Because B cells are responsible for antibody production, patients’ ability to produce antibodies that prevent the virus from entering and infecting a person’s cells is significantly muted when the B cells are depleted with aCD20 treatment. But the same patients are nonetheless able to mount very good responses of the second protective arm of their immune system, which uses T cells to eliminate cells once infected (thereby preventing viral spread to other cells), according to new research from the Perelman School of Medicine at the University of Pennsylvania in a new paper published in Nature Medicine.

“The message from this study is clear — it is worthwhile for patients with MS receiving aCD20 treatment to get a COVID-19 vaccine, which will prevent severe illness,” said one of the senior authors E. John Wherry, PhD, chair of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute for Immunology. “Based on this body of evidence, we urge patients with MS receiving aCD20 treatment to get a COVID-19 vaccine if they haven’t already.”

The study measured both the antibody and T cell responses in 20 patients with MS who were undergoing aCD20 treatment, compared to those in a group of healthy controls. None of the participants in the study had prior clinical signs or symptoms of COVID-19. Researchers analyzed plasma and peripheral blood mononuclear cell samples five times over the study period: prior to the first vaccine dose, 10-12 days following the first vaccine dose, prior to the second vaccine dose, 10-12 days following the second vaccine dose, and 25-30 days following the second vaccine dose.

All healthy control subjects generated both anti-spike and anti-receptor-binding domain (RBD) antibodies following the first dose of mRNA vaccine, and the level of antibody increased further after the second dose. However, in patients with MS, the antibody response was far more varied. By 30 days after the second vaccine dose, 85% of participants developed anti-spike antibodies, and 50% mounted anti-RBD responses. For those subjects who did have detectable antibodies, the magnitude of response was generally lower, and the response was delayed compared to the control group.

The timing of a patient’s last aCD20 infusion — typically administered every six months — played a significant role in the immune response mounted. Patients with MS with higher percentages of circulating B cells prior to the vaccine had more robust antibody responses to the vaccine.

“This data not only reveal that patients undergoing anti-CD20 infusions are still able to mount important COVID-19 vaccine responses which are likely to protect from severe illness, but also informs our clinical practices in how we advise patients with MS and other autoimmune disorders on such therapies,” said another of the paper’s senior authors Amit Bar-Or, MD, FRCPC director of the Center for Neuroinflammation and Experimental Therapeutics and chief of the Division of MS and Related Disorders. “For example, knowing that responses are weakest immediately following an anti-CD20 infusion, we can now advise patients to wait a number of months after their therapy to get a COVID-19 vaccine.”

Researchers found that patients who had undergone aCD20 treatments had subpopulations of T cells that responded similarly to vaccination as healthy control subjects. Patients who underwent aCD20 therapy generated robust CD4 and CD8 T cell responses to the COVID-19 vaccination. Further, the CD8 T cell response was especially robust among the subgroup of patients with MS who didn’t generate RBD antibodies. This observation reveals that even without circulating B cells, the COVID-19 vaccine effectively primed patients’ immune response to the virus.

“Often when determining if a patient mounted a proper response to an mRNA vaccine, we test for the presence of antibodies, but this method neglects an entire arm of a person’s immune response,” said one of the lead authors Sokratis A. Apostolidis, MD, a fellow in the Department of Rheumatology. “Measuring both antibodies and T-cell response gives us a more complete picture of a patient’s immune response, and reveals that patients who can’t generate antibodies as well as a healthy person are actually still protected by the COVID-19 vaccine.”

The researchers do note that due to the limited antibody responses mounted by patients receiving aCD20 treatments, they might not be able to neutralize the virus as quickly before it infects other cells, which could result in them being contagious carriers of the virus for a longer period of time.

This work was supported by grants from the NIH (AI105343, AI082630, AI108545, AI155577, AI149680, AI152236, P30-AI0450080, R01 AI118694, UC4 DK112217, T32 AR076951-01, T32 CA009140, U19AI082630, UM1 AI144288, NMSS SI-2011-37160). This work was also supported by NIH contract (Nr. 75N9301900065).

Funding was also provided by the Allen Institute for Immunology, Chen Family Research Fund, the National Multiple Sclerosis Society-American Brain Foundation Clinician Scientist Award, the Parker Institute for Cancer Immunotherapy, the Penn Center for Research on Coronavirus and Other Emerging Pathogens, the University of Pennsylvania Perelman School of Medicine COVID Fund, the University of Pennsylvania Institute for Immunology Glick COVID-19 research award, the University of Pennsylvania Perelman School of Medicine 21st Century Scholar Fund, a philanthropic gift from Jeffrey Lurie, Joel Embiid, Josh Harris, and David Blitzer, the Penn Center for Neuroinflammation and Experimental Therapeutics and the Melissa and Paul Anderson Fund.

Nations with more urban populations and strong international travel links were worst affected by the pandemic, the study shows.

Mortality rates and levels of restrictions — such as lockdowns and travel bans — were found to be lowest in countries previously thought to be at greatest risk from Covid-19.

A team of researchers from the NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA) from the University of Edinburgh worked with the World Health Organization (WHO) African Region to identify factors affecting mortality rates during Africa’s first two Covid-19 waves and the timing of the first reported cases.

Professor Mark Woolhouse, TIBA Director, who co-led the study, said: “Our study shows very clearly that multiple factors influence the extent to which African countries are affected by Covid-19. These findings challenge our understanding of vulnerability to pandemics.

“Our results show that we should not equate high levels of preparedness and resilience with low vulnerability.

“That seemingly well-prepared, resilient countries have fared worst during the pandemic is not only true in Africa; the result is consistent with a global trend that more developed countries have often been particularly hard hit by Covid-19.”

Among 44 countries of the WHO African Region with available data, South Africa had the highest mortality rate during the first wave between May and August 2020, at 33.3 deaths recorded per 100,000 people. Cape Verde and Eswatini had the next highest rates at 17.5 and 8.6 deaths per 100,000, respectively. At 0.26 deaths recorded per 100,000, the lowest mortality rate was in Uganda.

South Africa also recorded the highest mortality rate during the second wave between December 2020 and February 2021, at 55.4 deaths per 100,000. Eswatini and Botswana recorded rates of 39.8 and 17.7 deaths per 100,000, respectively. The lowest rate was in Mauritius, which recorded no deaths during the second wave.

“The early models which predicted how Covid-19 would lead to a massive number of cases in Africa were largely the work of institutions not from our continent. This collaboration between researchers in Africa and Europe underlines the importance of anchoring analysis on Africa’s epidemics firmly here,” said Dr. Matshidiso Moeti, WHO Regional Director for Africa and co-author. We can no longer focus our understanding of disease transmission purely on the characteristics of a virus — Covid-19 operates within a social context which has a major impact on its spread.”

As well as those with large urban populations and strong international travel links, countries with high rates of HIV were also more likely to have higher mortality rates. This may be because people with HIV often have other health conditions that put them at greater risk from Covid-19, the team suggests.

The weak link between mortality rate and the timing or severity of government-imposed restrictions on day-to-day activities is shows the impact of the wide range of application and enforcement of these restrictions across the region, making a consistent impact pattern difficult to discern. Restrictions during peaks of infection are well documented to have interrupted transmission in the region.

The findings show that the earliest recorded cases of Covid-19 were in counties where most people live in urban areas, with strong international travel links and greater testing capacity. Algeria was the first of 47 African countries to report a case, on 25 February 2020. Most countries had recorded cases by late March 2020, with Lesotho the last to report one, on 14 May 2020.

Researchers document higher deaths during the second wave, as compared to the first. The peak of infections during the second wave was also higher, with 675 deaths across the continent on 18 January 2021 compared with 323 during the first wave peak on 5 August 2020. Potential under-reporting was accounted for in the analysis.

Dr Sarah Puddicombe, NIHR’s Assistant Director for Global Health Research, said: “This study offers compelling results which challenge accepted views of epidemic preparedness and resilience in Africa. It is one of a series of important contributions that the TIBA partnership, working with governments and the WHO Regional Office has made to inform local, national and pan-African responses to the Covid-19 pandemic.”

The study, published in the journal Nature Medicine, was supported by the UK National Institute for Health Research and the Darwin Trust of Edinburgh. It also involved researchers from the Universities of Nairobi, Ghana and Hong Kong.

While risk factors for hospitalization and poor outcomes are well documented in adults, less is known about the clinical factors associated with COVID disease severity in children.

In an effort to aid mitigation strategies for children who are at high risk of developing severe COVID disease, a group of physicians at Monroe Carell Jr. Children’s Hospital at Vanderbilt studied data from 45 children’s hospitals around the country — 20,000 patients were included.

“This is one of the largest multicenter studies of children with COVID-19 in the United States,” said James Antoon, MD, PhD, FAAP, assistant professor of Pediatrics at Children’s Hospital and lead author of the study.

“And given the recent, concerning increases in COVID cases nationwide and the fact that the vast majority of children remain unvaccinated and susceptible, these findings should be taken into account when considering preventive strategies in schools and planning vaccinations when available for children less than 12 years of age,” he said.

The study, “Factors Associated with COVID-19 Disease Severity in U.S. Children,” published in the Journal of Hospital Medicine, determined the factors associated with severe disease and poor health outcomes among children presenting to the hospital with COVID. These included older age and chronic co-morbidities such as obesity, diabetes and neurologic conditions, among others.

“These factors help identify vulnerable children who are most likely to require hospitalization or develop severe COVID-19 disease,” said Antoon. “Our findings also highlight children who should be prioritized for COVID-19 vaccines when approved by the FDA.”

The retrospective cohort study noted that approximately 1 out of every 4 children admitted to the hospital with COVID developed severe disease and required ICU care during April and September, 2020.

“Across the country there is a raging debate on how best to protect children and schools from COVID-19,” said Antoon. “Some children are at increased risk for more severe disease and many of them are not yet eligible for vaccination against COVID.

“With schools opening and some already in session, these children need to be protected by vaccinating as many people as possible while also using practical strategies to limit spread, such as masking, distancing and ventilation.”

Study investigators hope that the findings will buoy mitigation efforts that proved most beneficial for children and adolescents during the pandemic, including remote learning, social distancing, hand-washing and mask-wearing both for students and teachers.

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Materials provided by Vanderbilt University Medical Center. Original written by Jessica Pasley. Note: Content may be edited for style and length.

Early in the pandemic, COVID-19 outbreaks from choir performances indicated that singing carries a potential infection risk, but less is known about the risks of airborne infection from wind instruments. To help keep performers, audiences and music students safe, Tehya Stockman, Shelly Miller and colleagues wanted to examine aerosol production and flow from various musical activities, as well as test different mitigation strategies.

The researchers examined the extent and velocity of air jets, or plumes, coming from singers’ and actors’ mouths and from wind instruments, such as the flute, clarinet, trumpet and saxophone. They also measured airborne respiratory particles, or aerosols, and carbon dioxide levels emanating from the performers. They found that aerosol concentrations coming from the bell of a clarinet were comparable to singing. Placing a surgical mask over a singer’s face or over the clarinet bell substantially reduced plume velocities and lengths and decreased aerosol concentrations in front of the masks. The team then used these measurements to model viral transmission in indoor and outdoor environments, finding that the lowest risk of airborne COVID-19 infection occurred at less than 30 minutes of exposure indoors and less than 60 minutes outdoors. These findings could help musical rehearsals and performances resume in a safer manner for musicians and audiences, the researchers say.

The authors acknowledge funding from an international coalition of more than 95 musical organizations.

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Materials provided by American Chemical Society. Note: Content may be edited for style and length.