Fight cancer and Covid-19

MADRID (EFE).— Virulent infectious agents such as the SARS-CoV-2 coronavirus can induce tissue damage, and now a study led by the University of California, San Diego, proposes a new approach to treating Covid-19: using an experimental cancer drug.

Twelve years ago, cancer researchers at the university center identified a molecule that helps cancer cells survive by transporting harmful inflammatory cells to tumor tissue.

In the new research, the scientists show that the molecule does the same thing in Covid-19-infected lung tissue and that the molecule can be suppressed with a repurposed cancer drug.

The work, published in Science Translational Medicine, represents a new approach to prevent irreversible organ damage from diseases such as Covid-19 and MRSA (methicillin-resistant Staphylococcus aureus), which does not improve with the type of antibiotics used for staph infections.

The two key players in this approach are inflammatory cells called myeloid cells and the enzyme PI3K gamma.

Myeloid cells belong to the innate immune system—the immunity we are born with before being exposed to pathogens in the environment—and act very quickly to eliminate deadly agents such as SARS-CoV-2.

The work shows that drugs capable of preventing the recruitment of harmful myeloid cells in tissues infected by serious agents have a “significant” beneficial effect in preserving tissue function if administered at a sufficiently early stage of infection, says researcher Judith Varner.

Most Covid drugs target the virus, either by preventing infection or by stopping the virus from making more of itself. The current approach targets the host to prevent the immune system from overreacting or fibres from building up in the lungs.

Myeloid cells protect, but they can also do a lot of damage, Varner explains. If you have a small infection, they spring into action, killing bacteria, releasing alerts that recruit more powerful “killer” immune cells and producing substances that can heal the damage.

But if the infection is too strong, there is an overproduction of these warning signals and the substances they release to kill infectious agents can also affect the patient, as occurs in Covid.

PI3K gamma promotes the movement of myeloid cells into cancerous tissues, as the team discovered twelve years ago. The current work shows that PI3K gamma also helps move myeloid cells into tissues infected with SARS-CoV-2.

This finding led the team to believe that a cancer drug that inhibits PI3K gamma, called eganelisib, might be effective in suppressing inflammation in Covid-19 by blocking the enzyme’s ability to move myeloid cells into infected tissue.

Researchers sequenced lung tissue from Covid patients and saw that many of their lung cells were dying and there was a huge increase in myeloid cells. They also found the same thing in infected mice.

The team found that eganelisib — not yet approved by the U.S. Food and Drug Administration — blocks myeloid cells from entering the tissue so they can’t do all that damage. Further studies will determine whether it can actually reverse the damage, say the researchers, who found the same results in mice infected with MRSA.