Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation.

COVID-19, caused by the SARS-CoV-2 virus, has developed into a global health crisis, causing over 2 million deaths and changing people's daily life the world over Current main-stream diagnostic methods in the laboratory include nucleic acid PCR tests and direct viral antigen tests for detecting active infections, and indirect human antibody tests specific to SARS-CoV-2 to detect prior exposure In this Perspective, we briefly describe the PCR and antigen tests and then focus mainly on existing antibody tests and their limitations including inaccuracies and possible causes of unreliability False negatives in antibody immunoassays can arise from assay formats, selection of viral antigens and antibody types, diagnostic testing windows, individual variance, and fluctuation in antibody levels Reasons for false positives in antibody immunoassays mainly involve antibody cross-reactivity from other viruses, as well as autoimmune disease The spectrum bias has an effect on both the false negatives and false positives For assay developers, not only improvement of assay formats but also selection of viral antigens and isotopes of human antibodies need to be carefully considered to improve sensitivity and specificity For clinicians, the factors influencing the accuracy of assays must be kept in mind to test patients using currently imperfect but available tests with smart tactics and realistic interpretation of the test results

COVID-19 Antibody Tests and Their Limitations.

Serological cross-reaction and coinfection of dengue and COVID-19 in Asia: Experience from Indonesia.

Laboratory testing for the diagnosis of COVID-19.

Introduction: A novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported via nucleic acid identification in December, 2019. Accuracy of SARS-CoV-2 diagnostic assays has emerged as a major barrier to COVID-19 diagnosis, particularly in cases requiring urgent or emergent treatment.Areas covered: In this review, we explore the major reasons for false-positive and false-negative SARS-CoV-2 test results. How clinical characteristics, specific respiratory comorbidities and SARS-CoV-2 vaccination impact on existing diagnostic assays are highlighted. Different COVID-19 management algorithms based on each test and limitations are thoroughly presented.Expert opinion: The diagnostic accuracy and the capacity of every available assay, which need to be interpreted in the light of the background incidence of SARS-CoV-2 infection in the communities in which they are used, are essential in order to minimize the number of falsely tested cases. Automated testing platforms may enhance diagnostic accuracy by minimizing the potential for human error in assays' performance. Prior immunization against SARS-CoV-2 impairs the utility of serologic testing of suspected COVID-19 cases. Future avenues of research to evaluate lung tissue innate immune responses hold promise as a target for research to optimize SARS-CoV-2 and future infections' testing accuracy.

https://www.tandfonline.com/doi/pdf/10.1080/17476348.2021.1917389

False-positive and false-negative COVID-19 cases: respiratory prevention and management strategies, vaccination, and further perspectives.

BACKGROUND: Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity. METHODS: We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities. RESULTS: Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID-19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E-5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E-4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein. CONCLUSIONS: Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health.

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Shlomit Keler

Papers

Potential Antigenic Cross-reactivity Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Dengue Viruses.

P073 Clinical efficacy of CFTR modulator therapy in patients carrying the I1234V mutation