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: 10435570
• 负责人: John Glenn Morris
• 金额: $ 19.06万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10435570
• 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; animal coronavirus; cohort; coronavirus disease; cross reactivity; human coronavirus; mortality; neutralizing antibody; novel coronavirus; pandemic disease; population based; post-COVID-19; 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.

项目概要/摘要 在世界许多地区，包括大多数发达国家，新冠肺炎疫情对人们的生活产生了重大影响 发病率和死亡率，截至报告时向世卫组织报告了超过 3500 万例病例和超过 100 万人死亡 提交本提案。然而，也有观察表明，严重疾病和死亡 在某些国家和地区，特别是非洲部分地区，这种情况发生的频率较低。虽然这 感知到的疾病严重程度的降低可能只是一个报告假象，有人认为这 严重程度的降低是由于这些人群中预先存在的免疫力（基于之前接触过的病毒） 与 SARS-CoV-2 交叉反应的病毒。 2020 年 3 月 19 日，海地发现首例新冠肺炎病例。新增病例在第一季度达到顶峰 六月的一周，逐渐下降到九月几乎没有；截至十月初，海地已 共有 8,792 例确诊感染病例和 229 例与新冠病毒相关的死亡病例。数量很可能是 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的支持来自于临床观察，并且 据报道，有症状个体的样本中检测阳性率>80%。然而，猛烈的攻击 预计病例高峰后出现的重症病例和死亡病例并未出现，增加了可能性 该人群中已有一定程度的免疫力。 我们的研究小组过去 5 年来一直在海地从事 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，其中包括人类血液样本 地方性冠状病毒和两种先前未描述的可能具有人畜共患病起源的冠状病毒。我们 假设海地 SARS-CoV-2 相关疾病严重程度的下降是跨学科因素的作用 对海地流行的一种或多种病毒（可能包括这些冠状病毒）有反应。在这个 探索性 R21，我们将利用现有海地队列中新冠病毒感染前后的血液样本 女性和美国控制人员寻找先前对 SARS-CoV-2 具有免疫力以及与新冠病毒有交叉反应的证据 我们已经识别出的冠状病毒。具体目标包括： 具体目标 1：从一组海地妇女和美国对照人群中筛查新冠肺炎前的血清样本 存在针对 SARS-CoV-2 和海地冠状病毒的中和抗体； 具体目标 2：在女性中筛查针对海地冠状病毒的交叉反应抗体 感染 SARS-CoV-2；和 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。

项目成果

Isolation of a Novel Recombinant Canine Coronavirus From a Visitor to Haiti: Further Evidence of Transmission of Coronaviruses of Zoonotic Origin to Humans.

• DOI: 10.1093/cid/ciab924
• 发表时间: 2022-08-24
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Independent infections of porcine deltacoronavirus among Haitian children.

• DOI: 10.1038/s41586-021-04111-z
• 发表时间: 2021-12
• 期刊: Nature
• 影响因子: 64.8
• 作者: Lednicky JA;Tagliamonte MS;White SK;Elbadry MA;Alam MM;Stephenson CJ;Bonny TS;Loeb JC;Telisma T;Chavannes S;Ostrov DA;Mavian C;Beau De Rochars VM;Salemi M;Morris JG Jr
• 通讯作者: Morris JG Jr

SARS-CoV-2 infections in infants in Haiti 2020-2021; evidence from a seroepidemiological cohort.

海地2020-2021婴儿的SARS-COV-2感染；来自血清ePIDEMIologic Stole的证据。

• DOI: 10.1371/journal.pone.0273482
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7