CV19: Downstream sample analyses from 3 NHP species infected with SARS-CoV-2

Over the last three months. COVID-19 has emerged as a major pandemic. SARS-CoV-2. the causative agent of COVID-19. has remarkable infectiousness and pathogenicity. particularly in causing acute respiratory distress syndrome (ARDS) in the elderly and people with immunocompromising conditions.1 The CDC have reported that 8 out of 10 deaths reported in the US related to COVID-19 are in adults 65 years and older. Similar to many other pulmonary infectious diseases. the elderly present with atypical symptoms when infected with SARS-CoV-2 and initial signs of infection may be missed resulting in ongoing infection transmission. The high numbers of individual (residents and caregivers) testing positive and succumbing to COVID-19 in nursing homes suggests that this scenario may be occurring but we need to separate out slow diagnosis from the possibility that the elderly develop more acute primary symptoms that make them more likely to infect others. 
 No vaccine or therapeutic currently exists for SARS-CoV-2 infection or COVID-19 disease. and studies to identify animal models have only recently been completed. Several of those studies were performed at Texas Biomedical Research Institute (Texas Biomed) through the Southwest National Research Primate Center (SNPRC). SNPRC infected the common marmoset. rhesus macaque and the baboon with SARS-CoV-2. The three species had differing infection outcomes. Marmosets were highly resistant and show limited infection. symptoms and pathology. Rhesus macaques developed short term viremia. clinical symptoms and pathology but recovered quickly. Baboons developed viremia. clinical symptoms and pathology and had slower recovery than rhesus macaques. More importantly SNPRC also performed SARS-CoV-2 infection in elderly animals for all three species and the impact of age was most evident in baboons. and in baboons and macaques more than marmosets. The studies design was for a 14-day infection period to determine if any or all species and age groups could be infected with SARS-CoV-2 and exhibit symptoms similar to humans. Extensive sample collection occurred throughout all studies. including non-infected age-matched controls. Therefore. Texas Biomed has an array of banked samples from 3 species of NHP. two age groups. and infected and non-infected controls. 
 We propose five analyses of banked samples to increase our understanding of SARS-CoV-2 infection and the host response in old age. Aim 1 will investigate whether the pulmonary environment during infection results in oxidation of host innate molecules and a possible link to COVID-19 Acute Respiratory Distress Syndrome (CARDS). Aim 2 will determine the phenotype and function of resident and infiltrating innate immune cells during infection with a focus on the initiation and maintenance of a cytokine storm. Aim 3 will dissect the T and B cell response in lung and lymph nodes during early infection that may lead to relevant information about long term protective immunity. Aim 4 will focus on the virus during infection. determining whether viral mutations occur and whether they differ between species and age. Aim 5 will support in-depth analyses of formalin fixed tissues with a goal of viewing infection beyond the lung and identifying correlates of infection progression in organs such as the brain. heart and intestine. Data from these 5 aims will be published as a result of these primary studies. or generate essential preliminary data for R01 grant submissions on SARS-CoV-2 and COVID-19.