From our labs and clinics: The top 10 COVID-19 science stories of 2021

A teen girl standing in the street with COVID-10 related symbols around her (masks, viruses, etc.)
Research across Boston Children's Hospital delved into SARS-CoV-2 and its effects, as well as COVID-19 diagnostics, vaccines, and therapeutics. (Image: Adobe Stock/Illustration: Dave Chrisom, Boston Children's Hospital)

As COVID-19 waxed, waned, morphed, and waxed again this year, research was taking place throughout Boston Children’s Hospital. Ongoing national studies the hospital is leading or co-leading include Overcoming COVID-19, a CDC-funded study on COVID-19 and multisystem inflammatory syndrome in children (MIS-C); IMPACC, examining immune responses in people hospitalized with COVID-19; and MUSIC, studying MISC’s long-term outcomes. A recap of 2021 learnings follows.


1. More insights on multisystem inflammatory syndrome in children

Data from the Overcoming COVID-19 study, led by Adrienne Randolph, MD, MSc, refined our understanding of MIS-C, helping distinguish it from severe, acute COVID-19 in children. Both conditions can cause severe respiratory symptoms. However, MIS-C tends to cause more extreme inflammation, more often affects the skin and mucous membranes, and more commonly causes severe cardiovascular problems.

Separately, Overcoming COVID-19 showed that initial treatment with both IV immunoglobin and steroids better protected children’s hearts than IV immunoglobulin alone. It also reduced need for additional treatments.

And a genetic study led by Janet Chou, MD, identified changes in several genes related to immune responses in children with MIS-C that may increase susceptibility to inflammation.

2. COVID-19 complications emerge

About 1 in 5 children and teens hospitalized with COVID-19 or MIS-C have neurologic involvement, reported Kerri LaRovere, MD. This was mostly fatigue, headache, confusion, trouble walking or crawling, and loss of taste or smell. However, some patients developed serious complications like stroke, encephalitis, and Guillain-Barre syndrome.

Boston Children’s Heart Center found a worrying link between COVID-19 and blood clots in children with congenital heart defects, even when COVID-19 symptoms were minor.

And a study of adults hospitalized with COVID-19, led by Paolo Fiorina, MD, PhD, found that many developed abnormally high blood sugar levels. Patients with hyperglycemia had more need for oxygen, ventilation, and intensive care. Moreover, many had abnormal pancreatic hormones and elevated glucose even after recovering from COVID-19.


3. COVID-19 vaccination protected teens during Delta 

Two independent studies, in Israel and the U.S., found that COVID-19 vaccination strongly protects 12- to 18-year-olds against both infection and serious illness. The U.S. Overcoming COVID-19 study also showed that COVID-19 can have serious effects in this age group. Watch for more details in 2022.

4. Reassurance on vaccine myocarditis

Myocarditis, or heart-muscle inflammation, is a rare side effect of COVID-19 vaccination in youth, males especially. A national study led by Jane Newburger, MD, MPH, found that symptoms are usually mild and short-lived. However, because some patients had cardiac MRI evidence of myocardial injury, the researchers urge long-term monitoring for heart effects.

5. Emerging protein-based COVID vaccines

Protein-based COVID-19 vaccines are easier to manufacture and store than current mRNA vaccines and could be more readily available to low- and middle-income countries. They include two candidates from Boston Children’s Precision Vaccines Program and the lab of Hidde Ploegh, PhD. Both vaccines use only the receptor-binding domain of the spike protein — not the full spike. But each used different methods to stimulate immune responses. Both elicited strong immunity in mice.

6. Rapid saliva test detects COVID-19 variants

Rose Lee, MD, and collaborators at the Wyss Institute developed a low-cost, rapid, saliva-based COVID-19 test system that gives a readout from users’ spit within about an hour. In experiments, it accurately diagnosed COVID-19 and discriminated between variants. The researchers hope to see it scaled for home or point-of-care use worldwide.

7. Repurposed alcoholism drug shows potential

Judy Lieberman, MD, PhD, and Hao Wu, PhD, reported last year that dusulfiram quiets pyroptosis, a fiery, inflammatory cell death that can occur in serious infections. Colleagues at Harvard Medical School and the Veterans Administration wondered if it could help fight COVID-19. They teamed up on an observational study of veterans using disulfiram and found a 34 percent lower risk for COVID-19 and possibly lower mortality. If these findings are confirmed, disulfiram (Antabuse) could be a useful tool.


8. SARS-CoV-2, our respiratory tract, and interferons

Responses to SARS-CoV-2 in the nose and throat predict who will or won’t develop severe COVID-19, reported José Ordovás-Montañés, PhD, Bruce Horwitz, MD, PhD, and collaborators. Analyzing patients’ nasal swabs with single-cell RNA sequencing, they found that in people with mild symptoms, cells in the nose responded vigorously, with high activation of genes stimulated by interferon. In severe COVID-19, nasal responses, particularly responses to interferon, were markedly blunted. 

Next, Ivan Zanoni, PhD, and his colleagues found that not all interferons are alike in COVID-19. People with mild disease produced high levels of protective Type 3 interferons (lambda 1 and lambda 3) in the nose, throat, and mouth. People with more severe disease produced non-protective lambda 2 and Type 1 interferons that may contribute to inflammation and allow SARS-CoV-2 to go to the lungs.

9. Drivers of COVID-19 lung inflammation

Researchers led by Talal Chatila, MD, revealed a key instigator of runaway lung inflammation in COVID-19. Excess levels of the Notch4 protein receptor on regulatory T-cells divert the cells from tissue repair and immune suppression toward a more inflammatory stance. On the plus side, mice given an anti-Notch4 antibody had less lung injury and fewer fatalities.

10. Deconstructing SARS-CoV-2

Bing Chen, PhD, produced multiple structural insights on the ever-evolving coronavirus and its spikes. One study revealed why the Alpha and Beta variants spread more quickly than the original virus: Mutations made the spikes more stable, thus better able to initiate infection. Another study showed why the Delta variant is so contagious: Its spikes are adept at initiating fusion between the viral membrane and our cell membranes, giving Delta quick entry. Chen is now studying the effects of Omicron’s mutations.


Boston Children’s Computational Health Informatics Program showed that analyzing our online “fingerprints” — from Google searches to tweets to Facebook-based surveys — can provide real-time insights on SARS-CoV-2. While these tools can’t predict the future, they can help the experts prepare for new variants…or even new pandemics.

Learn more about COVID-19 research at Boston Children’s Hospital and our science advances for 2021.

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