Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework (preprint)

BackgroundThe mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against SARS-CoV-2 infection in phase 3 clinical trials, including among older adults. To inform COVID-19 vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. MethodsWe systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged [≥]50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022 and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19-related hospitalization, and COVID-19-related death following [≥]2 vaccine doses. Random-effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-squared testing. Evidence certainty was assessed per GRADE framework. Results24 non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged [≥]50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64-0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62-0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57-0.78]), COVID-19-related hospitalization (RR 0.65 [95% CI 0.53-0.79]) and COVID-19-related death (RR 0.80 [95% CI 0.64-0.99]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2>75%) except death (I2=0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized-controlled trial data. ConclusionMeta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections; hospitalizations; and deaths with the mRNA-1273 versus BNT162b2 vaccine in older adults aged [≥]50 years. SUMMARY POINTSO_LIThe COVID-19 pandemic has disproportionately affected older adults, as this population is generally more susceptible to infection and severe outcomes due to immune senescence and underlying comorbidities. C_LIO_LIThe 2 available mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against SARS-CoV-2 infection in phase 3 clinical trials, including among older adults. C_LIO_LITo inform COVID-19 vaccine selection, this systematic literature review and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 among older adults in real-world settings. C_LIO_LIVaccination with homologous primary or booster mRNA-1273 was associated with significantly lower risk of infection (including asymptomatic, symptomatic, and severe infections), hospitalization, and death due to COVID-19 than vaccination with BNT162b2 in older adults aged [≥]50 years. C_LI

Characterization of Long COVID Definitions and Clinical Coding Practices (preprint)

Background: Long COVID characterized as post-acute sequelae of SARS-CoV-2 (PASC) has no universal clinical case definition. Recent efforts have focused on understanding long COVID symptoms and electronic health records (EHR) data provides a unique resource for understanding this condition. The introduction of the International Classification of Diseases (ICD)-10 code U09.9 for - Post COVID-19 condition, unspecified to identify patients with long COVID has provided a method of evaluating this condition in EHRs, however, the accuracy of this code is unclear. Objective: Our study aimed to characterize the utility and accuracy of the U09.9 code across three healthcare systems - The Veterans Health Administration (VHA), Beth Israel Deaconess Medical Center (BIDMC) and The University of Pittsburgh Medical Center (UPMC) against patients identified with long COVID via a chart review by operationalizing the World Health Organization (WHO) and Centers for Disease Control (CDC) definitions. Methods: COVID positive patients with either a U07.1 ICD code or positive polymerase chain reaction (PCR) test within these healthcare systems were identified for chart review. Among this cohort we sampled patients based on two approaches i) with a U09.9 code and ii) without a U09.9 code but with a new onset PASC related ICD code, which allows us to assess the sensitivity of the U09.9 code. To operationalize the long COVID definition based on health agency guidelines, we grouped symptoms into a core cluster of 11 commonly reported symptoms among long COVID patients and an extended cluster, that captured all other symptoms by disease domain. Patients having at least 2 symptoms persisting for >=60 days that were new onset after their COVID infection, with at least one symptom in the core cluster, were labeled as having long COVID per chart review. We compared the performance of the code across three health systems and across different time periods of the pandemic. Results: A total of 900 patient charts were reviewed across 3 healthcare systems. The prevalence of long COVID among the cohort with the U09.9 ICD code, based on the operationalized WHO definition was between 23.2%-62.4% across these healthcare systems. We also evaluated a less stringent version of the WHO definition and the Centers for Disease Control (CDC) definition and observed an increase in the prevalence of long COVID at all three healthcare systems. Conclusions: This is one of the first studies to evaluate the U09.9 code against a clinical case definition for long COVID, as well as the first to apply this definition to EHR data using a chart review approach on a nationwide cohort across multiple healthcare systems. This chart review approach can be implemented at other EHR systems to further evaluate the utility and performance of the U09.9 code.

Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines in Immunocompromised Individuals: A Systematic Review and Meta-Analysis Using the GRADE Framework (preprint)

Introduction: Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response following vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) versus BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. Methods: The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals [≥]18 years of age; outcomes of interest were SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed for randomized and observational studies using the Risk of Bias 2 tool and the Newcastle-Ottawa Scale, respectively. Evidence was evaluated using the GRADE framework. Results: Overall, 22 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR 0.87, 95% CI 0.79-0.96; P=0.0054; I2=61.9%), COVID-19-associated hospitalization (RR 0.83, 95% CI 0.76-0.90; P<0.0001; I2=0%), and COVID-19-associated mortality (RR 0.62, 95% CI 0.43-0.89; P=0.011; I2=0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials and evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. Conclusion: This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.

Resolving the developmental mechanisms of coagulation abnormalities characteristic of SARS-CoV2 based on single-cell transcriptome analysis (preprint)

The COVID-19 outbreak caused by the SARS-CoV-2 virus has developed into a global health emergency. In addition to causing respiratory symptoms following SARS-CoV-2 infection, COVID-19-associated coagulopathy (CAC) is the main cause of death in patients with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors, patients who died in the hypercoagulable phase of CAC, and patients in the fibrinolytic phase of CAC. Among these, we collected 61,187 cells, which were enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in response to SARS-CoV-2 infection, CD9highCCR2high monocyte-derived mo promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating CXCR-GNB/G-PI3K-AKT. This sequence of events is the main process contributing the development of coagulation disorders subsequent to SARS-CoV-2 infection. In the characteristic coagulation disorder caused by SARS-CoV-2, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in an increase in sugar uptake, such as that via the glycosaminoglycan synthesis pathway, in CAC coagulation disorders. In addition, high levels of reactive oxygen species generated in response elevated iron levels promote the activation of unsaturated fatty acid metabolic pathways in endothelial cell subgroups, including vascular endothelial cells. This in turn promotes the excessive production of the toxic peroxidation by-product malondialdehyde, which exacerbates both the damage caused to endothelial cells and coagulation disorders.

Characterizing the use of the ICD-10 Code for Long COVID in 3 US Healthcare Systems (preprint)

The International Classification of Diseases (ICD)-10 code (U09.9) for post-acute sequelae of COVID-19 (PASC) was introduced in October of 2021. As researchers seek to leverage this billing code for research purposes in large scale real-world studies of PASC, it is of utmost importance to understand the functional use of the code by healthcare providers and the clinical characteristics of patients who have been assigned this code. To this end, we operationalized clinical case definitions of PASC using World Health Organization and Centers for Disease Control guidelines. We then chart reviewed 300 patients with COVID-19 from three participating healthcare systems of the 4CE Consortium who were assigned the U09.9 code. Chart review results showed the average positive predictive value (PPV) of the U09.9 code ranged from 40.2% to 65.4% depending on which definition of PASC was used in the evaluation. The PPV of the U09.9 code also fluctuated significantly between calendar time periods. We demonstrated the potential utility of textual data extracted from natural language processing techniques to more comprehensively capture symptoms associated with PASC from electronic health records data. Finally, we investigated the utilization of long COVID clinics in the cohort of patients. We observed that only an average of 24.0% of patients with the U09.9 code visited a long COVID clinic. Among patients who met the WHO PASC definition, only an average of 35.6% visited a long COVID clinic.

Genetic characterization of SARS-CoV-2 from cross-border trucks and containers in Kashgar Prefecture, Xinjiang Uygur Autonomous Region, China

Kashgar is a prefecture in Xinjiang Uygur Autonomous Region. China. Kashgar Prefecture (KP) is a land-cargo port connecting China with central Asian countries and Europe. Frequent transportation of cargo has increased the risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) introduction into China, which has increased the pressure on coronavirus disease-2019 (COVID-19) prevention and control. In November 2020, an imported virus-induced COVID-19 outbreak occurred in KP. To investigate the genetic characterization of SARS-CoV-2 that contaminated the trucks and containers, and the potential of border rapid logistics system to serve as carriers for SARS-CoV-2 transmission, thirty-five SARS-CoV-2-positive nucleic-acid samples collected from KP cross-border trucks and containers from 6-10 November 2020 were subjected into SARS-CoV-2 genomic sequencing and comparative analyses. The results showed that the median (minimum to maximum) Ct value of ORF1ab was 37.64 (28.91-39.81) . and that of the N gene was 36.50 (26.35-39.30), and the median (minimum to maximum) of the reads mapping ratio to SARS-CoV-2 was 51.95% (0.86%-99.31%), which indicated low viral loads in these environmental samples. Eighteen of 35 samples had genomic coverage >70%. According to the Pango nomenclature, 18 SARS-CoV-2 sequences belonged to six lineages (B.1, B.I.1, B.1.9. B.1.1.220, B.1.153 and B.1.465), three of which (B.I. B.1.1 and 8.1.153) were found in case samples from the same period of four China-neighboring countries. Analyses of nucleotide mutations and phylogenetic trees showed that the genome sequences of SARS-CoV-2 collected from the same location were similar. Four of 18 sequences were in a sub-lineage with the representative strain of COVID-19 outbreak in KP, one of which had 1 or 2 differences in nucleotide mutation sites with the strain that caused the COVID-19 outbreak in KP, which indicated high homology in the viral genome. We showed that cross-border trucks and containers were contaminated by various genotypes of SARS-CoV-2 from other countries during the outbreak in KP. and in which contained the parental virus of the KP cases. These trucks and containers served as carriers for SARS-CoV-2 introduction from other countries to cause local transmission. Our results provide important references for COVID-19 prevention-and-control strategies in border ports and tracing of outbreak sources in China.

Clinical features and forecast indexes of the disease severity of SARS-CoV-2: a retrospective cohort study comparing the wild-type strain and the Delta VOC (preprint)

BackgroundA novel variant of SARS-CoV-2, the Delta variant of concern (VOC), on disease severity is very unclear. In this retrospective study, we compared the clinical characteristics and the outcomes of patients infected with the Delta VOC and with wild-type strains during the local outbreak in Xi'an and Wuhan, China.MethodsThe clinical information pertaining to the 2927 cases (between February 10 and March 8, 2020) infected with wild-type strains and the 993 cases (between December 22, 2021and February 17, 2022) infected with the Delta VOC were extracted. The clinical characteristics and outcomes were compared the cohort of wild-type infection with the cohort of Delta VOC.ResultsAmong patients younger than 18 years old, the proportion of patients infected with the Delta VOC was significantly higher than that of patients infected with wild-type strains (12.2% vs. 0.3%). In cases with mild and moderate illness, the proportion of patients was higher in the Delta VOC group than that in the wild-type strain (40.9% and 56.6% vs. 0.70% and 3.10%). However, in severe and critical patients, the proportion of patients was significantly less in the Delta VOC group than that in the wild-type strain (1.6% and 0.9% vs. 24.2% and 72.0%). In cases with severe or critical illness, and in the Delta VOC cohort or the wild-type cohort, the prognosis of patients with lymphocytes blood levels that gradually rising is good after treatment, while the prognosis of patients with lymphocytes blood levels that remain low is poor and even death(p<0.001). The Cox regression analysis revealed that the infection with the lineage of the wide-type strain had a higher risk than the Delta VOC in deteriorating to critical illness (hazards ratio 2.54[95%CI 1.279–5.026]; p = 0.008).ConclusionsUnder the two different anti-epidemic situations and anti-epidemic strategies, infection with the Delta VOC is characterized by younger patients, milder illness, and decreased risk of disease prognosis, compared with the SARS-CoV-2 wild-type lineage; lymphopenia is an effective predictor of deterioration in patients with Delta VOC and wild-type strains, calling for clinicians to understand of characteristics of them according to the different anti-epidemic situations and anti-epidemic strategies, and to guide clinical decision-making.

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: international observational federated study based on electronic health records through the 4CE consortium ARDS after SARS-CoV-2 infection on young adult (preprint)

Purpose : In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. Methods : A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. Results : Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS ( 7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). Conclusion : Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

SurvMaximin: Robust Federated Approach to Transporting Survival Risk Prediction Models (preprint)

ObjectiveFor multi-center heterogeneous Real-World Data (RWD) with time-to-event outcomes and high-dimensional features, we propose the SurvMaximin algorithm to estimate Cox model feature coefficients for a target population by borrowing summary information from a set of health care centers without sharing patient-level information. Materials and MethodsFor each of the centers from which we want to borrow information to improve the prediction performance for the target population, a penalized Cox model is fitted to estimate feature coefficients for the center. Using estimated feature coefficients and the covariance matrix of the target population, we then obtain a SurvMaximin estimated set of feature coefficients for the target population. The target population can be an entire cohort comprised of all centers, corresponding to federated learning, or can be a single center, corresponding to transfer learning. ResultsSimulation studies and a real-world international electronic health records application study, with 15 participating health care centers across three countries (France, Germany, and the U.S.), show that the proposed SurvMaximin algorithm achieves comparable or higher accuracy compared with the estimator using only the information of the target site and other existing methods. The SurvMaximin estimator is robust to variations in sample sizes and estimated feature coefficients between centers, which amounts to significantly improved estimates for target sites with fewer observations. ConclusionsThe SurvMaximin method is well suited for both federated and transfer learning in the high-dimensional survival analysis setting. SurvMaximin only requires a one-time summary information exchange from participating centers. Estimated regression vectors can be very heterogeneous. SurvMaximin provides robust Cox feature coefficient estimates without outcome information in the target population and is privacy-preserving.

SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021 (preprint)

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.

ZBP1 induces inflammatory signaling via RIPK3 and promotes SARS-CoV-2-induced cytokine expression (preprint)

COVID-19 caused by the SARS-CoV-2 virus remains a threat to global health. The disease severity is mediated by cell death and inflammation, which regulate both the antiviral and the pathological innate immune responses. ZBP1, an interferon-induced cytosolic nucleic acid sensor, facilitates antiviral responses via RIPK3. Although ZBP1-mediated cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway that depends on ubiquitination and RIPK3s scaffolding ability independently of cell death. In human cells, ZBP1 associates with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. RIPK1 and ZBP1 are ubiquitinated to promote TAK1- and IKK-mediated inflammatory signaling. Additionally, RIPK1 recruits the p43/41-caspase-8-p43-FLIP heterodimer to suppress RIPK3 kinase activity, which otherwise promotes inflammatory signaling in a kinase activity-dependent manner. Lastly, we show that ZBP1 contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK1-RIPK3-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspase-8. Our results suggest the ZBP1 pathway contributes to inflammation in response to SARS-CoV-2 infection.

The IT Labor Market in Pandemic Conditions (preprint)

In this ongoing project, we investigate how the COVID-19 epidemic affects the IT labor market, and, accordingly, how organizations choose to hire IT employees in the current situation. Using a quarterly dataset of 30,678 IT job postings from a large online employment website, we perform descriptive analysis and logistic regression to examine the relationships between pandemic severity and work arrangements (remote vs. on-site), work schedules (part-time vs. full time), and organizational sectors (commercial vs. government vs. non-profit). Our results reveal that the IT market in the summer quarter (June, July, and August) is better than in the previous period, for both part-time and remote job postings. Also, pandemic severity is positively associated with the incidence of on-site IT hires. For governments and non-profit organizations (NPOs) such as hospitals and schools, “frontline” IT support professionals were highly prized, whereas commercial employers, including tech giants, were more interested in growing a remote IT workforce. In our conclusions, we discuss the balance between the trajectory of diagnosed infections and the fluctuations of the labor market, specifically in the IT sector.

SARS-CoV-2 transmission and control in a hospital setting: an individual-based modelling study (preprint)

BackgroundDevelopment of strategies for mitigating the severity of COVID-19 is now a top global public health priority. We sought to assess strategies for mitigating the COVID-19 outbreak in a hospital setting via the use of non-pharmaceutical interventions such as social distancing, self-isolation, tracing and quarantine, wearing facial masks/ personal protective equipment. MethodsWe developed an individual-based model for COVID-19 transmission among healthcare workers in a hospital setting. We calibrated the model using data of a COVID-19 outbreak in a hospital unit in Wuhan in a Bayesian framework. The calibrated model was used to simulate different intervention scenarios and estimate the impact of different interventions on outbreak size and workday loss. ResultsWe estimated that work-related stress increases susceptibility to COVID-19 infection among healthcare workers by 52% (90% Credible Interval (CrI): 16.4% - 93.0%). The use of high efficacy facial masks was shown to be able to reduce infection cases and workday loss by 80% (90% CrI: 73.1% - 85.7%) and 87% (CrI: 80.0% - 92.5%), respectively. The use of social distancing alone, through reduced contacts between healthcare workers, had a marginal impact on the outbreak. A strict quarantine policy with the isolation of symptomatic cases and a high fraction of pre-symptomatic/ asymptomatic cases (via contact tracing or high test rate), could only prolong outbreak duration with minimal impact on the outbreak size. Our results indicated that a quarantine policy should be coupled with other interventions to achieve its effect. The effectiveness of all these interventions was shown to increase with their early implementation. ConclusionsOur analysis shows that a COVID-19 outbreak in a hospitals non-COVID-19 unit can be controlled or mitigated by the use of existing non-pharmaceutical measures.

Banks, Money, and the Zero Lower Bound on Deposit Rates (preprint)

We develop a New Keynesian model where all payments between agents require bank deposits through deposits-in-advance constraints, bank deposits are created through disbursement of bank loans, and banks face a convex lending cost. At the zero lower bound on deposit rates (ZLBD), changes in policy rates affect activity through both real interest rates and banks’ net interest margins (NIM). At estimated credit supply elasticities, the Phillips curve is very flat at the ZLBD, because inflationary pressures increase NIM. This strongly increases credit and thereby output, but it dampens inflation by relaxing price setters’ credit rationing constraint. At the ZLBD, monetary policy has far larger effects on output relative to inflation, and Taylor rules stabilize output less effectively than rules that also respond to credit. For post-COVID-19 policy, this suggests urgency in returning inflation to targets, avoidance of negative policy rates, and a strong influence of credit conditions on rate setting.

Support for Small Businesses Amid COVID-19 (preprint)

A sizeable proportion of enterprises, especially SMEs, assisted by the government, will fail to repay. Should a screening mechanism then be applied to deter those most likely to default from seeking such financial assistance? The answer depends on the relative weights attached to the competitive objectives of stabilisation and allocative efficiency. For this purpose, we develop a two-sector equilibrium model featuring oligopolistic small businesses with asymmetric private information and a screening contract. The sector adversely affected in a pandemic can apply for government loans to reopen later. A pro-allocation government sets a harsh default sanction to deter entrepreneurs with bad projects thereby improving productivity in the long run, at the cost of persistent unemployment, whereas a pro-stabilisation government sets a lenient default sanction. The optimal default sanction balances the trade-off between allocation and stabilisation. Finally, we solve for the optimal default sanction numerically and conduct comparative statics.

COVID-19 Literature Knowledge Graph Construction and Drug Repurposing Report Generation (preprint)

To combat COVID-19, both clinicians and scientists need to digest vast amounts of relevant biomedical knowledge in scientific literature to understand the disease mechanism and related biological functions. We have developed a novel and comprehensive knowledge discovery framework, COVID-KG to extract fine-grained multimedia knowledge elements (entities and their visual chemical structures, relations, and events) from scientific literature. We then exploit the constructed multimedia knowledge graphs (KGs) for question answering and report generation, using drug repurposing as a case study. Our framework also provides detailed contextual sentences, subfigures, and knowledge subgraphs as evidence.

Epidemiological and clinical characteristics in patients with SARS-CoV-2 antibody negative probable COVID-19 in Wuhan (preprint)

Abstract Background Patients with suspected COVID-19 might be admitted to hospital. We aimed to describe the characteristic of SARS-CoV-2 antibody negative probable COVID-19 patients and give some suggestions to manage suspected COVID-19 patients. Methods We analyzed 616 confirmed COVID-19 patients and 35 SARS-CoV-2 antibody negative probable COVID-19 patients who were admitted in Wuhan Union Hospital from February 13, 2020 to February 16, 2020. Telephone interviews were conducted and medical records were reviewed for epidemiological, clinical, laboratory and radiographic data. Results Of the 35 SARS-CoV-2 antibody negative probable COVID-19 patients, all of them had tested at least 3 times of nucleic acid, 3 were believed to be non-SARS-CoV-2 infection. Compared with confirmed patients, antibody negative probable patients were younger (P=0.017), exhibited similar symptoms and chest CT images, had higher lymphocyte count (P=0.004) and albumin level (P<0.001), showed lower lactate dehydrogenase level (P=0.011) and erythrocyte sedimentation rate (P<0.001). During hospitalization, all the 35 patients had contacted with confirmed COVID-19 patients, but all used general face mask for protection and maintained a social distance of more than one meter from each other. All the isolation wards were kept ventilation and disinfected once a day. After discharged from hospital, all of them had negative nucleic acid tests and no one developed symptoms again. Conclusions The conditions of patients with AbN probable COVID-19 were less critical than those of patients with confirmed COVID-19. Room ventilation and daily disinfection, wearing face masks, and maintaining social distance might be helpful to prevent patients from hospital acquired COVID-19 infection.