Frontline respiratory care drives disease innovation

As Omicron, a fast-spreading variant of the virus behind COVID-19 started to sweep the world in late 2021, doctors and researchers at China’s Beijing Chao-Yang Hospital braced themselves for the coming waves of infected patients.

“As a national key specialist facility, we have the most complete respiratory support technology system in China,” says Zhaohui Tong, a doctor and vice-president of Beijing Chao-Yang Hospital.

Teams of researchers led by Tong, and hospital colleague and pharmacist Zhuoling An, had significant experience in critical care of patients with respiratory diseases. So they rapidly identified the risk factors that might mean patients infected with Omicron would become seriously ill¹.

Soon, the team was guiding hospitals across China in the best way to identify and manage critically ill patients infected with the deadly strain.

The SARS-CoV-2 virus behind COVID-19 is just one of many possible causes for acute respiratory distress syndrome, a life-threatening condition that Tong and his colleagues routinely treat.

“This condition has a high mortality rate, so timely and effective treatment is crucial for survival,” explains Tong, who also leads the Beijing Institute of Respiratory Diseases, a research institute housed at Beijing Chao-Yang Hospital.

Beyond respiratory illnesses, the hospital is also committed to addressing emerging challenges in healthcare such as microbial resistance to antibiotics. “Beijing Chao-Yang Hospital is actively exploring research directions aimed at improving quality of life and providing a scientific basis for developing new standards of care,” says Tong.

A long fight

As a veteran of the medical response to the 2003 SARS epidemic, and one of China’s leading respiratory care physicians, Tong was quickly called to the frontline when COVID-19 first emerged in Wuhan in late 2019. The initial fight against the new virus was an intensive, all-consuming experience for Tong, who rarely did anything but focus on work over that time.

During that period, Tong’s Chao-Yang team adapted the use of extracorporeal membrane oxygenation (ECMO) for seriously ill patients. This technique oxygenates blood without the use of a person’s lungs. A pump draws blood outside the body into artificial lungs, or a machine called a membrane oxygenator, then returns oxygenated blood into the body. Bypassing the lungs allows a patient to rest and minimizes the risk of ventilator-associated lung injury, Tong says.

At the height of the pandemic, Tong’s team — along with collaborators led by critical care doctor, Haibo Qiu, at Southeast University in Nanjing — also identified acute kidney injury (AKI) as an unexpectedly common severe complication of COVID-19². In their study, of 671 patients admitted to 19 hospitals in China in January and February 2020, 39% developed AKI, with almost 75% cases ending in death.

As the number of COVID-19 cases skyrocketed, and more data emerged, Tong’s team performed a larger meta-analysis³ of around 13,000 patients and found an average 17% incidence of AKI. Up to 5% of patients with AKI later required kidney replacements, they also found. Despite those numbers, aspects of AKI remain a mystery, Tong says. “The data suggests that the incidence of AKI in hospitalized patients decreased during the current pandemic, but the reasons for this are unknown.”

Now, four years after the onset of the pandemic, Tong’s team is turning attention to long COVID, a condition in which patients experience symptoms, such as extreme fatigue or heart palpitations weeks or months after the virus is no longer detectable in the body. Long COVID now afflicts about 65 million individuals worldwide⁴.

“Given that patients still suffer from organ dysfunction, it is necessary to develop appropriate rehabilitation intervention strategies to promote patients’ recovery and help improve their quality of life,” Tong says.

Developing remedies

Tong, An, and their colleagues have also helped conduct tests on an antiviral oral drug called Azvudine⁵ for its efficacy against SARS CoV-2. Azvudine inhibits the replication of viral RNA and received approval from the Chinese National Medical Products Administration in July 2021 to treat HIV-1 infections in adults. In July 2022, it received conditional approval in China for the treatment of COVID-19.

The researchers conducted a retrospective study comparing the recovery of 317 COVID-infected patients who were treated with Azvudine, to another 487 patients who received only supportive care.

Beyond COVID-19, Tong and his team are also investigating another deadly respiratory disease, pneumocystis pneumonia⁶, a fungal infection of the lungs. It is one of the leading causes of death worldwide of people who are immunocompromised, such as people who have HIV or are on immune-suppressant drugs following an organ transplant.

To develop effective remedies, Tong’s team is working with another colleague, Kan Zhai, a pulmonary medicine researcher, to look into how the immune system responds when exposed to the infection. Using single-cell sequencing techniques, the researchers dissected how T cells, a key component of the immune system, proliferated and changed in pneumonia-infected mice.

Intelligent healthcare

Attuned to advances in medical research, Tong and his team are now preparing for “the era of intelligent healthcare,” Tong says. These include techniques that use artificial intelligence to help doctors with diagnosis or surgery, or to create personalized treatment plans. One research programme at Beijing Chao-Yang Hospital is developing predictive models based on genomics, epigenetics and other multi-omics data to help predict the risk of disease onset and progression.

Looking to the future, Tong sees larger challenges emerging in healthcare that will require international collaboration to solve. One is the issue of antibiotic resistance. “There is a global need to strengthen the monitoring and control of antibiotic resistance, and to promote the concept of rational use of antibiotics,” Tong says.

“For a clinician, it’s difficult to balance scientific research with clinical work,” Tong says. But, he argues, the Beijing Chao-Yang Hospital’s approach of conducting research in response to challenges seen in the clinic is the best way to improve the diagnosis and treatment of any disease.

This feature was supported by Jiangsu Hengrui.