Document Type

Capstone Experience

Graduation Date

8-2020

Degree Name

Master of Public Health

Department

Epidemiology

First Committee Member

Mark Kortepeter, MD, MPH

Second Committee Member

David Brett-Major, MD, MPH

Third Committee Member

Sharon Medcalf, Ph.D.

Abstract

Members of the family Coronaviridae, including the severe acute respiratory syndrome coronaviruses (SARS-CoV-1 and SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV) and seasonal human coronaviruses (HCoV-HKU1and HCoV-OC43), are highly communicable respiratory viruses; SARS-CoV-1, SARS-CoV-2, and MERS can cause severe disease, while seasonal human coronaviruses present with mild to moderate illness. Coronavirus envelope spike (S) glycoproteins are involved in receptor binding and cell fusion, and are the primary target for a neutralizing humoral response. The S protein is comprised of the S1 and S2 subunits; the S1 subunit contains the receptor-binding domain (RBD), while the S2 subunit mediates fusion and cell entry. A conformational native S protein exists as a membrane-anchored S protein trimer. Stabilized pre-fusion S protein ectodomain (S-2P) trimers have been developed as vaccine candidates for SARS-CoV-1, SARS-CoV-2, and MERS-CoV (Corbett). Here, we investigated the humoral immune response in COVID-19 patients using a serological assay based on coronavirus S-2P trimers. Response kinetics were characterized, as well as associations between the magnitude of the response and prior HCoV exposure with disease severity and outcomes. Significant trends were observed that may be important in efficacious vaccine design and serological surveillance.

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