Meta-analysis of the robustness of COVID-19 diagnostic kit performance during the early pandemic.

BACKGROUND: Accurate detection of SARS-CoV-2 is necessary to mitigate the COVID-19 pandemic. However, the test reagents and assay platforms are varied and may not be sufficiently robust to diagnose COVID-19. METHODS: We reviewed 85 studies (21 530 patients), published from five regions of the world, to highlight issues involved in the diagnosis of COVID-19 in the early phase of the pandemic. All relevant articles, published up to 31 May 2020, in PubMed, BioRiXv, MedRiXv and Google Scholar, were included. We evaluated the qualitative (9749 patients) and quantitative (10 355 patients) performance of RT-PCR and serologic diagnostic tests for real-world samples, and assessed the concordance (5538 patients) between test performance in meta-analyses. Synthesis of results was done using random effects modelling and bias was evaluated according to QUADAS-2 guidelines. RESULTS: The RT-PCR tests exhibited heterogeneity in the primers and reagents used. Of 1957 positive RT-PCR COVID-19 participants, 1585 had positive serum antibody (IgM±IgG) tests (sensitivity 0.81, 95% CI 0.66 to 0.90). While 3509 of 3581 participants RT-PCR negative for COVID-19 were found negative by serology testing (specificity 0.98, 95% CI 0.94 to 0.99). The chemiluminescent immunoassay exhibited the highest sensitivity, followed by ELISA and lateral flow immunoassays. Serology tests had higher sensitivity and specificity for laboratory approval than for real-world reporting data. DISCUSSION: The robustness of the assays/platforms is influenced by variability in sampling and reagents. Serological testing complements and may minimise false negative RT-PCR results. Lack of standardised assay protocols in the early phase of pandemic might have contributed to the spread of COVID-19.

Meta-Analysis of Robustness of COVID-19 Diagnostic Kits During Early Pandemic.

BACKGROUND: Accurate detection of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is necessary to mitigate the coronavirus disease-19 (COVID-19) pandemic. However, the test reagents and assay platforms are varied and may not be sufficiently robust to diagnose COVID-19. METHODS: We reviewed 85 studies (21,530 patients), published from five regions of the world, to highlight issues involved in the diagnosis of COVID-19 in the early phase of the pandemic, following the standards outlined in the PRISMA statement. All relevant articles, published up to May 31, 2020, in PubMed, BioRiXv, MedRiXv, and Google Scholar, were included. We evaluated the qualitative (9749 patients) and quantitative (10,355 patients) performance of RT-PCR and serologic diagnostic tests for real-world samples, and assessed the concordance (5,538 patients) between methods in meta-analyses. RESULTS: The RT-PCR tests exhibited heterogeneity in the primers and reagents used. Of 1,957 positive RT-PCR COVID-19 participants, 1,585 had positive serum antibody (IgM +/- IgG) tests (sensitivity 0.81, 95%CI 0.66-.90). While 3,509 of 3581 participants RT-PCR negative for COVID-19 were found negative by serology testing (specificity 0.98, 95%CI 0.94-0.99). The chemiluminescent immunoassay exhibited the highest sensitivity, followed by ELISA and lateral flow immunoassays. Serology tests had higher sensitivity and specificity for laboratory-approval than for real-world reporting data. CONCLUSIONS: The robustness of the assays/platforms is influenced by variability in sampling and reagents. Serological testing complements and may minimize false negative RT-PCR results. Lack of standardized assay protocols in the early phase of pandemic might have contributed to the spread of COVID-19.

COVID-2019 - A comprehensive pathology insight.

Corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2), a highly contagious single stranded RNA virus genetically related to SARS CoV. The lungs are the main organs affected leading to pneumonia and respiratory failure in severe cases that may need mechanical ventilation. Occasionally patient may present with gastro-intestinal, cardiac and neurologic symptoms with or without lung involvement. Pathologically, the lungs show either mild congestion and alveolar exudation or acute respiratory distress syndrome (ARDS) with hyaline membrane or histopathology of acute fibrinous organizing pneumonia (AFOP) that parallels disease severity. Other organs like liver and kidneys may be involved secondarily. Currently the treatment is principally symptomatic and prevention by proper use of personal protective equipment and other measures is crucial to limit the spread. In the midst of pandemic there is paucity of literature on pathological features including pathogenesis, hence in this review we provide the current pathology centered understanding of COVID-19. Furthermore, the pathogenetic pathway is pivotal in the development of therapeutic targets.