A multidisciplinary team of clinicians and researchers at Brigham and Women鈥檚 Hospital is leading clinical initiatives and research to better understand why some patients who recover from COVID-19 experience long-term health complications.
While it鈥檚 still unclear how many patients experience long-term symptoms, such as persistent flu-like symptoms, chronic fatigue and brain fog, following COVID-19 illness, some studies estimate that 10 percent of patients in the U.S. have ongoing symptoms.
鈥淭he Brigham is leading a number of clinical trials and research efforts to try and understand exactly what鈥檚 causing these long-term effects in some COVID-19 patients,鈥� said Jean Marie Connors, MD, a former hematologist at the Brigham. 鈥淭he Brigham has the depth of clinical expertise, the scientific knowledge and expert, multidisciplinary teams to help solve this difficult problem.鈥�
A variety of neurological health complications have been shown to persist in some patients who recover from COVID-19. Some patients who recover from their illness may continue to experience neuropsychiatric issues, including fatigue, 鈥榝uzzy brain,鈥� or confusion.
鈥淚n the current absence of direct therapies to treat long-term effects of COVID-19, we can offer the most up-to-date, evidenced-based care to manage patients鈥� symptoms,鈥� said , a Brigham neurologist. 鈥淔or neurological symptoms, this may include prescribing a medication for mental fog, physical therapy for mobility problems, or psychotherapy for individuals with psychiatric issues, such as anxiety or depression.鈥�
To understand the long-term neurological complications of COVID-19, Dr. Bhattacharyya is launching a study that will use advanced imaging to examine the brains of patients who鈥檝e recovered from COVID-19. The study will use the Brigham鈥檚 7 Tesla (7T) magnetic resonance imaging (MRI) scanner鈥攐ne of only a few in the country to be approved for clinical use鈥攁nd functional MRI (fMRI) to examine functioning and connectivity in the brain. The research could pinpoint differences in the brains of patients who develop long-term symptoms.
鈥淲e might discover a 鈥榙anger signal鈥� that is being sent to the brain in these patients who haven鈥檛 fully recovered from COVID-19,鈥� said Dr. Bhattacharyya. 鈥淚f we can find regions in the brain that are making these patients feel unwell, we might uncover ways to modulate these brain areas that could help these individuals feel better again.鈥�
Additionally, Brigham neurologists , and , have launched a trial to examine how COVID-19 influences the immune system in patients with multiple sclerosis (MS). The trial assesses the short and long-term outcomes of COVID-19 infection in MS patients and how certain immunotherapeutic treatments used to treat MS impact COVID-19 outcomes.
At the Brigham鈥檚 Division of Cardiovascular Medicine, several teams are leading trials that could answer pressing questions about the long-term effects of COVID-19 on the heart.
鈥淎bout a third of patients who are hospitalized for COVID-19 have evidence in their blood tests of injury to their hearts,鈥� said , a cardiologist at the Brigham. 鈥淲e understand from at the Brigham that this damage isn鈥檛 the result of the coronavirus directly infecting the heart. Rather, the heart damage is caused by the inflammation the virus triggers. This can then cause long-term heart problems, such as abnormal heart rhythms or heart attacks.鈥�
Currently, Dr. Libby is collaborating on a study investigating how COVID-19 affects the endothelial cells in the large and small blood vessels. He recently published a paper in the proposing that the major complications associated with COVID-19 likely involve altered endothelium functioning.
Some patients who recover from COVID-19 experience various long-term complications of the lungs. These individuals may have ongoing pulmonary dysfunction, like difficulty breathing and shortness of breath. Others never regain normal lung function.
鈥淪tudies have shown that many patients with COVID-19 have increased clotting activity that is driven by inflammation,鈥� said Dr. Connors. 鈥淚n COVID-19 patients, these blood clots can appear in the small vessels inside the lungs and heart as well as in the bigger pulmonary arteries and large veins in the legs. The clots can lead to scarring in the lungs, which can impair blood flow and reduce the capacity of the lungs.鈥�
, a pulmonologist and critical care physician at the Brigham, notes that most blood clotting can be resolved through the rapid use of anticoagulants. However, some major clotting events may lead to long-term pulmonary complications, like chronic shortness of breath, or even a pulmonary embolism, which can be fatal in some cases.
鈥淭here are some long-term effects that might result in patients who experienced low oxygen levels due to a severe case of COVID-19,鈥� said Dr. Lamas. 鈥淪ome long-term effects may also result from advanced treatment options, like being on a ventilator for weeks or months.鈥�
For patients with long-term smell disturbances, Brigham otolaryngologists , and , have recommended 鈥渙lfactory training鈥� to some patients. This technique has been used in other types of virus-associated smell loss. For several months, patients smell different odors (e.g., cinnamon, lemon) for five minutes in the morning and evening. The therapy aims to stimulate olfactory nerves and get them to regenerate.
鈥淚n previous research on smell loss from other cold viruses, patients are more likely to improve with olfactory training,鈥� said Dr. Bergmark. 鈥淲e need to study these patients further to understand whether olfactory training is an effective treatment for long-term smell loss. We鈥檙e currently doing that by collecting data on these patients and tracking them over time.鈥�
It鈥檚 not clear why long-term complications persist in some patients who recover from COVID-19. However, most experts agree that the long-term effects of COVID-19 are associated with the coronavirus鈥� ability to trigger a massive inflammatory response in some individuals.
鈥淭his inflammation, which results in blood clotting in blood vessels in the lungs, heart, brain, kidneys, and even legs,鈥� said Dr. Connors. 鈥淭his clotting can injure blood vessels, leading to scarring of these vessels and a wide range of long-term health complications.鈥�
Some research shows that people who have long-term effects had a moderate or severe case of COVID-19, whereas those who were asymptomatic or had a mild case didn鈥檛 develop long-term symptoms. That said, the opposite has also been observed.
鈥淚鈥檝e taken care of COVID-19 patients who were catastrophically sick in the ICU and have had remarkable recoveries, versus other patients who had a mild case, were never hospitalized, and are now dealing with ongoing, debilitating health problems,鈥� said Dr. Lamas. 鈥淲e don鈥檛 yet have an explanation for these observations.鈥�
At present, Dr. Lamas is caring for a patient who recovered from a mild case of COVID-19 in March. The patient hadn鈥檛 been hospitalized or received advanced care for the illness. And yet, this patient often feels 鈥減rofoundly fatigued,鈥� has heart palpitations and trouble concentrating.
鈥淎t this time, there鈥檚 nothing measurable on diagnostic tests that physicians can see to explain these patients鈥� lingering symptoms,鈥� said Dr. Lamas. 鈥淚t鈥檚 why some of these long-term patients have questioned whether their symptoms are 鈥榓ll in their head.鈥� That鈥檚 why we鈥檙e doing everything possible to better understand why these long-term symptoms are happening.鈥�
Some COVID-19 patients who stay in the Brigham鈥檚 ICU receive follow-up care in the post-ICU clinic. There, pulmonologists like Dr. Lamas and , along with mental health experts like , and Stacey Salomon, LICSW, care for patients with long-term complications. Some experience mental health conditions as a result of a long stay in the ICU. These include post-traumatic stress disorder (PTSD), anxiety or depression.
鈥淪ome patients in our post-ICU clinic had been very ill, were on a ventilator for weeks and had a high risk for death,鈥� said Dr. Lamas. 鈥淭hat said, we鈥檙e also seeing patients coming to the post-ICU clinic who weren鈥檛 hospitalized or admitted to the ICU. Some of these people are young, otherwise healthy and only had a mild case of COVID-19. And yet, now they have a constellation of long-term symptoms, such as fatigue, brain fog and an inability to concentrate.鈥�
While the U.S. Food and Drug Administration (FDA) has approved the antiviral drug , there still is no direct therapy that can treat the long-term symptoms of COVID-19. What if these long-term effects could be prevented?
In October, the Brigham launched a national clinical trial that aims to prevent the development of blood clots in patients with enduring symptoms of COVID-19. Dr. Connors is the study鈥檚 national principal investigator; is the trial鈥檚 chairman.
鈥淲e鈥檙e using an anticoagulant to prevent thrombosis and hopefully pulmonary microvascular thrombosis that鈥攁long with inflammation which can damage the lungs, heart and kidneys鈥攊s causing these long-term symptoms,鈥� said Dr. Connors. 鈥淲e believe this could be a promising way to prevent some patients鈥� long-term problems after recovery.鈥�
The Brigham team enrolled participants from around the country. These patients were newly diagnosed with COVID-19 and did not require hospitalization. During the study, patients either received an antiplatelet agent, an anti-coagulant or a placebo. .
鈥淲e still have so much to learn about the long-term health complications of COVID-19,鈥� said Dr. Lamas. 鈥淏ut I鈥檓 encouraged by the fact that these patients overcame their illness. Whenever I care for a critically ill patient, who was intubated, paralyzed and deeply sedated for weeks, it鈥檚 extraordinarily powerful to see them get better and go back to their lives.鈥�
