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.

项目摘要/摘要 在包括大多数发达国家在内的世界许多地区，Covid19对 发病率和死亡率，有超过3500万例 提交此提案。但是，也有观察表明严重疾病和死亡 在某些国家和地区，尤其是非洲的部分地区，发生的频率较低。同时 人们认为疾病严重程度的降低可能只是报道工具，有人建议这 严重程度的降低是由于这些人群中预先存在的免疫力所致，基于事先暴露 与SARS-COV-2交叉反应的病毒。 2020年3月19日在海地发现了第一个COVID19案件。 六月一周，到9月，几乎没有逐渐下降；截至10月初，海地有 报告总共有8,792次确认感染和229例相关死亡。可能是 海地报道的病例严重低估了实际的感染数量，这是由于实验室的限制 测试能力。对更高的实际病例数的支持来自临床观察结果，并且 报告的有症状个体样本的测试阳性率> 80％。但是， 严重的案件和死亡预计尚未发生峰值，这增加了可能性 在该人群中有一定程度的先前免疫力。 我们的研究小组在过去的5个 年。我们已经从人类血液样本中分离并测序了多个冠状病毒，包括人 特有冠状病毒和两个以前未描述的冠状病毒可能具有人畜共患病。我们 假设在海地中与SARS-COV-2相关的疾病严重程度的降低是交叉的函数 对海地循环的一种或多种病毒的反应性，包括这些冠状病毒。在这个 探索性R21我们将利用现有的海地同类群体前后血液样本 妇女和来自美国的控制，以寻求先前对SARS-COV-2免疫的证据，并与之交叉反应 我们已经确定的冠状病毒。具体目的包括： 特定目的1：筛查海地妇女队列中的杂化血清样品和美国对照组 对SARS-COV-2和海地冠状病毒的中和抗体的存在； 特定目标2：筛查女性针对海地冠状病毒的交叉反应抗体 感染SARS-COV-2；和 特定目标3：针对从人类分离的海地冠状病毒的T细胞激活的筛查。

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.

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