Recent COVID-19 infection is associated with increased mortality in the ambulatory surgery population.

BACKGROUND: The effect of COVID-19 infection on post-operative mortality and the optimal timing to perform ambulatory surgery from diagnosis date remains unclear in this population. Our study was to determine whether a history of COVID-19 diagnosis leads to a higher risk of all-cause mortality following ambulatory surgery. METHODS: This cohort constitutes retrospective data obtained from the Optum dataset containing 44,976 US adults who were tested for COVID-19 up to 6 months before surgery and underwent ambulatory surgery between March 2020 to March 2021. The primary outcome was the risk of all-cause mortality between the COVID-19 positive and negative patients grouped according to the time interval from COVID-19 testing to ambulatory surgery, called the Testing to Surgery Interval Mortality (TSIM) of up to 6 months. Secondary outcome included determining all-cause mortality (TSIM) in time intervals of 0-15 days, 16-30 days, 31-45 days, and 46-180 days in COVID-19 positive and negative patients. RESULTS: 44,934 patients (4297 COVID-19 positive, 40,637 COVID-19 negative) were included in our analysis. COVID-19 positive patients undergoing ambulatory surgery had higher risk of all-cause mortality compared to COVID-19 negative patients (OR = 2.51, p < 0.001). The increased risk of mortality in COVID-19 positive patients remained high amongst patients who had surgery 0-45 days from date of COVID-19 testing. In addition, COVID-19 positive patients who underwent colonoscopy (OR = 0.21, p = 0.01) and plastic and orthopedic surgery (OR = 0.27, p = 0.01) had lower mortality than those underwent other surgeries. CONCLUSIONS: A COVID-19 positive diagnosis is associated with significantly higher risk of all-cause mortality following ambulatory surgery. This mortality risk is greatest in patients that undergo ambulatory surgery within 45 days of testing positive for COVID-19. Postponing elective ambulatory surgeries in patients that test positive for COVID-19 infection within 45 days of surgery date should be considered, although prospective studies are needed to assess this.

Comment on: "Risk of Erectile Dysfunction in Male Patients with Gout Treated with Febuxostat or Allopurinol: A Propensity Score-Matched Cohort Study"/Authors' Reply to Huang and Zhang: Comment on "Risk of Erectile Dysfunction in Male Patients with Gout Treated with Febuxostat or Allopurinol: A Propensity Score-Matched Cohort Study"

[...]a time frame could be set before the Covid-19 epidemic attack in January 2020, owing to the association between Covid-19 infection (ICD-10-CM B34.2, U07.1, U07.2, J12.81, J12.82, B97.29) and new-onset ED, which was recently detected in the same database [6]. According to the National Institute for Health and Care Excellence (NICE) guideline [15], treat-to-target (T2T) approach should be adhered to with serum urate level of at least < 360

Discovery of 3-phenyl-1,2,4-oxadiazole derivatives as a new class of SARS-CoV-2 main protease inhibitors.

The ongoing COVID-19 pandemic has led to massive infections and deaths and caused tremendous grief among the people. Although vaccines have played an important role in fighting COVID-19, the situation that the protective effect of current vaccines significantly decreases against mutated strains reminds us of the pressing need for developing effective antiviral therapeutics. The main protease (Mpro) is a key enzyme for SARS-CoV-2 viral replication and transcription and an attractive target for drug development. In this research, we report a new series of Mpro inhibitors containing 3-phenyl-1,2,4-oxadiazole. Structure-activity relationship (SAR) studies led to the discovery of the most active compound, 16d, which showed an IC50 value of 5.27 ± 0.26 µM. Collectively, we obtained a new small molecular inhibitor targeting SARS-CoV-2 Mpro, which contains a new scaffold. This compound could be taken as a lead compound for subsequent drug discovery against SARS-CoV-2.

CCT: Lightweight compact convolutional transformer for lung disease CT image classification.

Computed tomography (CT) imaging results are an important criterion for the diagnosis of lung disease. CT images can clearly show the characteristics of lung lesions. Early and accurate detection of lung diseases helps clinicians to improve patient care effectively. Therefore, in this study, we used a lightweight compact convolutional transformer (CCT) to build a prediction model for lung disease classification using chest CT images. We added a position offset term and changed the attention mechanism of the transformer encoder to an axial attention mechanism module. As a result, the classification performance of the model was improved in terms of height and width. We show that the model effectively classifies COVID-19, community pneumonia, and normal conditions on the CC-CCII dataset. The proposed model outperforms other comparable models in the test set, achieving an accuracy of 98.5% and a sensitivity of 98.6%. The results show that our method achieves a larger field of perception on CT images, which positively affects the classification of CT images. Thus, the method can provide adequate assistance to clinicians.

Case report: Myocarditis following COVID-19 protein subunit vaccination.

We report findings in a 34-year-old female patient who presented with fulminant myocarditis 8 days after receiving the first dose of the ZF2001 RBD-subunit vaccine against coronavirus disease 2019 (COVID-19). Autopsy showed severe interstitial myocarditis, including multiple patchy infiltrations of lymphocytes and monocytes in the myocardium of the left and right ventricular walls associated with myocyte degeneration and necrosis. This report highlights the details of clinical presentations and autopsy findings of myocarditis after ZF2001 (RBD-subunit vaccine) vaccination. The correlation between vaccination and death due to myocarditis is discussed.

COVID-19 CT image segmentation method based on swin transformer.

Owing to its significant contagion and mutation, the new crown pneumonia epidemic has caused more than 520 million infections worldwide and has brought irreversible effects on the society. Computed tomography (CT) images can clearly demonstrate lung lesions of patients. This study used deep learning techniques to assist doctors in the screening and quantitative analysis of this disease. Consequently, this study will help to improve the diagnostic efficiency and reduce the risk of infection. In this study, we propose a new method to improve U-Net for lesion segmentation in the chest CT images of COVID-19 patients. 750 annotated chest CT images of 150 patients diagnosed with COVID-19 were selected to classify, identify, and segment the background area, lung area, ground glass opacity, and lung parenchyma. First, to address the problem of a loss of lesion detail during down sampling, we replaced part of the convolution operation with atrous convolution in the encoder structure of the segmentation network and employed convolutional block attention module (CBAM) to enhance the weighting of important feature information. Second, the Swin Transformer structure is introduced in the last layer of the encoder to reduce the number of parameters and improve network performance. We used the CC-CCII lesion segmentation dataset for training and validation of the model effectiveness. The results of ablation experiments demonstrate that this method achieved significant performance gain, in which the mean pixel accuracy is 87.62%, mean intersection over union is 80.6%, and dice similarity coefficient is 88.27%. Further, we verified that this model achieved superior performance in comparison to other models. Thus, the method proposed herein can better assist doctors in evaluating and analyzing the condition of COVID-19 patients.

Characterizing cancer and COVID-19 outcomes using electronic health records.

PURPOSE: Patients with cancer often have compromised immune system which can lead to worse COVID-19 outcomes. The purpose of this study is to assess the association between COVID-19 outcomes and existing cancer-specific characteristics. PATIENTS AND METHODS: Patients aged 18 or older with laboratory-confirmed COVID-19 between June 1, 2020, and December 31, 2020, were identified (n = 314 004) from the Optum® de-identified COVID-19 Electronic Health Record (EHR) derived from more than 700 hospitals and 7000 clinics in the United States. To allow sufficient observational time, patients with less than one year of medical history in the EHR dataset before their COVID-19 tests were excluded (n = 42 365). Assessed COVID-19 outcomes including all-cause 30-day mortality, hospitalization, ICU admission, and ventilator use, which were compared using relative risks (RRs) according to cancer status and treatments. RESULTS: Among 271 639 patients with COVID-19, 18 460 had at least one cancer diagnosis: 8034 with a history of cancer and 10 426 with newly diagnosed cancer within one year of COVID-19 infection. Patients with a cancer diagnosis were older and more likely to be male, white, Medicare beneficiaries, and have higher prevalences of chronic conditions. Cancer patients had higher risks for 30-day mortality (RR 1.07, 95% CI 1.01-1.14, P = 0.028) and hospitalization (RR 1.04, 95% CI 1.01-1.07, P = 0.006) but without significant differences in ICU admission and ventilator use compared to non-cancer patients. Recent cancer diagnoses were associated with higher risks for worse COVID-19 outcomes (RR for mortality 1.17, 95% CI 1.08-1.25, P<0.001 and RR for hospitalization 1.10, 95% CI 1.06-1.14, P<0.001), particularly among recent metastatic (stage IV), hematological, liver and lung cancers compared with the non-cancer group. Among COVID-19 patients with recent cancer diagnosis, mortality was associated with chemotherapy or radiation treatments within 3 months before COVID-19. Age, black patients, Medicare recipients, South geographic region, cardiovascular, diabetes, liver, and renal diseases were also associated with increased mortality. CONCLUSIONS AND RELEVANCE: Individuals with cancer had higher risks for 30-day mortality and hospitalization after SARS-CoV-2 infection compared to patients without cancer. More specifically, patients with a cancer diagnosis within 1 year and those receiving active treatment were more vulnerable to worse COVID-19 outcomes.

COVID-19 Outcomes in Myasthenia Gravis Patients: Analysis From Electronic Health Records in the United States

Background Myasthenia gravis (MG) is an autoimmune, neuromuscular condition and patients with MG are vulnerable due to immunosuppressant use and disease manifestations of dyspnea and dysphagia during the coronavirus disease 2019 (COVID-19) pandemic. Methods We conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset. Primary outcomes, such as hospitalization, ventilator use, intensive care unit (ICU) admission, and death in COVID-19 patients with MG, were compared with those of COVID-19 patients without MG: the subgroups of non-MG included those with rheumatoid arthritis (RA), systemic lupus (SLE), and multiple sclerosis (MS). We further analyzed factors affecting mortality, such as age, race/ethnicity, comorbidities, and MG treatments. Results Among 421,086 individuals with COVID-19, there were 377 patients with MG, 7,362 patients with RA, 1,323 patients with SLE, 1,518 patients with MS, and 410,506 patients without MG. Patients with MG were older and had more comorbidities compared with non-MG patients and had the highest rates of hospitalization (38.5%), ICU admission (12.7%), ventilator use (3.7%), and mortality (10.6%) compared with all other groups. After adjusting for risk factors, patients with MG had increased risks for hospitalization and ICU compared with patients with non-MG and with RA but had risks similar to patients with SLE and with MS. The adjusted risk for ventilator use was similar across all groups, but the risk for mortality in patients with MG was lower compared with the SLE and MS groups. Among patients with MG, age over 75 years and dysphagia were predictors for increased COVID-19 mortality, but the recent MG treatment was not associated with COVID-19 mortality. Conclusions COVID-19 patients with MG are more likely to be admitted to the hospital and require ICU care. Older age and patients with dysphagia had an increased risk of mortality.

Deep Learning-Based Automatic CT Quantification of Coronavirus Disease 2019 Pneumonia: An International Collaborative Study.

OBJECTIVE: We aimed to develop and validate the automatic quantification of coronavirus disease 2019 (COVID-19) pneumonia on computed tomography (CT) images. METHODS: This retrospective study included 176 chest CT scans of 131 COVID-19 patients from 14 Korean and Chinese institutions from January 23 to March 15, 2020. Two experienced radiologists semiautomatically drew pneumonia masks on CT images to develop the 2D U-Net for segmenting pneumonia. External validation was performed using Japanese (n = 101), Italian (n = 99), Radiopaedia (n = 9), and Chinese data sets (n = 10). The primary measures for the system's performance were correlation coefficients for extent (%) and weight (g) of pneumonia in comparison with visual CT scores or human-derived segmentation. Multivariable logistic regression analyses were performed to evaluate the association of the extent and weight with symptoms in the Japanese data set and composite outcome (respiratory failure and death) in the Spanish data set (n = 115). RESULTS: In the internal test data set, the intraclass correlation coefficients between U-Net outputs and references for the extent and weight were 0.990 and 0.993. In the Japanese data set, the Pearson correlation coefficients between U-Net outputs and visual CT scores were 0.908 and 0.899. In the other external data sets, intraclass correlation coefficients were between 0.949-0.965 (extent) and between 0.978-0.993 (weight). Extent and weight in the top quartile were independently associated with symptoms (odds ratio, 5.523 and 10.561; P = 0.041 and 0.016) and the composite outcome (odds ratio, 9.365 and 7.085; P = 0.021 and P = 0.035). CONCLUSIONS: Automatically quantified CT extent and weight of COVID-19 pneumonia were well correlated with human-derived references and independently associated with symptoms and prognosis in multinational external data sets.

Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

A wearable AIEgen-based lateral flow test strip for rapid detection of SARS-CoV-2 RBD protein and N protein.

Accurate and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significant for early tracing, isolation, and treatment of infected individuals, which will efficiently prevent large-scale transmission of coronavirus disease 2019 (COVID-19). Here, two kinds of test strips for receptor binding domain (RBD) and N antigens of SARS-CoV-2 are established with high sensitivity and specificity, in which AIE luminogens (AIEgens) are utilized as reporters. Because of the high brightness and resistance to quenching in aqueous solution, the limit of detection can be as low as 6.9 ng/mL for RBD protein and 7.2 ng/mL for N protein. As an antigen collector, an N95 mask equipped with a test strip with an excellent enrichment effect would efficiently simplify the sampling procedures. Compared with a test strip based on Au nanoparticles or fluorescein isothiocyanate (FITC), the AIEgen-based test strip shows high anti-interference capacity in complex biosamples. Therefore, an AIEgen-based test strip assay could be built as a promising platform for emergency use during the pandemic.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Lipid in Chips: A Brief Review of Liposomes Formation by Microfluidics.

Liposomes are ubiquitous tools in biomedical applications, such as drug delivery, membrane science and artificial cell. Micro- and nanofabrication techniques have revolutionized the preparation of liposomes on the microscale. State-of-the-art liposomal formation on microfluidic chips and its associated applications are introduced in this review. We attempt to provide a reference for liposomal researchers by comparing various microfluidic techniques for liposomes formation.

Contactless In-Home Monitoring of the Long-Term Respiratory and Behavioral Phenotypes in Older Adults With COVID-19: A Case Series.

Currently, there is a limited understanding of long-term outcomes of COVID-19, and a need for in-home measurements of patients through the whole course of their disease. We study a novel approach for monitoring the long-term trajectories of respiratory and behavioral symptoms of COVID-19 patients at home. We use a sensor that analyzes the radio signals in the room to infer patients' respiration, sleep and activities in a passive and contactless manner. We report the results of continuous monitoring of three residents of an assisted living facility for 3 months, through the course of their disease and subsequent recovery. In total, we collected 4,358 measurements of gait speed, 294 nights of sleep, and 3,056 h of respiration. The data shows differences in the respiration signals between asymptomatic and symptomatic patients. Longitudinally, we note sleep and motor abnormalities that persisted for months after becoming COVID negative. Our study represents a novel phenotyping of the respiratory and behavioral trajectories of COVID recovery, and suggests that the two may be integral components of the COVID-19 syndrome. It further provides a proof-of-concept that contactless passive sensors may uniquely facilitate studying detailed longitudinal outcomes of COVID-19, particularly among older adults.

The social and occupational consequences of the COVID-19 pandemic among patients with multiple sclerosis in three distinct populations: A web-based cross-sectional survey

Background The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the disease COVID-19, has caused a pandemic that has rapidly affected the whole world and caused a significant threat to public health. The aim of this study was to investigate and analyze the social and occupational effects of the COVID-19 pandemic on patients with multiple sclerosis (MS) in three different countries: China, Spain, and Cuba. Methods A cross-sectional survey was designed to assess the social and occupational effects of the COVID-19 pandemic in MS patients in these three countries, using a 25-item anonymous online questionnaire, structured into three sections. Quantitative data are expressed as mean (standard deviation), and quantitative data as absolute frequency and percentage. Results A total of 361 participants responded to the questionnaire: 194 from China, 104 from Spain, and 63 from Cuba. We found no cases of COVID-19 among Chinese patients with MS, and few cases in Spain and Cuba. Respondents reported different levels of impact on relationships with friends, family, and colleagues, and patients in all three countries described increased use of digital or social media platforms. Spanish patients reported a significantly less negative impact than those in Cuba and China. Mental and cognitive effects were similar in all three countries, although China seemed to have a better situation. We also found that the time spent exercising decreased at specific points during the pandemic, but with few changes in dietary habits. Patients reported little or no change in their means of transport in all three countries. Most patients in all three countries reported little or no physical deterioration, especially in Chinese patients (82.47%), compared to the Spanish (70.20%) and Cuban respondents (73.02%). In general, patients from all three countries demonstrated confidence in overcoming the COVID-19 pandemic, although to a lesser extent among Spanish respondents. Conclusions During the pandemic, family support was more effective in China than in Cuba and Spain. Neither COVID-19 infections nor the number of MS relapses increased significantly during lockdown in any of the three countries. Regarding their economic situation, Spanish MS patients reported a significantly less severe negative impact than those in Cuba and China. Patients from all three countries used digital or social media platforms more frequently, probably to maintain personal relationships. Chinese and Cuban respondents were more confident of the control of the pandemic than the Spanish, who were more pessimistic.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

Twin girls infected with SARS-CoV-2

This article reports the diagnosis and treatment of twin girls who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Hunan Province, China. The twin girls, aged 1 year and 2 months, were admitted on January 29, 2020 due to fever for one day and cough and sneezing for two days respectively. Both recovered after symptomatic treatment. The two girls had mild symptoms and rapid recovery, suggesting that children with SARS-CoV-2 infection may be mild and have a good prognosis. There were differences in the clinical symptoms and imaging findings between the twin girls, suggesting that SARS-CoV-2 infection has diverse clinical features in children.

COVID-19 severity and outcome in multiple sclerosis: Results of a national, registry-based, matched cohort study.

BACKGROUND: Risk factors associated with coronavirus disease 2019 (COVID-19) severity in patients with multiple sclerosis (MS) have been described. Recent improvements in supportive care measures and increased testing capacity may modify the risk of severe COVID-19 outcome in MS patients. This retrospective study evaluates the severity and outcome of COVID-19 in MS and characterizes temporal trends over the course of the pandemic in the United States. METHODS: We conducted a comparative cohort study using de-identified electronic health record (EHR) claims-based data. MS patients diagnosed with COVID-19 between February 2, 2020 and October 13, 2020 were matched (1:2) to a control group using propensity score analysis. The primary outcome was a composite of intensive care unit (ICU) admission, mechanical ventilation, and/or death. RESULTS: A total of 2,529 patients (843 MS and 1,686 matched controls) were included. Non-ambulatory and pre-existing comorbidities were independent risk factors for COVID-19 severity. The risk for the severe composite outcome was lower in the late cohorts compared with the early cohorts. CONCLUSIONS: The majority of MS patients actively treated with a disease-modifying therapy (DMT) had mild disease. The observed trend toward a reduction in severity risk in recent months suggests an improvement in COVID-19 outcome.

Predicting In-hospital Mortality Using D-Dimer in COVID-19 Patients With Acute Ischemic Stroke.

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy, and D-dimer levels have been used to predict disease severity. However, the role of D-dimer in predicting mortality in COVID-19 patients with acute ischemic stroke (AIS) remains incompletely characterized. Methods: We conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record dataset. Patients were included if they were 18 or older, had been hospitalized within 7 days of confirmed COVID-19 positivity from March 1, 2020 to November 30, 2020. We determined the optimal threshold of D-dimer to predict in-hospital mortality and compared risks of in-hospital mortality between patients with D-dimer levels below and above the cutoff. Risk ratios (RRs) were estimated adjusting for baseline characteristics and clinical variables. Results: Among 15,250 patients hospitalized with COVID-19 positivity, 285 presented with AIS at admission (2%). Patients with AIS were older [70 (60-79) vs. 64 (52-75), p < 0.001] and had greater D-dimer levels at admission [1.42 (0.76-3.96) vs. 0.94 (0.55-1.81) µg/ml FEU, p < 0.001]. Peak D-dimer level was a good predictor of in-hospital mortality among all patients [c-statistic 0.774 (95% CI 0.764-0.784)] and among patients with AIS [c-statistic 0.751 (95% CI 0.691-0.810)]. Among AIS patients, the optimum cutoff was identified at 5.15 µg/ml FEU with 73% sensitivity and 69% specificity. Elevated peak D-dimer level above this cut-off was associated with almost 3 times increased mortality [adjusted RR 2.89 (95% CI 1.87-4.47), p < 0.001]. Conclusions: COVID-19 patients with AIS present with greater D-dimer levels. Thresholds for outcomes prognostication should be higher in this population.

Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors.

The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global pandemic coronavirus disease (COVID-19), but no specific antiviral drug has been proven effective for controlling this pandemic to date. In this study, several 2-((indol-3-yl)thio)-N-benzyl-acetamides were identified as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors. After a two-round optimization, a new series of 2-((indol-3-yl)thio)-N-benzyl-acetamides was designed, synthesized, and evaluated for SARS-CoV-2 RdRp inhibitory effect. Compounds 6b2, 6b5, 6c9, 6d2, and 6d5 were identified as potent inhibitors with IC50 values of 3.35 ± 0.21 µM, 4.55 ± 0.2 µM, 1.65 ± 0.05 µM, 3.76 ± 0.79 µM, and 1.11 ± 0.05 µM, respectively; the IC50 of remdesivir (control) was measured as 1.19 ± 0.36 µM. All of the compounds inhibited RNA synthesis by SARS-CoV-2 RdRp. The most potent compound 6d5, which showed a stronger inhibitory activity against the human coronavirus HCoV-OC43 than remdesivir, is a promising candidate for further investigation.