Further testing for peripheral antibodies and nasopharyngeal PCR has added value to diagnosing COVID-19 patients formerly screened as negative based on exposure and symptoms. Laurentiu Craciunas reports on the diagnostic lessons learned from a COVID-19 session.
As background to several presentations in a special ‘Lessons Learned’ session on COVID-19 infection, the annual meeting heard how the SARS-CoV-2 virus enters human cells by binding its spike protein to the angiotensin-converting enzyme 2 (ACE2) receptors presented by multiple organs such as lungs, heart, ovaries and testes. The timeline for test positivity includes a succession of exposure, development of symptoms, and identification of viral RNA by PCR, followed by the development of antibodies.
Testing for COVID-19, which is now essential in IVF clinics, aims to guide patient management and the use of personal protective equipment (PPE) in order to protect patients, their contacts and medical staff against infection. However, Cristina González-Ravina, Director of the Andrology and Endocrinology Laboratories at IVI Seville, emphasised the uncertainties related to the optimal testing pathways as ‘there is insufficient information to recommend a specific algorithm or testing programme’.
Taking a lead from ESHRE’s guidance on restarting ART treatments published on 5 May, González-Ravina recommended screening patients based on past medical history, symptoms and contacts prior to their clinic appointments.(1) However, her introduction to the serologic (antibody) tests presently available for COVID-19 highlighted their unclear accuracy and implications for decision making. She described molecular testing by high-performance PCR, as ‘essential for clinical decisions, but the false negative rate varies according to the quality and timing of the sample collection’.
To shed more light on the usefulness of serological and molecular tests in diagnosing COVID-19 patients who screened negative, González-Ravina presented the results of a cohort study involving 2729 women attending for IVF treatment. They had molecular testing with PCR on nasopharyngeal swabs and serologic testing using IgM and IgG antibodies from peripheral blood. Based on either positive IgM antibodies (12 women) or positive PCR (3 women) to confirm active infection, one in every 200 women (0.6%) who screened negative initially had her treatment postponed as a result of additional testing. González-Ravina thus recommended triage alone for countries with low or reducing viral prevalence but advised that serological and PCR testing may increase the safety of clinical decisions in countries with high transmission rates.
During this same well attended session, Scott Nelson from the University of Glasgow presented additional data obtained by PCR and antibody testing in 522 healthcare professionals in 30 fertility clinics across Europe. The prevalence of post-exposure was 4.02% (21 staff members) as assessed by the presence of IgG antibodies. Only one (0.19%) pre-symptomatic healthcare worker tested positive for active infection; however, testing allowed tracing, isolation and prevention of infection transmission to other members of the staff, patients and general public.
Data from Nelson’s clinic group were interpreted in relation to a recent Lancet study from Spain in which just under 5% of the 61,075 subjects tested positive for IgG, suggesting an increasing role of future vaccination for the development of antibodies, as opposed to relying on herd immunity.(2)
1. See https://www.eshre.eu/Home/COVID19WG
2. Pollan M, Pérez-Gómez B, Pastor-Barriuso R, et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet 2020; doi.org/10.1016/S0140-6736(20)31483-5