Predictors of Nonseroconversion After SARS-CoV-2 Infection

Weimin Liu; Ronnie M. Russell; Frederic Bibollet-Ruche; Ashwin N. Skelly; Scott Sherrill-Mix; Drew A. Freeman; Regina Stoltz, Emily Lindemuth; Fang-Hua Lee; Sarah Sterrett; Katharine J. Bar; Nathaniel Erdmann; Sigrid Gouma; Scott E. Hensley; Thomas Ketas; Albert Cupo; Victor M. Cruz Portillo; John P. Moore; Paul D. Bieniasz; Theodora Hatziioannou; Greer Massey; Mary-Beth Minyard; Michael S. Saag; Randall S. Davis; George M. Shaw; William J. Britt; Sixto M. Leal, Jr.; Paul Goepfert; Beatrice H. Hahn


Emerging Infectious Diseases. 2021;27(9):2454-2458. 

In This Article

Abstract and Introduction


Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2–specific antibodies. We show that nonseroconversion is associated with younger age and higher reverse transcription PCR cycle threshold values and identify SARS-CoV-2 viral loads in the nasopharynx as a major correlate of the systemic antibody response.


Coronavirus disease (COVID-19) is typically diagnosed by reverse transcription PCR (RT-PCR) amplification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from nasopharyngeal fluids.[1] RT-PCR yields cycle threshold (Ct) values that are inversely correlated with viral loads[2] and thus provide an estimate of the number of SARS-CoV-2 RNA copies in the sample. Serologic assays complement COVID-19 diagnosis by documenting past infections. In most persons, binding and neutralizing antibodies develop within 1–3 weeks after onset of symptoms,[3] and titers correlate with disease severity.[4]

Initial serosurveys identified antibodies in nearly 100% of persons with RT-PCR–confirmed SARS-CoV-2 infection.[5] However, more recent studies have shown that seroconversion rates are surprisingly variable.[6–10] For example, a multicenter study from Israel reported that 5% of participants remained seronegative despite a positive test result on a nasal swab specimen.[6] In contrast, a seroprevalence study from New York found that 20% of persons with a positive RT-PCR test result did not seroconvert.[8] Another study from Germany reported that 85% of confirmed infected COVID-19 contacts failed to develop antibodies.[9] To examine the reasons for these differences, we investigated the relationship between seroconversion and demographic, clinical, and laboratory data in a convenience sample of convalescent persons recruited at the University of Alabama at Birmingham (Birmingham, Alabama, USA) in 2020.