Northwestern researchers continue investigation on all aspects of COVID-19 pandemic

Northwestern Medicine scientists continue to investigate all aspects of the COVID-19 pandemic, from molecular mechanisms of infection to childhood hospitalization and response to a single dose of vaccine.

One dose not enough for previously infected

Thomas McDade, PhD, professor of Medical Social Sciences, was senior author of the study published in EClinical Medicine.

One dose of an mRNA vaccine administered to patients previously infected with COVID-19 generated antibody responses of varying strength, according to a Northwestern Medicine study published in EClinical Medicine.

These findings suggest that one dose is not enough for people previously infected with COVID-19, according to Thomas McDade, PhD, professor of Medical Social Sciences and senior author of the study.

Prior exposure to SARS-CoV-2 does not guarantee a robust antibody response to the first dose of current mRNA vaccines.”

Thomas McDade, PhD, Professor, Weinberg College of Arts and Sciences

Researchers took patient samples from a large Northwestern study that used a home-based antibody test, requiring just a single drop of blood from a simple finger prick. The participants were analyzed in three groups: those who had previously recovered from confirmed COVID-19, those who were seropositive to prior infection without an acute diagnostic positive test, and those who were seronegative to SARS-CoV-2 before vaccination.

Measures include anti-SARS-Cov-2 spike receptor binding antibody concentrations and the subsequent ability of those antibodies to neutralize spike protein binding to the angiotensin-converting enzyme (ACE2) receptor, the primary pathway by which SARS-CoV-2 enters human cells. .

According to the study, patients with confirmed COVID-19 showed a robust response to a single vaccine dose, but individuals who were only seropositive — possibly due to a mild or asymptomatic infection — showed a generally weaker response to a single vaccine dose.

These findings suggest caution in adopting immunologic “priming” for people previously infected with COVID-19. If their case was mild, a single dose of mRNA vaccine might not provide them with complete protection. Since there are few methods to accurately measure the severity of COVID-19 infection after hospitalization, patients previously infected with COVID-19 should receive two injections to be safe, according to McDade.

“To ensure maximum protection against emerging variants, two doses are recommended,” McDade said.

The researchers plan to continue the follow-up of this patient cohort, with the goal of identifying the frequency of reinfection and vaccine breakthrough infections — findings that McDade said could prove helpful if dangerous variants emerge and spread.

This study was supported by National Science Foundation grant 2035114 and National Institutes of Health grant 3UL1TR001422-06S4.

Antiviral mechanisms fight COVID-19

Judd Hultquist, PhD, assistant professor of medicine in the Division of Infectious Diseases, was a co-author of the study published in Molecular Cell.

A small group of interferon-stimulated proteins helps determine the efficiency of SARS-CoV-2 replication, according to a study published in Molecular Cell.

These findings highlight host determinants of COVID-19 severity and offer potential therapeutic strategies, according to Judd Hultquist, PhD, assistant professor of medicine in the Division of Infectious Diseases and a co-author of the study.

“We found that the body has a large number of antiviral proteins that can protect against SARS-CoV-2 – some even appear to offer broad antiviral protection, as they have been previously found to protect against other viruses such as HIV and the flu virus” Hultquist said, “However, SARS-CoV-2 appears to have defensive strategies that help protect it against some of these factors.”

Interferons are signaling proteins released by different cell types in response to the presence of nearby pathogens. The release of interferons activates the innate immune response, but advanced age and conditions such as cardiovascular disease or obesity can weaken the innate immune response. Proper functioning of the innate immune response is critical to preventing serious illness in COVID-19 patients, Hultquist said.

In the current study, researchers examined which genes are activated in response to interferon stimulation in human airway epithelial cells. Next, researchers measured the activity of these proteins in inhibiting SARS-CoV-2 replication.

Hultquist and his collaborators found that a small subset of interferon-stimulated proteins helped control viral infection by inhibiting entry into cells and preventing viral RNA synthesis. However, the virus has countermeasures.

One protein, BST2, helps prevent SARS-CoV-2 from leaving cells and spreading throughout the body. It is directly counteracted by the viral protein Orf7a, negating its function. BST2 also plays a role in the antiviral response to HIV infection, but is counteracted by the HIV protein Vpu.

These findings highlight potential therapeutic pathways, Hultquist said, including restoring BST2 function.

“Ultimately, we hope these results help define the factors underlying a genetic predisposition to severe COVID-19, while also providing new potential targets for therapeutic development,” Hultquist said. “In the future, we want to begin investigating the molecular mechanisms that allow these antiviral factors to work to see if they can be applied more broadly to provide protection against a wide variety of pathogenic viruses.”

This study was funded by National Institutes of Health grants UL1 TR002389, UL1 TR001422, and P30 CA060553.

Lower COVID-19 hospitalization for children

Yuan Luo, PhD, associate professor of Preventive Medicine in the Department of Health and Biomedical Informatics, was senior author of the study published in Frontiers in Pediatrics.

According to a study published in Frontiers in Pediatrics, the national hospitalization rate for COVID-19 for children was 20 times smaller than the rate for adults until April 2021.

According to Yuan Luo, PhD, associate professor of Preventive Medicine in the Department of Health, the timing of hospitalizations was similar between children and adults, ruling out child-to-adult transmission as a major source of infection, as seen in some other respiratory diseases. and biomedical informatics and senior author of the study.

“This study was designed at a time when it was suspected that childhood infections and hospitalization could have a major impact on adults,” said Luo, who is also a professor at the McCormick School of Engineering and a member of the Robert H. Lurie Comprehensive Cancer Center. Center of Northwestern University. “So the much lower hospitalization rates for children, as well as the lack of clear evidence of pediatric trends ahead of adult trends, speak against that suspicion, although more detailed data and analysis would shed more light on this topic.”

Researchers evaluated COVID-19 hospitalizations reported to the U.S. Department of Health and Human Services from July 2020 to April 2021. Using census estimates, the study authors calculated weekly hospitalizations per 100,000 children and adults, both nationally and nationally. as per region.

In total, they found a weekly median of 906 hospital admissions for children and 38,675 hospital admissions for adults, 1.2 per 1000,000 children and 15.1 per 100,000 adults. Using a univariate point of change analysis, they identified peaks in hospital admissions. Findings of hospital admissions for adults and children rose sharply in the week of October 23 and peaked during the first two weeks of January.

The lack of a clear lead in the timing of pediatric hospitalizations compared to adults suggests that child-to-adult transmission is less common in COVID-19 compared to other respiratory illnesses, such as the flu or the common cold. However, this doesn’t mean children are safe — teething problems from COVID-19 continue to rise, so vaccine approval for children under 12 and vigilant surveillance could facilitate efforts to reduce COVID-19 in children, said Meghan Hutch, a student in the Driskill Graduate Program in Life Sciences (DGP) and lead author of the study.

“As national efforts continue to focus on vaccinating teens and adults, it is not clear how COVID-19 can continue to affect the younger, pediatric population and affect our national efforts to achieve hearing immunity,” Hutch said. “In addition, with the emergence of the Delta variant, continued monitoring of disease activity, especially in our vulnerable, unvaccinated populations, is critical in guiding our management and response to the pandemic.”


Reference magazine:

Demonbreun, AR, et al. (2021) Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected individuals. Clinical medicine.

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