Lung Autopsies of COVID-19 Patients Reveal Treatment Clues

Lung autopsy and plasma samples from people who died of COVID-19 have provided a clearer picture of how the SARS-CoV-2 virus spreads and damages lung tissue.

Scientists at the National Institutes of Health and their collaborators say the information, published in Science Translational Medicine, could help predict severe and prolonged COVID-19 cases, particularly among high-risk people, and inform effective treatments.

Although the study was small—lung samples from 18 cases and plasma samples from six of those cases—the scientists say their data revealed trends that could help develop new COVID-19 therapeutics and fine-tune when to use existing therapeutics at different stages of disease progression. The findings include details about how SARS-CoV-2, the virus that causes COVID-19, spreads in the lungs, manipulates the immune system, causes widespread thrombosis that does not resolve, and targets signaling pathways that promote lung failure, fibrosis and impair tissue repair. The researchers say the data are particularly relevant to caring for COVID-19 patients who are elderly, obese, or have diabetes—all considered high-risk populations for severe cases. Study samples were from patients who had at least one high-risk condition.

The study included patients who died between March and July 2020, with time of death ranging from three to 47 days after symptoms began. This varied timeframe allowed the scientists to compare short, intermediate, and long-term cases. Every case showed findings consistent with diffuse alveolar damage, which prevents proper oxygen flow to the blood and eventually makes lungs thickened and stiff.

They also found that SARS-CoV-2 directly infected basal epithelial cells within the lungs, impeding their essential function of repairing damaged airways and lungs and generating healthy tissue. The process is different from the way influenza viruses attack cells in the lungs. This provides scientists with additional information to use when evaluating or developing antiviral therapeutics.

Researchers at NIH’s National Institute of Allergy and Infectious Diseases led the project in collaboration with the National Institute of Biomedical Imaging and Bioengineering and the U.S. Food and Drug Administration. Other collaborators included the Institute for Systems Biology in Seattle; University of Illinois, Champaign; Saint John’s Cancer Institute in Santa Monica, California.; the USC Keck School of Medicine in Los Angeles; University of Washington Harborview Medical Center, Seattle; University of Vermont Medical Center, Burlington; and Memorial Sloan Kettering Cancer Center in New York City.

Broadly protective antibodies could lead to better flu treatments and vaccines

A newly identified set of three antibodies could lead to better treatments and vaccines against influenza, according to a paper published this week in Science. 

Researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, isolated the antibodies from a person sick with the flu five days after the onset of symptoms.

They found that the antibodies, which bind to neuraminidase (NA) proteins on the surface of influenza viruses, provided broad protection against several different strains of influenza when tested both in vitro and in mice.

Most influenza vaccines are designed to stimulate an immune response against another protein found on the surface of the influenza virus called hemagglutinin (HA). However, HA proteins change frequently as the virus evolves. As a result, people must receive a new seasonal influenza vaccination every year to be protected against currently circulating influenza viruses. NA proteins change more slowly than HA proteins and thus could be a good target for an influenza vaccine that provides long-term protection.

In the new study, the researchers took antibody-producing cells from the blood of a volunteer sick with H3N2 influenza and screened for monoclonal antibodies (mAbs). Monoclonal antibodies are antibodies which are designed to bind to a single target. The mAbs the researchers found were tested in the laboratory for their ability to bind to different kinds of influenza proteins. Of 45 mAbs tested, three bound to NA proteins of an H3N2 influenza virus strain. Upon further testing, these three mAbs also bound to NA proteins from multiple other types of influenza viruses.

To see whether these three mAbs could help prevent the influenza virus from infecting mammalian cells, the researchers treated mice with the mAbs and then infected them with different types of influenza viruses. The mAbs inhibited many kinds of NA proteins from different types of influenza viruses, and protected most of the mice from severe influenza infections. Mice given lethal doses of H3N2 influenza virus survived when treated with low doses of the three antibodies.

If additional testing supports these early results, the researchers suggest that these potent mAbs could become the basis for a new antiviral treatment. Additionally, the antibodies could inform development of new influenza vaccines designed to induce similar antibodies that could provide broader and longer-lasting immunity than current HA-based influenza vaccines.