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

项目概要/摘要 在世界许多地区，包括大多数发达国家，COVID 19对 发病率和死亡率，截至2010年12月31日，向世卫组织报告的病例超过3500万例，死亡超过100万例。 提交这份提案。然而，也有观察表明， 在某些国家和区域，特别是在非洲部分地区，发生的频率较低。虽然这 感觉到的疾病严重程度的降低可能只是一个报告的假象，有人认为， 严重程度的降低是由于这些人群中预先存在的免疫力，基于先前暴露于 与SARS-CoV-2交叉反应的病毒。 第一例COVID 19病例于2020年3月19日在海地发现。新病例在第一个 6月的一周，逐渐下降到9月几乎没有;截至10月初，海地 共报告了8，792例确诊感染和229例新冠病毒相关死亡。很可能， 由于实验室条件的限制，海地报告的病例严重低估了实际感染人数。 测试能力。支持更高的实际病例数来自临床观察， 在有症状个体的样本中，报告的测试阳性率>80%。然而， 预计在病例高峰之后出现的重症病例和死亡病例并未出现， 在这个人群中已经存在一定程度的免疫力。 我们的研究小组在过去的5年里一直在海地从事NIH支持的病毒发现研究。 年我们从人类血液样本中分离出多种冠状病毒并进行测序，包括人类 地方性冠状病毒和两种以前未描述的可能具有人畜共患起源的冠状病毒。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的函数， 对在海地传播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，我们将使用来自海地现有队列的COVID前后血液样本， 妇女和美国对照组，以寻找对SARS-CoV-2的先前免疫力和对 冠状病毒，我们已经确定。具体目标包括： 具体目标1：从海地妇女和美国对照队列中筛查COVID前血清样本， 存在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细胞活化。

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.