Tag: dexamethasone

Why COVID Cases Vary in Severity

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Researchers working with ‘humanised mice’ have found why some mild cases of COVID tip over into more severe and life-threatening disease.

An estimated 80 to 90% of people infected with COVID experience only mild cases while 10 to 20% face more severe or life-threatening symptoms.

Yale University researchers working with mice they have engineered to possess human-like immune systems may have found why this is so. Their findings,  published in Nature Biotechnology revealed that the causes of severe COVID may lie in our own antiviral inflammatory response to the virus.

The study also showed that two well-known therapies, monoclonal antibodies and the steroid dexamethasone, can help treat COVID infections. But in the case of the antibodies, treatment is only effective if administered early in the course of disease. In the case of steroids, it’s only effective if administered during later stages of the disease.

Standard laboratory animals and humans have different immune responses, which has made it difficult for scientists to pinpoint the tipping point between mild and severe cases of COVID, so mice engineered to have a human-like immune system, were able to offer an answer.

“If you infect a standard laboratory mouse with SARS-CoV-2 they will get infected, but not get seriously ill,” said Flavell, Sterling Professor of Immunobiology at Yale and senior author of the paper. “But our humanised mice get sick and just don’t get better. Their whole immune system is on fire.”

The research team introduced SARS-CoV-2 virus taken from seriously ill human patients into the nasal passages of their humanised mice and then followed the course of the disease.

They found that the infected mice exhibited the same symptoms as severely ill human patients, such as lung damage, weight loss, and a heightened, persistent inflammatory immune response that damages tissues. They then treated the mice with monoclonal antibodies which specifically target the virus, and were  found to be effective if given before or very early after infection but did little to stifle symptoms if administered in later stages of infections.

Conversely, during the early stages of infection the immune suppressant dexamethasone was fatal to mice when it suppressed the initial immune response that was crucial to combat the virus. However, during later stages of disease, it helped clear infection  by suppressing the inflammatory response that had begun damaging organs.

“Early in the course of disease, a strong immune response is crucial for survival,” said first author Esen Sefik. “Later in the disease, it can be fatal.”

The humanised mice models might also reveal strong clues to the causes and potential treatments of so-called long and severe COVID, the scientists said.

Source: Yale University

Dexamethasone in Cancer Surgery Boosts Survival Rates

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The survival of patients with breast, pancreatic and certain other cancers could be extended if given the anti-nausea drug dexamethasone during surgery. 

This finding comes from a large study being presented at the ANESTHESIOLOGY® 2021 annual meeting.

A drug with an already great range of uses including COVID treatment, dexamethasone is given to patients to prevent nausea and vomiting after surgery and during chemotherapy. Researchers found dexamethasone can improve mid- to long-term outcomes in patients with non-immunogenic cancers (those that don’t provoke a strong immune response) such as sarcoma and cancers of the breast, uterus, ovary, esophagus, pancreas, thyroid, bones and joints.

“Dexamethasone has positive and negative effects – it inhibits cancer growth, but also suppresses the immune system,” said senior author Maximilian Schaefer, MD, PhD. “Previous research has reported that in cancers in which the immune system controls cancer growth, the positive and negative effects of dexamethasone balance each other, so there is no benefit. Ours is the first large study to show that for a wide variety of cancers where the immune system does not play a major role, the positive effects seem to predominate.”

Researchers analysed the records of over 74 000 patients who had surgeries to remove non-immunogenic cancerous tumours, about a third of whom received dexamethasone during surgery. After 90 days, 209 (0.83%) of the patients who had received dexamethasone died vs 1543 (3.2%) of patients without the drug.

After accounting for confounding factors, including that dexamethasone is often administered to younger patients, there was still a 21% reduced risk of dying within one year after surgery for those who received the drug. It was also shown to be particularly beneficial for patients with cancers of the ovary, uterus or cervix.

“Based on our data, physician anesthesiologists should feel more confident in administering dexamethasone to patients undergoing surgery for non-immunogenic cancers,” said Dr Schaefer. “It not only helps with nausea, but it also may result in improved survival.”

Source: American Society of Anesthesiologists