J Biol Regul Homeost Agents. May-Jun 2021; 35(3):881-887. doi: 10.23812/21-163-A.


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Sensitivity of serology assay in Covid-19 diagnosis: does the antigen matter?

Sitzia C#1, Pistelli L#2, Cardani R3, Renna LV3, Ranucci M4, Carrara M2, Borlini S2, Clerici P5, Rampoldi B6, Cornetta M6, Corsi-Romanelli M1,6.

Author information

1  Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
2  Residency Program in Clinical Pathology and Clinical Biochemistry, University of Milan, Milan, Italy.
3  Biobank BioCor, Service of Laboratory Medicine1-Clinical Pathology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
4  Department of Cardiothoracic and Vascular Anesthesia and Intensive Care Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
5  Microbiology Unit, Hospital of Legnano, ASST Ovest Milanese, Italy.
6  Operative Unit 1 – Clinical Pathology, Department of Pathology and Laboratory medicine, I.R.C.C.S. Policlinico San Donato, San Donato Milanese, Milan, Italy.
#  Contributed equally


Since the spreading of Sar-CoV-2 in March 2020, many serologic tests have been developed to identify antibody responses. Indeed, different commercial kits are directed against different antigens and could utilise different methods thereby triggering confusion and criticism. Here, we compared two Food and Drug Administration (FDA)-approved automatized assays that detect IgG responses against spike or nucleocapsid protein of Sars-Cov-2 virus in 127 subjects among healthcare workers of IRCCS Policlinico San Donato (MI), Italy. We observed different kinetics of IgG responses, demonstrating the importance of timing of sampling to correctly interpret the results both for infection diagnosis and for epidemiologic studies. We observed that Anti-N response starts earlier than Anti-S1/S2 response but also decreases earlier, affecting the sensitivity of the tests at different time points. Combining two different assays, designed against different antigens, could reduce false negative results. Finally, we observed a patient who produced anti-nucleocapsid IgG, but not anti-spike IgG. In conclusion, we investigated antibody responses in Covid-19 disease, aiming to direct clinicians and laboratory scientists to correctly interpret serologic results by always paying attention to clinical history correlation, timing of sampling, methods and antigens used, to avoid false negative results and obtain relevant epidemiologic data.


IgG kinetics, Sars-Cov-2, antibody responses, long-term immunity, serological test

Publication type

  • Journal Article

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