Bruce Levy

Researchers around the world are beginning to document the array of complex symptoms that persist for many patients after they recover from their initial infection with the SARS-CoV-2 virus. The Brigham recently established a COVID Recovery Center (CRC) to centralize, streamline and advance clinical care for these patients. “Long-hauler COVID,” or post-acute sequelae of SARS-CoV-2 (PASC), are not yet well understood. By combining its strengths in research and clinical care, the Brigham seeks to advance global efforts to elucidate and address the physical and psychological impacts of this new disease.

Bruce Levy, MD, chief of the Pulmonary and Critical Care Medicine Division, is the medical director of the Lung Center that houses the new CRC. He sat down with CRN to discuss contemporary understandings of PASC and the efforts underway to care for patients experiencing it.

Patients who have recovered from COVID-19 can experience wide-ranging lingering symptoms. What areas of research appear to be most pressing?

BL: There are five domains of scientific investigation that we’re thinking are going to be of highest priority to patients. These include research on the social determinants of patients’ health, how patients respond immunologically to the viral infection, and what the pulmonary, vascular and neurological/psychological consequences of the infection are.

In particular, we’re looking at how the infection leaves its mark on the lungs, which can remain injured or inflamed. Some people have persistent lung involvement and many more have trouble breathing, with symptoms of coughing and shortness of breath. The virus seems to have a predilection for the small vessels in the body, so this can involve injury to highly vascular organs like the heart, lung and kidneys. There are gastrointestinal issues as well, and problems with smell, diet, and taste. Then there’s a broad area of fundamental research that needs to occur related to brain health: research on “brain fog,” headache, cognition, mood, anxiety, depression, peripheral neurological problems, fatigue, sleep disorders and more.

What are some of the hypotheses circulating on the causes of these long-term symptoms?

BL: Some of the clinical patterns that we’re seeing in PASC may relate to the consequences of the virus itself; some may relate to the body’s immune response to the virus; and others may relate to complications of organ injury in the setting of the overarching response to infection. Some people have a constellation of symptoms that overlap with what’s called post-intensive care syndrome, a condition that sometimes affects patients who have been treated in an intensive care unit (ICU). But there are many COVID-19 patients who were not in the ICU or even hospitalized who have developed PASC symptoms.

Underlying comorbidities and age-related changes in our bodies also appear to be important factors influencing the extent of patients’ recovery from COVID-19. Lastly, the social determinants of health have a big impact on how this syndrome presents and progresses, and we’re still learning about these important risk factors for PASC.

In the early weeks of the CRC’s operation, have any patterns emerged in the types of issues patients are encountering?

BL: In its initial weeks of operation, the CRC has been seeing patients most commonly with pulmonary symptoms, but the range of systems is broad – from head to toe – with symptoms related to brain health the second most common seen to date in the CRC. Still, we need more information on what this syndrome looks like across the population, and that’s why the National Institutes of Health is sponsoring the development of a large observational cohort across the nation to try to gather additional information on the clinical spectrum of PASC.

Is a syndrome like PASC unique to COVID-19 or have some of these symptoms been observed after other viral infections?

BL: Some of these symptoms, but maybe not all, have been seen after other viruses. For example, lung injury, fibrosis and scarring were seen after SARS, a related coronavirus infection identified in 2003. Chronic fatigue syndrome has some shared features with PASC and is thought to stem from a post-acute infection from other pathogens. Some of the PASC symptoms have also been reported post-influenza. PASC may relate to the shared pathophysiology of a post-infectious or post-viral syndrome, writ large, and it may have some shared features with symptoms that follow other infections.

Because we care for many patients that receive immune modulatory therapies for cancer, after transplant or for systemic diseases of chronic inflammation, it is important to distinguish between symptoms that are truly post-acute and symptoms of a persistent COVID-19 infection, which a minority of patients may experience when they haven’t yet cleared the virus even four to six weeks after being infected. Persistence might require more directed antiviral-therapy, and at the CRC we’re seeing those patients in conjunction with our infectious disease colleagues.

How is the CRC positioned to respond to the challenges that patients with post-COVID-19 symptoms face?

BL: Many of the symptoms that patients with PASC are experiencing are non-specific, and routine screening, laboratory imaging and functional testing frequently does not identify the origin of the symptoms. Patients and primary care providers are searching for answers and help addressing why the acute SARS-CoV-2 infection fails to completely resolve. The CRC was created as a multidisciplinary center to help coordinate care for those with PASC afflicted by a range of symptoms. In a patient’s initial visit to the clinic, they are evaluated by one or more subspecialty providers based on their symptoms and the CRC is resourced to help the PASC patients navigate our health system for clinical evaluation, advanced testing and the development of care plans.

We are also setting up a monthly, multidisciplinary, patient-focused clinical conference in collaboration with our colleagues interested in PASC at Massachusetts General Hospital, in which we will share cases that we think are instructional or believe are important in the care of these patients.  PASC is a new entity, and there are not necessarily clear medicinal therapies that are available yet. Through the center, in addition to newly emerging therapies, we plan to support our patients through social work and patient support groups, making sure they know that they’re not alone in this journey. Importantly, we are also planning in the CRC to provide patients an opportunity to participate in urgently needed PASC research so we can develop a better understanding of the mechanisms underlying PASC and new therapeutic approaches to promote the resolution of COVID-19 and PASC. Now, one year into the COVID-19 pandemic, PASC is another newly characterized illness and we’re just starting to scratch the surface of its impact.

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