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

SARS-CoV-2 与从海地人类中分离出的冠状病毒的交叉反应

• 批准号: 10285071
• 负责人: John Glenn Morris
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-21 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10285071
• 关键词: 2019-nCoV; Africa; Age; Animals; Antibodies; Blood; Blood specimen; COVID-19; Case Study; Cellular Immunity; Cessation of life; Clinical; Cohort Studies; Collaborations; Coronavirus; Country; Developed Countries; Development; Disease; Dominican Republic; Elements; Exposure to; Fever; Funding; Genetic; Geographic Locations; Haiti; Haitian; Hospitals; Human; Humoral Immunities; Immunity; Individual; Infection; Kaposi Sarcoma; Laboratories; Morbidity - disease rate; Morphologic artifacts; Opportunistic Infections; Outcome; Persons; Population; Public Health; Recovery; Reporting; Research; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2 antibody; SARS-CoV-2 immunity; SARS-CoV-2 infection; Sampling; Serum; Severities; Severity of illness; Structure; T-Cell Activation; Testing; Time; United States National Institutes of Health; Viral; Virus; Vital Statistics; Woman; Zoonoses; cohort; coronavirus disease; cross reactivity; human coronavirus; mortality; neutralizing antibody; novel coronavirus; pandemic disease; population based; screening

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.

项目摘要/摘要 在世界许多地区，包括大多数发达国家，新冠病毒对以下方面产生了重大影响 发病率和死亡率，截至#年，向世卫组织报告的病例超过3500万例，死亡100多万例 提交本建议书。然而，也有观察表明，严重的疾病和死亡 在某些国家和区域，特别是包括非洲部分地区，这种情况发生的频率较低。虽然这件事 感觉到的疾病严重程度的下降可能只是一种报告人工制品，有人建议这 严重程度的降低是由于这些人群中先前存在的免疫力，基于先前接触 与SARS-CoV-2交叉反应的病毒。 首例新冠状病毒感染病例于2020年3月19日在海地确诊。新病例在第一个月达到高峰 6月的一周，到9月逐渐下降到几乎为零；截至10月初，海地已 报告共有8,792例确诊感染和229例与冠状病毒感染有关的死亡。这很可能是因为 由于实验室的限制，海地报告的病例严重低估了实际感染人数。 测试能力。对更高的实际病例数量的支持来自临床观察， 在有症状的个人样本中，报告的&gt；检测阳性率为80%。然而，对中国的冲击 预计将在病例高峰之后出现的严重病例和死亡病例并未发生，这增加了 在这个人群中存在某种程度的预先存在的免疫力。 在过去的5年里，我们的研究小组一直在海地从事由NIH支持的病毒发现研究 好几年了。我们已经从人的血液样本中分离并测序了多种冠状病毒，包括人类 地方性冠状病毒和两种以前未描述的冠状病毒，可能源于人畜共患病。我们 假设海地与SARS-CoV-2相关的疾病严重程度的下降是交叉- 对海地流行的一种或多种病毒的反应性，可能包括这些冠状病毒。在这 探索性R21我们将利用来自海地现有队列的冠状病毒感染前后的血液样本 妇女和美国对照人员寻找对SARS-CoV-2先前的免疫力和对 我们已经确认的冠状病毒。具体目标包括： 具体目标1：从海地妇女队列和美国对照人群中筛选冠状病毒感染前血清样本 存在针对SARS-CoV-2和海地冠状病毒的中和抗体； 具体目标2：在妇女中筛查针对海地冠状病毒的交叉反应抗体 感染SARS-CoV-2；以及 具体目标3：筛选针对从人类分离的海地冠状病毒的T细胞激活。