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Treating Covid-19 early to save patients’ lives, urges the SARS veteran

KY Yuen

Photographer: Isaac Lawrence / AFP via Getty Images

Hong Kong’s foremost pandemic doctor sees a way out of ICU for thousands of Covid-1

9 patients: blocking them from entering in the first place

After giving pause 17 years ago with the outbreak of severe acute respiratory syndrome, Yuen Kwok-Yung is advocating early and aggressive hospitalization and treatment to minimize the devastation of illness and death. From Hong Kong Covid-19 death rate of 2% on Friday, well below global average, gives weight to the approach.

Most SARS-CoV-2 therapies are licensed for use in critically ill patients, in some cases supported by research still under discussion. Yuen, Henry Fok Professor of Infectious Diseases at Hong Kong University for 15 years, is to admitting patients with minimal disease so that they can be isolated, monitored and treated as needed.

“In places like the UK and the US, usually if you have mild symptoms, you’re not to admitted in a hospital – you just have to wait at home until you feel very bad or short of breath, “he explained to Zoom from his office.” But basically to admit any patient, even without many symptoms, to hospital for isolation. “

The strategy reduces transmission in the community and allows patients to enter a clinical trial and receive experimental treatment soon after developing a fever or showing other signs of disease worsening, Yuen said. This is critical because the amount of SARS-CoV-2 virus or “viral load” in patients peaks when symptoms appear, similar to the flu.

Microbiologist, Surgeon, Doctor

Yuen, who Graduated from the University of Hong Kong in 1981 and has the rare distinction of being a microbiologist, surgeon and physician, he has been at the forefront of the city’s response to infectious epidemics for decades. In 1998 he and colleagues described the first dozen patients with the H5N1 strain of avian influenza. Five years later, them reported SARS in a patient visiting Hong Kong from Guangzhou, China.

Yuen recalls the trial and error involved in rescuing patients from SARS, which was also caused by a coronavirus. Soon after, he identified “a time bomb “of environmental and social conditions that he predicted would inevitably lead to more deadly coronavirus outbreaks.

That prediction came true in December, when the first cases of a a mysterious pneumonia came to light in Wuhan, in the Chinese province of Hubei. Hong Kong has responded to the novel coronavirus by preparing tests and advising citizens to wear masks.

Meanwhile, Yuen’s lab was conducting research which led to the first cluster reported among family members in which human-to-human transmission of the novel coronavirus occurred. In February, he joined the joint WHO-China mission to investigate the country’s timely response, and his lab has since reported a number of important findings, including the first confirmed SARS-CoV-2. reinfection.

Bitter lesson

“This is all an extension of our experience in 2003,” said Yuen. “We have nothing to brag about because we learned bitterly from the 2003 SARS.”

The emergence of an unknown virus to which no one has immunity has created a desperate need for effective treatments. Hong Kong doctors are using several experimental infusions including convalescent plasma – a mix of factors extracted from the blood of cured patients – and interferon, a protein of the immune system.

However, they are also using the antivirals ribavirin and Kaletra preliminary results released Thursday by a A study by the World Health Organization involving 11,266 patients in 30 countries found that patient deaths did not decrease. Yuen said he was not surprised by the WHO study results because the drugs were not given immediately after the patients became ill.

“No antivirals will work if given late,” he said. The drugs were also given individually, rather in combinations that could increase their impact, he said.

“Modestly active”

“We know that a drug is not good because all of these are very modestly active,” Yuen said. “We need early cocktail therapy to get good results.”

Giving a combination of ribavirin, Kaletra, and interferon to patients in the first week of illness reduced the time needed to clear the virus by six days and hospitalization by one week, compared to administering Kaletra alone, Yuen and colleagues. they demonstrated in a study in May.

The study, published in the medical journal The Lancet, recruited 127 patients from February 10 to March 20, more than half of the Covid-19 cases reported in Hong Kong during that period. Patients started treatment about five days after developing symptoms.

“With the memory of the 2003 SARS pandemic, most of the Covid-19 patients in Hong Kong have accepted antiviral treatment, which explains our high recruitment rate,” wrote Yuen and his team.

Sixteen years earlier, Yuen and many of the same group showed that a cocktail of ribavirin and Kaletra prevents serious illness and death in SARS patients. Saudi Arabia researchers said earlier this month that Kaletra administered with interferon improved survival in hospitalized patients with Middle Eastern respiratory syndrome, also caused by a coronavirus. The effect was greatest when treatment was started within a week of symptom onset, the authors said, noting “an important effect of treatment time on mortality.”

Interferon response

There is increasing evidence for early use of interferon in some patients. Successful studies published in the journal Science last month showed that about 14% of critically ill patients with Covid-19 have insufficient levels of the substance, which orchestrates defenses against viral pathogens.

Read more: Covid doctors find a turning point in life-threatening cases

If the body mounts a good Interferon response when viral load is low can limit subsequent viral replication and prevent dangerous inflammation, Yuen said. A late or delayed response of interferon to a high viral load, however, can cause severe lung damage. “This is really disastrous,” he said. This made interferon injections the “backbone” of early treatments.

Some doctors outside Hong Kong agree with Yuen’s approach. Early use of antivirals can suppress viral load and prevent the severe hyperinflammatory response that some patients develop in their second week of illness, said Richard Russell, respiratory physician and senior clinical researcher in the University’s Nuffield Department of Medicine. of Oxford, which is also conducting studies on patients with Covid-19.

Yuen’s strategy indicated how many existing antivirals can be has repurposed and collaborated with immunomodulatory drugs as a bridge until protective vaccines are available, said Steven Opal, a professor of clinical medicine at Brown University in Providence, Rhode Island.

Dexamethasone, a low-cost generic anti-inflammatory, was found in June that it reduced deaths by nearly a third among Covid-19 patients undergoing mechanical ventilation. The Oxford University study confirmed what Yuen had observed with SARS patients in 2003: that the drug could suppress the excessive immune reaction, sometimes called a cytokine storm, in deteriorating patients who showed signs of inflammation.

Dexamethasone and Gilead Science Inc.’s remdesivir helps patients with more advanced diseases, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “The only thing we need to do is get a lot more early infection interventions to prevent people from needing hospitalization,” he said in one. interview with the American Lung Association this month.

Antibodies specifically designed to fight coronavirus can also help, Fauci said. US President Donald Trump has credited Regeneron Pharmaceuticals Inc.’s antibody treatment with its recovery from infection.

Leprosy drug

Yuen’s team is also studying the potential of clofazimine, an inexpensive 50-year-old antimicrobial on the WHO List of Essential Leprosy Drugs. Studies in hamsters indicated that it could fight SARS-CoV-2 and prevent infection.

Hong Kong has taken swift and decisive action in response to Covid-19 due to the SARS legacy, Yuen said. He hopes others will learn from the current crisis about the need to prepare for and mitigate the risks of future pandemics.

“It is the 2003 experience that allowed us to walk another mile early,” said Yuen. “I hope that everyone in the world will learn this time that the emergence of infectious diseases is something that would happen more and more frequently. “

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