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Principal Investigator: Thomas Quinn
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2022
Award: $37,442
Funding agency: National Institute of Allergy and Infectious Diseases
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged as a global pandemic in early 2020. By the end July of 2022, over 560 million cases of SARS-CoV-2 have been confirmed, spanning almost all countries and accounting for > 6.3 million deaths. In the US, over 89 million cases of SARS-CoV-2 have been reported with over 1,002,000 deaths from COVID-19 disease. With widespread community transmission and with an urgent need for effective therapeutics and prophylaxis, there is a critical need to perform broad-scale population-based testing to better define population infection dynamics, vaccine coverage, transmission, and immunological and therapeutic responses to SARS-CoV-2 infection.
Convalescent plasma was demonstrated to be an effective intervention, reducing hospitalization by >50%, if given within 9 days of symptom onset. We participated in a multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults. In our study 1181 adults received a plasma transfusion. Among the 592 participants who received convalescent plasma 17(2.9%) were hospitalized, compared to 6.3% (37/589) who relieved control plasma, p<0.005. The greatest impact of the intervention was seen if the subjects received convalescent plasma5 days from symptom onset. Having abnormal c-reactive protein or absolute lymphocyte counts attenuated the impact of the intervention.
Using previously identified viral epitopes targeted by CD8+ T cells (n=52 epitopes) in individuals from the convalescent study (n=30 individuals), we assessed if T-cell epitopes in SARS-CoV-2 are mutated in the newly described Omicron VOC (n=50 mutations). We showed that within this population, only one low-prevalence epitope from the Spike protein, restricted to two HLA alleles and found in 2/30 (7%) individuals, contained a single amino acid change associated with the Omicron VOC. These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time.
We performed a serosurvey on samples from Maryland decedents who required an autopsy from 24 May through 30 November 2020. We were able to test the stored blood from 1906 individuals and determined that 305 (16%) had antibodies to SARS-CoV-2. Monthly seroprevalence increased from 11% to 22% over time and was consistently higher than state-level estimates. Hispanic ethnicity was associated with 2- to 3.2-fold higher seropositivity (P < .05) irrespective of sex. Deaths due to motor vehicle crash were associated with 62% increased seropositivity (aPR, 1.62 95% CI, 1.15-2.28) vs natural manner of death. Though seroprevalence was lower in decedents of illicit drug overdose vs non-overdose in early months, this shifted, and seroprevalence was comparable by November 2020.Our study demonstrates how readily available, cost-effective data can be leveraged in a systematic way to provide real-time information on potential signals of infectious disease spread.
We developed a serological testing algorithm to differentiate vaccinated, previously infected, and unexposed individuals using standard enzyme-linked immunosorbent assay (ELISA) and lateral flow technology to apply in our emergency department (ED) serosurvey. We developed and validated this approach using 1960 samples from individuals with known SARS-CoV-2 infection and vaccination status. The sample sets included NIH phase 1 vaccine trial (20-003) participants, health care workers who were vaccinated or infected, potential convalescent plasma donors, hospitalized patients, and pre pandemic controls from the ED. Using these samples, we demonstrated that our algorithm could accurately identify samples from vaccinated individuals (sensitivity 100, specificity 98.8%) and previously infected individuals (sensitivity 84.4%, specificity 100%). We performed a serosurvey at the Johns Hopkins Hospital ED from March 16 to April 30 2020 (1536 samples) and January 11 to March 10, 2021 (2824 samples). We demonstrated that in inner city Baltimore, white women and men had the lowest prevalence of infection both in 2020 and 2021. In the 2021 survey, white women accounted for 9% of all infections in 2021 but 27% of all vaccinations. For all other groups, the prevalence of exposure to SARS-CoV-2 was higher than the frequency of vaccination. By the spring of 2021, Hispanic patients had the highest evidence of prior SARS-CoV-2 infection within any ethnic group, at 38%. Our study highlights disparities based on sex and race/ethnicity in SARS-CoV-2 prevalence and vaccine distribution within metropolitan Baltimore during the spring of 2021.
We conducted a serosurvey from 30th November 2020 to 8th January 2021, at the Rakai Community Cohort Study and twenty-six health facilities in South-Central Uganda. Samples were collected from 753 health care workers (HCW) and from 227 population-cohort participants who reported either a fever, cough, loss of taste and appetite during the survey period. Additionally, 636 specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda. The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% 95%CI: 23.5, 29.8 with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the survey participants, 15.6% 95%CI: 10.9, 20.3 had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% 95%CI: 1.2, 3.5 were reactive. Our findings high level of infection to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><AIDS Virus><Accident and Emergency department><Accounting><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adult><Adult Human><Age><Ageusia><Algorithms><Alleles><Allelomorphs><Amino Acids><Antibody Response><Antigenic Determinants><Antigens><Appetite><Attenuated><Automobile collision><Automobile crash><Autopsy><Avidity><Baltimore><Binding><Binding Determinants><Blood><Blood Plasma><Blood Reticuloendothelial System><C-reactive protein><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 antibody><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 death><COVID-19 exposure><COVID-19 fatality><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced mortality><COVID-19 infected patient><COVID-19 infection><COVID-19 mortality><COVID-19 patient><COVID-19 positive patient><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 virus><COVID19><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 death><COVID19 fatality><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 patient><COVID19 positive patient><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 virus><CV-19><CV19><Car collision><Car crash><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cessation of life><China><Clinical><CoV-2><CoV2><Cohort Studies><Communicable Diseases><Communities><Concurrent Studies><Coughing><Country><Data><Death><Desire for food><Diagnostic><Differences between sexes><Differs between sexes><Disease><Disorder><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><ELISA><Emergency Department><Emergency room><Enzyme-Linked Immunosorbent Assay><Epidemiology><Epitopes><Ethnic Origin><Ethnic People><Ethnic Population><Ethnic group><Ethnic individual><Ethnicity><Ethnicity People><Ethnicity Population><Fever><Frequencies><General Population><General Public><Genetic Alteration><Genetic Change><Genetic defect><HIV><Health Care Providers><Health Facilities><Health Personnel><Health care facility><Healthcare Facility><Healthcare Providers><Healthcare worker><Hispanic><Hospital Admission><Hospitalization><Hospitals><Human Immunodeficiency Viruses><Illicit Drugs><Immune><Immune response><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Individual><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><International><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Investigation><Jobs><Kinetics><LAV-HTLV-III><LYT3><Lateral><Low Prevalence><Lymphadenopathy-Associated Virus><Lymphocyte Count><Lymphocyte Number><Mainland China><Maryland><Molecular Interaction><Motor vehicle collision><Motor vehicle crash><Mutate><Mutation><NIH><National Institutes of Health><Occupations><Overdose><Participant><Patients><Pattern><Persons><Phase><Plasma><Plasma Serum><Population><Prevalence><Professional Positions><Prophylactic treatment><Prophylaxis><Proteins><Proteins, specific or class, C-reactive><Pyrexia><Race><Racial Group><Racial Stocks><Randomized Controlled Trials><Reporting><Research Specimen><Reticuloendothelial System, Serum, Plasma><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 associated death><SARS-CoV-2 associated fatality><SARS-CoV-2 associated mortality><SARS-CoV-2 death><SARS-CoV-2 exposure><SARS-CoV-2 fatality><SARS-CoV-2 induced death><SARS-CoV-2 induced fatality><SARS-CoV-2 induced mortality><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 mortality><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV2><SARS-CoV2 antibody><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Sampling><Series><Serology><Serology test><Seroprevalences><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Sex Differences><Sexual differences><Signal Transduction><Signal Transduction Systems><Signaling><Specificity><Specimen><Survey Instrument><Surveys><Symptoms><T cell response><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Technology><Testing><Therapeutic><Time><Total Lymphocyte Count><Transfusion><Transmission><Uganda><United States National Institutes of Health><Vaccinated><Vaccination><Vaccinee><Vaccines><Vehicle crash><Vehicular collision><Vehicular crash><Viral><Virus-HIV><Woman><Wuhan coronavirus><adulthood><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after severe acute respiratory distress syndrome CoV-2 infection><ages><aminoacid><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><base><biological signal transduction><care facilities><cohort><community spread><community transmission><community-level spread><community-level transmission><convalescent plasma><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 antibody><coronavirus disease 2019 associated death><coronavirus disease 2019 associated fatality><coronavirus disease 2019 associated mortality><coronavirus disease 2019 death><coronavirus 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2><death in COVID><death in COVID-19><death in SARS-CoV-2><death in coronavirus disease><death in coronavirus disease 2019><death in severe acute respiratory syndrome coronavirus 2><deploy vaccines><distribute vaccines><effective intervention><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><enzyme linked immunoassay><epidemiologic><epidemiological><ethnicity group><evaluate efficacy><examine efficacy><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><fatality due to COVID-19><fatality due to COVID19><fatality due to SARS-CoV-2><fatality due to coronavirus disease 2019><fatality due to severe acute respiratory syndrome coronavirus 2><febrile><febris><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following severe acute respiratory distress syndrome CoV-2 infection><genome 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respiratory syndrome coronavirus 2 death><severe acute respiratory syndrome coronavirus 2 fatality><severe acute respiratory syndrome coronavirus 2 induced death><severe acute respiratory syndrome coronavirus 2 induced fatality><severe acute respiratory syndrome coronavirus 2 induced mortality><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 mortality><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 related death><severe acute respiratory syndrome coronavirus 2 related fatality><severe acute respiratory syndrome coronavirus 2 related mortality><sex><sex-dependent differences><sex-related differences><sex-specific differences><taste loss><therapeutic response><therapeutically effective><therapy response><thymus derived lymphocyte><traffic collision><traffic crash><transmission process><treatment provider><treatment response><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination study><vaccination trial><vaccine deployment><vaccine distribution><vaccine roll-out><vaccine rollout><vaccine study><vaccine trial><variants of concern><virtual>