February 21, 2022 Jane E. Dee

Advanced testing of the heart and lungs may reveal why some people who have recovered from COVID-19 still have shortness of breath. This testing is highly specialized and available only at a few sites nationwide, including at Yale.

Many patients continue to have ongoing symptoms well after their initial SARS-CoV-2 infection. Symptoms are not limited to those who required hospitalization or ICU admission and commonly occur in those with a history of mild COVID-19. Patients often have normal findings on tests such as lung function testing, chest X rays or CT scans. Physicians at the Winchester Center for Lung Disease (WCLD) have been exploring additional ways to evaluate patients with post-COVID-19 conditions, who are also known as “Long Haulers.”

The WCLD physicians, in collaboration with the Yale Pulmonary Vascular Disease Program (PVDP), use a technique called invasive cardiopulmonary exercise testing (iCPET) to identify the cause of shortness of breath in patients who have recovered from mild cases of COVID-19 but have persistent respiratory symptoms. These patients had undergone conventional testing, such as pulmonary function tests, echocardiogram, chest imaging, or standard exercise tests with either normal results or results that did not explain why they were still short of breath. Some also completed supervised out-patient rehabilitation programs with little success, said PVDP Director Inderjit Singh, MBChB, of the Pulmonary, Critical Care & Sleep Medicine (Yale-PCCSM) section in the Department of Internal Medicine at Yale School of Medicine.

Singh and colleagues, including PVDP Associate Director Phillip Joseph, MD, recently published original research in CHEST Journal in which they discussed how patients who have recovered from mild cases of COVID-19 without cardiopulmonary disease have a marked reduction in their peak oxygen consumption. Singh said this is because of impaired oxygen extraction by the muscles.

“What we found was that exercise limitation was reduced not because of abnormal functioning of the heart or lungs, but a limitation from an impaired ability to extract oxygen from the blood,” Joseph explained. “The heart and lungs were doing their job, the patients were breathing in oxygen and their hearts were delivering it to the exercising muscles, but there was an impaired ability to extract oxygen and use it.”

The study was done in collaboration with Brigham and Women’s Hospital in Boston. The iCPET testing was conducted on patients with persistent symptoms on average about 11 months after the initial infection. “The concern we have is that despite individuals having mild COVID, they still have persistent symptoms for almost a year. It is critical to understand why patients continue to have these limitations as many are extremely debilitated,” said Denyse D. Lutchmansingh, MBBS, who also contributed to the study.

The researchers also found that the patients were hyperventilating when they exercised. “Normally, your ventilation rate increases as you exercise,” Singh explained. “In these patients, we found that in the earlier stages of exercise they exhibited an exaggerated, or out of proportion response that gave them the sensation of shortness of breath. These two factors, in combination, contributed to their persistent shortness of breath, fatigue, and exercise intolerance.”

The team is planning more studies. “We’re drawing blood when the patients are at rest and at the peak of exercise to see if there’s any circulating biomarker that could explain our findings,” said Singh.

Other Yale collaborators include Paul M. Heerdt, MD, PhD; Marjorie Cullinan, RT; Mridu Gulati, MD; and Jennifer D. Possick, MD.

The Post-COVID Recovery Program at the Winchester Clinic for Lung Disease provides comprehensive evaluation of persistent respiratory symptoms related to prior SARS-CoV-2 infection (COVID-19).

The Yale Pulmonary Vascular Disease Program is a comprehensive center for the evaluation and treatment of pulmonary hypertension, acute and chronic pulmonary embolism, and unexplained shortness of breath. The program also participates in research in pulmonary hypertension with multiple, ongoing studies.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within YSM’s Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSM’s website, or follow them on Facebook and Twitter.