Northwestern Investigates COVID-19: Maternal Vaccinations, Burnout and Therapeutic Targets

Northwestern Medicine investigators continue to study the impact of the COVID-19 pandemic on health and society, from maternal vaccinations and antibody response to reducing burnout amongst healthcare workers and identifying novel therapeutic targets.  

Rapid Antigen Tests and Detecting SARS-CoV-2 Variants  

Sensitivity of nasal swab rapid antigen tests was similar when detecting the Omicron and Delta variants in persons infected with the SARS-CoV-2, according to findings published in Annals of Internal Medicine. The study demonstrated that serial testing improved the performance of rapid antigen testing for SARS-CoV-2.  

Chad Achenbach, ’02 MD, ’02 MPH, associate professor of Medicine in the Division of Infectious Diseases and of Preventive Medicine, and Robert Murphy, MD, ’81 GME, the John Philip Phair Professor of Infectious Diseases and executive director of the Robert J. Havey, MD Institute for Global Health, were co-authors of the study.  

Investigators compared the performance of rapid antigen tests in detecting the SARS-CoV-2 Delta and Omicron variants. Between October 2021 and January 2023, more than 5,700 asymptomatic study participants across the U.S. took at-home rapid antigen tests and collected samples for reverse transcriptase polymerase chain reaction (RT-PCR) laboratory tests every 48 hours for 15 days. 

Final RT-PCR results showed that 58 participants tested positive for the Delta variant and 149 participants tested positive for the Omicron variant. A total of 109 participants had at least two RT-PCR-positive results 48 hours apart, and among this group rapid antigen testing sensitivity did not differ significantly between participants infected with either variant. 

Results also showed that from 69 participants who had positive RT-PCR results for less than 48 hours (singleton RT-PCR positivity), less than 10 percent had positive rapid antigen test results within one week, and those with the Delta variant consistently tested negative on rapid antigen tests.  

“Our data suggest that serial testing continues to be important in improving the performance of Ag-RDTs. Future work to increase our understanding of persons with singleton RT-PCR positivity is needed to determine the public health significance of a false-negative Ag-RDT result in this subpopulation,” according to the authors.  

This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health.  

Identifying Potential Therapeutic Targets for COVID-19  

Investigating protein-protein interactions in the SAR-CoV-2 virus can improve the understanding of the mechanisms of COVID-19 infection and host response as well as inform new treatment and prevention, as detailed in a recent study published in Nature Biotechnology.  

“Real-world evidence from Electronic Health Record data, when coupled with high-throughput multi-omic data, can be an effective multi-modal discovery paradigm that drives therapeutic development and drug repurposing,” said Yuan Luo, PhD, associate professor of Preventive Medicine in the Division of Health and Biomedical Informatics and chief AI officer at the Northwestern Clinical and Translational Sciences (NUCATS) Institute and the Institute for Augmented Intelligence in Medicine, who was a co-author of the study.  

Using high-throughput experiments and mass spectrometry, the investigators developed a SARS-CoV-2 protein–protein interactome network which validated 218 previously known SARS-CoV-2 host transcription factors and revealed 361 new transcription factors.  

Notably, the investigators identified a previously unknown interaction between the viral protein ORF3a and transcription factor ZNF579. The team also screened more than 2,900 FDA-approved and drugs and identified 23 candidate drugs with anti-SARS-CoV-2 profiles.  

One drug in particular, carvedilol (which is commonly used to treat high blood pressure and heart failure), was associated with positive outcomes in COVID-19 patients and antiviral properties in a human lung cell line infected with SARS-CoV-2.  

The study is a prime example of how exploring viral–host protein–protein interactions can facilitate the discovery of novel therapeutics for viral infection, according to the authors.  

“Our study demonstrates the value of network systems biology to understand human–virus interactions and provides hits for further research on COVID-19 therapeutics,” the authors wrote.  

Luo is also member of the  Robert H. Lurie Comprehensive Cancer Center of Northwestern University. 

This work was supported in part by National Institutes of Health grant R01LM013337.  

COVID-19 Vaccination Increases Maternal and Infant Antibody Response  

Pregnant individuals who were vaccinated against COVID-19 during pregnancy demonstrated higher levels of maternal and umbilical cord blood antibodies compared to after initial SARS-CoV-2 infection, according to a Northwestern Medicine study published in Clinical Infectious Diseases.  

“Vaccination decreases risk and even prevents some of the serious maternal and obstetric complications associated with COVID-19 during pregnancy. Our work demonstrates that vaccination results in higher and longer lasting circulating antibodies in mom and higher antibody levels in baby at birth compared to infection,” said Leena Mithal, ’08 MD, ’16 MSCI, assistant professor of Pediatrics in the Division of Infectious Diseases and senior author of the study.  

In the study, Mithal’s team studied 351 pregnant individuals — 252 who were infected with SARS-CoV-2 infection and 99 who were vaccinated against COVID-19 during pregnancy. Levels of SARS-COV-2 antibodies were measured from maternal and umbilical cord blood samples and transplacental transfer ratios — the transfer of SARS-CoV-2 antibodies to the fetus — were compared across disease severity for individuals with SARS-COV-2 infections and infection versus vaccination.  

Overall, pregnant individuals with more severe SARS-CoV-2 infections demonstrated higher maternal and cord blood antibody levels, and maternal and cord blood antibody levels were higher after COVID-19 vaccination than after SARS-CoV-2 infection. Additionally, transplacental transfer ratios were higher after 90 days in vaccinated individuals compared to individuals infected with SARS-COV-2.  

The findings demonstrate that COVID-19 vaccination during pregnancy leads to higher and longer lasting maternal and infant antibody levels than from “natural” SARS-CoV-2 infection.  

“Maternal IgG antibody levels decrease over time in pregnant patients following both vaccination and natural infection, reinforcing the importance of vaccination even after infection and a potential booster dose if many months have elapsed from the initial series or in the context of new variants, to optimize protection of pregnant individuals and their infants,” according to the authors.  

Co-authors include Sebastian Otero, BA, a first-year medical student, Emily Miller, MD, MPH, ’11 GME, adjunct associate professor of Obstetrics and Gynecology in the Division of Maternal Fetal Medicine; Ashwin Sunderraj, a fourth-year medical student; Elisheva Shanes, MD, assistant professor of Pathology in the Divisions of Perinatal Pathology and Gynecologic Pathology; and Jeffery Goldstein, MD, PhD, assistant professor of Pathology in the Divisions of Perinatal Pathology and Autopsy. 

This work was supported by Friends of Prentice, the Stanley Manne Children’s Research Institute, the National Institute of Allergy and Infectious Diseases grant K23 AI139337, and the National Institute of Biomedical Imaging and Bioengineering grant K08 EB030120.  

Reducing Burnout Amongst Healthcare Workers During the Pandemic  

Burnout is an ongoing threat to the well-being of healthcare workers and the quality of patient care, having only been exacerbated by the COVID-19 pandemic. A recent Northwestern Medicine study published in the journal Frontiers in Health Services, however, found that maintaining positive psychological well-being, specifically feelings of positive affect and a sense of meaning and purpose in life, may help mitigate the impact of burnout amongst healthcare workers during the pandemic and in the future.  

“We found that while there was a significant burden of burnout among healthcare workers, those with well-being had lower rates, offering a potential area where research is needed to develop and test interventions to increase positive affect and a sense of purpose, to help improve the resiliency and psychological wellbeing of the healthcare workers who are essential to providing needed healthcare,” said Lisa Hirschhorn, MD, MPH, professor of Medical Social Sciences, of and Director of the Ryan Family Center for Global Primary Care at the Havey Institute of Global Health and senior author of the study.  

In the current study, the authors aimed to explore the association of depression, anxiety, positive affect, and meaning or purpose with burnout among healthcare workers from a large academic healthcare system in Chicago during the COVID-19 pandemic.  

The team utilized data collected from a cross-sectional survey conducted between September 29 and December 8, 2021, in which involved more than 2,400 healthcare workers participated. Of the participants, 81 percent were white, 82 percent were female, and 31 percent were between the ages of 30 and 39 years old.  

Survey results showed that 53 percent of participants were classified as having burnout, with registered nurses demonstrating the highest proportions of burnout at 64 percent.  

Higher rates of depression and anxiety were also associated with higher feelings of burnout while increased positive affect and meaning and purpose scores were associated with reduced feelings of burnout.  

According to the authors, further research is needed to better understand the effect of positive affect and meaning and purpose on reducing the negative impacts of burnout, depression, and anxiety among healthcare workers.  

“As a frontline healthcare worker, I can say that our work highlights a snapshot of the experiences with burnout among healthcare workers that predated the COVID-19 pandemic and is ongoing. Our work can support the development and implementation of interventions for healthcare workers alongside systemic changes that are needed to reduce burnout and improve working conditions,” said Jacqueline Bannon, PhD, BSN, RN, a postdoctoral fellow in the Institute for Sexual and Gender Minority Health and Wellbeing (ISGMH) and lead author of the study.  

Co-authors include Charlesnika Evans, PhD, MPH, professor of Preventive Medicine in the Division of Epidemiology, Melanie Freedman, a graduate student in the Clinical Psychology PhD program, Cerina Lee, a graduate student in the Health Sciences Integrated PhD Program (HSIP), Thanh-Huyen Vu, MD, PhD, research associate professor of Preventive Medicine in the Division of Epidemiology, Amisha Wallia, MD, ’11 MS, associate professor of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine, and of Preventive Medicine in the Division of Epidemiology, John Wilkins, MD, associate professor of Medicine in the Division of Cardiology and of Preventive Medicine in the Division of Epidemiology, and Judith Moskowitz, PhD, MPH, professor of Medical Social Sciences.  

This work was supported by the Northwestern University Clinical and Translational Sciences (NUCATS) Institute, the Northwestern Memorial Foundation and a grant from the Peter G. Peterson Foundation.