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Many of the biggest science breakthroughs of 2021 centered, unsurprisingly, around the story of the year: Covid-19. The entries to STAT Madness, our yearly bracket-style competition to choose the prior year’s most exciting biomedical discovery, reflected the priorities of science and humanity at large. Still, last year’s winners developed unique solutions for herpes and diabetes, a sign that among this highly competitive field, it’s anyone’s game. The first round of popular voting begins Tuesday, March 1, when the first-round pairings will be revealed, along with descriptions of all the entrants’ research.

Buoyed by the development and approval of safe and effective vaccines to protect against serious disease from Covid-19, this year’s contenders dove deeper into antiviral treatments and other pandemic solutions. Others expanded horizons in gene therapy, microbiome research, and surgery.

The round of 64 — selected from almost 100 entries — contains a batch of studies that address the problems created by a constantly evolving coronavirus and the threat of vaccine-escaping variants. Solutions put forward for this stage of the pandemic include an intranasal antiviral that targets a slow-to-evolve portion of the SARS-CoV-2 virus and a mask with embedded biosensors, primed to detect viral particles at the push of a button. Another entry highlights the development and testing of molnupiravir, Merck’s antiviral pill approved by the Food and Drug Administration last year to treat Covid-19 cases.

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Other research breakthroughs that made the field reflect paradigm shifts in medicine and diagnostics. Scientists tapped into the therapeutic potential of psychedelics, screening for non-hallucinogenic antidepressants; others probed the role of fungi in the gut microbiome, offering further evidence that certain microbes go hand-in-hand with unhealthy immune systems. Yet another contending team harnessed artificial intelligence to predict breast cancer risk with less biased results than previous deep-learning methods. Gene editing, meanwhile, continues to be fine-tuned: Entries cover an approach to use CRISPR on hundreds of genes simultaneously, a “dimmer switch” to regulate protein expression of edited genes, and epigenetic modifications to turn genes on and off entirely and pass the changes down to future generations.

No bracket is complete without wild cards; these entries’ originality shone through in their nominations. Greasy hair inspired one team to create a cure for obesity in mice. Another devised a microneedle patch for administering shots without the need of a trained professional. Entire cell processes were recreated in artificial, non-living cell-mimics the size of the real things. And one team performed the first full-tracheal transplant, lowering the recipient’s risk of death from accidental suffocation and giving her a new lease on life, while another implanted a microelectrode array in the visual cortex of a woman who had been blind for 16 years and restored rudimentary vision.

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STAT Madness — which is modeled on college basketball’s March Madness tournaments — is a bracket-style competition, but one with a not-so-hidden ulterior motive: Scanning through the entries should give readers an appreciation of the ingenuity and breadth of biomedical research being pursued around the U.S. Voting on www.statnews.com will continue through six single-elimination rounds before the winner of the popular vote is announced on April 4.

You can follow the action on Twitter using the hashtag #STATMadness.

Here are the teams selected for STAT Madness 2022. (There are fewer than 64 teams listed because some institutions have more than one entry.)

Allen Institute

Baylor College of Medicine

Beth Israel Deaconess Medical Center

Boston Children’s Hospital and Harvard Medical School

Brigham and Women’s Hospital

Broad Institute of MIT and Harvard

Children’s Hospital of Philadelphia

Duke University

Georgia State University

Gladstone Institutes

Institute for Systems Biology

Lahey Hospital & Medical Center

McGovern Institute for Brain Research at MIT

Memorial Sloan Kettering Cancer Center

MIT Koch Institute for Integrative Cancer Research

Mount Sinai Health System

New York University

NYU Rory Meyers College of Nursing

NYU School of Global Public Health

Perelman School of Medicine at the University of Pennsylvania

Saint Louis University

Stony Brook University

Texas A&M University College of Medicine

UC San Diego School of Medicine

UMass Chan Medical School

University of California, Davis

University of California, Irvine School of Medicine

University of Chicago Medicine

University of Florida

University of Iowa

University of North Carolina at Chapel Hill

University of Pennsylvania

University of Texas MD Anderson Cancer Center

University of Utah Health

University of Utah John A. Moran Eye Center

University of Virginia School of Medicine

Weill Cornell Medicine

Whitehead Institute

Wyss Institute for Biologically Inspired Engineering at Harvard University