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Principal Investigator: Karen Blake Jacobson
Organization: KAISER FOUNDATION RESEARCH INSTITUTE
Fiscal Year: 2024
Award: $193,320
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY / ABSTRACT
Since the emergence of SARS-CoV-2 in 2020, millions of pregnancies in malaria-endemic sub-Saharan Africa
have been impacted by SARS-CoV-2 infection. High rates of SARS-CoV-2 and malaria co-infections during
pregnancy will continue as new SARS-CoV-2 variants emerge and cause re-infections in subsequent waves.
SARS-CoV-2 and malaria in pregnancy are both associated with adverse birth and infant outcomes – including
preterm birth, low birth weight, and impaired growth and neurodevelopment – possibly mediated through
maternal inflammation. Data on long-term developmental effects of gestational SARS-CoV-2 in highly malaria
exposed populations are lacking. To address this gap, I will leverage samples and data from mother-infant dyads
enrolled in two complementary ongoing NIH-funded antimalarial chemoprevention trials in Busia, Uganda. In the
pregnancy trial, pregnant women are randomized to one of three antimalarial chemoprevention regimens and
followed through delivery; infants born to these women are being randomized in a separate clinical trial to receive
antimalarial chemoprevention or placebo and followed to age 4 years. These trials have coincided with Uganda’s
early SARS-CoV-2 surges, and preliminary data indicate high incidence of both SARS-CoV-2 and malaria during
pregnancy. Using clinical data and samples collected as part of the ongoing trials, I will test the hypothesis that
infants exposed to gestational SARS-CoV-2 will have impaired growth and neurodevelopment in early childhood
when compared with unexposed infants, and that this is mediated by maternal inflammation. I further hypothesize
that exposure to both SARS-CoV-2 and malaria in pregnancy increases adverse infant outcomes due to the
synergistic inflammatory effects of both pathogens. In Aim 1, I will use serologic testing of stored plasma samples
to retrospectively identify mothers who experienced SARS-CoV-2 during pregnancy and compare the growth of
infants with and without gestational SARS-CoV-2 exposure through age 4 years. In Aim 2, I will compare
neurocognitive test scores at ages 24 and 42 months among infants with and without gestational SARS-CoV-2.
In Aim 3, I will explore maternal proteomic immune signatures of SARS-CoV-2 in pregnancy and determine if
the effect of gestational SARS-CoV-2 on infant growth and neurodevelopment is mediated by specific
inflammatory pathways. This cohort is uniquely poised to address the impact of SARS-CoV-2 in pregnancy in a
malaria endemic setting, with longitudinal data and samples collected before widespread baseline SARS-CoV-
2 immunity. To accomplish these aims and become an independent translational researcher in tropical perinatal
infections, I have assembled an interdisciplinary mentorship team of experts in in infectious diseases, obstetrics,
pediatrics, neuropsychology, immunology, and global health. Results from this proposed study have immediate
implications for improving care of at-risk infants, and could identify diagnostic or therapeutic targets for future
clinical interventions.
Terms: <0-11 years old><2 year old><2 years of age><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><4 year old><4 years of age><Address><Adverse effects><Africa South of the Sahara><African><Age><Anti-malarials><Birth><Blood Plasma><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 exposure><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 immunity><COVID-19 infection><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 sequelae><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID-19 years><COVID19 infection><COVID19 virus><Caring><Cells Placenta-Tissue><Chemoprevention><Child><Child Youth><Childhood><Children (0-21)><Clinical><Clinical Data><Clinical Management><Clinical Trials><CoV-2><CoV2><Cohort Studies><Collaborations><Communicable Diseases><Complex><Concurrent Studies><Daraprim><Data><Data Set><Development><Diagnostic><Discipline of obstetrics><Enrollment><Epidemiology><Exclusion><Exposure to><Funding><Future><Generalized Growth><Gestation><Goals><Growth><IL-1><IL1><IQ Deficit><Immune><Immune response><Immunes><Immunity><Immunological response><Immunology><Impairment><Incidence><Infant><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Inflammation Mediators><Inflammatory><Interleukin I><Interleukin-1><Intervention><Intervention Strategies><Investigators><Knowledge><Long-Term Effects><Longterm Effects><Low Birth Weight Infant><Low-resource area><Low-resource community><Low-resource environment><Low-resource region><Low-resource setting><Lymphocyte-Stimulating Hormone><Macrophage Cell Factor><Malaria><Mediating><Mentorship><Mothers><NIH><National Institutes of Health><Neural Development><Neurocognitive><Neurocognitive Deficit><Neuropsychologies><Neuropsychology><Normal Placentoma><Obstetrics><Outcome><Paludism><Parturition><Pathway interactions><Pediatrics><Perinatal Infection><Placebos><Placenta><Placenta Embryonic Tissue><Placentome><Plasma><Plasma Serum><Plasmodium Infections><Population><Pregnancy><Pregnant Women><Premature Birth><Prematurely delivering><Preterm Birth><Prevention trial><Proteomics><Pyrimethamine><Randomized><Regimen><Research><Research Personnel><Research Resources><Researchers><Resource-constrained area><Resource-constrained community><Resource-constrained environment><Resource-constrained region><Resource-constrained setting><Resource-limited area><Resource-limited community><Resource-limited environment><Resource-limited region><Resource-limited setting><Resource-poor area><Resource-poor community><Resource-poor environment><Resource-poor region><Resource-poor setting><Resources><Reticuloendothelial System, Serum, Plasma><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 exposure><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 immunity><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 sequelae><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Serology test><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><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 coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 immunity><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Sham Treatment><Signal Pathway><Sub-Saharan Africa><Subsaharan Africa><Sulfadoxine><Sulformethoxine><Sulformetoxine><Sulforthomidine><Sulphormetoxin><T Helper Factor><Testing><Tissue Growth><Toddler><Training><Translational Research><Translational Science><Uganda><Underweight><United States National Institutes of Health><Vaccines><Woman><Wuhan coronavirus><age 2 years><age 4 years><aged 2 years><aged two years><ages><anti-malarial agents><anti-malarial drugs><career development><clinical significance><clinically significant><co-infection><cohort><coinfection><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 exposure><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 immunity><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 virus><cytokine><developmental><early childhood><enroll><epidemiologic><epidemiological><expectant mother><expecting mother><experience><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><fighting><four year old><four years of age><geographic population><global health><hCoV19><host response><immune system response><immunity against COVID-19><immunity against SARS-CoV-2><immunity against Severe acute respiratory syndrome coronavirus 2><immunity against coronavirus disease 2019><immunity to COVID-19><immunity to SARS-CoV-2><immunity to Severe acute respiratory syndrome coronavirus 2><immunity to coronavirus disease 2019><immunoresponse><improved><infant outcome><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammation marker><inflammatory marker><inflammatory mediator><intelligence quotient deficit><interventional strategy><kids><low birth weight><low birthweight><lymphocyte activating factor><nCoV2><neurocognitive decline><neurocognitive impairment><neurocognitive test><neurodevelopment><neuropsychologic><offspring><ontogeny><pathogen><pathway><pediatric><pregnant mothers><premature childbirth><premature delivery><preterm delivery><randomisation><randomization><randomly assigned><sequelae following COVID-19><sequelae following SARS-CoV-2 infection><sequelae of COVID-19><serology assay><seropositive><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><sham therapy><therapeutic target><translation research><translational investigation><translational investigator><translational researcher><translational scientist><two year old><two years of age><vigilance><wasting><youngster>