Clinical Research is a Major Gap in the Response to Emerging Respiratory Viral Infections

Identification: Uyeki, Timothy


Clinical Research is a Major Gap in the Response to Emerging Respiratory Viral Infections
Timothy Uyeki,
Influenza Division, CDC, Atlanta, GA
Background: Public health response to outbreaks of emerging respiratory viral infections focuses on identifying the pathogen, understanding the epidemiology, and control efforts. Nosocomial outbreaks of SARS and MERS have highlighted the importance of adherence to infection prevention and control measures. However, the inclusion of clinical research into outbreak response is not prioritized despite high mortality [e,g. 35% for MERS, 39% for A(H7N9)].    
Methods: The published literature and trials registered at were searched to identify data supporting clinical benefit, safety, and adverse effects of therapeutics, diagnostics, or other interventions for novel coronaviruses (SARS-CoV, MERS-CoV) or novel influenza A viruses (H5N1, H5N6, H7N9) associated with severe respiratory disease.
Results: No trials were conducted for SARS patients. Two phase 1 trials of MERS immunotherapeutics were implemented; two phase 2 trials of therapies for MERS patients were started, including convalescent plasma, and protease inhibitors plus interferon β-1b. No trials of diagnostic tests were conducted in novel coronavirus or novel influenza A virus patients. No trials of antivirals or other therapies were done for patients with H5N1, H5N6, or H7N9 virus infections. No trials assessed management of respiratory failure or the acute respiratory distress syndrome caused by SARS-CoV, MERS-CoV, or novel influenza A viruses. Observational studies of SARS reported increased risk of hemolytic anemia with ribavirin treatment and risk of avascular necrosis with high-dose corticosteroid treatment. An observational study reported that corticosteroid treatment of MERS was associated with delayed MERS-CoV RNA clearance. Observational studies in H7N9 patients reported that high-dose corticosteroids and delayed neuraminidase inhibitor treatment were associated with prolonged detection of H7N9 viral RNA, and high-dose corticosteroid treatment increased mortality risk.
Conclusions: Trials of interventions to optimize clinical management of MERS and H7N9 patients are urgently needed. Clinical research protocols with case record forms, rapid clinical data collection with rapid analyses and feedback, could be adapted and integrated into the emergency response to outbreaks of severe disease caused by emerging respiratory viruses.    


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