A novel cartridge for nucleic acid extraction, amplification and detection of infectious disease pathogens with the help of magnetic nanoparticles

Nucleic acid detection (NAD) based on real-time polymerase chain reaction (real-time PCR) is gold standard for infectious disease detection. Magnetic nanoparticles (MNPs) are widely used for nucleic acid extraction (NAE) because of their excellent properties. Microfluidic technology makes automated NAD possible. However, most of the NAD microfluidic chips are too complex to be applied to point-of-care (POC) testing. In this paper, a simple-structure cartridge was developed for POC detection of infectious diseases. This self-contained cartridge can be divided into a magnetic-controlled NAE part, a valve-piston combined fluidic control part and a PCR chip, which is able to extract nucleic acid from up to 500 μL of liquid samples by MNPs and finish the detection process from "sample in” to "answer out” automatically. Performance tests of the cartridges show that it met the demands of automated NAD. Results of on-cartridge detection of hepatitis B virus (HBV) demonstrated that this system has good uniformity and no cross-contamination between different cartridges, and the limit of detection (LOD) of this system for HBV in serum is 50 IU/mL. Multiplex detections of severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) with a concentration of 500 copies/mL were carried out on the system and 100% positive detection rate was achieved.

COVID-19 vaccination boosts the potency and breadth of the immune response against SARS-CoV-2 among recovered patients in Wuhan.

The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4+ T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants.

Pandemic paranoia in the general population: international prevalence and sociodemographic profile.

BACKGROUND: The term 'pandemic paranoia' has been coined to refer to heightened levels of mistrust and suspicion towards other people specifically due to the COVID-19 pandemic. In this study, we examine the international prevalence of pandemic paranoia in the general population and its associated sociodemographic profile. METHODS: A representative international sample of general population adults (N = 2510) from five sites (USA N = 535, Germany N = 516, UK N = 512, Australia N = 502 and Hong Kong N = 445) were recruited using stratified quota sampling (for age, sex, educational attainment) and completed the Pandemic Paranoia Scale (PPS). RESULTS: The overall prevalence rate of pandemic paranoia was 19%, and was highest in Australia and lowest in Germany. On the subscales of the PPS, prevalence was 11% for persecutory threat, 29% for paranoid conspiracy and 37% for interpersonal mistrust. Site and general paranoia significantly predicted pandemic paranoia. Sociodemographic variables (lower age, higher population size and income, being male, employed and no migrant status) explained additional variance and significantly improved prediction of pandemic paranoia. CONCLUSIONS: Pandemic paranoia was relatively common in a representative sample of the general population across five international sites. Sociodemographic variables explained a small but significant amount of the variance in pandemic paranoia.

The Relationship between Medical Staff's Emotional Labor, Leisure Coping Strategies, Workplace Spirituality, and Organizational Commitment during the COVID-19 Pandemic

Many medical issues have gradually emerged under the severe impact of the COVID-19 pandemic, which has not only changed the medical culture but also tested medical staffs' response abilities, emotional pressure, sense of identity, and belonging to the organization. The relationships among medical staffs' emotional labor, leisure coping strategies, workplace spirituality, and organizational commitment during the COVID-19 pandemic are explored in this study. With medical staffs as the research subjects, a questionnaire survey was conducted using convenience sampling;a total of 360 questionnaires were distributed and 330 were returned, for a recovery rate of 91%. There were 300 valid questionnaires after 30 invalid questionnaires were excluded, for an effective recovery rate of 90%. SPSS and AMOS software were used for statistical analysis. According to the research results: (1) emotional labor had a significant effect on workplace spirituality, (2) workplace spirituality had a significant impact on organizational commitment, (3) emotional labor had a negative and significant impact on organizational commitment, (4) emotional labor had a significant impact on leisure coping strategies, and (5) the mediating effect of workplace spirituality between emotional labor and organizational commitment was not significant. Finally, relevant practical suggestions are provided based on the results of this study.

Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020

Background The changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China. Method From January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes. Result A total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world. Conclusions The predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

Pandemic paranoia, general paranoia, and their relationships with worry and beliefs about self/others - A multi-site latent class analysis.

BACKGROUND: During the COVID-19 pandemic, an increase in paranoid thinking has been reported internationally. The development of the Pandemic Paranoia Scale (PPS) has provided a reliable assessment of various facets of pandemic paranoia. This study aimed to (i) identify classes of individuals with varying levels of general paranoia and pandemic paranoia, and (ii) examine associations between classification and worry, core beliefs, and pro-health behaviours. METHODS: An international sample of adults (N = 2510) across five sites completed the Revised-Green Paranoid Thoughts Scale and the PPS. Latent class analysis (LCA) was conducted using these two paranoia variables. Classes were compared on trait worry (Penn State Worry Questionnaire), beliefs about self/others (Brief Core Schema Scales), and pro-health behaviour. RESULTS: Three latent classes emerged: Class 1 with low R-GPTS and PPS scores, Class 2 with a high R-GPTS score and a moderate PPS score, and Class 3 with high R-GPTS and PPS scores. Compared to Class 1, Classes 2-3 were associated with more worry and negative self- and other-beliefs. Class 3 was further characterised by greater positive-self beliefs and less engagement in pro-health behaviours. Engagement in pro-health behaviours was positively correlated with interpersonal mistrust and negatively correlated with paranoid conspiracy and persecutory threat. CONCLUSIONS: Individuals with a general paranoia tendency were more likely to respond to the global health threats in a suspicious and distrusting way. Our findings suggested that worry and negative self/other beliefs may contribute to not just general paranoia but also pandemic paranoia. The preliminary finding of a link between pro-health behaviours and interpersonal mistrust warrants further examination.

Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

Serum surfactant protein D in COVID-19 is elevated and correlated with disease severity.

BACKGROUND: The serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated. METHODS: We performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People's Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed. RESULTS: In the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, P<0.001), while the serum levels of SP-D in the recovery period were decreased dramatically than that in the acute phase (mean value ± SD, 129.5 ± 51.7 vs 292.9 ± 130.7 ng/ml, P<0.001), and so were for the stratified patients. The chest CT imaging scores were considerably higher in the severe group compared with those in the mild group (median value, 10.0 vs 9.0, P = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, P<0.001), and so were for the stratified patients. ROC curve analysis revealed that areas under the curve of lymphocyte counts (LYM), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and SP-D for severe COVID-19 were 0.719, 0.833, 0.817, 0.837, and 0.922, respectively. Correlation analysis showed that the SP-D levels were negatively correlated with LYM (r = - 0.320, P = 0.047), while positively correlated with CRP (r = 0.658, P<0.001), IL-6 (r = 0.471, P = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, P<0.001), chest CT imaging score on admission (r = 0.695, P<0.001) and length of stay (r = 0.420, P = 0.008). Multivariate logistic regression model analysis showed that age (P = 0.041, OR = 1.093) and SP-D (P = 0.008, OR = 1.018) were risk factors for severe COVID-19. CONCLUSIONS: Elevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.

Clinical characteristics of COVID-19 patients with complications: implications for management.

BACKGROUND: A novel coronavirus disease 2019 (COVID-19) has caused outbreaks worldwide, and the number of cases is rapidly increasing through human-to-human transmission. Because of the greater transmission capacity and possible subsequent multi-organ damage caused by the virus, it is crucial to understand precisely and manage COVID-19 patients. However, the underlying differences in the clinical features of COVID-19 with and without comorbidities are not fully understood. AIM: The objective of this study was to identify the clinical features of COVID-19 patients with and without complications to guide treatment and predict the prognosis. METHOD: We collected the clinical characteristics of COVID-19 patients with and without different complications, including hypertension, cardiovascular disease and diabetes. Next, we performed a baseline comparison of each index and traced the dynamic changes in these factors during hospitalization to explore the potential associations. RESULT: A clinical index of differential expression was used for the regression to select top-ranking factors. The top-ranking clinical characteristics varied in each subgroup, such as indices of liver function, renal function and inflammatory markers. Among them, the indices of renal function were highly ranked in all subgroups and displayed significant differences during hospitalization. CONCLUSION: Organ functions of COVID-19 patients, particularly renal function, should be cautiously taken care of during management and might be a crucial factor for a poor prognosis of these patients with complications.

Persistently Reduced Pulmonary Function and Quality of Life in Patients With Mild COVID-19 One Year After Discharge: a Cohort Study (preprint)

Purpose: The epidemiological and clinical features, pathogenesis, and complications of patients with COVID-19 in the acute phase have been well described, but the long-term prognosis and rehabilitation of the patients remain largely unknown. Methods: 39 COVID-19 patients were followed up at 3, 6, and 12 months after discharge. The mental health, pulmonary function, exercise capacity, and quality of life were assessed by Self-Depression Scale and the Self Anxiety Scale, pulmonary function test, 6MWT, 36-Item Short-Form, respectively. Results: Total 33 survivors completed the assessment, 40.8 ± 0.8 years, body mass index= 22.7 ±1.3 kg/m 2 . The length of hospital stays was 19.6 ± 6.6 d. One year after discharge, the mean scores of SDS and SAS showed decreasing trends from 3-months to 12-months post-discharge. 6 patients (18.2%) had FVC <80% of the predicted value, 12 patients (36.4%) had FEV1 <80% of the predicted value. And 9 (27.3%), 3 (9.1%), and 2 (6.1%) of the patients showed reduced FEF25, FEF50, and FEF75 (<70% expected values), respectively. The mean 6MWD values increased significantly from 397±25.4 m at 3-months to 514±40.8 m at 12-months. Conclusions: the impaired pulmonary function in mild COVID-19 survivors was noted after 12 months discharging from hospital. The exercise capacity, mental status, and health status were lower than those of the normal population.

Aptamer Blocking Strategy Inhibits SARS-CoV-2 Virus Infection

Eine Aptamer-Blockierungsstrategie zur Hemmung der SARS-CoV-2-Infektion wird von Honglin Chen, Yanling Song, Chaoyong Yang et?al. in ihrem Forschungsartikel demonstriert (DOI: 10.1002/ange.202100225). Eine Aptamer-Sonde wurde so konstruiert, dass sie an das Spike-Protein von SARS-CoV-2 bindet, was die Infektion des Virus hemmt, indem es die Interaktion des Virus mit ACE2-Rezeptoren auf der Zellmembran blockiert.

Frailty as a predictor of mortality among patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: A large number of studies have explored the association between frailty and mortality among COVID-19 patients, with inconsistent results. The aim of this meta-analysis was to synthesize the evidence on this issue. METHODS: Three databases, PubMed, Embase, and Cochrane Library, from inception to 20th January 2021 were searched for relevant literature. The Newcastle-Ottawa Scale (NOS) was used to assess quality bias, and STATA was employed to pool the effect size by a random effects model. Additionally, potential publication bias and sensitivity analyses were performed. RESULTS: Fifteen studies were included, with a total of 23,944 COVID-19 patients, for quantitative analysis. Overall, the pooled prevalence of frailty was 51% (95% CI: 44-59%). Patients with frailty who were infected with COVID-19 had an increased risk of mortality compared to those without frailty, and the pooled hazard ratio (HR) and odds ratio (OR) were 1.99 (95% CI: 1.66-2.38) and 2.48 (95% CI: 1.78-3.46), respectively. In addition, subgroup analysis based on population showed that the pooled ORs for hospitalized patients in eight studies and nursing home residents in two studies were 2.62 (95% CI: 1.68-4.07) and 2.09 (95% CI: 1.40-3.11), respectively. Subgroup analysis using the frailty assessment tool indicated that this association still existed when using the clinical frailty scale (CFS) (assessed in 6 studies, pooled OR = 2.88, 95% CI: 1.52-5.45; assessed in 5 studies, pooled HR = 1.99, 95% CI: 1.66-2.38) and other frailty tools (assessed in 4 studies, pooled OR = 1.98, 95% CI: 1.81-2.16). In addition, these significant positive associations still existed in the subgroup analysis based on study design and geographic region. CONCLUSION: Our study indicates that frailty is an independent predictor of mortality among patients with COVID-19. Thus, frailty could be a prognostic factor for clinicians to stratify high-risk groups and remind doctors and nurses to perform early screening and corresponding interventions urgently needed to reduce mortality rates in patients infected by SARS-CoV-2.

Elevated Serum Pentraxin-3 Levels is Positively Correlated to Disease Severity and Coagulopathy in COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is highly contagious and deadly and is associated with coagulopathy. Pentraxin-3(PTX3) participates in innate resistance to infections and plays a role in thrombogenesis. PURPOSE: The present study aimed to investigate the role of PTX3 in coagulopathy in patients with COVID-19. METHODS: A retrospective study, including thirty-nine COVID-19 patients, enrolled in Hunan, China, were performed. The patients were classified into the D-dimer_L (D-dimer <1mg/L) and D-dimer_H (D-dimer≥1mg/L) groups basing on the plasma D-dimer levels on admission. Serum PTX3 levels were detected by enzyme-linked immunosorbent assays and compared between those two groups, then receiver operating characteristic (ROC) curve analysis, correlation analysis, and linear regression models were performed to analyze the association between PTX3 and D-dimer. RESULTS: Our results showed that serum PTX3 levels (median values, 10.21 vs. 3.36, P<0.001), computerized chest tomography (C.T.) scores (median values, 10.0 vs. 9.0, P<0.05), and length of stay (LOS) (mean values, 16.0 vs. 10.7, P=0.001) in the D-dimer_H group were significantly higher than that in D-dimer_L group. ROC curve analysis revealed that the AUC of white blood corpuscle counts, C-reaction protein, erythrocyte sedimentation rate, and PTX3 for COVID-19 were 0.685, 0.863, 0.846, and 0.985, respectively. Correlation analysis showed that there was a positive relationship between PTX3 and D-dimer (r=0.721, P<0.001), chest CT imaging score (r=0.418, P=0.008), and LOS (r=0.486, P=0.002). Multiple linear regression analysis showed that the coefficient of determination was 0.657 (P < 0.001). CONCLUSION: Serum level of PTX3 was positively correlated with disease severity and coagulopathy. Detection of serum PTX3 level could help identify severer patients on admission and may be a potential therapeutic target for coagulopathy in patients with COVID-19.

Exploiting an early warning nomogram for predicting the risk of ICU admission in COVID-19 patients: A multi-center study in China (preprint)

Background: Novel coronavirus disease 2019 (COVID-19) is a global public health emergency. Here, we developed and validated a practical model based on the data from a multi-center cohort in China for early identification and prediction of which patients will be admitted to the intensive care unit (ICU). Methods: Data of 1087 patients with laboratory-confirmed COVID-19 were collected from 49 sites between January 2 and February 28, 2020, in Sichuan and Wuhan. Patients were randomly categorized into the training and validation cohorts (7:3). The least absolute shrinkage and selection operator and logistic regression analyzes were used to develop the nomogram. The performance of the nomogram was evaluated for the C-index, calibration, discrimination, and clinical usefulness. Further, the nomogram was externally validated in a different cohort. Results: The individualized prediction nomogram included 6 predictors: age, respiratory rate, systolic blood pressure, smoking status, fever, and chronic kidney disease. The model demonstrated a high discriminative ability in the training cohort (C-index = 0.829), which was confirmed in the external validation cohort (C-index = 0.776). In addition, the calibration plots confirmed good concordance for predicting the risk of ICU admission. Decision curve analysis revealed that the prediction nomogram was clinically useful. Conclusion: We established an early prediction model incorporating clinical characteristics that could be quickly obtained on hospital admission, even in community health centers. This model can be conveniently used to predict the individual risk for ICU admission of patients with COVID-19 and optimize the use of limited resources.

Impact of Coronavirus Disease 2019 on Pulmonary Function in Early Convalescence Phase (preprint)

Objective: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods: A prospective retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-minute walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results: 57 patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p=0.019), higher lung total severity score（TSS）and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion: Impaired diffusing-capacityDeclining DLCO, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase.

Nucleotide analog inhibitors, including broad-spectrum remdesivir and favipiravir, have shown promise in in vitro assays and some clinical studies for COVID-19 treatment, this despite an incomplete mechanistic understanding of the viral RNA-dependent RNA polymerase nsp12 drug interactions. Here, we examine the molecular basis of SARS-CoV-2 RNA replication by determining the cryo-EM structures of the stalled pre- and post- translocated polymerase complexes. Compared with the apo complex, the structures show notable structural rearrangements happening to nsp12 and its co-factors nsp7 and nsp8 to accommodate the nucleic acid, whereas there are highly conserved residues in nsp12, positioning the template and primer for an in-line attack on the incoming nucleotide. Furthermore, we investigate the inhibition mechanism of the triphosphate metabolite of remdesivir through structural and kinetic analyses. A transition model from the nsp7-nsp8 hexadecameric primase complex to the nsp12-nsp7-nsp8 polymerase complex is also proposed to provide clues for the understanding of the coronavirus transcription and replication machinery.

Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur.

The antineoplastic drug carmofur is shown to inhibit the SARS-CoV-2 main protease (Mpro). Here, the X-ray crystal structure of Mpro in complex with carmofur reveals that the carbonyl reactive group of carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 µM) and is a promising lead compound to develop new antiviral treatment for COVID-19.

Structure of the RNA-dependent RNA polymerase from COVID-19 virus.

A novel coronavirus [severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)] outbreak has caused a global coronavirus disease 2019 (COVID-19) pandemic, resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase [(RdRp), also named nsp12] is the central component of coronaviral replication and transcription machinery, and it appears to be a primary target for the antiviral drug remdesivir. We report the cryo-electron microscopy structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-angstrom resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified ß-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics that target viral RdRp.