Hong Kong’s leading pandemic doctor has found a way out of intensive care for thousands of Covid-19 patients: preventing them from entering first.
After intense experiences 17 years ago with the outbreak of acute respiratory respiratory syndrome, Yuen Kwok-Yung promotes early, aggressive hospitalization and treatment to reduce destructive disease and death. Hong Kong’s 2% Covid-19 mortality rate on Friday, lower than global average, lends weight to strategy.
Most therapies for SARS-CoV-2 are approved for use in patients with severe disease, in some cases supported by research still in question. Yuen, Henry Fok’s professor of infectious diseases at the University of Hong Kong for 15 years, is amininpatients with minimal pain so they can be isolated, monitored and treated as needed.
“In places like the UK and US, usually if you have mild symptoms, no amininted to a hospital at all – you just wait at home until you feel very bad or you have shortness of breath, ”he explained over Zoom from his office. “But we really are aminin any patient, even without many symptoms, to the hospital to be isolated. “
The approach reduces community delivery, and allows patients to enter a clinical trial and receive experimental treatment immediately after having a fever or showing other signs of worsening disease, Yuen said. That is critical because the amount of SARS-CoV-2 virus or “viral load” in patients increases around the time symptoms appear – such as the flu.
Microbiologist, Surgeon, Physician
Yuen, who graduated from the University of Hong Kong in 1981 and with the rare distinction of being a microbiologist, surgeon and physician, has spearheaded the city’s response to infectious outbreaks over the decades. In 1998, he and colleagues described the first dozen patients suffering from H5N1 strain of avian influenza. Five years later, they SARS reported to a patient visiting Hong Kong from Guangzhou, China.
Yuen recalls the trial and error involved in saving patients from SARS, also caused by a coronavirus. Soon, he recognized “a time bomb ”of environmental and social conditions he predicted would inevitably result in a more deadly outbreak of coronavirus.
That prophecy was fulfilled in December, when the first cases of a mysterious pneumonia was found in Wuhan, China’s Hubei province. Hong Kong responded to the novel coronavirus by preparing tests and advising citizens to wear masks.
In the meantime, Yuen’s lab is conducting research that leads to first reported cluster of family members where human transmission of the new coronavirus took place. In February, he joined the WHO-China Joint Mission to investigate the country’s early response and his lab reported a number of important findings, including the first confirmed SARS-CoV-2 re-statement
“All of this is an extension of our 2003 experience,” Yuen said. “We have nothing to brag about because we have learned bitterly since 2003 SARS.”
The appearance of an unknown virus in which no one has immunity creates a desperate need for effective treatment. Hong Kong doctors use many experimental infusions including convalescent plasma – a mixture of factors derived from patients’ recovered blood – and interferon, a protein of the immune-system.
They also use the antivirals ribavirin and Kaletra, though preliminary results released Thursday from a A World Health Organization-led trial involving 11,266 patients in 30 countries found that they did not reduce the death toll. Yuen said he was not surprised by the results of the WHO study because the drugs were not given immediately after patients became ill.
“No antiviral will work if given too late,” he said. The drugs are also administered alone, in combinations that can add to their effect, he said.
“We know that one drug is not good because they are all very modest 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 reduces the time to clean the virus by six days and shortens hospitalization by one week, compared to giving Kaletra alone, Yuen showed 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 at the time. Treatment began with patients about five days after developing symptoms.
“In memory of the SARS pandemic in 2003, most patients with Covid-19 in Hong Kong accepted antiviral treatment, which explained our high recruitment rate,” Yuen and his team wrote.
Sixteen years before this, Yuen and many from the same group showed that a cocktail of ribavirin and Kaletra prevented serious illness and death in SARS patients. Saudi Arabian researchers said earlier this month that Kaletra was given interferon improved survival in patients hospitalized with Middle East respiratory syndrome, also caused by a coronavirus. The effect is greatest when treatment begins within a week of symptom onset, the authors said, citing “an important time-to-treatment effect on mortality.
Evidence is mounting for early use of interferon in some patients. Blockbuster studies published by the journal Science last month showed that about 14% of critically ill Covid-19 patients have insufficient substance levels, burning defenses against viral pathogens.
Read More: Covid Doctors Find a Turning Point in Life-Threatening Cases
If the body is mounted well interferon response when viral load is low, it can limit subsequent viral replication and prevent dangerous inflammation, Yuen said. A late or delayed interferon response to a high viral load, though, can trigger severe lung damage. “It will definitely be a disaster,” he said. These interferon injections are made “spine” of early treatment.
Some doctors outside Hong Kong agree with Yuen’s approach. Using antivirals early can suppress viral load and prevent the hyper-inflammatory response some patients develop in their second week of illness, said Richard Russell, a respiratory physician and senior clinical researcher at Nuffield Department of Medicine at the University of Oxford, which also conducts studies on Covid-19 patients.
Yuen’s approach points to how many antiviruses already exist repurposed and partnered with drugs that modulate the immune system as a bridge until protective vaccines are used, said Steven Opal, professor of clinical medicine at Brown University in Providence, Rhode Island.
Dexamethasone, a cheap, common anti-inflammatory, is found in June to reduce the deaths of nearly one-third of Covid-19 patients receiving mechanical ventilation. A study at Oxford University confirms what Yuen observed in SARS patients in 2003: that the drug can eliminate excess resistance, sometimes called a cytokine storm, to the worsening patient showing signs of inflammation.
Dexamethasone at Gilead Science Inc. Remdesivir can help patients with more advanced disease, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “One thing we really need to do is get a lot of interventions for early infection to prevent people from going into need of hospitalization,” he told a interview with the American Lung Association this month.
Antibodies specifically designed to fight coronavirus can also help, Fauci said. US President Donald Trump is credited Antibody treatment by Regeneron Pharmaceuticals Inc. in his recovery from infection.
Yuen’s team is also investigating the potential of clofazimine, a cheap, 50-year-old antimicrobial that is on the WHO list of essential drugs for leprosy. Studies in hamsters have indicated that it can fight SARS-CoV-2 and prevent infection.
Hong Kong has taken swift and decisive action in response to Covid-19 due to the legacy of SARS, 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 was the 2003 experience that allowed us to walk a mile early,” Yuen said. “I am hope that everyone in the world will know by this time that emerging infectious disease is something that happens more often. “