Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications.

We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.

COVID-19 Autopsies, Oklahoma, USA.

OBJECTIVES: To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020. METHODS: Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs. RESULTS: A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis. CONCLUSIONS: SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.

Lessons from Theranos - Restructuring Biomedical Innovation.

After raising more than $700 million, Elizabeth Holmes, the founder and chief executive officer of a healthcare startup once valued at $10 billion, was found guilty on four charges of defrauding investors. Founded in 2003, Theranos Inc. was a privately held corporation that aimed to disrupt the diagnostics industry with rapid, direct-to-consumer laboratory testing using only "a drop of blood" and the company's patented Nanotainer technology. By exploiting gaps in regulatory policy, Theranos brought its panel of laboratory tests to patients without pre-market review or validation from peer-reviewed scientific research. Investigations into Theranos' dubious operations and inaccurate test results exposed the failed venture which had squandered millions of dollars. Theranos affected the lives and health of patients further disrupting an already tenuous relationship between healthcare and the public - the importance of which cannot be understated in the setting of the COVID-19 pandemic. As medical systems address a national public health crisis and pervasive structural inequities, we must align stakeholder incentives between industry and academic biomedical innovation to rebuild trust with our patients.

External quality assessment of COVID-19 real time reverse transcription PCR laboratories in India.

Sudden emergence and rapid spread of COVID-19 created an inevitable need for expansion of the COVID-19 laboratory testing network across the world. The strategy to test-track-treat was advocated for quick detection and containment of the disease. Being the second most populous country in the world, India was challenged to make COVID-19 testing available and accessible in all parts of the country. The molecular laboratory testing network was augmented expeditiously, and number of laboratories was increased from one in January 2020 to 2951 till mid-September, 2021. This rapid expansion warranted the need to have inbuilt systems of quality control/ quality assurance. In addition to the ongoing inter-laboratory quality control (ILQC), India implemented an External Quality Assurance Program (EQAP) with assistance from World Health Organization (WHO) and Royal College of Pathologists, Australasia. Out of the 953 open system rRTPCR laboratories in both public and private sector who participated in the first round of EQAP, 891(93.4%) laboratories obtained a passing score of > = 80%. The satisfactory performance of Indian COVID-19 testing laboratories has boosted the confidence of the public and policy makers in the quality of testing. ILQC and EQAP need to continue to ensure adherence of the testing laboratories to the desired quality standards.

A review of studies on the COVID-19 epidemic crisis disease with a preventive approach.

BACKGROUND: COVID-19 is a highly contagious acute respiratory syndrome and has been declared a pandemic in more than 209 countries worldwide. At the time of writing, no preventive vaccine has been developed and tested in the community. This study was conducted to review studies aimed at preventing the spread of the coronavirus worldwide. METHODS: This study was a review of the evidence-based literature and was conducted by searching databases, including Google Scholar, PubMed, and ScienceDirect, until April 2020. The search was performed based on keywords including "coronavirus", "COVID-19", and "prevention". The list of references in the final studies has also been re-reviewed to find articles that might not have been obtained through the search. The guidelines published by trustworthy organizations such as the World Health Organization and Center for Disease Control have been used in this study. CONCLUSION: So far, no vaccine or definitive treatment for COVID-19 has been invented, and the disease has become a pandemic. Therefore, observation of hand hygiene, disinfection of high-touch surfaces, observation of social distance, and lack of presence in public places are recommended as preventive measures. Moreover, to control the situation and to reduce the incidence of the virus, some of the measures taken by the decision-making bodies and the guidelines of the deterrent institutions to strengthen telecommuting of employees and reduce the presence of people in the community and prevent unnecessary activities, are very important.

Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists.

Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or 'virus spreaders'. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID-19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.

COVID-19-another influential event impacts on laboratory medicine management.

BACKGROUND: Before public health emergencies became a major challenge worldwide, the scope of laboratory management was only related to developing, maintaining, improving, and sustaining the quality of accurate laboratory results for improved clinical outcomes. Indeed, quality management is an especially important aspect and has achieved great milestones during the development of clinical laboratories. CURRENT STATUS: However, since the coronavirus disease 2019 (COVID-19) pandemic continues to be a threat worldwide, previous management mode inside the separate laboratory could not cater to the demand of the COVID-19 public health emergency. Among emerging new issues, the prominent challenges during the period of COVID-19 pandemic are rapid-launched laboratory-developed tests (LDTs) for urgent clinical application, rapid expansion of testing capabilities, laboratory medicine resources, and personnel shortages. These related issues are now impacting on clinical laboratory and need to be effectively addressed. CONCLUSION: Different from traditional views of laboratory medicine management that focus on separate laboratories, present clinical laboratory management must be multidimensional mode which should consider consolidation of the efficient network of regional clinical laboratories and reasonable planning of laboratories resources from the view of overall strategy. Based on relevant research and our experience, in this review, we retrospect the history trajectory of laboratory medicine management, and also, we provide existing and other feasible recommended management strategies for laboratory medicine in future.

Evaluation of the analytical performance and specificity of a SARS-CoV-2 transcription-mediated amplification assay.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires fast and accurate high-throughput diagnostic tools. To evaluate the analytical performance of the Hologic Aptima transcription-mediated amplification (TMA) assay for detection of SARS-CoV-2 RNA from respiratory samples we analysed 103 clinical and proficiency panel samples pre-tested by real-time RT-PCR (Altona, RealStar) and found a positive percent agreement (sensitivity) of 95.7 % and a negative percent agreement (specificity) of 100 %. The limit of detection of the Aptima test was 150 copies/mL determined as 95 % detection probability. To further assess the Aptima assay's specificity we prospectively analysed 7545 clinical specimens from the upper and lower respiratory tract sent for the purpose of routine SARS-CoV-2 screening. SARS-CoV-2 RNA was detected in 16/7545 (0.2 %) samples by the TMA assay and confirmed independently by the Xpert SARS-CoV-2 RT-PCR (Cepheid); in one case a previous discrepant result was confirmed as true SARS-CoV-2 infection in a subsequent sample from the same patient. Results from the Aptima SARS-CoV-2 TMA assay agreed well with RT-PCR and showed an excellent specificity in a large number of routine specimens despite the low prevalence at that time of the pandemic, indicating that this assay can be used even for screening purposes.

Assessment of Specimen Pooling to Conserve SARS CoV-2 Testing Resources.

OBJECTIVES: To establish the optimal parameters for group testing of pooled specimens for the detection of SARS-CoV-2. METHODS: The most efficient pool size was determined to be five specimens using a web-based application. From this analysis, 25 experimental pools were created using 50 µL from one SARS-CoV-2 positive nasopharyngeal specimen mixed with 4 negative patient specimens (50 µL each) for a total volume of 250 µL. Viral RNA was subsequently extracted from each pool and tested using the CDC SARS-CoV-2 RT-PCR assay. Positive pools were consequently split into individual specimens and tested by extraction and PCR. This method was also tested on an unselected group of 60 nasopharyngeal specimens grouped into 12 pools. RESULTS: All 25 pools were positive with cycle threshold (Ct) values within 0 and 5.03 Ct of the original individual specimens. The analysis of 60 specimens determined that 2 pools were positive followed by identification of 2 individual specimens among the 60 tested. This testing was accomplished while using 22 extractions/PCR tests, a savings of 38 reactions. CONCLUSIONS: When the incidence rate of SARS-CoV-2 infection is 10% or less, group testing will result in the saving of reagents and personnel time with an overall increase in testing capability of at least 69%.

Point-of-care testing for the detection of SARS-CoV-2: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of the Food and Drug Administration Emergency Use Authorization (FDA-EUA) authorized point-of-care tests (POCTs) for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: A systematic literature search was conducted using the PubMed, Embase, and Web of Science databases for articles published till August 10, 2020. We included studies providing information regarding diagnostic test accuracy of FDA-EUA POCTs for SARS-CoV-2 detection. The methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The review protocol is registered in the International Prospective Register of Systematic Reviews (protocol number CRD42020202248). RESULTS: We included 26 studies describing a total of 3242 samples. The summary sensitivity and specificity were 0.94 [95% confidence interval (CI): 0.88-0.97] and 1.00 (95% CI: 0.99-1.00), respectively. The area under the summary receiver operating characteristic curve was 1.00 (95% CI: 0.99-1.00). A pooled analysis based on the index test revealed a summary sensitivity and specificity of Cepheid Xpert Xpress SARS-CoV-2 [0.99 (95% CI: 0.97-1.00) and 0.99 (95% CI: 0.94-1.00, respectively)] and ID NOW COVID-19 [0.78 (95% CI: 0.74-0.82) and 1.00 (95% CI: 0.98-1.00), respectively]. CONCLUSIONS: FDA-EUA POCTs, especially molecular assays, have high sensitivity, specificity, and overall diagnostic accuracy for detecting SARS-CoV-2. If approved, FDA-EUA POCTs can provide a rapid and practical way to identify infected individuals early on and help to limit the strain on the healthcare system. However, more high-quality clinical data are required to support our results.

SARS-CoV-2 infection serology validation of different methods: Usefulness of IgA in the early phase of infection.

BACKGROUND AND AIMS: A novel coronavirus (SARS-CoV-2) was isolated from the respiratory samples of patients with pneumonia as showed by the sequence analysis of the virus genomes obtained in Wuhan, China. The antibody response to SARS-CoV-2 is not well understood yet, but the availability of sensitive and specific serological assays will be crucial for the early diagnosis of infection, for epidemiological studies and for defining the presence of neutralizing antibodies in response to a possible vaccine. MATERIALS AND METHODS: We tested and compared the performances of one chemiluminescent immunoassay (CLIA), two enzyme-linked immunosorbent assay (ELISA) and an electrochemiluminescence immunoassay (ECLIA). RESULTS: The ECLIA serological assay performed best and may be a valid screening method for SARS-COV-2 infection. The IgA detected by the ELISA assay might be a more reliable and stable early serological marker than IgM. Instead, IgGs, as expected, showed stable level after 10 days from symptoms onset. CONCLUSION: The ECLIA method could be used as screening test, considering both the excellent performance and the cost per single test; while ELISA assay for IgG and IgA, which are present at a higher level than IgM and last longer, might be used as confirmatory test.