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.     

Patient and Clinical Factors at Admission Affect the Levels of Neutralizing Antibodies Six Months after Recovering from COVID-19

The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAb^high, n = 153) and low (NAb^low, n = 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAb^low group, a larger proportion of the NAb^high group received corticosteroids (38.8% vs. 22.4%, p = 0.002) and IVIG therapy (26.5% vs. 16.3%, p = 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%, p = 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L; p = 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L; p = 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL; p = 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) μg/L; p = 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L; p = 0.014) levels, but low SpO₂ levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%; p = 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657–0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.     

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.     

COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

Renin–angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin‐converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus‐2 (SARS‐CoV‐2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease‐19 (COVID‐19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS‐CoV‐2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID‐19 infection.     

新型冠状病毒感染肺炎患者肝酶异常的机制探究

目的探索和分析新型冠状病毒感染肺炎(NCP)患者发生肝损伤的可能机制。方法综合分析已报道文献中NCP患者的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)等肝酶变化情况与疾病状态的相关性;基于肝组织单细胞测序数据(GSE115469)分析新冠病毒受体血管紧张素转换酶2(ACE2)在肝组织中的表达;采用RNA-seq方法分析半肝切除急性肝损伤小鼠模型肝切除后不同时间点残肝组织中Ace2的表达及与其表达相关的转录因子。统计学方法采用t检验和Spearman秩相关分析。结果部分新冠病毒感染者发生了ALT、AST异常升高,且NCP重症患者ALT、AST升高的比率及程度均高于非重症患者。肝组织单细胞测序和免疫组织化学检测结果显示,ACE2在正常肝组织中只在胆管上皮细胞表达,而在肝细胞中表达极低。在小鼠半肝切除急性肝损伤模型中,Ace2在术后第1天的急性损伤期表达下调,但在术后第3天的肝细胞增殖高峰期表达升高至正常水平的2倍以上,并在肝脏恢复、肝细胞增殖停止的第7天恢复到正常水平。这一现象是否提示ACE2表达阳性的胆管上皮细胞参与了部分肝切除后的肝再生过程,值得进一步的研究。RNA-seq数据中有77个转录因子与Ace2表达呈正相关(r>0.2,FDR<0.05),主要富集在腺体腔管表皮细胞的发育、分化、形态生成以及细胞增殖等功能。结论除了NCP患者过度激活的炎症反应可导致肝损伤外,胆管上皮细胞来源肝实质细胞的代偿性增生所致病毒受体ACE2在肝组织中的表达上调,可能是新型冠状病毒感染肝细胞造成肝组织损伤的可能机制。     

Establishment and evaluation of a 30-minute detection method for SARS-CoV-2 nucleic acid using a novel ultra-fast real-time PCR instrument

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is still raging worldwide. Efficient, fast and low-cost severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection methods are urgently needed.MethodsA rapid PCR temperature change mode was explored by moving the reaction tube between the independent temperature modules with large temperature differences and a portable ultra-fast real-time PCR instrument were developed. We established a rapid SARS-CoV-2 test method using the ultra-fast real-time PCR instrument, a China Food and Drug Administration-certified SARS-CoV-2 reagent and optimized reaction condition. The analytical and clinical performances of the rapid tests were evaluated by comparing with the standard SARS-CoV-2 tests.ResultsThe new temperature change mode can effectively shorten the amplification reaction time and be successfully used in the development of the ultra-fast real-time PCR instrument. The rapid SARS-CoV-2 test method was established and the time to yield results were greatly shortened from 81 min of the standard test to 31 min. Specificity of the rapid test was assessed and no non-specific amplification (0/63) was observed. The limits of detection of the rapid and standard tests were similar. Clinical performance was evaluated using 184 respiratory specimens from patients with suspected SARS-CoV-2 infection. The positive agreement between the rapid and standard tests was 100% (67/67), the negative agreement was 97.4% (114/117), and the kappa statistic was 0.965 (P<0.001). No significant differences in the Ct values for each target gene were observed between the rapid test and the standard test (P>0.05).ConclusionsWe had developed a 30-minute detection method for SARS-CoV-2 nucleic acid using a novel ultra-fast real-time PCR instrument. The rapid test method may impact on patient management.     

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。     

Mycoplasma pneumoniae detections before and during the COVID-19 pandemic: results of a global survey, 2017 to 2021

Background Mycoplasma pneumoniae respiratory infections are transmitted by aerosol and droplets in close contact.AimWe investigated global M. pneumoniae incidence after implementation of non-pharmaceutical interventions (NPIs) against COVID-19 in March 2020.MethodsWe surveyed M. pneumoniae detections from laboratories and surveillance systems (national or regional) across the world from 1 April 2020 to 31 March 2021 and compared them with cases from corresponding months between 2017 and 2020. Macrolide-resistant M. pneumoniae (MRMp) data were collected from 1 April 2017 to 31 March 2021.ResultsThirty-seven sites from 21 countries in Europe, Asia, America and Oceania submitted valid datasets (631,104 tests). Among the 30,617 M. pneumoniae detections, 62.39% were based on direct test methods (predominantly PCR), 34.24% on a combination of PCR and serology (no distinction between methods) and 3.37% on serology alone (only IgM considered). In all countries, M. pneumoniae incidence by direct test methods declined significantly after implementation of NPIs with a mean of 1.69% (SD ± 3.30) compared with 8.61% (SD ± 10.62) in previous years (p < 0.01). Detection rates decreased with direct but not with indirect test methods (serology) (–93.51% vs + 18.08%; p < 0.01). Direct detections remained low worldwide throughout April 2020 to March 2021 despite widely differing lockdown or school closure periods. Seven sites (Europe, Asia and America) reported MRMp detections in one of 22 investigated cases in April 2020 to March 2021 and 176 of 762 (23.10%) in previous years (p = 0.04).ConclusionsThis comprehensive collection of M. pneumoniae detections worldwide shows correlation between COVID-19 NPIs and significantly reduced detection numbers.     

COVID‐19 cardiac involvement in a 38‐day old infant

The spectrum of clinical manifestations of coronavirus disease 2019 in children is yet to be fully elucidated. We report the case of an infant who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and developed mild cardiovascular inflammation, a novelty for patients of very young age, that contributes to defining the puzzling nature of this disease in pediatric patients. The potential cardiovascular involvement of SARS‐CoV‐2 in children should always be taken into account.     

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.     

COVID‐19 infection in a paucisymptomatic infant: Raising the index of suspicion in epidemic settings

Few children have been reported to have been affected by novel coronavirus disease 2019 (COVID‐19); it is unclear whether children are less likely to be infected or rather display fewer symptoms. We present the case of a 32‐day‐old boy infected by COVID‐19 that presented with an upper air way infection which resolved spontaneously and did not require any therapy. We argue that in epidemic settings children presenting with any mild symptom potentially attributable to COVID‐19 should be considered contagious until proven otherwise, and that management must be guided by clinical conditions.     

结核病患者接种新型冠状病毒疫苗的专家建议

新型冠状病毒肺炎疫情仍在全球大范围流行,作为控制疫情的重要措施,新型冠状病毒疫苗接种正在全球范围内推广。结核病人群是新型冠状病毒感染和疾病重症化的高危人群,应优先考虑疫苗接种。但是,对于结核病患者是否能够接种以及如何接种新型冠状病毒疫苗,目前暂无足够多的高质量循证医学证据。为此,中华医学会结核病学分会基于世界卫生组织有关建议,以及我国相关技术指南,结合结核病患者实际情况,提出针对这一特殊人群疫苗接种的专家指导意见,建议除处于抗结核强化期治疗或合并其他病情不稳定慢性疾病的活动性结核病患者外,均应接种新型冠状病毒疫苗。     

Scutellaria barbata D. Don Inhibits the Main Proteases (Mpro and TMPRSS2) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged to severely impact the global population, creating an unprecedented need for effective treatments. This study aims to investigate the potential of Scutellaria barbata D. Don (SB) as a treatment for SARS-CoV-2 infection through the inhibition of the proteases playing important functions in the infection by SARS-CoV-2. FRET assay was applied to investigate the inhibitory effects of SB on the two proteases involved in SARS-CoV-2 infection, M^pro and TMPRSS2. Additionally, to measure the potential effectiveness of SB treatment on infection inhibition, cellular models based on the Calu3 and VeroE6 cells and their TMPRSS2- expressing derivatives were assessed by viral pseudoparticles (Vpp) infection assays. The experimental approaches were conjugated with LC/MS analyses of the aqueous extracts of SB to identify the major constituent compounds, followed by a literature review to determine the potential active components of the inhibitory effects on protease activities. Our results showed that SB extracts inhibited the enzyme activities of M^pro and TMPRSS2. Furthermore, SB extracts effectively inhibited SARS-CoV-2 Vpp infection through a TMPRSS2-dependent mechanism. The aqueous extract analysis identified six major constituent compounds present in SB. Some of them have been known associated with inhibitory activities of TMPRSS2 or M^pro. Thus, SB may effectively prevent SARS-CoV-2 infection and replication through inhibiting M^pro and TMPRSS2 protease activities.     

Circulating biomarkers of left ventricular hypertrophy in pediatric coarctation of the aorta

Objective: Patients undergoing surgical repair of aortic coarctation have a 50% risk of pathologic left ventricular remodeling (increased left ventricular mass or relative wall thickness). Endothelin 1, ST2, galectin 3, norepinephrine and B‐natriuretic pep‐ tide are biomarkers that have been associated with pathologic LV change in adult populations but their predictive value following pediatric coarctation repair are not known.
Hypothesis: Biomarker levels at coarctation repair will predict persistent left ven‐ tricular remodeling at 1‐year follow up.
Design: Prospective, cohort study of 27 patients’ age 2 days‐12 years with coarcta‐ tion of the aorta undergoing surgical repair. Echocardiograms were performed pre‐ operation, postoperation, and at 1‐year follow‐up. Plasma biomarker levels were measured at the peri‐operative time points. Association between biomarker concen‐ trations and echocardiographic parameters was assessed.
Results: Neither left ventricular mass index nor relative wall thickness varied from pre‐op to post‐op. At pre‐op, relative wall thickness was elevated in 52% and left ventricular mass index was elevated in 22%; at follow‐up, relative wall thickness was elevated in 13% and left ventricular mass index was elevated in 8%. Presence of re‐ sidual coarctation did not predict left ventricular remodeling (AUC 0.59; P > .05). Multivariable receiver operating characteristic curve combining pre‐op ST2 and en‐ dothelin 1 demonstrated significant predictive ability for late pathologic left ven‐ tricular remodeling (AUC 0.85; P = .02).
Conclusions: Persistent left ventricular hypertrophy and abnormal relative wall thick‐ ness at intermediate‐term follow‐up was rare compared to previous studies. A model combining pre‐op endothelin 1 and ST2 level demonstrated reasonable accuracy at predicting persistent abnormalities in this cohort. Larger studies will be needed to validate this finding and further explore the mechanism of persistent left ventricular remodeling in this population.