Thrombotic microangiopathy with kidney involvement in a patient with coronavirus disease 2019: A case report and literature review (preprint)

Background and aim: Millions of people worldwide have suffered from coronavirus disease 2019 (COVID-19). COVID-19 can lead to coagulopathy and thrombosis, presenting as pulmonary artery thromboembolism, deep vein thrombosis, and thrombotic microangiopathy (TMA), the latter being a rare finding in affected patients’ kidneys. Prior reports have rarely addressed the pathophysiology, clinical presentations, and therapeutic options in patients with COVID-19-associated TMA. Case presentation: We herein described a case of renal biopsy-proven TMA after COVID-19 in a 36-year-old woman. Initial examination revealed inflammation, acute kidney injury (AKI), anemia, and thrombocytopenia. She was diagnosed with hemolytic uremic syndrome, pulmonary infection, and COVID-19. After treatment, her condition stabilized but remained hemodialysis-dependent after discharge. One week later, she was re-hospitalized, and physical examination showed anemia and bilateral lower extremity edema. Abdominal ultrasound showed increased bilateral kidney echogenicity. Whole-exome sequencing detected an unknown variant of the C3 gene associated with hemolytic uremic syndrome susceptibility type 5/complement C3 deficiency. Kidney biopsy showed renal artery lesions, including small arteriole endothelial swelling, intimal thickening, mucinous degeneration, luminal occlusion, and small arterial wall necrosis. She received plasma exchange and steroids with significant renal function recovery. Conclusion: TMA likely contributed to AKI after COVID-19,thus supporting the notion that TMA plays an important role in the pathogenesis of COVID-19-related kidney injury. When diagnosing and treating COVID-19 patients with abnormal renal function, clinicians should incorporate kidney biopsy and genetic testing for the complement system, identify renal-limited and systemic TMA, and treat accordingly, which can improve patient outcomes.

Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine (preprint)

As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains the same mRNA backbone as the original BNT162b2 vaccine, modified by the incorporation of XBB.1.5-specific sequence changes in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation that adopts a flexible and predominantly open one-RBD-up state, with high affinity binding to the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and the phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose primary series in naive mice. Strong S-specific Th1 CD4+ and IFN{gamma}+ CD8+ T cell responses were also observed. These findings, together with prior experience with variant-adapted vaccine responses in preclinical and clinical studies, suggest that the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine is anticipated to confer protective immunity against dominant SARS-CoV-2 strains. ONE-SENTENCE SUMMARYThe monovalent Omicron XBB.1.5-adapted BNT162b2 mRNA vaccine encodes a prefusion-stabilized spike immunogen that elicits more potent neutralizing antibody responses against homologous XBB.1.5 and other circulating sublineage pseudoviruses compared to the bivalent Wild Type + Omicron BA.4/5 BNT162b2 vaccine, thus demonstrating the importance of annual strain changes to the COVID-19 vaccine.

Transferable Graph Neural Fingerprint Models for Quick Response to Future Bio-Threats (preprint)

Fast screening of drug molecules based on the ligand binding affinity is an important step in the drug discovery pipeline. Graph neural fingerprint is a promising method for developing molecular docking surrogates with high throughput and great fidelity. In this study, we built a COVID-19 drug docking dataset of about 300,000 drug candidates on 23 coronavirus protein targets. With this dataset, we trained graph neural fingerprint docking models for high-throughput virtual COVID-19 drug screening. The graph neural fingerprint models yield high prediction accuracy on docking scores with the mean squared error lower than $0.21$ kcal/mol for most of the docking targets, showing significant improvement over conventional circular fingerprint methods. To make the neural fingerprints transferable for unknown targets, we also propose a transferable graph neural fingerprint method trained on multiple targets. With comparable accuracy to target-specific graph neural fingerprint models, the transferable model exhibits superb training and data efficiency. We highlight that the impact of this study extends beyond COVID-19 dataset, as our approach for fast virtual ligand screening can be easily adapted and integrated into a general machine learning-accelerated pipeline to battle future bio-threats.

In-Depth Ethical Analysis of the COVID-19 Vaccine Rollout for Migrant Workers in the Gulf Countries.

During the initial COVID-19 vaccine rollout, supplies were scarce, necessitating rationing. Gulf countries, hosting millions of migrant workers, prioritized nationals over migrants for vaccination. As it turned out, many migrant workers found themselves waiting behind nationals to get vaccinated for COVID-19. Here, we discuss the public health ethical concerns surrounding this approach and call for fair and inclusive vaccine allocation policies. First, we examine global justice through the lens of statism, where distributive justice applies only to sovereign state members, and cosmopolitanism, advocating equal justice distribution for all humans. We propose a cooperativist perspective, suggesting that new justice obligations can arise between people beyond national ties. In cases of mutually beneficial cooperation, such as migrant workers contributing to a nation's economy, equal concern for all parties is required. Second, the principle of reciprocity further supports this stance, as migrants significantly contribute to host countries' societies and economies. Additional ethical principles-equity, utilitarianism, solidarity, and nondiscrimination-are essentially violated when excluding non-nationals in vaccine distribution. Finally, we argue that prioritizing nationals over migrants is not only ethically indefensible, but it also fails to ensure full protection for nationals and hampers efforts to curb COVID-19 community spread.

The impact of the COVID-19 epidemic on tuberculosis control in China.

BACKGROUND: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country. METHODS: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline. FINDINGS: The notified number of TB patients decreased sharply in the 1st week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19. INTERPRETATION: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established. FUNDING: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180).

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

Impact of the COVID-19 pandemic on inflammatory bowel disease care in Taiwan: A multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a great impact on healthcare system and patients. This study aimed to evaluate the effect of the COVID-19 pandemic on the perceptions of patients with inflammatory bowel disease (IBD). METHODS: fdb 9.1.450/W UnicodeThis prospective multicenter study was conducted between July 2021 and December 2021. Patients with IBD answered a structured questionnaire, and their degree of anxiety was assessed using a visual analogue scale (VAS) before and after reading educational materials. RESULTS: fdb 9.1.450/W UnicodeA total of 225 (47.67%) patients with Crohn's disease, 244 (51.69%) with ulcerative colitis and 3 (0.64%) with indeterminate colitis were enrolled. Common concerns were adverse events from vaccination (20.34%), and higher risks of developing severe COVID-19 (19.28%) and COVID-19 infection (16.31%) than the general population. Medications deemed by the patients to increase the risk of COVID-19 were immunomodulators (16.10%), anti-tumor necrosis factor-α antagonists (9.96%), and corticosteroids (9.32%). Thirty-five (7.42%) patients self-discontinued IBD medication, of whom 12 (34.28%) had worse symptoms. Older age (>50 years) (OR 1.10, 95% CI 1.01-1.19, p = 0.03), IBD-related complications (OR 1.16, 95% CI 1.04-1.28, p = 0.01), education status below senior high school (OR 1.22, 95% CI 1.08-1.37, p = 0.001), and residing in north-central Taiwan (OR 1.21, 95% CI 1.10-1.34, p < 0.001) were associated with more anxiety. None of the enrolled patients contracted COVID-19. The anxiety VAS score (mean ± SD) improved after reading the educational materials (3.84 ± 2.33 vs. 2.81 ± 1.96, p < 0.001). CONCLUSIONS: The medical behavior of IBD patients was influenced by the COVID-19 pandemic, and their anxiety could be mitigated after education.

The Impact of the COVID-19 Pandemic on Green Finance and Carbon Dioxide Emissions: Empirical Evidence from China (preprint)

The Chinese government has expressed great confidence in the role of green finance in fulfilling its carbon neutrality commitment. However, the effectiveness of green finance, especially under the impact of emergencies such as the COVID-19 pandemic scenario, requires further examination. Using data from 2000 to 2020 in China, the correlation between green finance and carbon dioxide (CO2) emissions has been analyzed, both in BaU scenario and the COVID-19 scenario. The following conclusions were drawn: (1) In BaU scenario, green finance can effectively reduce CO2 emissions, especially through government green expenditure and green credit; (2) In COVID-19 scenario, although there is no direct relationship between the pandemic and carbon emissions, the data shows that the pandemic has hindered the progress of green finance, weakened its ability to curb carbon emissions, and indirectly led to an increase in carbon emissions. This study not only clarifies the mechanism by which the COVID-19 pandemic affects carbon emissions through the green finance system but also addresses the common problem of data scarcity in green finance research.

Atrial Fibrillation After mRNA-1273 SARS-CoV-2 Vaccination: Case Report with Literature Review.

Importance: COVID-19 vaccination has been associated with various adverse outcomes. Although studies have reported cases of arrhythmia after COVID-19 vaccination, the precise underlying mechanism remains to be elucidated. Objective: Here, we report the case of a patient who developed atrial fibrillation after receiving the mRNA-1273 vaccine and describe our findings in light of relevant cases in the literature. Design Setting and Participants: This is a case report and a review of the relevant literature. A 55-year-old woman presented to our clinic with a history of paroxysmal atrial fibrillation, hypertension, and mild mitral valve prolapse. The patient developed atrial fibrillation 3 days after receiving a COVID-19 vaccine. She was diagnosed with moderate-to-severe tricuspid regurgitation and severe mitral regurgitation, and underwent valve repair surgery. To obtain relevant articles (December 2020 through August 2022), we searched the following key words on PubMed: atrial fibrillation and COVID-19 vaccination. Results: A total of 5 relevant case reports were identified. COVID-19 vaccination led to arrhythmia, including atrial fibrillation, within 14 days. Conclusions and Relevance: Cases of patients developing arrhythmia after COVID-19 vaccination have been increasingly reported. Although the underlying mechanism remains unclear, we hypothesize that mRNA vaccination may lead to arrhythmia and associated valve diseases. Thus, before administering mRNA-1273 vaccines to patients with a history of valvular heart disease or atrial fibrillation, the patients' cardiologists must be consulted.

COVID-19 epidemic and public health interventions in Shanghai, China: Statistical analysis of transmission, correlation and conversion

Background The Shanghai COVID-19 epidemic is an important example of a local outbreak and of the implementation of normalized prevention and disease control strategies. The precise impact of public health interventions on epidemic prevention and control is unknown. Methods We collected information on COVID-19 patients reported in Shanghai, China, from January 30 to May 31, 2022. These newly added cases were classified as local confirmed cases, local asymptomatic infections, imported confirmed cases and imported asymptomatic infections. We used polynomial fitting correlation analysis and illustrated the time lag plot in the correlation analysis of local and imported cases. Analyzing the conversion of asymptomatic infections to confirmed cases, we proposed a new measure of the conversion rate (Cr). In the evolution of epidemic transmission and the analysis of intervention effects, we calculated the effective reproduction number (Rt). Additionally, we used simulated predictions of public health interventions in transmission, correlation, and conversion analyses. Results (1) The overall level of Rt in the first three stages was higher than the epidemic threshold. After the implementation of public health intervention measures in the third stage, Rt decreased rapidly, and the overall Rt level in the last three stages was lower than the epidemic threshold. The longer the public health interventions were delayed, the more cases that were expected and the later the epidemic was expected to end. (2) In the correlation analysis, the outbreak in Shanghai was characterized by double peaks. (3) In the conversion analysis, when the incubation period was short (3 or 7 days), the conversion rate fluctuated smoothly and did not reflect the effect of the intervention. When the incubation period was extended (10 and 14 days), the conversion rate fluctuated in each period, being higher in the first five stages and lower in the sixth stage. Conclusion Effective public health interventions helped slow the spread of COVID-19 in Shanghai, shorten the outbreak duration, and protect the healthcare system from stress. Our research can serve as a positive guideline for addressing infectious disease prevention and control in China and other countries and regions.

A nitrous oxide abuser presenting with cerebral venous thrombosis: A case report

The present study describes the case of a 25-year-old male patient who presented to the emergency department with severe headache and vertigo lasting for 3 days. The patient did not have a recent history of trauma. He was vaccinated with a second dose of the AstraZeneca COVID-19 vaccine ~1 month prior, and he suffered from a vitamin B12 deficiency due to nitrous oxide abuse. Upon an examination of his vital signs, he was found to have a body temperature of 36.4˚C, a pulse rate of 64 beats per minute, a respiratory rate of 18 breaths per minute and a blood pressure of 119/68 mmHg. A neurological examination only revealed left homonymous upper quadrantanopia. The serum platelet count of the patient was 361x1,000/µl and he had elevated D-dimer levels (0.98 µg/ml). A provisional clinical diagnosis of acute cerebrovascular accident was made. A computed tomography scan of the head revealed an abnormal hyperattenuation in the straight sinus and bilateral transverse sinuses. A diagnosis of cerebral sinovenous thrombosis (CSVT) was made following a consultation with a neurologist. The patient was treated with enoxaparin at 6,000 IU, levetiracetam at 1,000 mg and mannitol at 100 ml via an intravenous drip. After admission, magnetic resonance venography revealed the absence of flow in the straight sinus and bilateral transverse sinuses. A thrombophilic investigation revealed a plasma homocysteine level of 59.03 µmol/l (upper normal limit, 15.39 µmol/l), a vitamin B12 level of <148 (lower normal limit, 187 pg/ml). CSVT secondary to homocystinemia was diagnosed. The treatment included anticoagulation and vitamin B12 supplementation. The patient was administered vitamin B12 at 500 mcg twice per day, pyridoxine at 50 mg per day, folic acid at 5 mg two times per day and edoxaban at 60 mg per day. After 7 days of treatment, his headache and quadrantanopia were improved, and the patient was discharged.

A Text Mining Approach to Covid-19 Literature

The novel coronavirus disease - COVID-19 is a historic catastrophe that has caused many devastating impacts on human life and wellness. Researchers in academia and industry strive to understand the causes of this pandemic disease and find new therapeutics combating it. Consequently, the number of COVID-19 related publications increases rapidly, and it is too difficult for medical researchers and practitioners to keep up with the latest research and development. Literature filtering and categorization, and knowledge discovery can use text mining as a powerful tool. In this paper, we propose a text mining method to explore the categories of COVID-19 related themes and identify the standard methodologies that have been used. We discuss the potential limitations of this preliminary study and present future perspectives related to COVID-19 research. This paper provides an quantitative and qualitative mixed analysis example of using some research papers by data mining method to dig out several hidden information and set up a foundation for data scientists to develop more effective algorithms to deal with COVID-19 related problems.

A Host-Harbored Metabolic Susceptibility of Coronavirus Enables Broad-Spectrum Targeting (preprint)

Host-based antivirals could offer broad-spectrum therapeutics and prophylactics against the constantly-mutating viruses including the currently-ravaging coronavirus, yet must target cellular vulnerabilities of viruses without grossly endangering the host. Here we show that the master lipid regulator SREBP1 couples the phospholipid scramblase TMEM41B to constitute a host “metabolism-to-manufacture” cascade that maximizes membrane supplies to support coronaviral genome replication, harboring biosynthetic enzymes including Lipin1 as druggable viral-specific-essential (VSE) host genes. Moreover, pharmacological inhibition of Lipin1, by a moonlight function of the widely-prescribed beta-blocker Propranolol, metabolically uncouples the SREBP1-TMEM41B cascade and consequently exhibits broad-spectrum antiviral effects against coronaviruses, Zika virus, and Dengue virus. The data implicate a metabolism-based antiviral strategy that is well tolerated by the host, and a potential broad-spectrum medication against current and future coronavirus diseases.

Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses (preprint)

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.

Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction.

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1-2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.

Development of Clinical Risk Scores for Detection of COVID-19 in Suspected Patients During a Local Outbreak in China: A Retrospective Cohort Study

Objectives: To develop and internally validate two clinical risk scores to detect coronavirus disease 2019 (COVID-19) during local outbreaks. Methods: Medical records were extracted for a retrospective cohort of 336 suspected patients admitted to Baodi hospital between 27 January to 20 February 2020. Multivariate logistic regression was applied to develop the risk-scoring models, which were internally validated using a 5-fold cross-validation method and Hosmer-Lemeshow (H-L) tests. Results: Fifty-six cases were diagnosed from the cohort. The first model was developed based on seven significant predictors, including age, close contact with confirmed/suspected cases, same location of exposure, temperature, leukocyte counts, radiological findings of pneumonia and bilateral involvement (the mean area under the receiver operating characteristic curve [AUC]:0.88, 95% CI: 0.84–0.93). The second model had the same predictors except leukocyte and radiological findings (AUC: 0.84, 95% CI: 0.78–0.89, Z = 2.56, p = 0.01). Both were internally validated using H-L tests and showed good calibration (both p > 0.10). Conclusion: Two clinical risk scores to detect COVID-19 in local outbreaks were developed with excellent predictive performances, using commonly measured clinical variables. Further external validations in new outbreaks are warranted.

Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against Omicron (preprint)

The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the antibodies' epitopes and genotypes. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their binding patterns. We found that the epitopes of one class of antibodies were significantly less affected by Omicron mutations than other classes. Binding and virus neutralization experiments show that such antibodies can effectively inhibit the immune escape of Omicron. Cryo-EM results show that this class of antibodies utilizes a conserved mechanism to neutralize SARS-CoV-2. Our results greatly help us deeply understand the impact of Omicron mutations. At the same time, it also provides guidance and insights for developing Omicron antibodies and vaccines.