Comparison of clinical characteristics between patients with coronavirus disease 2019 (COVID-19) who retested RT-PCR positive versus negative: a retrospective study of data from Nanjing

BackgroundThe epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been reported. However, the prevalence of retesting positive by RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated patient characteristics, remain unclear.MethodsWe included 90 confirmed cases of COVID-19 treated in the Nanjing Public Health Center from January 20, 2020 to February 16, 2020 in this retrospective study. All patients completed treatment for COVID-19 and were retested by RT-PCR for SARS-CoV-2 4–20 days after completion of therapy. The clinical characteristics between patients with who retested positive versus negative by RT-PCR were compared, and the factors predictive of positive retesting were analyzed. Positive retesting was modeled with the area under the receiver operating characteristic curve (AUC).ResultsThe age range of the study population was 0.8–97 years, and all patients were cured or showed improvement. A total of 10 (11%) patients retested positive by RT-PCR 4–20 days after completion of therapy. As compared with patients who retested negative, those who retested positive had a lower percentage of pre-admission fever, a higher percentage of post-admission fever, a lower percentage of bilateral lung infection, higher white blood cell (WBC) count and creatine phosphokinase, and lower hypersensitive c-reactive protein (hs-CRP), interleukin-6 and erythrocyte sedimentation rates (all P<0.05). Logistic regression analysis of the above eight key variables showed that lower hs-CRP and higher WBC were independently associated with positive retesting by RT-PCR. A combination of hs-CRP and WBC were predictive of positive retesting, with an AUC of 0.859.ConclusionsPatients with COVID-19 who retested positive by RT-PCR for SARS-CoV-2 had mild symptoms and better blood testing results. A combination of hs-CRP and WBC may predict positive retesting by RT-PCR; however, the sensitivity and specificity should be studied further.     

Pneumothorax in a COVID-19 Pneumonia Patient without Underlying Risk Factors

Coronavirus disease 2019 (COVID-19) has been recognized as a worldwide pandemic. However, the clinical course of COVID-19 remains poorly characterized. Although some cases of pneumothorax have been reported, they all had pulmonary complications or were managed with mechanical ventilation. We herein report a case of pneumothorax that developed even though the patient had no pulmonary underlying diseases and had never been managed with mechanical ventilation. In the present case, a lung bulla was found on chest computed tomography during treatment for COVID-19. We concluded that COVID-19 affected the formation of the lung bulla and induced the complication of pneumothorax.     

Application of artificial intelligence in COVID-19 medical area: a systematic review

BackgroundCoronavirus disease 2019 (COVID-19) has caused a large-scale global epidemic, impacting international politics and the economy. At present, there is no particularly effective medicine and treatment plan. Therefore, it is urgent and significant to find new technologies to diagnose early, isolate early, and treat early. Multimodal data drove artificial intelligence (AI) can potentially be the option. During the COVID-19 Pandemic, AI provided cutting-edge applications in disease, medicine, treatment, and target recognition. This paper reviewed the literature on the intersection of AI and medicine to analyze and compare different AI model applications in the COVID-19 Pandemic, evaluate their effectiveness, show their advantages and differences, and introduce the main models and their characteristics.MethodsWe searched PubMed, arXiv, medRxiv, and Google Scholar through February 2020 to identify studies on AI applications in the medical areas for the COVID-19 Pandemic.ResultsWe summarize the main AI applications in six areas: (I) epidemiology, (II) diagnosis, (III) progression, (IV) treatment, (V) psychological health impact, and (VI) data security. The ongoing development in AI has significantly improved prediction, contact tracing, screening, diagnosis, treatment, medication, and vaccine development for the COVID-19 Pandemic and reducing human intervention in medical practice.DiscussionThis paper provides strong advice for using AI-based auxiliary tools for related applications of human diseases. We also discuss the clinicians’ role in the further development of AI. They and AI researchers can integrate AI technology with current clinical processes and information systems into applications. In the future, AI personnel and medical workers will further cooperate closely.     

Clinical and Microbiological Features of Asymptomatic SARS-CoV-2 Infection and Mild COVID-19 in Seven Crewmembers of a Cruise Ship

Objective To describe the clinical features and clinical course of individuals diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild coronavirus disease (COVID)-19. Patients The study participants consisted of 7 crewmembers of the passenger cruise-liner, Diamond Princess, who were admitted to our hospital after becoming infected with SARS-CoV-2 aboard the ship. Methods The data on patient background and biochemical test results were obtained from the patients'' medical records. All patients had a chest X-ray, and a throat swab and sputum samples were sent for culture on admission. Results The median age of the 7 patients, of whom 4 were male and 3 were female, was 39 years (range: 23-47 years). On admission, none of them had fever, but 4 (57%) had a cough. None of them showed any signs of organ damage on laboratory testing. Chest X-ray showed pneumonia in one individual, which resolved spontaneously, while the other 6 had normal chest X-ray findings. Culture of throat swabs and sputum samples revealed that 4 patients (57%) had bacterial upper respiratory infections (Haemophilus influenzae, Klebsiella pneumoniae, and Staphylococcus aureus). The period from a positive polymerase chain reaction (PCR) test to negative conversion ranged from 5 to 13 days, with a median of 8 days. Conclusion Healthy young adults without risk factors who acquire SARS-CoV-2 infection may have an asymptomatic infection or may experience mild COVID-19. In addition to obesity, an older age, underlying illness, and being overweight can lead to a risk of exacerbation; thus, hospital management for such individuals may be desirable. Culturing respiratory samples may be useful for diagnosing secondary bacterial pneumonia.     

Host Protective Immunity against Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) and the COVID-19 Vaccine-Induced Immunity against SARS-CoV-2 and Its Variants

The world is now apparently at the last/recovery stage of the COVID-19 pandemic, starting from 29 December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the progression of time, several mutations have taken place in the original SARS-CoV-2 Wuhan strain, which have generated variants of concern (VOC). Therefore, combatting COVID-19 has required the development of COVID-19 vaccines using several platforms. The immunity induced by those vaccines is vital to study in order to assure total protection against SARS-CoV-2 and its emerging variants. Indeed, understanding and identifying COVID-19 protection mechanisms or the host immune responses are of significance in terms of designing both new and repurposed drugs as well as the development of novel vaccines with few to no side effects. Detecting the immune mechanisms for host protection against SARS-CoV-2 and its variants is crucial for the development of novel COVID-19 vaccines as well as to monitor the effectiveness of the currently used vaccines worldwide. Immune memory in terms of the production of neutralizing antibodies (NAbs) during reinfection is also very crucial to formulate the vaccine administration schedule/vaccine doses. The response of antigen-specific antibodies and NAbs as well as T cell responses, along with the protective cytokine production and the innate immunity generated upon COVID-19 vaccination, are discussed in the current review in comparison to the features of naturally induced protective immunity.     

Clinical symptoms,comorbidities and complications in severe and non-severe patients with COVID-19: A systematic review and meta-analysis without cases duplication

Background:The pandemic of COVID-19 poses a challenge to global healthcare. The mortality rates of severe cases range from 8.1% to 38%, and it is particularly important to identify risk factors that aggravate the disease.Methods:We performed a systematic review of the literature with meta-analysis, using 7 databases to identify studies reporting on clinical characteristics, comorbidities and complications in severe and non-severe patients with COVID-19. All the observational studies were included. We performed a random or fixed effects model meta-analysis to calculate the pooled proportion and 95% confidence interval (CI). Measure of heterogeneity was estimated by Cochran''s Q statistic, I² index and P value.Results:A total of 4881 cases from 25 studies related to COVID-19 were included. The most prevalent comorbidity was hypertension (severe: 33.4%, 95% CI: 25.4%–41.4%; non-severe 21.6%, 95% CI: 9.9%–33.3%), followed by diabetes (severe: 14.4%, 95% CI: 11.5%–17.3%; non-severe: 8.5%, 95% CI: 6.1%–11.0%). The prevalence of acute respiratory distress syndrome, acute kidney injury and shock were all higher in severe cases, with 41.1% (95% CI: 14.1%–68.2%), 16.4% (95% CI: 3.4%–29.5%) and 19.9% (95% CI: 5.5%–34.4%), rather than 3.0% (95% CI: 0.6%–5.5%), 2.2% (95% CI: 0.1%–4.2%) and 4.1% (95% CI: −4.8%–13.1%) in non-severe patients, respectively. The death rate was higher in severe cases (30.3%, 95% CI: 13.8%–46.8%) than non-severe cases (1.5%, 95% CI: 0.1%–2.8%).Conclusion:Hypertension, diabetes and cardiovascular diseases may be risk factors for severe COVID-19.     

Neutralizing Antibodies in COVID-19 Patients and Vaccine Recipients after Two Doses of BNT162b2

The evaluation of the neutralizing capacity of anti-SARS-CoV-2 antibodies is important because they represent real protective immunity. In this study we aimed to measure and compare the neutralizing antibodies (NAbs) in COVID-19 patients and in vaccinated individuals. One-hundred and fifty long-term samples from 75 COVID-19 patients were analyzed with a surrogate virus neutralization test (sVNT) and compared to six different SARS-CoV-2 serology assays. The agreement between the sVNT and pseudovirus VNT (pVNT) results was found to be excellent (i.e., 97.2%). The NAb response was also assessed in 90 individuals who had received the complete dose regimen of BNT162b2. In COVID-19 patients, a stronger response was observed in moderate–severe versus mild patients (p-value = 0.0006). A slow decay in NAbs was noted in samples for up to 300 days after diagnosis, especially in moderate–severe patients (r = −0.35, p-value = 0.03). In the vaccinated population, 83.3% of COVID-19-naive individuals had positive NAbs 14 days after the first dose and all were positive 7 days after the second dose, i.e., at day 28. In previously infected individuals, all were already positive for NAbs at day 14. At each time point, a stronger response was observed for previously infected individuals (p-value < 0.05). The NAb response remained stable for up to 56 days in all participants. Vaccinated participants had significantly higher NAb titers compared to COVID patients. In previously infected vaccine recipients, one dose might be sufficient to generate sufficient neutralizing antibodies.     

Clinical,laboratory, and imaging features of pediatric COVID-19: A systematic review and meta-analysis

Pediatric cases of coronavirus disease 2019 (COVID-19) have been reported. This meta-analysis was aimed at describing the clinical, laboratory, and imaging characteristics of children with COVID-19 based on published data of pediatric COVID-19 cases.Search of PubMed, Embase, Web of Sciences, Science Direct, and Google Scholar for articles published until December 14, 2020, that described the clinical, laboratory, and imaging features of children with COVID-19. Data were extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled results.Clinical data from 2874 children with COVID-19 from 37 articles were finally included for quantitative analyses. Fever (48.5%, 95% CI: 41.4%–55.6%) and cough (40.6%, 95% CI: 33.9%–47.5%) were the most common symptoms; asymptomatic infection and severe cases, respectively, accounted for 27.7% (95% CI: 19.7%–36.4%) patients and 1.1% of the 1933 patients included. Laboratory tests showed 5.5% (95% CI: 2.8%–8.9%) of the patients had lymphopenia. The pooled prevalence of leukopenia was 7.3% (95% CI: 3.4%–12.2%), and the C-reactive protein level was high in 14.0% (95% CI: 6.8%–22.8%). Chest computed tomography showed unilateral and bilateral lesions, and ground-glass opacity in 29.4% (95% CI: 24.8%–34.3%) and 24.7% (95% CI: 18.2%–31.6%), and 32.9% (95% CI: 25.3%–40.9%), respectively, and normal in approximately 36.0% (95% CI: 27.7%–44.7%).We found that children with COVID-19 had relatively mild disease, with quite a lot of asymptomatic infections and low rate of severe illness. Data from more regions are needed to determine the prevention and treatment strategies for children with COVID-19.     

Persisting Neutralizing Activity to SARS-CoV-2 over Months in Sera of COVID-19 Patients

The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein and the N-protein, as well as the neutralizing activity (NAbs) against SARS-CoV-2 in the blood of moderately afflicted COVID-19 patients, needs further longitudinal investigation. Several new serological methods to examine these parameters were developed, validated and applied in three patients of a family which underwent an ambulatory course of COVID-19 for six months. The virus load had almost completely disappeared after about four weeks. Serum IgA levels to the S1-RBD-protein and, to a lesser extent, to the N-protein, peaked about three weeks after clinical disease onset but declined soon thereafter. IgG levels rose continuously, reaching a plateau at approximately six weeks, and stayed elevated over the observation period. Virus-neutralizing activity reached a peak about 4 weeks after disease onset but dropped slowly. The longitudinal associations of virus neutralization and the serological immune response suggest immunity in patients even after a mild clinical course of COVID-19.     

糖皮质激素在SARS、MERS治疗中的应用进展及对COVID-19治疗的启示

COVID-19是一种新发的急性呼吸道传染性疾病,其病原与严重急性呼吸综合征（severe acute respiratory syndrome, SARS）和中东呼吸综合征（Middle East respiratory syndrome, MERS）的病原同为冠状病毒,目前针对COVID-19的治疗尚缺乏有效的抗病毒药物。糖皮质激素广泛应用于危重症患者的救治,但其使用有可能带来各种不良反应,甚至危及患者生命,如何适时适量应用糖皮质激素一直是针对这类疾病治疗的争论焦点之一。本文对既往SARS、MERS等病毒性肺炎治疗中糖皮质激素使用情况进行综述,以期为COVID-19治疗提供借鉴。     

A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients

Abstract

Coronavirus disease 2019 (COVID-19) is a global public health emergency with many clinical facets, and new knowledge about its pathogenetic mechanisms is deemed necessary; among these, there are certainly coagulation disorders. In the history of medicine, autopsies and tissue sampling have played a fundamental role in order to understand the pathogenesis of emerging diseases, including infectious ones; compared to the past, histopathology can be now expanded by innovative techniques and modern technologies. For the first time in worldwide literature, we provide a detailed postmortem and biopsy report on the marked increase, up to 1 order of magnitude, of naked megakaryocyte nuclei in the bone marrow and lungs from serious COVID-19 patients. Most likely related to high interleukin-6 serum levels stimulating megakaryocytopoiesis, this phenomenon concurs to explain well the pulmonary abnormal immunothrombosis in these critically ill patients, all without molecular or electron microscopy signs of megakaryocyte infection.     

Persistence of Neutralizing Antibodies to SARS-CoV-2 in First Wave Infected Individuals at Ten Months Post-Infection: The UnIRSA Cohort Study

Longitudinal mapping of antibody-based SARS-CoV-2 immunity is critical for public health control of the pandemic and vaccine development. We performed a longitudinal analysis of the antibody-based immune response in a cohort of 100 COVID-19 individuals who were infected during the first wave of infection in northern Italy. The SARS-CoV-2 humoral response was tested using the COVID-SeroIndex, Kantaro Quantitative SARS-CoV-2 IgG Antibody RUO Kit (R&D Systems, Bio-Techne, Minneapolis, USA) and pseudotype-based neutralizing antibody assay. Using sequential serum samples collected from 100 COVID-19 recovered individuals from northern Italy—mostly with mild disease—at 2 and 10 months after their first positive PCR test, we show that 93% of them seroconverted at 2 months, with a geometric mean (GeoMean) half-maximal neutralization titer (NT50) of 387.9. Among the 35 unvaccinated subjects retested at 10 months, 7 resulted seronegative, with an 80% drop in seropositivity, while 28 showed decreased anti-receptor binding domain (RBD) and anti-spike (S) IgG titers, with a GeoMean NT50 neutralization titer dropping to 163.5. As an NT50 > 100 is known to confer protection from SARS-CoV-2 re-infection, our data show that the neutralizing activity elicited by the natural infection has lasted for at least 10 months in a large fraction of subjects.     

2019冠状病毒病研究纪实:至2020年3月11日

2019年12月1日,武汉市出现首例不明原因肺炎病例,2020年1月8日确认病原体为新型冠状病毒,2020年1月31日世界卫生组织(WHO)将病原体暂命名为2019新冠病毒(2019-nCoV),2020年2月8日国家卫健委将该不明原因肺炎命名为新型冠状病毒肺炎(简称新冠肺炎,novel coronavirus pneumonia),2020年2月11日,WHO依据规则将新冠肺炎正式命名为2019冠状病毒病(COVID-19),同一天,国际病毒分类委员会将2019新冠病毒正式命名为严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)。2020年3月11日,WHO将新冠疫情流行趋势升级为全球大流行状态。新冠疫情暴发后,国内外研究人员迅速开展流行病学调查、短时间内分离鉴定病毒、开展病原学研究、建立检测方法、完善诊疗方案、探索致病机制、研发药物和疫苗,有效阻止了国内疫情蔓延,也为世界疫情防控赢得了时间窗口。本文拟以时间为轴线,从病原体、病毒宿主、流行病学、检测方法、致病机制和临床诊疗6个方面记述2019冠状病毒病研究的重要进展。     

Chemiluminescence Immunoassay Based Serological Immunoassays for Detection of SARS-CoV-2 Neutralizing Antibodies in COVID-19 Convalescent Patients and Vaccinated Population

The development of rapid serological detection methods re urgently needed for determination of neutralizing antibodies in sera. In this study, four rapid methods (ACE2-RBD inhibition assay, S1-IgG detection, RBD-IgG detection, and N-IgG detection) were established and evaluated based on chemiluminescence technology. For the first time, a broadly neutralizing antibody with high affinity was used as a standard for the quantitative detection of SARS-CoV-2 specific neutralizing antibodies in human sera. Sera from COVID-19 convalescent patients (N = 119), vaccinated donors (N = 86), and healthy donors (N = 299) confirmed by microneutralization test (MNT) were used to evaluate the above methods. The result showed that the ACE2-RBD inhibition assay calculated with either ACE2-RBD binding inhibition percentage rate or ACE2-RBD inhibiting antibody concentration were strongly correlated with MNT (r ≥ 0.78, p < 0.0001) and also highly consistent with MNT (Kappa Value ≥ 0.94, p < 0.01). There was also a strong correlation between the two evaluation indices (r ≥ 0.99, p < 0.0001). Meanwhile, S1-IgG and RBD-IgG quantitative detection were also significantly correlated with MNT (r ≥ 0.73, p < 0.0001), and both methods were highly correlated with each other (r ≥ 0.95, p < 0.0001). However, the concentration of N-IgG antibodies showed a lower correlation with the MNT results (r < 0.49, p < 0.0001). The diagnostic assays presented here could be used for the evaluation of SARS-CoV-2 vaccine immunization effect and serological diagnosis of COVID-19 patients, and could also have guiding significance for establishing other rapid serological methods to surrogate neutralization tests for SARS-CoV-2.     

新型冠状病毒肺炎诊断研究进展

新型冠状病毒肺炎(COVID-19)疫情以来,疾病的高传染性使确诊人数剧增,同时死亡人数也在日益增加。现全球已有200余个国家或地区出现感染病例。疾病的早诊可以有效控制疾病传播,同时使感染者得到有效的隔离和救治,提高生存率。目前,中国COVID-19的控制取得了阶段性胜利。本文对COVID-19的临床表现、实验室检查、...