Evaluation of four commercial severe acute respiratory coronavirus 2 antibody tests

IntroductionNumerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital.MethodsThis study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses.ResultsThe varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11–15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed.ConclusionsOur results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis.     

Risk of transmission of severe acute respiratory syndrome coronavirus 2 by transfusion: A literature review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus responsible for coronavirus disease 2019 (COVID-19). The emergence of this virus in Wuhan, China, at the end of 2019 and its worldwide spread to reach the pandemic stage has raised concerns about the possible risk that it might be transmissible by transfusion. This theoretical risk is further supported by reports of the detection of viral RNA in the blood of some infected individuals. To further address this risk, a thorough PubMed literature search was performed to systematically identify studies reporting data on the detection of SARS-CoV-2 RNA in blood or its components. Complementary searches were done to identify articles reporting data on the in vitro infectivity of blood components. At least 23 articles presenting data on the detection of SARS-CoV-2 RNA in blood, plasma, or serum were identified. Of these, three studies reported on blood donors with COVID-19 infection identified after donation, and no cases of transfusion transmission were identified. A few studies mentioned results of in vitro infectivity assays of blood components in permissive cell lines, none of which were able to detect infectious virus in blood or its components. Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biologic sample and infectivity requires a minimal RNA load, which is rarely, if ever, observed in blood components. Overall, the available evidence suggests that the risk of transmission of SARS-CoV-2 by transfusion remains theoretical.     

False positive results in severe acute respiratory coronavirus 2 (SARS-CoV-2) rapid antigen tests for inpatients

Severe acute respiratory syndrome coronavirus 2 rapid antigen detection (RAD) test kits are widely used as primary screening test in Japan because rapid diagnosis of coronavirus disease 2019 (COVID-19) is critical for infection control. We report cases with RAD test false-positive results in a ward for patients with disabilities. RAD tests potentially evoke hospital operational risk. It is desirable that performing PCR test appropriately when patients admitted to a medical treatment ward with COVID-19 symptoms instead of RAD test.     

Coronavirus disease (COVID-19) associated delayed-onset fulminant myocarditis in patient with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

A healthy 35-year-old man was admitted to a rural hospital with coronavirus disease (COVID-19). During 14 days of hospitalization, he had no symptoms and was not given supplemental oxygen. About 3 weeks after discharge, he was re-admitted to the same hospital with new-onset continuous fever and general weakness. At the time of his second admission, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RT-PCR was performed on a retro-nasal swab and the result was negative. Four days after admission, the patient was transferred to our intensive care unit (ICU) following deterioration of his respiratory and haemodynamic conditions, where he received mechanical ventilation, intra-aortic balloon pumping, and veno-arterial extracorporeal membrane oxygenation. A nasopharyngeal swab was obtained again at ICU admission, but RT-PCR was negative for SARS-CoV-2. All antibody titres measured against other viruses were low. Blood cultures were negative, and no bacteria were observed in sputum samples. However, SARS-CoV-2 RNA was detected by RT-PCR from sections obtained by myocardial biopsy. The patient's final diagnosis was delayed-onset SARS-CoV-2-induced fulminant myocarditis (FM). We strongly suggested that one of the proposed mechanisms of COVID-19-related myocardial injury will be the direct invasion of SARS-CoV-2 into cardiomyocytes even if delayed-onset. And this is the first case of delayed-onset FM in which diagnosis of active myocarditis was proven by pathological examination following endomyocardial biopsy and SARS-CoV-2 was detected in the myocardium by RT-PCR.     

关注SARS-CoV-2致病机制的研究

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）传染性强,可导致患者出现严重急性呼吸道感染（SARI）和多器官系统功能损害。SARS-CoV-2致病机制尚不明确,推测免疫炎症反应紊乱在其发生发展中发挥至关重要的作用。结合相关领域的研究进展,梳理SARS-CoV-2可能的致病机制,厘清未来研究方向,具有重要临床意义。     

Extracorporeal membrane oxygenation for coronavirus disease 2019-associated acute respiratory distress syndrome: Report of two cases and review of the literature

BACKGROUNDCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, is a worldwide pandemic. Some COVID-19 patients develop severe acute respiratory distress syndrome and progress to respiratory failure. In such cases, extracorporeal membrane oxygenation (ECMO) treatment is a necessary life-saving procedure.CASE SUMMARYTwo special COVID-19 cases—one full-term pregnant woman and one elderly (72-year-old) man—were treated by veno-venous (VV)-ECMO in the Second People’s Hospital of Zhongshan, Zhongshan City, Guangdong Province, China. Both patients had developed refractory hypoxemia shortly after hospital admission, despite conventional support, and were therefore managed by VV-ECMO. Although both experienced multiple ECMO-related complications on top of the COVID-19 disease, their conditions improved gradually. Both patients were weaned successfully from the ECMO therapy. At the time of writing of this report, the woman has recovered completely and been discharged from hospital to home; the man remains on mechanical ventilation, due to respiratory muscle weakness and suspected lung fibrosis. As ECMO itself is associated with various complications, it is very important to understand and treat these complications to achieve optimal outcome.CONCLUSIONVV-ECMO can provide sufficient gas exchange for COVID-19 patients with acute respiratory distress syndrome. However, it is crucial to understand and treat ECMO-related complications.     

新型冠状病毒的研究现状与实验室诊断

新型冠状病毒(SARS-CoV-2)在全球范围内的传播对世界公共健康构成了巨大威胁。目前,预防和治疗SARS-CoV-2的选择仍然非常有限。解析病毒感染宿主的致病机制及治疗性疫苗的研制迫在眉睫。与此同时,研发快速、有效的SARS-CoV-2实验室检测技术,对于实现快速确诊感染病例、排除疑似病例、促进疫情的防控与临床救治至关重要。该文首先从SARS-CoV-2的结构特征、分子遗传变异特征、致病机制及潜在的药物靶点等方面介绍了“如何认识SARS-CoV-2”;同时立足于临床检验,重点介绍了现有的病毒实验室检测技术及问题解析、即时检验及高通量病毒筛查芯片等病毒筛查新技术,回答了“如何检测SARS-CoV-2”。最后对实验室从业人员如何安全防护进行了要点总结。     

Factors affecting the sensitivity of quantitative severe acute respiratory syndrome coronavirus 2 antigen test

IntroductionThe accuracy of nucleic acid amplification tests (NAATs) is affected by various factors; however, studies examining the factors affecting the accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test (QAT) are limited.MethodsA total of 347 nasopharyngeal samples were collected from patients with coronavirus disease 2019 (COVID-19), and the date of onset was obtained from the electronic medical records. The SARS-CoV-2 antigen level was measured using Lumipulse Presto SARS-CoV-2 Ag (Presto), while NAAT was performed using the Ampdirect 2019-nCoV Detection Kit.ResultsPresto had a sensitivity rate of 95.1% (95% confidence interval: 92.8–97.4) in detecting the SARS-CoV-2 antigen in 347 samples. The number of days from symptom onset to sample collection was negatively correlated with the amount of antigen (r = −0.515) and sensitivity of Presto (r = −0.711). The patients’ age was lower in the Presto-negative samples (median age, 39 years) compared with that in the Presto-positive samples (median age, 53 years; p < 0.01). A significant positive correlation was observed between age (excluding teenagers) and Presto sensitivity (r = 0.764). Meanwhile, no association was found between the mutant strain, sex, and Presto results.ConclusionPresto is useful for the accurate diagnosis of COVID-19 owing to its high sensitivity when the number of days from symptom onset to sample collection is within 12 days. Furthermore, age may affect the results of Presto, and this tool has a relatively low sensitivity in younger patients.     

Potential for false-positive results with quantitative antigen tests for SARS-CoV-2: A case of a child with acute respiratory infection

The quantitative antigen test based on the chemiluminescent enzyme immunoassay for SARS-CoV-2 has been used in international airports for quarantine in Japan. While cases of false-positive rapid antigen tests for SARS-CoV-2 were reported, false-positive cases of the quantitative antigen test with clinical information are rare. Here, we report a case of acute respiratory infection whose quantitative antigen test for SARS-CoV-2 was suspected to be false positive. A 9-month-old boy who presented with fever and rhinorrhea was admitted to our hospital under the Quarantine Act. He was diagnosed with COVID-19 based on the quantitative antigen test for SARS-CoV-2 performed at the quarantine station. None of the accompanying family members were positive for COVID-19. Nucleic acid amplification tests (NAAT) for SARS-CoV-2 were all negative, and multiplex polymerase chain reaction detected human rhinovirus or enterovirus infection. This case suggests that the results of the quantitative antigen test should be interpreted together with clinical information, and NAAT should be performed when false-positive results are suspected to avoid unnecessary isolation.     

Clinical features and outcomes of coronavirus disease 2019 in early infants in Japan: A case series and literature review

The clinical picture in early infants with COVID-19 has been described in a limited number of reports, mainly from European countries, United States, and China, but not Japan. Although several reports suggested that early infants can develop more severe COVID-19 disease than older children, risk factors for severe illness and differences according to nationality or ethnicity remain unclear. We report a case series of 13 infants ≤90 days old with COVID-19 in Japan. All patients had mild outcomes and did not require respiratory support or intensive care.     

Clinical improvement in a patient with severe coronavirus disease 2019 after administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.     

Persistent viral shedding of severe acute respiratory syndrome coronavirus 2 after treatment with bendamustine and rituximab: A case report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12–20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.     

A retrospective analysis of clinical efficacy of ribavirin in adults hospitalized with severe COVID-19

IntroductionCoronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking.MethodsA total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay.Results68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63–1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay.ConclusionsIn hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.     

Review of the risk factors for SARS-CoV-2 transmission

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which has lasted for nearly a year, has made people deeply aware of the strong transmissibility and pathogenicity of SARS-CoV-2 since its outbreak in December 2019. By December 2020, SARS-CoV-2 had infected over 65 million people globally, resulting in more than 1 million deaths. At present, the exact animal origin of SARS-CoV-2 remains unclear and antiviral vaccines are now undergoing clinical trials. Although the social order of human life is gradually returning to normal, new confirmed cases continue to appear worldwide, and the majority of cases are sporadic due to environmental factors and lax self-protective consciousness. This article provides the latest understanding of the epidemiology and risk factors of nosocomial and community transmission of SARS-CoV-2, as well as strategies to diminish the risk of transmission. We believe that our review will help the public correctly understand and cope with SARS-CoV-2.     

Effectiveness of adjunctive corticosteroid therapy in patients with severe COVID-19: A retrospective cohort study

BACKGROUNDThe effectiveness of adjunctive corticosteroid use in patients with coronavirus disease 2019 (COVID-19) remains inconclusive.AIMTo investigate the effectiveness of adjunctive corticosteroid therapy in patients with severe COVID-19.METHODSWe conducted a retrospective analysis of the difference in several outcomes between patients with severe COVID-19 who received corticosteroid therapy (the corticosteroid group) and patients with severe COVID-19 who did not receive corticosteroid therapy (the non-corticosteroid group).RESULTSSeventy-five patients were included in this study. Of these, 47 patients were in the corticosteroid group and 28 patients were in the non-corticosteroid group. There were no differences between the two groups in the total length of hospital stay, the length of intensive care unit stay, high-flow oxygen days, non-invasive ventilator days, invasive ventilation days, and mortality rate. Total lesion volume ratio, consolidation volume ratio and ground-glass opacity volume ratio in the corticosteroid group decreased significantly on day 14, while those in the non-corticosteroid group did not show a significant decrease.CONCLUSIONOur results show that adjunctive corticosteroid use did not significantly improve clinical outcomes in severe COVID-19 patients, but might promote the absorption of pulmonary lesions. Larger multicenter randomized controlled studies may be needed to confirm this.