SARS-CoV-2 Correlates of Protection in a Latino-origin Population

Abstract On March 11, 2020 the World Health Organization (WHO) designated a pandemic situation due to the global circulation of the novel coronavirus SARS-CoV-2, causing the disease COVID-19 (shttps://www.who.int/dg/speeches/detail/who-director). The rapid circulation and spread of this virus lead to a significant impact to the healthcare systems with an important societal disruption. Particularly susceptible has been the Black and Latino American origin population (REF). In addition to the demographic and social environment it is no know if the genetic background plays a predominant role on that outcome. In 42 states plus Washington D.C., Hispanics/Latinos make up a greater share of confirmed cases than their share of the population. In eight states, it''s more than four times greater (shorturl.at/yKUY6). A great deal of efforts has been deployed at global level to contain, mitigate and to understand the circulation, transmission and immune response among others to this virus. However, there is a huge lack of knowledge particularly in the dynamic of the immune response to this virus. The U.S. Federal Drug Administration (FDA) acknowledge that this is a critical issue as a better immunological characterization can help identify who has been infected and developed antibodies that may protect from future infection as well as identify those still at risk (https://www.fda.gov/news). One additional problem is that the correlation between the antibodies titers and their neutralizing capabilities is poorly understood. Due to it, is difficult to anticipate the level of protection of an individual having specific antibodies against SARS-CoV-2. So understanding the mechanisms driving the serological, humoral and cellular immune responses associated to the host genetic and how they correlate with protection against SARS-CoV-2 is mandatory. In this application we are proposing to expand the testing of IgG and IgM to SARS-CoV-2 virus to an extended Latino-origin population and to better characterize the immune response. This will allow us to identify potential immune or susceptible subjects, to correlate the level of antibodies with the level of protection, to plan in advance which subjects are eligible for a vaccine administration when available and other public health policies. We will take advantage of two assays developed by Dr. Sariol and Co-PI Espino to detect specific IgG and IgM antibodies to SARS-CoV-2. Both assays have been submitted to the FDA for Emergency Use Authorization (Submission Number: EUA201115 for IgG and EUA202043 for IgM assays). As part of this application we will expand the methods to two new assays that will be used as confirmatory. One inhibition ELISA for IgG detection and a MAC ELISA for IgM detection. Also the PI Lopez, representing the Puerto Rico Science, Technology and Research Trust (PRSTRT) will guarantee the access to samples across the Island trough the Local Clinical Laboratories Network. Another corner stone of this application is that the PIs, Co-PI and collaborator has previous and ongoing record of collaboration (PI Sariol with PIs D. Weiskopf and M. Lopez, Co- PI Espino and collaborators J. Brien and A.K Pinto. Also PI D. Weiskopf with collaborator A. Grifoni). One essential component of this application is the expansion and consolidation of a biobank including samples already collected by PIs. Sariol and Lopez as part of an IRB approved protocol. This protocol will provide the ground to continue collecting sequential samples from patients or volunteers in the period of five years of this application. In addition, as mentioned above, samples will be collected as part of an Island-wide network initiative including private laboratories conducting clinical diagnostic for COVID-19. PI Lopez has been involved in the settlement and development of such network and will bring the samples collected in support of the Puerto Rican SeroNet initiative. Such sources of samples will allow to collect samples not only from healthy or COVID-19 probable infected subjects, if not, from patients having other viral or infectious diseases like dengue, Zika, Chikungunya, Influenza, Respiratory Syncytial Virus, Mycoplasma that can be cofounding factors in the outcome of COVID0-19. Without doubt, some of those pathogens will circulate in the study population (and are already circulating like dengue and influenza) at some point during the duration of this program. One unique aspect of our applications is the wide approach proposed, from epidemiology to applied basic science, to better understand the uniqueness of COVID-19 phenomenon. In addition, once this program is established, it will be extended to recruit and to follow up individual receiving any SARS-CoV-2 vaccine candidate. The specific Aims we are proposing are as follow: 1. Expansion and consolidation of a comprehensive Infectious Diseases Repository Biobank (IDRB) and of a serologic diagnostic platform. 2. Characterization of the humoral immune response to SARS-CoV-2 virus in Puerto Rico by identifying the real prevalence of antibodies to this virus and its correlation with their neutralization capabilities, quality of the neutralization and disease outcome. 3. Dissection of the T cell''s immune phenotypes and its correlation with the serological immune response, cytokine profile and disease outcome. 4. HLA characterization and correlates with the immune response and disease outcome