faster way to find anti-coronavirus peptides candidates.Methods In this study, we integrated several state-of-the-art machine learning methodologies to build nine classification models for the prediction of ACovPs. These models were pretrained using deep neural networks, and the performance of our ensemble model, ACP-Dnnel, was evaluated across three datasets and independent dataset.Results The highest accuracy of ACP-Dnnel reaches 98%, and the MCC value exceeds 0.9. On three different datasets, its average accuracy is 96.33%. After the latest independent data set validation, ACP-Dnnel improved at MCC, Sn and ACC values by 10.1%, 16.4% and 7.3% respectively. It is suggested that ACP-Dnnel can be helpful for the laboratory identification of ACovPs, speeding up the anti-coronavirus peptide drug discovery and development. We constructed the web server of anti-coronavirus peptides prediction and it is available at http://150.158.148.228:5000/.

Precautions against COVID-19 reduce respiratory virus infections among children in Southwest China

Acute respiratory tract infections pose a serious threat to the health of children worldwide, with viral infections representing a major etiology of this type of disease. Protective measures such as mask-wearing, social distancing, and hand hygiene can be effective in curbing the spread of severe acute respiratory syndrome coronavirus 2. These precautions may also have an impact on the spread of other respiratory viruses. In this study, we retrospectively compared the respiratory virus infections of children in Southwest China before and after the outbreak of COVID-19. Nasopharyngeal swabs were collected from 1578 patients under 14 years old with acute respiratory tract infection symptoms before and after COVID-19 pandemic. Nine common respiratory viruses including human bocavirus, human rhinoviruses, human coronaviruses, human adenoviruses, human metapneumovirus, respiratory syncytial virus, influenza A virus, influenza B virus, and parainfluenza virus were measured by advanced fragment analysis. The respiratory virus infection rates among children of all ages and genders in Southwest China under the precautions against COVID-19 pandemic were significantly lower than that of the same period before the pandemic. Our findings indicate that public health measures implemented during the COVID-19 pandemic, including strict mask-wearing, social distancing, and hand hygiene, may be effective in preventing the transmission of other respiratory viruses in children, thereby controlling the spread of infections.

PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application (preprint)

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.

Connections between Various Disorders: Combination Pattern Mining Using Apriori Algorithm Based on Diagnosis Information from Electronic Medical Records

Objective. Short-term or long-term connections between different diseases have not been fully acknowledged. This study was aimed at exploring the network association pattern between disorders that occurred in the same individual by using the association rule mining technique. Methods. Raw data were extracted from the large-scale electronic medical record database of the affiliated hospital of Xuzhou Medical University. 1551732 pieces of diagnosis information from 144207 patients were collected from 2015 to 2020. Clinic diagnoses were categorized according to “International Classification of Diseases, 10th revision”. The Apriori algorithm was used to explore the association patterns among those diagnoses. Results. 12889 rules were generated after running the algorithm at first. After threshold filtering and manual examination, 110 disease combinations (support≥0.001, confidence≥60%, lift>1) with strong association strength were obtained eventually. Association rules about the circulatory system and metabolic diseases accounted for a significant part of the results. Conclusion. This research elucidated the network associations between disorders from different body systems in the same individual and demonstrated the usefulness of the Apriori algorithm in comorbidity or multimorbidity studies. The mined combinations will be helpful in improving prevention strategies, early identification of high-risk populations, and reducing mortality.

Dynamical Behavior of SEIR-SVS Epidemic Models with Nonlinear Incidence and Vaccination

For some infectious diseases such as mumps, HBV, there is evidence showing that vaccinated individuals always lose their immunity at different rates depending on the inoculation time. In this paper, we propose an age-structured epidemic model using a step function to describe the rate at which vaccinated individuals lose immunity and reduce the age-structured epidemic model to the delay differential model. For the age-structured model, we consider the positivity, boundedness, and compactness of the semiflow and study global stability of equilibria by constructing appropriate Lyapunov functionals. Moreover, for the reduced delay differential equation model, we study the existence of the endemic equilibrium and prove the global stability of equilibria. Finally, some numerical simulations are provided to support our theoretical results and a brief discussion is given.

Combating the SARS-CoV-2 Omicron variant with non-Omicron neutralizing antibodies (preprint)

The highly mutated and transmissible Omicron variant has provoked serious concerns over its decreased sensitivity to the current coronavirus disease 2019 (COVID-19) vaccines and evasion from most anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies (NAbs). In this study, we explored the possibility of combatting the Omicron variant by constructing bispecific antibodies based on non-Omicron NAbs. We engineered ten IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and REGN10987 by fusing the single-chain variable fragments (scFvs) of two antibodies through a linker and then connecting them to the Fc region of IgG1. Surprisingly, eight out of ten bispecific antibodies showed high binding affinity to the Omicron receptor-binding domain (RBD) and exhibited extreme breadth and potency against pseudotyped SARS-CoV-2 variants of concern (VOCs) including Omicron, as well as authentic Omicron(+R346K) variants. Six bispecific antibodies containing the cross-NAb GW01 neutralized Omicron variant and retained their abilities to neutralize other sarbecoviruses. Bispecific antibodies inhibited Omicron infection by binding to the ACE2 binding site. A cryo-electron microscopy (cryo-EM) structure study of the representative bispecific antibody FD01 in complex with the Omicron spike (S) revealed 5 distinct trimers and one unique bi-trimer conformation. The structure and mapping analyses of 34 Omicron S variant single mutants elucidated that two scFvs of the bispecific antibody synergistically induced the RBD-down conformation into 3-RBD-up conformation, enlarged the interface area, accommodated the S371L mutation, improved the affinity between a single IgG and the Omicron RBD, and hindered ACE2 binding by forming bi-trimer conformation. Our study offers an important foundation for anti-Omicron NAb design. Engineering bispecific antibodies based on non-Omicron NAbs may provide an efficient solution to combat the Omicron variant.

Prevalence and predictors of post-traumatic stress disorder in patients with cured coronavirus disease 2019 (COVID-19) one month post-discharge Prevalencia y predictores de TEPT en pacientes recuperados de COVID-19 un mes después del alta 新型冠状病毒肺炎患者 (COVID-19) 出院一个月后创伤后应激障碍的患病率和预测因素

Background: Coronavirus disease 2019 (COVID-19) can place an immense psychological strain on the infected patient. The psychological distress can linger after the initial recovery from the infection. Objective: This study aimed to evaluate the prevalence and predictors of provisional post-traumatic stress disorder (PTSD) in patients with cured COVID-2019. Methods: The baseline survey was conducted from 10 to 25 February 2020 in patients with COVID-19 in a designated hospital. Demographic and clinical characteristics were acquired, and depression and anxiety levels were assessed, using the 9-item Patient Health Questionnaire and 7-item Generalized Anxiety Disorder scale, respectively. A follow-up survey was conducted 1 month post-discharge. PTSD symptoms were measured by the Impact of Event Scale-6 (IES-6) and patients’ perception of supportive care during hospitalization was investigated using a self-developed questionnaire. Results: In total, 114 patients completed both the baseline and follow-up surveys. Of these, 41 (36.0%) met the cut-off score for provisional PTSD diagnosis according to the IES-6. Female gender [odds ratio (OR) = 4.69, 95% confidence interval (CI) 1.54–14.37], educational level of high school or below (OR = 15.49, 95% CI 1.13–212.71), higher anxiety levels (OR = 1.34, 95% CI 1.12–1.61) and lower perceptions of emotional support during hospitalization (OR = 0.41, 95% CI 0.17–0.96) predicted a higher risk for provisional PTSD. Conclusions: PTSD is commonly seen in patients with COVID-19 1 month post-discharge. Female patients, and patients with lower educational levels, higher anxiety levels and lower perceptions of emotional support during hospitalization may be more likely to develop PTSD in the near future. Enhancing emotional support during hospitalization could help to prevent PTSD in patients with COVID-19. HIGHLIGHTS More than one-third ofpatients met the diagnostic criteria of probable PTSD 1 month post-discharge. Providing timely emotional support during hospitaliza-tion may be one of the key measures for preventing PTSD in patients with COVID-19.

PBL Teaching In Ultrasonography Resident Standardization Training In The COVID-19 Pandemic (preprint)

Objective: To study the effect of problem-based learning (PBL) method in ultrasonography (US) resident standardization training during the COVID-19 pandemic.Methods: Forty-six residents were randomly divided into two groups to participate in a 30-day US training program. The residents in the observation group underwent the PBL combined with lecture-based learning (LBL) mode, while the residents in the control group participated in an integration of the LBL mode alone, with 23 residents in each group. The basic theoretical test, practical examination, and questionnaire were used to evaluate the teaching effect of the PBL+ LBL mode and the LBL mode alone. Results: The basic theoretical pre-test score of observation group had no significant differences with that of the control group. The post-test theoretical score and practical score were higher in the observation group than that of the control group with significant differences (P<0.01). The results of the questionnaire showed that resident’s satisfaction in the observation group with PBL combined with LBL method was 96%, which was significantly higher than that of the control group with LBL mode alone (80%) (P<0.05).Conclusion: The combination of PBL with LBL method has obvious advantages over the LBL mode alone in the training of US residents during the COVID-19 pandemic.

An Open Natural Language Processing Development Framework for EHR-based Clinical Research: A case demonstration using the National COVID Cohort Collaborative (N3C) (preprint)

While we pay attention to the latest advances in clinical natural language processing (NLP), we can notice some resistance in the clinical and translational research community to adopt NLP models due to limited transparency, interpretability, and usability. In this study, we proposed an open natural language processing development framework. We evaluated it through the implementation of NLP algorithms for the National COVID Cohort Collaborative (N3C). Based on the interests in information extraction from COVID-19 related clinical notes, our work includes 1) an open data annotation process using COVID-19 signs and symptoms as the use case, 2) a community-driven ruleset composing platform, and 3) a synthetic text data generation workflow to generate texts for information extraction tasks without involving human subjects. The corpora were derived from texts from three different institutions (Mayo Clinic, University of Kentucky, University of Minnesota). The gold standard annotations were tested with a single institution's (Mayo) ruleset. This resulted in performances of 0.876, 0.706, and 0.694 in F-scores for Mayo, Minnesota, and Kentucky test datasets, respectively. The study as a consortium effort of the N3C NLP subgroup demonstrates the feasibility of creating a federated NLP algorithm development and benchmarking platform to enhance multi-institution clinical NLP study and adoption. Although we use COVID-19 as a use case in this effort, our framework is general enough to be applied to other domains of interest in clinical NLP.

Associations Between the Use of Non-Steroidal Anti-Inflammatory Drugs and Adverse Outcomes Among Patients with COVID-19: A Systematic Review and Meta-Analysis (preprint)

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes in COVID-19 patients. Therefore, this study aimed to synthesize the existing evidence on associations between the use of NSAIDs and adverse outcomes among patients with COVID-19.Methods: Systematic search of WHO COVID-19 Database, Medline, The Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to August 10, 2021, as well as a supplementary search of Google Scholar. We included comparative observational studies and randomized controlled trials that enrolled patients with COVID-19 who took NSAIDs before or after diagnosis of COVID-19. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-anlysis on the main outcomes, as well as selected subgroup analyses stratified by the type of NSAID.Fingings: Fifteen non-randomized studies evaluating 24700 adult COVID-19 patients were identified. The use of NSAIDs in patients with COVID-19, compared with no use of NSAIDs, was not significantly associated with an elevated mortality (odds ratio [OR]=0.94, 95% confidence interval [CI]: 0.87 to 1.02), or an increased probability of ICU admission (OR=1.35, 95% CI: 0.73 to 2.49), requiring mechanical ventilation (OR=1.23, 95% CI: 0.71 to 2.13), or administration of supplemental oxygen (OR=0.99, 95% CI: 0.91 to 1.08). The subgroup analyses revealed that the use of ibuprofen (OR=1.22, 95% CI: 0.32 to 4.60), etoricoxib (OR=0.36, 95% CI: 0.02 to 6.49) or celecoxib (zero deaths in both groups) were not associated with an increased risk of death in COVID-19 patients, compared with not using any NSAID.Interpretation: Fever is one of the main clinical symptoms of COVID-19. According to our findings, NSAIDs such as ibuprofen can be used to treat fever in COVID-19 patients safely.Funding: None to declare. Declaration of Interest: None to declare.

Risk Factors for Poor Prognosis in Children and Adolescents With COVID-19: A Systematic Review and Meta Analysis (preprint)

Background: The prognosis of children and adolescents with COVID-19 obtain increasing attention worldwide. This study provides the first systematic review and meta-analysis to identify risk factors which predict poor prognosis in this group.Methods: Electronic databases from inception to March, 2021 were searched for cohort studies, case-control studies and case series that investigated risk factors for poor prognosis of children and adolescents with COVID-19. We estimated the summary effect size by use of random-effects models and the 95% confidential interval (CI).Findings: We identified 33 studies, comprising 32,225 individuals. The risk of bias were generally high. In children and adolescents with COVID-19, risk of death was significantly increased in patients with MIS-C complication (odds ratio [OR]=58.00, 95% CI 6.39 to 526.79) and in need for intensive care (OR=15.25, 95% CI 1.98 to 117.44). Congenital heart disease (OR=2.90, 95% CI 1.26 to 6.67), chronic pulmonary disease (OR=3.45, 95% CI 1.47 to 8.07), and gastrointestinal symptoms (OR=2.11, 95% CI 1.43 to 3.12) increased the odds to be admitted to ICU; MIS-C complication (OR=70.00, 95% CI 6.51 to 752.27) and neurological diseases (OR=2.51, 95% CI 1.03 to 6.15) increased the odds of respiratory support; neurological diseases (OR=4.59, 95% CI 1.99 to 10.61), obesity (OR=2.51, 95% CI 2.02 to 3.12), C-reactive protein (CRP) level ≥80mg/L (OR=11.70, 95% CI 4.37 to 31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76 to 236.44) on admission increased the odds of progression to severe/critical disease.Interpretation: Very low to moderate quality evidence found that MIS-C, congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, and gastrointestinal symptoms, in need for intensive care, elevated CRP and D-dimer are risk factors for poor prognosis in children and adolescents with COVID-19.Funding: None.Declaration of Interests: The authors declare that they have no competing interests.

Electrospun polyvinyl butyral/ berberine membranes for antibacterial air filtration

At the beginning of 2020, the whole world suffered from the new coronavirus (COVID-19). Wearing a mask was believed to reduce the spread of the virus. The core material of a mask required good air permeability and efficient filtration. Electrospun materials may match these requirments. By electrospinning, we prepared polyvinyl butyral (PVB)/berberine hydrochloride (BH) membranes onto the spunbonded nonwovens. The composite meshes showed a porous structures, good air permeability (164±16 mm/s) and air filtration efficiency 96.4% for PM 0.3, 100% for PM 2.5, with pressure drop (108 Pa). Moreover, with the addition of BH, the as-spun membranes showed good antibacterial property for staphylococcus aureus. Furthermore, the prepared PVB/berberine membranes had good hydrophobicity with water contact angle higher than 140°. These results indicated that the fabricated PVB/berberine membranes have potential applications in mask and air filtration.

Strategies for Supplying Face Masks to the Population of Taiwan During the COVID-19 Pandemic. (preprint)

Background The use of face masks has become ubiquitous in Taiwan during the early COVID-19 pandemic. A name-based rationing system was established to enable the population of Taiwan to purchase face masks. This study is to assess the extent and fairness of face mask supply to the public in Taiwan.Methods The weekly face marks supplies were collected from name-based rationing system administrative statistics included national health insurance card and e-Mask selling record. National registered population statistics by age, gender, and district were collected from department of statistics ministry of the interior. The number of COVID-19 non-imported cases of Taiwan was collected from Taiwan centers of disease control.Results A total of 146,831,844 person times purchase records from February 6, 2020, to July 19, 2020, the weekly average face mask supply is 0.5 mask (per person) at the start of name-based rationing system, and gradually expanded to the maximum 5.1 masks (per person). Comparing the highest weekly total face mask supply (from Apr 9, 2020, to Apr 15, 2020) in aged 0–9 -, 10–19 -, 20–29 -, 30–39 -, 40–49 -, 50–69 -, 60–69 -,70–79 -, 80–89 -, 90–99, and > 100 years to the register population showed similar distribution between mask supplied people and total population (all standardized difference < 0.1).Conclusions The masks supply strategies has gradually escalated the number of face masks for the public, it not only has dominant decreased the barrier of acquiring face mask, but a fair supply for total population use of Taiwan.

Post-Infection Cognitive Impairments in Elderly Patients with COVID-19 (preprint)

Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for the prevention of cognitive decline in elderly population. This study aims to assess cognitive status and longitudinal decline at 6 months post-infection in elderly patients recovered from COVID-19.Methods: This cross-sectional study recruited 1013 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to March 13, 2020. In total, 262 uninfected living spouses of COVID-19 patients were selected as controls. Subjects were examined for their current cognitive status using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and longitudinal cognitive decline using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.Findings: COVID-19 patients had significantly lower TICS-40 scores (patients: 29.73±6.13; controls: 30.74±5.95, p=0.016) and higher IQCODE scores (patients: 3.40±0.81; controls: 3.15±0.39, p<0.001) than the controls. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients (TICS-40: 22.98±7.12 vs. 30.46±5.53, p<0.001; IQCODE: 4.06±1.39 vs. 3.33±0.68, p<0.001) and controls (TICS-40: 22.98±7.12 vs. 30.74±5.95, p<0.001; IQCODE: 4.06±1.39 vs. 3.15±0.39, p<0.001). Severe COVID-19 patients had a higher proportion of cases with a current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients and controls. COVID-19 severity (OR: 8.142, 95% CI: 5.007-13.239) was associated with worse current cognitive function. Older age (OR: 1.024, 95% CI: 1.003 to 1.046), COVID-19 severity (OR: 2.277, 95% CI: 1.308 to 3.964), mechanical ventilation (OR: 5.388, 95% CI: 3.007 to 9.656), and hypertension (OR: 1.866, 95% CI: 1.376 to 2.531) were associated with an increased risk of longitudinal cognitive decline.Interpretation: SARS-CoV-2 infection is associated with delayed cognitive decline in elderly population. COVID-19 patients with risk factors, including severe disease, older age, mechanical ventilation, and hypertension, should be intensively monitored for delayed cognitive decline. Funding: National Natural Science Foundation of China.Conflict of Interest: We declared no conflict of interests.Ethical Approval: The study protocols were approved by the institutional review boards of the hospitals. Verbal informed consent was obtained from all participants prior to the survey.

Strategies for Supplying Face Masks to the Population of Taiwan During the COVID-19 Pandemic (preprint)

Background: The use of face masks has become ubiquitous in Taiwan during the COVID-19 pandemic. A name-based rationing system was established to enable the population of Taiwan to purchase affordable medical face masks on-site and on the electronic platform (eMask). This study is to assess the extent and fairness of face mask supply to the public during the COVID-19 pandemic in Taiwan.Methods: This was a retrospective longitudinal study. The weekly face mask supply statistics were collected from name-based rationing system administration and included the National Health Insurance Card and eMask selling records. National registered population statistics by age, gender, and district were collected from the Ministry of the Interior Department of Statistics.Findings: Purchase records showed that the weekly average face mask supply was 0·5 mask per person at the beginning of the name-based rationing system and gradually increased to a maximum of 5·1 masks per person. Comparing monthly total face mask supply in aged 0-9,10-19, 20-59, and aged ≥60 years to the register population in Taiwan, exception first month implementation, the other period showed a similar distribution of mask supply to that to the total population. Comparing the highest weekly face mask supply among 0–9, 10–19, 20–29, 30–39, 40–49, 50–69, 60–69, 70–79, 80–89, 90–99, and ≥100 years age groups showed a similar distribution of mask supply to the total population.Interpretation: This study showed that mask supply ensured fair distribution throughout the population of Taiwan.Funding Statement: None.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: Using de-identified data, this study was exempt from informed consent.

Antibody-dependent enhancement (ADE) of SARS-CoV-2 infection in recovered COVID-19 patients: studies based on cellular and structural biology analysis (preprint)

Antibody-dependent enhancement (ADE) has been reported in several virus infections including dengue fever virus, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infection. To study whether ADE is involved in COVID-19 infections, in vitro pseudotyped SARS-CoV-2 entry into Raji cells, K562 cells, and primary B cells mediated by plasma from recovered COVID-19 patients were employed as models. The enhancement of SARS-CoV-2 entry into cells was more commonly detected in plasma from severely-affected elderly patients with high titers of SARS-CoV-2 spike protein-specific antibodies. Cellular entry was mediated via the engagement of Fc{gamma}RII receptor through virus-cell membrane fusion, but not by endocytosis. Peptide array scanning analyses showed that antibodies which promote SARS-CoV-2 infection targeted the variable regions of the RBD domain. To further characterize the association between the spike-specific antibody and ADE, an RBD-specific monoclonal antibody (7F3) was isolated from a recovered patient, which potently inhibited SARS-Cov-2 infection of ACE-2 expressing cells and also mediated ADE in Raji cells. Site-directed mutagenesis the spike RBD domain reduced the neutralization activity of 7F3, but did not abolish its binding to the RBD domain. Structural analysis using cryo-electron microscopy (Cryo-EM) revealed that 7F3 binds to spike proteins at a shift-angled pattern with one up and two down RBDs, resulting in partial overlapping with the receptor binding motif (RBM), while a neutralizing monoclonal antibody that lacked ADE activity binds to spike proteins with three up RBDs, resulting in complete overlapping with RBM. Our results revealed that ADE mediated by SARS-CoV-2 spike-specific antibodies could result from binding to the receptor in slightly different pattern from antibodies mediating neutralizations. Studies on ADE using antibodies from recovered patients via cell biology and structural biology technology could be of use for developing novel therapeutic and preventive measures for control of COVID-19 infection.

Clinical analysis of gastrointestinal bleeding in patients with severe coronavirus disease (COVID-19): A retrospective observational study (preprint)

Background: The epidemic of Novel coronavirus disease 2019(COVID-19) has attracted the great attention of people all over the world. Gastrointestinal bleeding in patients with COVID-19 has been studied rarely. We mean to investigate the clinical characteristics of gastrointestinal bleeding in patients with severe coronavirus disease (COVID-19).Methods: Nineteen severe COVID-19 patients with gastrointestinal bleeding were retrospectively studied. Clinical data, including medical history, symptoms, laboratory characteristics, and treatment, were collected and analyzed. We also compared the characteristics of patients with different degrees of bleeding.Results: Fourteen patients (73.6%) were men. Mean age was 63.8 (±15.6) years. Most patients (89.4%) had no history of gastrointestinal bleeding. The most common presentation of gastrointestinal bleeding was a positive fecal occult blood test (15/19 cases, 78.9%). Fifteen patients (78.9%) did not require blood transfusion. Five of 15 patients (33%) received anticoagulants and antiplatelet drugs before gastrointestinal bleeding in the mild bleeding group, and 2/4 (50%) in the severe bleeding group. Four of 15 patients (27%) died in the mild bleeding group and no patients died in the severe bleeding group.Conclusions: The presentations of gastrointestinal bleeding in severe COVID-19 patients are not obvious, and frequent fecal occult blood test is needed to detect gastrointestinal bleeding early. Patients receiving anticoagulants and antiplatelet drugs need a close observation for gastrointestinal bleeding. Gastrointestinal bleeding may not increase the mortality, after giving blood transfusion support therapy.