Hong Kong’s best pandemic doctor sees a way out of intensive care for thousands of Covid-1
After sober experiences 17 years ago with the outbreak of severe acute respiratory syndrome, Yuen Kwok-Yung advocates premature, aggressive hospitalization and treatment to minimize debilitating illness and death. Hong Kong 2% deaths from Covid-19 from Friday, well below global average emphasizes the approach.
Most treatments for SARS-CoV-2 are approved for use in seriously ill patients, in some cases supported by research that is still in doubt. Yuen, Henry Fok Professor of Infectious Diseases at the University of Hong Kong for 15 years, is admitthings with patients with minimal illness so that they can be isolated, monitored and treated if necessary.
“In places like the UK and the US, you are not usually if you have mild symptoms admitted to a hospital at all – you just have to wait at home until you feel very bad or you have shortness of breath, ”he explained to Zoom from his office. “But we basically admit all patients, even without much symptoms, entered the hospital for isolation. ”
The strategy reduces transmission in the community and allows patients to enter a clinical trial and receive experimental treatment shortly after developing a fever or showing other signs of a worsening disease, Yuen said. This is critical because the amount of SARS-CoV-2 virus or “viral load” in patients peaks around the time 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 doctor, has been at the forefront of the city’s response to infectious outbreaks for decades. In 1998, he and colleagues described the first dozen patients affected by the H5N1 strain of avian influenza. Five years later, they reported SARS in a patient visiting Hong Kong from Guangzhou, China.
Yuen recalls the trials and tribulations involved in rescuing patients from SARS, also caused by a coronavirus. Shortly afterwards, he identified “a time bomb ”of environmental and social conditions, which he predicted would inevitably result in more deadly coronavirus outbreaks.
This prediction came true in December, when the first cases of a mysterious pneumonia emerged in Wuhan, China’s Hubei province. Hong Kong responded to the new coronavirus by preparing tests and advising citizens on wearing masks.
Meanwhile, Yuen’s laboratory conducted research that led to first reported cluster among family members in which human-to-human transmission of the new coronavirus occurred. In February, he joined the WHO-China Joint Mission to investigate the country’s early response, and his laboratory has since reported a number of important findings, including the first confirmed SARS-CoV-2. re-infection.
“All of this is an extension of our experience in the year 2003,” Yuen said. “We have nothing to brag about because we learned bitterly from 2003 SARS.”
The appearance of an unknown virus against which no one has immunity created a desperate need for effective treatments. Hong Kong doctors use several experimental infusions inclusive convalescent plasma – a mixture of factors extracted from the recovered patient’s blood – and interferon, an immune system protein.
However, they also use the antiviral drugs ribavirin and Kaletra preliminary results published Thursday from a The World Health Organization-led trial involving 11,266 patients in 30 countries found that they did not reduce patient deaths. Yuen said he was not surprised by the results of the WHO study because the drugs were not administered shortly after patients became ill.
“No antiviral drug works if given late,” he said. The drugs were also administered individually, rather in combinations that could increase their impact, he said.
“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 the disease reduced the time to remove the virus by six days and shortened hospitalization by one week compared to giving Kaletra alone, Yuen and colleagues in a study in May.
The trial, published in The Lancet Medical Journal, recruited 127 patients from February 10 to March 20 – more than half of the Covid-19 cases reported in Hong Kong during this period. Patients began treatment about five days after developing symptoms.
“In memory of the 2003 SARS pandemic, most patients with Covid-19 in Hong Kong accepted antiviral therapy, which explained our high recruitment rate,” wrote Yuen and his team.
Sixteen years earlier, Yuen and many from the same group showed that a cocktail of ribavirin and Kaletra prevented serious illness and death in SARS patients. Saudi Arabia researchers said earlier this month that Kaletra provided with interferon improved survival in patients hospitalized with respiratory syndrome in the Middle East, 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 time for treatment effect on mortality.”
Evidence for early interferon use is increasing in some patients. Blockbuster studies published by the journal Science last month showed that approx. 14% of critical Covid-19 patients have inadequate levels of the drug, orchestrating defenses against viral pathogens.
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If the body mounts a good interferon response, when the viral load is low, it can limit subsequent viral replication and prevent dangerous inflammation, Yuen said. However, a late or delayed interferon response to a high viral load can trigger severe lung damage. “This is really catastrophic,” he said. Injections of interferon have been made as the “backbone” in early treatments.
Some doctors outside Hong Kong agree with Yuan’s approach. Using antiviral drugs early can suppress viral load and prevent the severe hyperinflammatory reaction that some patients develop in their second week of illness, said Richard Russell, a respirator and senior clinical researcher at the Nuffield Department of Medicine at the University of Oxford, who is also conducting studies in Covid-19 patients.
The Yu’s strategy has pointed out how several existing antiviral drugs can be rebuilt and partnered with immunomodulatory drugs as a bridge until protective vaccines become available, said Steven Opal, clinical professor of medicine at Brown University in Providence, Rhode Island.
Dexamethasone, a cheap, generic anti-inflammatory, var found in June to reduce deaths by nearly a third among Covid-19 patients receiving mechanical ventilation. The study from the University of Oxford confirmed what Yuen had observed with SARS patients in 2003: that the drug could dampen the immune overreaction, sometimes called a cytokine storm, in aggravated patients who showed signs of inflammation.
Dexamethasone and Gilead Science Inc.’s remdesivir help patients with more advanced disease, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “The only thing we really need is to get a lot more surgery for early infection to prevent people from continuing to need hospitalization,” he said in interview with the American Lung Association this month.
Antibodies specifically designed to fight coronavirus can also help, Fauci said. US President Donald Trump credited Regeneron Pharmaceuticals Inc.’s antibody treatment with his recovery from infection.
Yu’s team is also exploring the potential of clofazimin, a low-cost, 50-year-old antimicrobial drug that is on the WHO’s list of important drugs for leprosy. Studies in hamsters have shown that it can fight SARS-CoV-2 and prevent infection.
Hong Kong took swift and decisive action in response to Covid-19 because of SARS ‘legacy, Yuen said. He hopes others will learn from the current crisis about the need to prepare for and reduce the risk of future pandemics.
“It’s the 2003 experience that allowed us to walk another mile early,” Yuen said. “I hope that everyone in the world this time will learn that the new infectious disease is something that would happen more and more often. ”