Cross-reactivity of SARS-CoV-2 with coronaviruses isolated from humans in Haiti

Project Summary/Abstract In many parts of the world, including most developed countries, COVID19 has had a major impact on morbidity and mortality, with over 35 million cases and over 1 million deaths reported to WHO at the time of submission of this proposal. However, there are also observations suggesting that severe disease and death have occurred less frequently in certain countries and regions, including, in particular, parts of Africa. While this perceived decrease in severity of illness may simply be a reporting artifact, it has been suggested that this decrease in severity is due to pre-existing immunity within these populations, based on prior exposure to viruses which cross-react with SARS-CoV-2. The first COVID19 case was identified in Haiti on March 19, 2020. New cases peaked during the first week of June, with a gradual decline to almost none by September; as of the beginning of October, Haiti has reported a total of 8,792 confirmed infections and 229 COVID-related deaths. It is likely that the number of reported cases in Haiti grossly underestimates the actual number of infections, due to limitations in laboratory testing capacity. Support for a much higher actual case number comes from clinical observations, and a reported test positivity rate of >80% among samples from symptomatic individuals. However, the onslaught of severe cases and deaths which was expected to follow the case peak has not occurred, raising the possibility of some level of pre-existing immunity in this population. Our research group has been engaged in NIH-supported virus discovery studies in Haiti for the past 5 years. We have isolated and sequenced multiple coronaviruses from human blood samples, including human endemic coronaviruses and two previously undescribed coronaviruses that may have a zoonotic origin. We hypothesize that the decrease in severity of illness associated with SARS-CoV-2 in Haiti is a function of cross- reactivity to one or more viruses circulating in Haiti, including, possibly, these coronaviruses. In this exploratory R21 we will make use of pre- and post-COVID blood samples from an existing cohort of Haitian women and from U.S. controls to look for evidence of prior immunity to SARS-CoV-2 and cross-reactivity to the coronaviruses which we have identified. Specific Aims include: Specific Aim 1: Screening of pre-COVID serum samples from a cohort of Haitian women and U.S. controls for the presence of neutralizing antibody to SARS-CoV-2 and Haitian coronaviruses; Specific Aim 2: Screening for cross-reacting antibodies directed against Haitian coronaviruses among women infected with SARS-CoV-2; and Specific Aim 3: Screening for T-cell activation directed against Haitian coronaviruses isolated from humans.