key: cord-0751236-f6xj8njc
authors: Chatzidimitriou, Maria; Chatzopoulou, Fani; Gavriilaki, Eleni; Chatzivasileiou, Panagiota; Rousis, Dimitris; Meletis, Georgios; Chatzidimitriou, Dimitrios
title: Repeated Negative Serological Testing in Otherwise Healthy Patients With Coronavirus Disease 2019
date: 2020-07-29
journal: J Infect Dis
DOI: 10.1093/infdis/jiaa453
sha: 556152ea9669df1cb923a95b6a0ece8bca1707ee
doc_id: 751236
cord_uid: f6xj8njc

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products were measured in these seronegative patients using the complement C3/ C4 reagent kit (Abbott). Immunoglobulin levels (IgA, IgG, IgM) were also measured in these patients (Abbott). The study was performed according to the Helsinki Declaration. Written informed consent was obtained from all patients.

Median age of patients was 22 years, ranging from 22 to 62, and the majority of them were male (61%). Among 26 patients, IgG antibodies were positive in 24 patients. Mean IgG levels were 1.129 (index) with a standard deviation of 6.879. Regarding IgM antibodies, mean IgM levels were 0.489 (index) with a standard deviation of 0.843. Only 4 patients were positive for IgM antibodies.

Detailed history was recorded in the 2 seronegative patients (both IgM and IgG). They were otherwise healthy individuals, a male aged 26 years and a female aged 43 years. Although both had a positive molecular test, the clinical course of infection was mild. Symptoms included anosmia and fatigue in both patients and grade 1 fever in one. The serological testing was repeated 10 days after the first negative results, within 20-29 days after the molecular testing. Immunoglobulin M and IgG remained negative by all methods. Complement testing was negative. Immunoglobulin levels were within normal limits. No signs or symptoms of an underlying disease were documented during the presentation or the 2-month follow-up of the patients.

It is interesting to note that there are only a few reports of persistently seronegative patients after COVID-19 [1] . Zhang et al [1] have documented seronegative patients at different time points, but it remains unclear whether there were persistently seronegative patients in their cohort. Furthermore, COVID-19 diagnosis was not confirmed with molecular testing [1] . Solodky et al [2] included patients with molecular testing. Among positive patients, 4 of 14 otherwise healthy individuals remained negative 15 days after the infection. However, this testing was performed only with 1 method and not repeated over time [2] . In addition, no data were reported on the severity of infection.

Furthermore, a recent study has reported an excellent specificity and sensitivity of the Abbott's antibody testing [3] . Optimal measurement was defined within the time period used in our study. Given that seronegative patients were also tested with additional methods in our study, these patients are considered true negative. A potential explanation of seronegative results in our patients could be their mild course of infection. Given that severe COVID-19 is life-threatening [4, 5] , linking the severity of infection with seropositivity would be useful for guiding management of COVID-19.

In conclusion, our prospective study suggests that serological testing is useful for the majority of patients. Nevertheless, a small percentage of otherwise healthy individuals remained seronegative despite documented infection. Further prospective studies are needed to highlight the clinical usefulness of serological testing.

Author contributions. M. C., F. C., and E. G. drafted and edited the manuscript. M. C., F. C., P. C., and D. C. performed laboratory testing. D. R. and D. C. edited and approved the final manusctipt.

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

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Thessaloniki, Greece, 3 Hematology Department-BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece, 4 Labnet Laboratories, Thessaloniki, Greece