Northwestern researchers continue to tackle every facet of COVID-19 pandemic

As the COVID-19 pandemic nears the two-year mark, Northwestern Medicine scientists continue to tackle every facet of the disease, from investigating coronavirus vaccines' potential for providing immunity against similar coronaviruses to developing novel rapid antigen-based tests and examining disparities in COVID-19 case and mortality rates in Chicago.

Coronavirus vaccines may provide cross-protective immunity

Northwestern Medicine investigators have shown for the first time that coronavirus vaccines and prior coronavirus infections can provide broad immunity against other, similar coronaviruses.

The findings, recently published in the Journal of Clinical Investigation, build a rationale for universal coronavirus vaccines that could prove useful for future epidemics.

Until our study, what hasn't been clear is if you get exposed to one coronavirus, could you have cross-protection across other coronaviruses? And we showed that is the case."

Pablo Penaloza-MacMaster, PhD, assistant professor of Microbiology-Immunology, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and senior author of the study

Plasma from humans who had been vaccinated against SARS-CoV-2 produced antibodies that were cross-reactive (potentially providing protection) against SARS-CoV-1 and the common cold coronavirus, OC43. The study also found mice immunized with a SARS-CoV-1 vaccine developed in 2004 generated immune responses that protected them from intranasal exposure by SARS-CoV-2. Lastly, the study found prior coronavirus infections can protect against subsequent infections with other coronaviruses.

Mice that had been immunized with COVID-19 vaccines and later were exposed to the common cold coronavirus (HCoV-OC43, which is different from a SARS strain) were partially protected against the common cold, but the protection was much less robust, the study found. The reason, the scientists explain, is because both SARS-CoV-1 and SARS-CoV-2 are genetically similar — like cousins of one another — while the common cold coronavirus is more divergent from SARS-CoV-2.

"Our study helps us re-evaluate the concept of a universal coronavirus vaccine," Penaloza-MacMaster said. "It's likely there isn't one, but we might end up with a generic vaccine for each of the main families of coronaviruses, for example a universal Sarbecovirus vaccine for SARS-CoV-1, SARS-CoV-2 and other SARS-related coronaviruses; or a universal Embecovirus for HCoV-OC43 and HKU1 that cause common colds."

Co-authors include Nicole Palacio, a student in the Driskill Graduate Program in Life Sciences (DGP); Sarah Sanchez, a DGP student; and Igor Koralnik, MD, the Archibald Church Professor of Neurology and chief of Neuro-infectious Disease and Global Neurology in the Ken and Ruth Davee Department of Neurology.

This study was funded by the National Institutes of Health grant DP2 DA051912-01.

Listen to an episode of the Breakthroughs Podcast to learn more about this research.

Novel COVID-19 test detects viral proteins in minutes

Judd Hultquist, PhD, assistant professor of Medicine in the Division of Infectious Diseases, was a co-author of the study published in Biosensors and Bioelectronics.

Northwestern investigators have developed a novel antigen-based SARS-CoV-2 test for viral proteins detailed in a study published in the journal Biosensors and Bioelectronics. The technology addresses a need for more rapid, precise and sensitive SARS-CoV-2 tests as new variants of COVID-19 continue to emerge around the world.

The test uses high-resolution microscopy combined with a microcantilever-based sensor platform to detect SARS-CoV-2 nucleocapsids and receptor-binding domain proteins, both of which are essential for the virus to infect healthy host cells.

The investigators found the test demonstrated high sensitivity and selectivity when detecting antigens in nasopharyngeal swab samples from hospitalized patients who previously tested for COVID-19. According to the authors, test results took less than five minutes to retrieve with demonstrated high sensitivity, specificity and selectivity.

Despite the COVID-19 pandemic now entering its third year, we still have a long way to go to improve the accuracy, sensitivity and availability of rapid, point-of-care testing. Better diagnostic approaches are one critical tool towards keeping everyone safe as we prepare strategies for dealing with this virus over the long term."

Judd Hultquist, PhD, assistant professor of Medicine in the Division of Infectious Diseases and a co-author of the study

Co-authors include Steven Henrich, a student in the Medical Scientist Training Program (MSTP); Colby Thaxton, '04 MD, '07 PhD, '06, '08 GME, associate professor of Urology; Chao Qi, '99 PhD, director of Microbiology in the Department of Pathology; Lacy Simons, lab coordinator for the Center for Pathogen Genomics and Microbial Evolution; Judd Hultquist, PhD, assistant professor of Medicine in the Division of Infectious Diseases; and Egon Ozer, MD, PhD, ’08 GME, assistant professor of Medicine in the Division of Infectious Diseases and director of the Center for Pathogen Genomics and Microbial Evolution.

This work was supported by the National Heart, Lung and Blood Institute grant SUB/3U54HL119810-07S1: Rapid Diagnostics of SARS-C0V-2 of Asymptomatic People Returning to Work and School.

Opioid overdose deaths in Illinois during COVID-19

Howard Kim, MD, assistant professor of Emergency Medicine, was lead author of the study published in JAMA Health Forum.

Opioid overdose-related deaths and hospitalizations increased from July 2019 to June 2020 at the beginning of the COVID-19 pandemic, according to a recent Northwestern Medicine study published in JAMA Health Forum.

By obtaining data from the Centers for Disease Control and Prevention State Unintentional Drug Overdose Reporting System, investigators calculated a total of 6,058 unintentional opioid overdose-related deaths occurred in Illinois from July 2017 to June 2020.

They found that while deaths and hospitalizations were stable from July 2017 to June 2019, they increased from July 2019 to June 2020. The age of decedents was also increasingly 60 years or older.

Notably, from January to June 2020, the number of individuals who died from opioid overdose who identified as Black and Hispanic increased and exceeded the number of white individuals, the investigators found. During this period, approximately 61 percent of overdose deaths occurred in a person's home and half occurred with a bystander present.

Drug test results also revealed that from January to June 2020, 82 percent of tests were positive for fentanyl; the number of prescription opioid positive tests demonstrated no significant change.

The findings underscore the need to develop overdose prevention and harm reduction policies both at the state and national levels, according to the authors.

These data identify a critical opportunity for us to reduce opioid overdose deaths in Illinois. Many decedents did not receive naloxone to reduce their overdose, despite recently encountering a touchpoint for take-home naloxone distribution and overdosing with bystanders nearby. Given that fentanyl is now pervasive in the drug supply, we must increase our efforts to equip persons who use drugs and their friends and family with lifesaving naloxone."

Howard Kim, MD, assistant professor of Emergency Medicine and lead author of the study

Co-authors include Maryann Mason, PhD, associate professor of Emergency Medicine; Joseph Feinglass, PhD, research professor of Medicine in the Division of General Internal Medicine and Geriatrics and of Preventive Medicine in the Division of Public Health Practice; Danielle McCarthy, MD, associate professor of Emergency Medicine; and Patrick Lank, MD, 10 GME, assistant professor of Emergency Medicine.

This research was supported by the Davee Foundation.

Geographic disparities for COVID-19 case rates in Chicago

Brian Mustanski, PhD, professor of Medical Social Sciences and of Psychiatry and Behavioral Sciences, was lead author of the study published in the Annals of Epidemiology.

A Northwestern Medicine study found that SARS-CoV-2 infection rates were consistent among pairs of adjacent neighborhoods within Chicago, despite these neighborhoods having different COVID-19 case rates, according to findings published in the Annals of Epidemiology.

Since the beginning of the pandemic, Chicago has been an epicenter for COVID-19 cases and deaths in the U.S. Additional research found racial disparities in COVID-19 case rates and deaths in Chicago were prevalent since the start of the pandemic. However, few seroprevalence studies of racial and geographic disparities have further explored these associations.

For the current study, investigators surveyed five pairs of neighboring zip codes in Chicago with disparate COVID-19 case rates for prior SARS-CoV-2 infection. Dried blood spot samples were collected by participants in the summer of 2020 using at-home SARS-CoV-2 antibody tests developed by the investigators.

Final test results showed that the zip code pairs had similar seropositivity rates for anti-SARS-CoV-2 receptor binding domain IgG antibodies (indicating previous SARS-CoV-2 exposure) despite having very different COVID-19 case rates.

The findings highlight the importance of investigating other factors besides viral exposure, such as pre-existing chronic conditions, as potential drivers of inequity in COVID-19 case rates and patient outcomes, according to the authors.

"Overall, these findings of comparable exposure to SARS-CoV-2 across neighborhoods with very disparate COVID-19 case rates are consistent with social determinants of health, and the co-morbidities related to them, driving differences in COVID-19 rates across neighborhoods," the authors wrote.

Co-authors include Nanette Benbow, MA, research assistant professor of Psychiatry and Behavioral Sciences; Michael Newcomb, PhD, associate professor of Medical Social Sciences; Alexis Demonbreun, PhD, assistant professor of Pharmacology; Richard D’Aquila, MD, the Howard Taylor Ricketts, MD, Professor and associate vice president of Research; Elizabeth McNally, MD, PhD, the Elizabeth J. Ward Professor of Genetic Medicine and director of the Center for Genetic Medicine; and Thomas McDade, PhD, professor of Medical Social Sciences.

This work was supported by the National Science Foundation grant 2035114, the Northwestern University Office of Research, the Northwestern University Clinical and Translational Sciences (NUCATS) Institute, the National Institute of Health grant UL1TR001422, and Dr. Andrew Senyei and Noni Senyei.

Age differences in SARS-CoV-2 immune response

Bria Coates, MD, '08, '11 GME, assistant professor of Pediatrics in the Division of Critical Care, was senior author of the study published in the American Journal of Respiratory Cell and Molecular Biology.

Despite similar SARS-CoV-2 infection rates between children and adults, previous work has shown children are less likely to develop severe illness. A recent Northwestern Medicine study found that age-related differences in immune response to SARS-CoV-2 may increase adults' risk of developing severe COVID-19, according to findings published in the American Journal of Respiratory Cell and Molecular Biology.

"Since most viruses cause more severe illness in infants and young children compared to adults, we wanted to investigate why it is so unusual for children infected with SARS-CoV-2 to progress to severe COVID-19. Understanding why children are relatively protected from severe COVID-19 could help us develop strategies to protect others from severe disease," said Bria Coates, MD, '08, '11 GME, assistant professor of Pediatrics in the Division of Critical Care and senior author of the study.

For the study, Coates' team analyzed clinical outcomes and gene expression in the noses of children and adults infected with SARS-CoV-2, children infected with influenza or respiratory syncytial virus, and children and adults without a viral infection.

Overall, SARS-CoV-2 infection in both children and adults led to an interferon antiviral response in the nose. However, SARS-CoV-2-infected adults had increased expression of genes involved in immune responses including neutrophil activation and T-cell receptor signaling pathways compared to SARS-CoV-2-infected children, suggesting an increased risk of developing severe disease.

"Our findings suggest that the local interferon response does not drive differences in the clinical phenotypes associated with SARS-CoV-2 infection. Rather, age-related differences in the innate and adaptive immune response to SARS-CoV-2 infection in the upper respiratory tract may be critical risk factors for severe disease," the authors wrote.

This study was funded by the Stanley Manne Children's Research Institute, National Heart, Lung, and Blood Institute grant K08HL143127, and the American Thoracic Society.