Previous Humoral Immunity to the Endemic Seasonal Alphacoronaviruses NL63 and 229E Is Associated with Worse Clinical Outcome in COVID-19 and Suggests Original Antigenic Sin

Daniele Focosi; Angelo Genoni; Ersilia Lucenteforte; Silvia Tillati; Antonio Tamborini; Pietro Giorgio Spezia; Lorenzo Azzi; Andreina Baj; Fabrizio Maggi

doi:10.3390/life11040298

Previous Humoral Immunity to the Endemic Seasonal Alphacoronaviruses NL63 and 229E Is Associated with Worse Clinical Outcome in COVID-19 and Suggests Original Antigenic Sin

Life (Basel). 2021 Apr 1;11(4):298. doi: 10.3390/life11040298.

Authors

Daniele Focosi¹, Angelo Genoni², Ersilia Lucenteforte³, Silvia Tillati³, Antonio Tamborini⁴, Pietro Giorgio Spezia⁵, Lorenzo Azzi^{2

6}, Andreina Baj^{2

4}, Fabrizio Maggi^{2

4}

Affiliations

¹ North-Western Tuscany Blood Bank, Pisa University Hospital, 56124 Pisa, Italy.
² Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy.
³ Department of Clinical and Experimental Medicine, University of Pisa, 56100 Pisa, Italy.
⁴ Laboratory of Microbiology, ASST Sette Laghi, 21100 Varese, Italy.
⁵ Department of Translational Research, University of Pisa, 56100 Pisa, Italy.
⁶ Unit of Oral Medicine and Pathology, ASST Sette Laghi, 21100 Varese, Italy.

Abstract

Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral immunity. We show here that IgG against nucleocapsid protein of alphacoronavirus NL63 and 229E correlate with the World Health Organization's (WHO) clinical severity score ≥ 5 (incidence rate ratios was 1.87 and 1.80, respectively, and 1.94 for the combination). These laboratory findings suggest possible ADE of SARS CoV-2 infection by previous alphacoronavirus immunity.

Keywords: 229E; COVID-19; HKU1; NL63; OC43; SARS-CoV-2; convalescent plasma; neutralizing antibody.