The management of coronavirus disease 2019 (COVID-19)

In December 2019, a novel coronavirus causing severe acute respiratory disease occurred in Wuhan, China. It is an emerging infectious disease with widespread and rapid infectiousness. The World Health Organization declared the coronavirus outbreak to be a public health emergency of international concern on 31 January 2020. Severe COVID-19 patients should be managed and treated in a critical care unit. Performing a chest X-ray/CT can judge the severity of the disease. The management of COVID-19 patients includes epidemiological risk and patient isolation; treatment entails general supportive care, respiratory support, symptomatic treatment, nutritional support, psychological intervention, etc. The prognosis of the patients depends upon the severity of the disease, the patient's age, the underlying diseases of the patients, and the patient's overall medical condition. The management of COVID-19 should focus on early diagnosis, immediate isolation, general and optimized supportive care, and infection prevention and control.     

Tocilizumab for the treatment of severe coronavirus disease 2019

Tocilizumab, an interleukin-6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID-19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory-confirmed severe COVID-19 who received tocilizumab and completed 14 days of follow up. Twenty-five patients were included, median age was 58 years (interquartile range, 50-63) and the majority were males (92%). Co-morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0°C, 37.3°C (P = .043), and 37.0°C (P = .064), respectively. Corresponding median C-reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID-19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.     

Diagnostic accuracy of antibody-based rapid diagnostic tests in detecting coronavirus disease 2019: systematic review

IntroductionThe rapid transmission of coronavirus disease 2019 (COVID-19) requires a fast, accurate, and affordable detection method. Despite doubts of their diagnostic accuracy, rapid diagnostic tests (RDTs) are used worldwide due to their practicality. This systematic review aims to determine the diagnostic accuracy of antibody-based RDTs in detecting COVID-19.Material and methodsA literature search was carried out on five journal databases using the PRISMA-P 2015 method. We included all studies published up to February 2021. The risk of bias was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Diagnostic Test Accuracy Studies. Data regarding peer-review status, study design, test kit information, immunoglobulin class, target antigen, and the number of samples were extracted and tabulated. We estimated the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with a 95% confidence interval.ResultsThirty-three studies met the eligibility criteria. The pooled data results showed that the combined detection method of IgM or IgG had the highest sensitivity and NPV, which were 73.41% (95% CI: 72.22–74.57) and 75.34% (95% CI: 74.51–76.16), respectively. The single IgG detection method had the highest specificity and PPV of 96.68% (95% CI: 96.25–97.07) and 95.97% (95% CI: 95.47–96.42%), respectively.ConclusionsAntibody-based RDTs are not satisfactory as primary diagnostic tests but have utility as a screening tool.     

Controversial treatments: An updated understanding of the coronavirus disease 2019

An outbreak of severe acute respiratory syndrome-related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case-fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.     

Diagnostic performance of seven rapid IgG/IgM antibody tests and the Euroimmun IgA/IgG ELISA in COVID-19 patients

ObjectivesTo evaluate the diagnostic performance of seven rapid IgG/IgM tests and the Euroimmun IgA/IgG ELISA for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients.MethodsSpecificity was evaluated in 103 samples collected before January 2020. Sensitivity and time to seropositivity was evaluated in 167 samples from 94 patients with COVID-19 confirmed with RT-PCR on nasopharyngeal swab.ResultsSpecificity (confidence interval) of lateral flow assays (LFAs) was ≥91.3% (84.0–95.5) for IgM, ≥90.3% (82.9–94.8) for IgG, and ≥85.4% (77.2–91.1) for the combination IgM OR IgG. Specificity of the ELISA was 96.1% (90.1–98.8) for IgG and only 73.8% (64.5–81.4) for IgA. Sensitivity 14–25 days after the onset of symptoms was between ≥92.1% (78.5–98.0) and 100% (95.7–100) for IgG LFA compared to 89.5% (75.3–96.4) for IgG ELISA. Positivity of IgM OR IgG for LFA resulted in a decrease in specificity compared to IgG alone without a gain in diagnostic performance, except for VivaDiag. The results for IgM varied significantly between the LFAs with an average overall agreement of only 70% compared to 89% for IgG. The average dynamic trend to seropositivity for IgM was not shorter than for IgG. At the time of hospital admission the sensitivity of LFA was <60%.ConclusionsSensitivity for the detection of IgG antibodies 14–25 days after the onset of symptoms was ≥92.1% for all seven LFAs compared to 89.5% for the IgG ELISA. The results for IgM varied significantly, and including IgM antibodies in addition to IgG for the interpretation of LFAs did not improve the diagnostic performance.     

1例疑似新型冠状病毒肺炎患者的手术管理策略

回顾1例疑似新型冠状病毒肺炎(COVID-19)患者的急诊手术管理,医护团队根据COVID-19的感染特点,参照核应急演习及手术室特殊感染手术的防控要求,提出严密的隔离措施和管理计划策略,从患者的病情评估、术前准备、手术间及器材设备准备、手术人员管控、麻醉防护特点、术中护理关键点及术后环境、器械、用物处置的特殊性进行积极探索,以期为保障手术顺利进行及制定疑似/确诊COVID-19患者手术管理流程和感染防控规范提供依据。     

CD-sACE2 inclusion compounds: An effective treatment for coronavirus disease 2019 (COVID-19)

Coronaviruses are common human viruses and include the severe acute respiratory syndrome coronavirus (SARS-CoV), the middle east respiratory syndrome coronavirus and the SARS-CoV-2. Coronaviruses mainly bind to transmembrane receptor proteins on the human cell membrane through spike proteins (S-proteins), thus releasing the RNA of the virus into the interior of the host cell to cause an infection. In this article, we discuss the mechanism and production of cyclodextrin-soluble angiotensin-converting enzyme 2 (CD-sACE2) inclusion compounds in the treatment of SARS-CoV-2 infections by blocking S-proteins. On the basis of the current research evidence, we believe that CD-sACE2 inclusion compounds have the potential to treat COVID-19. We hope that our article can provide a theoretical basis for later experiments.     

The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): A Chinese perspective

2019 novel coronavirus (SARS-CoV-2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID-19). However, SARS-CoV-2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID-19 in China to better understand the transmission and diagnosis regarding this infectious disease.     

Diagnostic assays developed for the control of foot-andmouth disease in India

Foot-and-mouth disease(FMD) is a highly contagious and economically devastating disease of livestock, primarily affecting cattle, buffalo and pigs. FMD virus serotypes O, A and Asia1 are prevalent in India and systematic efforts are on to control and eventually eradicate the disease from the country. FMD epidemiology is complex due to factors like co-circulation, extinction, emergence and re-emergence of genotypes/lineages within the three serotypes, animal movement, diverse farm practices and large number of susceptible livestock in the country. Systematic vaccination, prompt diagnosis, strict biosecurity measures, and regular monitoring of vaccinal immunity and surveillance of virus circulation are indispensible features for the effective implementation of the control measures. Availability of suitable companion diagnostic tests is very important in this endeavour. In this review, the diagnostic assays developed and validated in India and their contribution in FMD control programme is presented.     

多排螺旋CT联合多平面重建技术在新型冠状病毒肺炎诊断中的应用

目的探讨多排螺旋CT联合多平面重组技术(MPR)在新型冠状病毒肺炎(COVID-19)早期筛查诊断中的应用价值。方法回顾性分析2020年1~2月我院发热门诊32例疑似COVID-19患者的影像资料,对比原始CT轴位图像和重建后高分辨CT(HRCT)轴位图像结合MPR重组技术对COVID-19影像特征的检出能力,并用SPSS 17.0软件对病灶检出率进行χ2检验分析。结果重建后的HRCT轴位图像可以清楚显示肺小叶内部结构变化,尤其是结合MPR重组技术后在显示跨叶段病灶、支气管充气征、血管束增粗征等病变上优于原始CT轴位图像,差异具有统计学意义(P<0.05)。结论COVID-19疫情爆发期,尽早使用多排螺旋CT扫描,重建HRCT轴位图像并联合运用MPR技术,能够更加直观、立体地显示病灶,为COVID-19的快速鉴别诊断提供更丰富的影像依据,从而早隔离、早治疗,控制疫情发展。     

Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review

BackgroundTocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear.ObjectivesTo synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19.SourcesPubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed.ContentPublished data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother–infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding.ImplicationsAlthough the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed.     

Diagnostic strategies for SARS-CoV-2 infection and interpretation of microbiological results

BackgroundTo face the current COVID-19 pandemic, diagnostic tools are essential. It is recommended to use real-time RT-PCR for RNA viruses in order (a) to perform a rapid and accurate diagnostic, (b) to guide patient care and management and (c) to guide epidemiological strategies. Further studies are warranted to define the role of serological diagnosis and a possible correlation between serological response and prognosis.ObjectivesThe aim was to guide clinical microbiologists in the use of these diagnostic tests and clinicians in the interpretation of their results.SourcesA search of literature was performed through PubMed and Google Scholar using the keywords SARS-CoV-2, SARS-CoV-2 molecular diagnosis, SARS-CoV-2 immune response, SARS-CoV-2 serology/antibody testing, coronavirus diagnosis.ContentThe present review discusses performances, limitations and use of current and future diagnostic tests for SARS-CoV-2.ImplicationsReal-time RT-PCR remains the reference method for diagnosis of SARS-CoV-2 infection. On the other hand, notwithstanding its varying sensitivity according to the time of infection, serology represents a valid asset (a) to try to solve possible discrepancies between a highly suggestive clinical and radiological presentation and negative RT-PCR, (b) to solve discrepancies between different PCR assays and (c) for epidemiological purposes.     

Novel PCR assay for differential detection and screening of erythrovirus B19 and erythrovirus V9

Diagnosis of erythrovirus B19 relies on serology and the detection of viral DNA. These techniques were believed to detect all field isolates because erythrovirus B19 has been known to undergo little genetic variation (1-2%). Recently, a distinct erythrovirus isolate termed V9, markedly different from erythrovirus B19 (>11% nucleotide disparity), was isolated from a child in France suffering from transient aplastic anemia. Standard PCR assays and serological tests failed to demonstrate an acute erythrovirus B19 infection. Subsequent sequencing of the erythrovirus V9 genome shows that the nucleotide discrepancies encompass the entire genome, indicating that standard erythrovirus B19 PCR assays will not reliably detect erythrovirus V9 DNA. As a tool for studying the epidemiological role and medical importance of this erythrovirus variant, a PCR assay is described that allows simultaneous detection of, and distinction between, erythrovirus B19 and the V9 isolate. Examination of 100 erythrovirus B19 IgM positive samples as well as plasma pools representing 100,000 Danish blood donor units for the presence of B19 and V9 DNA was performed. Despite the apparent absence of erythrovirus V9 in the clinical samples at present, the DNA sequence variability demonstrates that the erythrovirus group may be more divergent than thought previously and the child harboring this isolate may herald erythrovirus V9 as a possible emerging virus.     

Evaluation of antiviral therapies for coronavirus disease 2019 pneumonia in Shanghai,China

The aim of our study was to evaluate the therapeutic effect of antiviral drugs on coronavirus disease 2019 (COVID-19) pneumonia. Patients confirmed with COVID-19 pneumonia were enrolled and divided into seven groups according to the treatment option. Information including age, sex, and duration from illness onset to admission, clinical manifestations, and laboratory data at admission, and length of hospital stay were evaluated. The chest computed tomography (CT) imaging obtained at admission and after a 5-day treatment cycle were assessed. The clinical symptoms and laboratory tests at discharge were also assessed. At admission, no significant differences were found among the groups, including the duration from illness onset to admission, clinical symptoms, and main laboratory results. No significant differences were found among the groups in terms of the proportion of patients with pneumonia resolution (P = .151) after treatment or the length of hospital stay (P = .116). At discharge, 7 of 184 (4%) patients had a mild cough while their other symptoms had disappeared, and the proportion of patients with abnormal liver function and with increased leukocytes, neutrophils or erythrocyte sedimentation rate among the 184 patients were close to those at admission. According to the results, the inclusion of antiviral drugs in therapeutic regimens based on symptomatic treatment had no significant additional impact on the improvement in COVID-19 patients. In addition, the results of chest CT imaging, clinical manifestations, and laboratory tests at discharge were not completely consistent.     

Detection and analysis of clinical features of patients with different types of coronavirus disease 2019

This study was designed to investigate the change of various indexes in patients with different types of coronavirus disease 2019 (COVID‐19). Seventy‐five patients with COVID‐19 were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, and they were classified into moderate, severe and critically severe types according to the disease severity. The basic information, blood routine, pneumonia‐related blood indexes, immune‐related indexes along with liver, kidney and myocardial indexes in patients with different types were analyzed. The analysis of immune‐related indexes showed that the proportions of critically severe patients with abnormal interleukin‐2 (IL‐2) and IL‐4 were higher than those of severe and moderate patients. In addition, the proportion of patients with abnormal total cholesterol increased as the severity of disease increased, and the proportion in critically severe patients was significantly higher than that in moderate patients. The patients with a more severe COVID‐19 are older and more likely to have a history of hypertension. With the progression of COVID‐19, the abnormal proportion of total white blood cell, neutrophils, lymphocytes, IL‐2, IL‐4, and total cholesterol increased. The change of these indexes in patients with different COVID‐19 types could provide reference for the disease severity identification and diagnosis of COVID‐19. In addition, the change in the total cholesterol level suggested that COVID‐19 would induce some liver function damage in patients.     

Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019

ObjectiveTo determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19).MethodsFrom January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored.ResultsClearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.ConclusionsSARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.     

A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID-19. In the retrospective analysis, we report nine cases of COVID-19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.