A new study from the Keck School of Medicine of USX suggests that temporarily suppressing the body’s immune system early on during Covid-19 might help a patient avoid the worst outcome.

According to their research that was published in the Journal of Medical Virology, the body’s two main lines of defence, the innate and adaptive immune responses cause the immune system to go into overdrive in some patients, which may lead to fatal consequences.

What is the difference between innate and adaptive immune response?

When the body gets threatened by an infection, there are two lines of defence. The first line of defence, the innate immune response, kicks in right after the body gets infected by pathogens like viruses or bacteria.

The innate immune response targets the specific pathogen and tries to kill it and any cells damaged by it.

The second line of defence, the adaptive immune response, only kicks in days later if there are still any signs of the virus in the body. This response uses mechanisms such as T and B cells to help fight the virus.

But why would your own immune system harm you?

Your immune system responds differently to various viruses and bacteria. In the case of flu, the infection moves swiftly and the immune system kills almost all of the targeted cells within days.

But, in the case of Covid-19, the disease progresses much more slowly. When the immune system realises there is imminent danger, the second line of defence, the adaptive reaction, may kick in long before the sick cells are killed, interfering with the innate immune response’s ability to properly attack the intruder.

“The danger is, as the infection keeps going on, it will mobilize the whole of the adaptive immune response with its multiple layers,” explained Weiming Yuan, associate professor in the Department of Molecular Microbiology and Immunology at the Keck School of Medicine of USC, and co-corresponding author of the study in the press release.

“This longer duration of viral activity may lead to an overreaction of the immune system, called a cytokine storm, which kills healthy cells, causing tissue damage.”

Better, then suddenly worse

This may also explain why some Covid-19 patients seem to think they are on the mend, only to feel much worse.

“Some Covid-19 patients may experience a resurgence of the disease after an apparent easing of symptoms,” said Sean Du, adjunct researcher and lead author of the study. “It’s possible that the combined effect of the adaptive and the innate immune responses may reduce the virus to a low level temporarily. However, if the virus is not completely cleared, and the target cells regenerate, the virus can take hold again and reach another peak.”

A possible solution?

The research resulted in the possibility of treating this reaction in Covid-19 patients by trying to prevent this response from the immune system.

The team suggests proper immunosuppressant drugs early in the disease to avoid a serious onset of symptoms.

Small Chinese studies did show that immunosuppressants such as corticosteroids resulted in a more favourable outcome in patients with Covid-19.

The researchers will need to see if their data validates their current mathematical modelling, and they will have to do more pre-clinical studies first to see if this treatment is viable.

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Compiled by Marelize Wilke

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When concerns about catching the coronavirus encourage people to stay physically distant, that’s healthy. When those fears drive ailing people away from hospitals, though, it could be dangerous.

To such people, doctors say: Your emergency room is safe. And if you need to go, you should.

Hospitals are updating safety procedures in lots of ways, said Dr Patricia Best, an interventional cardiologist. She is an associate professor of internal medicine and cardiovascular diseases at Mayo Clinic College of Medicine and Science in Rochester, Minnesota.

“With this pandemic likely to go on for months, if not a year or longer, we need to make sure people are getting timely care for all of the things that they need,” she said. And that means if someone is “having something that on any other day, they would be calling an ambulance, they should call an ambulance”.

Driven by fear

Not everyone is. An April study in the Journal of the American College of Cardiology said admissions for a serious type of heart attack known as STEMI dropped 38% after 1 March, after the pandemic hit. In news reports, people have specifically cited coronavirus worries as the reason for avoiding hospitals.

Dr Phillip L. Coule, vice president and chief medical officer at the Augusta University Health System in Georgia, said admissions in his hospital were down by 25% to 40%.

“Some of that appears to be driven out of fear,” he said. “Certainly, some of it is driven out of cancelling elective cases, delaying procedures and things like that. But I’m quite certain that there is a component that is driven out of people not seeking health care because they’re concerned about the potential of becoming infected with Covid-19.”

That’s a bad idea, he said. “The risks posed by ignoring heart attack and strokes are far greater than the risks posed by Covid-19 and seeking health care.”

That holds true even in cities where the virus has hit hard, said Dr Alice Jacobs, professor of medicine at Boston University School of Medicine. She’s vice chair for clinical affairs in the department of medicine at Boston Medical Center and a past volunteer president of the American Heart Association.

Fast care is the key to survival, she said. “The relationship between opening the blocked artery causing the heart attack and the chance of dying is measured in minutes.” And hospital workers need extra time now to allow for coronavirus safety measures.

A separate entrance 

But Jacobs, lead author of new guidance for STEMI care during the pandemic released on Saturday by the AHA, said the entire emergency care process is adapting, starting in ambulances, which are being decontaminated and restocked with Covid-19 in mind.

At Coule’s facility, patients with Covid-19 symptoms are being diverted at the emergency room entrance to a separate area so they don’t mix with patients who have non-Covid-19 issues.

At Mayo Clinic, Best’s catheterisation lab – the part of the hospital that evaluates and treats heart patients – also has made changes. Some might be obvious. Patients are being met by workers in full protective gear, and family member access is restricted.

Other changes are technical. The temporary STEMI guidance, which Best co-wrote, suggests more intense cleaning procedures and cutting back on the number of workers exposed to potentially infected patients. Other experts have issued temporary guidance from the AHA to help protect stroke patients.

Away from hospitals, new safety measures at a family physician or urgent care clinic might vary, she said. But for a true emergency, people need to call 911 and be taken to an emergency room no matter what.

Concerns about people not heeding such advice led the leaders of eight health organisations, including the American College of Cardiology, Heart Rhythm Society and AHA, to issue a statement in April that said, “Calling 911 immediately is still your best chance of surviving or saving a life.”

A cardiac evaluation

Coule agreed.

“I’m a huge fan and proponent of using urgent cares and telemedicine and private physicians when appropriate,” he said. “But if you’re having … symptoms of heart attack or stroke, those are not viable solutions. Those are patients who need to be seen in an emergency department that’s qualified and capable of taking care of them. That’s true on any day, and that’s true during Covid-19.”

Coule follows his own advice.

“I actually had chest pain during this crisis,” he said. He was at work at the time and, as many people do, he pondered for a moment as to whether he really needed to go.

But not for long. He reported to the emergency department and got a cardiac evaluation, “and everything turned out great”. He was sent home at midnight and was back at work the next morning.

Fear of getting Covid-19 was never an issue. But he worries about a wave of people who have delayed care for all kinds of problems. It’s crucial they don’t, he said.

“I would tell my parents, who are both heart disease survivors, that if they needed a procedure, it’s perfectly safe to come in and have that procedure done now,” he said. “I wouldn’t worry about their safety or the potential for catching Covid-19 in the hospital.”

AHA News for HealthDay

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Many drugs are being tested to fight Covid-19, but now researchers report that blocking testosterone might help prevent the infection in men.

Italian men with prostate cancer on androgen-deprivation therapy (ADT) were less likely to get infected with Covid-19 and had less severe cases if they were infected, the researchers found.

Lead researcher Dr Andrea Alimonti, an oncologist at the Università della Svizzera Italiana in Bellinzona, Switzerland, thinks it might be worth trying this therapy on men with severe cases of Covid-19.

“This could give us a therapeutic window to treat patients that have been infected and haven’t gotten better, to see whether this therapy would lead them to recover faster or to decrease the severity of their symptoms,” he said.

Androgen-deprivation therapy

Alimonti’s interest was piqued when he saw data that men were more likely to develop Covid-19 than women and suffer more severe bouts of the disease.

Putting two and two together, he realised that an enzyme (TMPRSS2), which Covid-19 needs to infect cells, was blocked by androgen-deprivation therapy.

“For many years, we have known that androgen-deprivation therapy can block the level of this enzyme. My speculation was this could explain that androgen levels control this enzyme and why men can be infected and develop more severe symptoms, compared to women,” Alimonti said.

Based on this retrospective study, Alimonti doesn’t think this therapy should be used to treat men, in general, to possibly prevent Covid-19.

“We cannot say that the non-prostate cancer patient will benefit, because this needs to be validated in a prospective clinical study,” he explained.

For the study, Alimonti and his colleagues collected data on more than 4 500 men in the Veneto region of Italy.

The investigators found that men who had cancer had nearly two times the risk for Covid-19, but only four men getting ADT became infected, and none died.

Very interesting biology

When the researchers looked at more than 37 000 men with prostate cancer who were not taking ADT, 114 developed Covid-19 and 18 died. But among more than 79 000 men with other cancers, 312 developed Covid-19 and 57 died.

Dr Anthony D’Amico, a professor of radiation oncology at Harvard Medical School in Boston, thinks other factors might explain why men with prostate cancer are less likely to get Covid-19.

For one, men with prostate cancer receiving ADT aren’t immunosuppressed like other cancer patients, he said. Second, these men get one shot of ADT and can stay home, unlike other cancer patients who need frequent trips to the hospital for chemotherapy, which puts them at greater risk for infection.

“I don’t want to put a big damper on this. The biology is very interesting. There very well may be something there, but I think that there are confounders here,” D’Amico said.

Men shouldn’t be asking their doctors to start them on ADT in hopes of avoiding getting infected, he said.

Preliminary study

“If you’re on ADT, there may be some protective benefit, but I still would advise you to pay attention to the national guidelines on physical distancing, as well as frequent hand-washing, because it’s not proven that, in fact, ADT will protect you from getting the infection and if you get it it’ll be less severe, so I’m cautious,” D’Amico said.

Dr Manish Vira, system chief of urology at Northwell Cancer Institute in Lake Success, New York, agreed that men shouldn’t be seeking ADT.

“This study is very preliminary, and by no means is a definitive study to recommend changing treatment or treating patients with ADT,” he said. “ADT has its own set of side effects, and I agree it’s way too early to recommend this type of treatment.”

ADT can cause hot flashes, fatigue, loss of lean muscle mass, and in the long term, can cause a decrease in bone mineral density and metabolic and cardiovascular issues that affect patients who have diabetes. “So, this is certainly not something that’s easy as, say, taking a baby aspirin,” Vira explained.

The report was published on 6 May in the Annals of Oncology.

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