Viral load may impact the diagnostic performance of nasal swabs in nucleic acid amplification test and quantitative antigen test for SARS-CoV-2 detection

IntroductionCompared to nasopharyngeal swabs (NPS), there has been insufficient evaluation of the diagnostic performance of nasal swabs (NS) for the detection of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the nucleic acid amplification test (NAAT) and quantitative SARS-CoV-2 antigen test (QAT).MethodsWe prospectively compared healthcare worker-collected and flocked NS within nine days after symptom onset to paired NPS to detect SARS-CoV-2 in NAAT and QAT on the fully automated Lumipulse system. The agreement between sample types was evaluated, and cycle threshold (Ct) values and antigen levels were used as surrogate viral load measures.ResultsSixty sets of NPS and NS samples were collected from 40 patients with COVID-19. The overall agreements between NAAT and QAT samples were 76.7% and 65.0%, respectively. In NAAT, the Ct value of NS was significantly higher, 5.9, than that of NPS. Thirty-nine (95.1%) NS tested positive in 41 positive-paired NPS with Ct ≤ 30. The negative correlation was observed between antigen levels of NS in QAT and Ct values of NS in NAAT (r = ?0.88). In QAT, the antigen level of NS was significantly lower than that of NPS. Thirty-six (90.0%) NS tested positive in 40 positive-paired NPS with antigen levels >100 pg/mL, which were collected significantly earlier than those with antigen levels ≤100 pg/mL.ConclusionsIn NAAT and QAT, NS had limited performance in detecting SARS-CoV-2 compared to NPS. However, NS may be helpful for patients with COVID-19 with high viral loads or those in the early stages of the illness.     

2例新型冠状病毒肺炎粪便SARS-CoV-2核酸阳性临床启示

目前中国新型冠状病毒肺炎(COVID-19)疫情仍十分严峻,及时、早期地识别COVID-19患者是控制疫情的关键步骤。而新型冠状病毒(SARS-CoV-2)核酸检测作为诊断COVID-19的金标准,不但对检测技术提出更高的要求,同时对不同病程患者如何选择标本类型也是一个挑战。本文报道2例COVID-19确诊病例的诊疗经过,并分析采用不同类型标本检测SARS-CoV-2核酸的检出情况,为临床诊断COVID-19时如何选择标本类型和如何提高核酸检出率提供参考。     

Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019

In December 2019, a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and has now spread worldwide. There are no specific drugs for the disease caused by this virus, coronavirus disease 2019 (COVID-19). Considering that new synthesized drugs cannot be applied immediately to patients, conventional drug in new use is a feasible solution. Chloroquine, remdesivir, favipiravir, lopinavir, ribavirin, and ritonavir have shown efficacy to inhibit coronavirus in vitro. Pentoxifylline, a drug with anti-inflammatory, immunomodulatory, and bronchodilatory effects, has previously been shown to inhibit several viral infections. Immunological studies have shown that most patients with severe COVID-19 exhibit substantially elevated serum levels of pro-inflammatory cytokines. Pentoxifylline is a phosphodiesterase inhibitor that increases the levels of cyclic adenosine monophosphate, which in turn activates protein kinase, leading to a reduction in the synthesis of pro-inflammatory cytokines and immune cell migration. Here, we propose pentoxifylline, a drug with low cost and toxicity, as a possible treatment for COVID-19 based on its interesting properties.     

新型冠状病毒肺炎相关性急性胰腺炎：证据，挑战与思考

由新型冠状病毒（SARS-CoV-2）感染引起的新型冠状病毒肺炎（COVID-19）自2019年12月发病以来,现已全球大流行。COVID-19除影响呼吸系统外,还可造成全身多系统、多脏器的损害。目前关于COVID-19累及胰腺的证据十分有限,COVID-19患者中急性胰腺炎（AP）的发病率存在不确定性,其临床特征和发病机制也存在诸多疑问。在全球COVID-19流行仍未得到完全控制的背景下,由于目前对COVID-19与AP之间相互作用知之甚少,我们必须警惕他们之间可能存在的联系。临床上诸多治疗程序需要合理化,应采取有效的防护措施,在科学诊治患者的同时有效避免医护人员SARS-CoV-2感染。     

Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable

Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.     

Development of septic shock and prognostic assessment in critically ill patients with coronavirus disease outside Wuhan,China

BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit (ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease (COVID-19). METHODS: Patients confirmed with SARS-CoV-2 infection, who were admitted to the ICU of the Third People’s Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock. RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years (interquartile range [IQR] 59-67 years), and 10 (28.4%) patients were female. The median ICU length of stay was 16 days (IQR 8-23 days). Three (8.6%) patients died during hospitalization. Nine (25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock. CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled inflammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock.     

Beta receptor blocker therapy for the elderly in the COVID-19 era

When the coronavirus disease 2019 (COVID-19) pandemic spread globally from the Hubei region of China in December 2019, the impact on elderly people was particularly unfavorable. The mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was highest in older individuals, in whom frailty and comorbidities increased susceptibility to severe forms of COVID-19. Unfortunately, in older patients, the course of COVID-19 was often characterized by significant cardiovascular complications, such as heart failure decompensation, arrhythmias, pericarditis, and myopericarditis. Ensuring that the elderly have adequate therapeutic coverage against known cardiovascular diseases and risk factors is particularly important in the COVID-19 era. Beta blockers are widely used for the treatment and prevention of cardiovascular disease. The clinical benefits of beta blockers have been confirmed in elderly patients, and in addition to their negative chronotropic effect, sympathetic inhibition and anti-inflammatory activity are theoretically of great benefit for the treatment of COVID-19 infection. Beta blockers have not been clearly shown to prevent SARS-CoV-2 infection, but there is evidence from published studies including elderly patients that beta blockers are associated with a more favorable clinical course of COVID-19 and reduced mortality. In this minireview, we summarize the most important evidence available in the literature on the usefulness of beta blocker therapy for older patients in the context of the COVID-19 pandemic.     

Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection

T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4⁺ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARS-CoV-2–specific CD4⁺ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4⁺ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2–specific CD4⁺ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4⁺ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.     

No SARS-CoV-2 RNA detected in the convalescent plasma of COVID-19 patients with different disease severity

IntroductionConvalescent plasma transfusion (CPT), a potential therapy for coronavirus disease 2019 (COVID-19), requires strict quality control of the donor blood. Whether to confirm the disappearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA (RNAemia) in convalescent donor blood or not is unclear. Reports recommending the proof of viral disappearance from the blood are controversial. Foreseeing CPT in treating COVID-19 patients in Japan, we investigated RNAemia in 100 convalescent donors with mild, moderate, and severe COVID-19.MethodsBetween April 30 and July 30, 2020, we measured RNAemia in the plasma samples of donors with resolved COVID-19. Data on patients’ demographics, comorbidities, pneumonia, treatment, and real-time polymerase chain reaction results for SARS-CoV-2 were collected. Date of onset of initial symptoms or date of positive testing (for asymptomatic patients) were self-reported by the patients. Disease severity was defined as: no, mild, moderate oxygen demand, or severe (requiring mechanical ventilation).ResultsOf 100 donors (58 males [58.0%]; median age, 47 [range 22–69] years) screened as of July 30, 2020, 77 (77.0%); 19 (19.0%); and 4 (4.0%) had mild, moderate, and severe disease, respectively. Median time between onset and testing was 68.5 (range, 21–167) days. SARS-CoV-2 RNA was not detected in any of the plasma samples.ConclusionRNAemia was not found in recovered COVID-19 patients at least 21, 27, and 57 days after the onset of mild, moderate, and severe symptoms. Our study may contribute to determining a suitable time for collecting convalescent plasma from COVID-19 patients and to future CPT use.     

Immunochromatographic test for the detection of SARS-CoV-2 in saliva

We evaluated the rapid immunochromatographic test for severe acute respiratory coronavirus 2 (SARS-CoV-2) antigen detection using 16 saliva specimens collected from 6 COVID-19 hospitalized patients, and detected N-antigen in 4 of 7 RT-PCR positive specimens. This POCT detected SARS-CoV-2 antigen in saliva and would be useful for COVID-19 diagnosis.     

Distinctive features of severe SARS-CoV-2 pneumonia

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.     

冠状病毒疾病2019发病机制若干热点问题的思考

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）所致冠状病毒疾病2019（COVID-19）已构成国际关注的突发公共卫生事件。COVID-19传染性强,可导致患者出现严重呼吸道感染和多器官系统功能损害。COVID-19发病机制尚不明确,我们推测SARS-CoV-2直接致宿主靶细胞损伤及机体免疫炎症反应紊乱可能是COVID-19的主要致病机制。本文基于相关研究领域的进展,对COVID-19发病机制中的若干热点问题进行分析和讨论,并提出思考。     

A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis

The gold standard for the diagnosis of coronavirus disease 2019 (COVID-19) is a nucleic acid detection test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may occasionally reveal false-positive or false-negative results. Herein, we describe a case of a patient infected with human coronavirus NL63 (HCoV-NL63) who was falsely diagnosed with COVID-19 using the Ampdirect? 2019-nCoV detection kit (Shimadzu Corporation, Japan) and SARS-CoV-2 Detection Kit (TOYOBO co., ltd.), and was admitted to a COVID-19 hospital ward. We suspected a cross-reaction between HCoV-NL63 and SARS-CoV-2; however, the reported genome sequences of HCoV-NL63 and N1/N2 primers for SARS-CoV-2 do not correspond. Thus, the PCR result was supposed to be a false positive possibly due to contamination or human error. Although the issue of a false-negative result has been the focus of much attention to prevent the spread of the disease, a false positive is fraught with problems as well. Physicians should recognize that unnecessary isolation violates human rights and a careful diagnosis is indispensable when the results of laboratory testing for COVID-19 are unclear. Generally, in cases such as a duplicate PCR test was partially positive, either N1 or N2 alone was positive, PCR testing for two or more target regions resulted in a positive only for single region, a high cycle threshold >35 was obtained, a false positive should be suspected. Especially, when these conditions coincide, we should recognize the high likelihood of a false positive.     

新型冠状病毒IgM和IgG抗体不同检测方法在新型冠状病毒感染中的临床应用评价

目的探讨新型冠状病毒(SARS-CoV-2)IgM和IgG抗体不同检测方法在新型冠状病毒肺炎(COVID-19)中的应用。方法选取25例COVID-19患者,以同期20例排除SARS-CoV-2感染的患者作为对照组,分别采用磁微粒化学发光法和胶体金法检测所有对象的血清SARS-CoV-2 IgM和IgG抗体。同时检测COVID-19患者血清降钙素原(PCT)、铁蛋白及C反应蛋白(CRP)。结果化学发光法检测血清SARSCoV-2 IgM和IgG抗体的敏感性分别为48%和56%,特异性均为100%,胶体金法检测血清SARS-CoV-2 IgM和IgG抗体的敏感性分别为88%和76%,临床特异性均为100%。2种方法检测血清SARS-CoV-2 IgM和IgG抗体总符合率分别为68.9%和73.3%。25例COVID-19患者中有36%的患者血清PCT升高、72%的患者血清CRP升高、84%的患者血清铁蛋白水平升高。结论SARS-CoV-2 IgM和IgG抗体不同检测方法之间差异较大,用于COVID-19患者的临床诊断时应综合考虑。     

Prolonged presence of SARS-CoV-2 in a COVID-19 case with rheumatoid arthritis taking iguratimod treated with ciclesonide

We report a coronavirus disease 2019 (COVID-19) case with rheumatoid arthritis taking iguratimod. The patient who continued iguratimod therapy without dose reduction was treated with ciclesonide had an uneventful clinical course, but prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed after resolution of symptoms. The effects of disease-modifying antirheumatic drugs (DMARDs) and ciclesonide on clinical course and viral shedding remain unknown and warrant further investigation.