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Advancing Medical Research

Understanding Long-Haul COVID-19

Understanding Long-Haul COVID-19

Understanding Long-Haul COVID-19

Valentine’s Day broke Jen Singer’s heart.

On February 14, 2020, Jen, a 53-year-old writer from New Jersey, took a train from Newark to Boston to watch her college-age son run track. At the time, she didn’t think much about the fact that a person behind her coughed throughout the entire ride.

COVID-19 had been identified a few months earlier in Wuhan, China, but the novel coronavirus wasn’t yet seen as a threat in the United States. When Jen developed a low-grade fever and dry cough a few days later, she assumed she had a cold.

Her symptoms intensified a week later, while Jen was attending a writers’ retreat in Seattle. A local urgent care center tested her for influenza A and B, pneumonia, and strep throat; COVID-19 tests were not yet available. Jen’s tests came back negative and she flew home a few days later.

In late March, she developed shortness of breath while climbing the stairs in her home. The regular gym go-er — who kept pace with her sons while hiking in Sedona just a few months earlier — had to sit and rest between flights of stairs. When Jen consulted a physician via telemedicine in early April, the doctor recommended COVID-19 testing.

Three days later, Jen landed in the emergency room with pain beneath her ribs and shortness of breath. An electrocardiogram (EKG) revealed third-degree heart block, a heart rhythm abnormality that increases the risk of sudden cardiac death. Physicians implanted a pacemaker into Jen’s chest a few days later. The day after her surgery, she learned the results of her early April COVID-19 test: positive.

“I had no idea then that I’d joined a growing community of COVID survivors seeking answers for something entirely new to the planet,” Jen said. “Doctors are learning how to treat us as we go along and it is frustrating and frightening.”

Long-Haul COVID, Defined

Initially, healthcare providers thought that COVID-19, the disease caused by SARS-CoV-2, was an acute illness that typically resolved in about two weeks. However, as the pandemic has spread, it’s become evident that some people continue to experience symptoms weeks, and even months, after infection. According to the UK COVID Symptom Study, approximately 10% of people who’ve had COVID-19 experience prolonged symptoms.1 A study published in Obstetrics & Gynecology found that 25% pregnant or recently pregnant COVID-positive women had persistent symptoms eight weeks after symptom onset.2

Many of these patients call themselves “long-haulers.” According to a survey conducted by the Indiana University School of Medicine, fatigue, body aches, shortness of breath and difficulty concentrating are the most common long-haul symptoms, but some patients report heart palpitations, fever, continued loss of taste or smell, nausea or diarrhea, tremors, hair loss, and vision problems.3 Though their symptoms vary, long-haulers have one thing in common: frustration, and a desire for answers.

What Causes Long-Haul COVID-19?

Jen Singer’s medical history – she underwent multiple rounds of chemotherapy to treat non-Hodgkin’s lymphoma in 2007 -- increases her risk of heart problems, as one of the medications she received is known to damage the heart. But her cardiologist doesn’t think her heart block and subsequent heart failure was caused by cancer or chemotherapy. He believes that COVID-19 triggered cardiac sarcoidosis, a rare inflammatory condition that may be “triggered by an overreaction of the immune system after exposure to an infectious agent (such as bacteria or viruses),” according to the University of Ottawa Heart Institute.4

Jen Singer (left) with her 2 sons: Chris (middle), Nick (right)
Jen Singer (left) with her 2 sons: Chris (middle), Nick (right)

Continued inflammation and over-reactive immune responses to the virus are among the possible etiological explanations for long-haul COVID-19. A study published in a recent issue of Annals of the Rheumatic Diseases provides some support for this theory: researchers identified systemic autoantibodies (antibodies that mistakenly target the body’s own tissues) in nearly 70% of 29 hospitalized COVID-19 patients in the intensive care unit.5

Post-viral infection syndrome is another possible explanation. Physicians have long known that fatigue often persists months after viral infections; myalgic encephalomyelitis (also called chronic fatigue syndrome) can occur after infection with Ebola or the Epstein-Barr virus.6-7  Fatigue and continued respiratory symptoms are also common after viral respiratory infections, including influenza and severe acute respiratory syndrome, or SARS, another illness caused by a coronavirus.8-9

“There’s no question that viruses impact the body as a whole,” said Jay Purdy, MD, PhD, Vice President in anti-infectives at Pfizer. “The infection damages tissue and that tissue has to recover and regenerate and that’s not instantaneous.”

COVID-19 may also interfere with the function of the autonomic nervous system, which controls involuntary processes such as respiration, heart rate, blood pressure and digestion, at least in some patients.10 Some physicians think that inflammation of the vagus nerve, a key part of the autonomic nervous system, may explain why some COVID long-haulers experience fluctuations in heart rate, blood pressure and gastrointestinal function.11

Living in Limbo

The lingering effects of COVID-19 aren’t minimal. An August 2020 article published in The Journal of Infection noted that approximately 30% of previously employed patients who were hospitalized in France with COVID-19 were not back to work after three months.12 “There’s significant impact to patients, employers and families,” Dr. Purdy said.

Though physicians don’t yet have a standard treatment protocol for people suffering with long-haul COVID-19 symptoms — because symptoms vary and because there’s still so much to learn about this condition — doctors can help patients navigate uncertainty. “We can tell patients that nearly all cases of post-viral fatigue syndrome resolve over time,” Dr. Purdy said. “Unfortunately, we can’t quantify how long that will be and that’s frustrating for patients and physicians.”

When possible, physicians can and should offer treatment to relieve patients’ symptoms. Singer, for instance, is currently taking oral steroids to decrease the inflammation in her body and improve her heart function. Physicians can also support patients who are unable to return to work. “You can write a note that says this patient had presumptive COVID and is now suffering from post-COVID fatigue syndrome and they need to be excused or re-routed to other job responsibilities until they’re able to recover,” Dr. Purdy says.

Preventing Long-Haul COVID-19

To date, no one knows exactly why some people who contract COVID-19 go on to become long-haulers, while others recover relatively quickly. Some evidence suggests that older people are more likely to recover slowly, and one study of approximately 4000 people in the UK found that women were more than twice as likely as men to suffer COVID symptoms that lasted longer than a month.13 Women between the ages of 50 and 60 were the most likely to experience lasting symptoms, a finding that researchers said may be related to gender differences in immunological response.14 However, other possible explanations also exist.

Until researchers thoroughly understand the pathophysiology that triggers the development of long-haul COVID, prevention of initial COVID-19 infections is likely the best way to mitigate the physical, social, and societal strain of long-haul COVID-19. Wearing a mask in public and limiting exposure to others can decrease the risk of infection.

Vaccines may ultimately prove to be the most effective forms of long-haul COVID-19 prevention. “Once COVID-19 vaccines become available, my hope is that we as a globe can embrace vaccines and really knock down this infection so hopefully we don’t have patients in the ICU, we don’t have patients dying and we don’t have patients experiencing these long-term effects,” Dr. Purdy said.

SOURCES

  1. Greenhalgh, T., Knight, M., A’Court, C., Buxton, M., & Husain, L. (2020). Management of post-acute covid-19 in primary care. BMJ, m3026. doi: 10.1136/bmj.m3026. Retrieved from https://www.bmj.com/content/370/bmj.m3026
  2. Afshar, Y., Gaw, S., Flaherman, V., Chambers, B., Krakow, D., & Berghella, V. et al. (2020). Clinical Presentation of Coronavirus Disease 2019 (COVID-19) in Pregnant and Recently Pregnant People. Obstetrics & Gynecology, Publish Ahead of Print. doi: 10.1097/aog.0000000000004178. Retrieved from https://pubmed.ncbi.nlm.nih.gov/33027186/
  3. COVID-19 “Long-Hauler” Symptoms Survey Report. Indiana University School of Medicine and Survivor Corps. https://static1.squarespace.com/static/5e8b5f63562c031c16e36a93/t/5f459ef7798e8b6037fa6c57/1598398215120/2020+Survivor+Corps+COVID-19+%27Long+Hauler%27+Symptoms+Survey+Report+%28revised+July+25.4%29.pdf
  4. Cardiac Sarcoidosis. University of Ottawa Heart Institute. https://www.ottawaheart.ca/heart-condition/cardiac-sarcoidosis#:~:text=Cardiac%20sarcoidosis%20is%20a%20rare%20disease%20in%20which%20clusters%20of,the%20tissue%20of%20the%20heart
  5. Vlachoyiannopoulos, P., Magira, E., Alexopoulos, H., Jahaj, E., Theophilopoulou, K., Kotanidou, A., & Tzioufas, A. (2020). Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Annals Of The Rheumatic Diseases, annrheumdis-2020-218009. doi: 10.1136/annrheumdis-2020-218009. Retrieved from https://ard.bmj.com/content/early/2020/06/24/annrheumdis-2020-218009.full
  6. Scott, J., & Semple, M. (2017). Ebola virus disease sequelae: a challenge that is not going away. The Lancet Infectious Diseases, 17(5), 470-471. doi: 10.1016/s1473-3099(17)30027-0. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818139/
  7. Rasa, S., Nora-Krukle, Z., Henning, N., Eliassen, E., Shikova, E., & Harrer, T. et al. (2018). Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Journal Of Translational Medicine, 16(1). doi: 10.1186/s12967-018-1644-y. Retrieved from https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y
  8. Influenza. Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/influenza
  9. NGAI, J., KO, F., NG, S., TO, K., TONG, M., & HUI, D. (2010). The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology, 15(3), 543-550. doi: 10.1111/j.1440-1843.2010.01720.x. Retrieved from https://onlinelibrary.wiley.com/doi/full/10.1111/j.1440-1843.2010.01720.x
  10. Rubin, R. (2020). As Their Numbers Grow, COVID-19 “Long Haulers” Stump Experts. JAMA, 324(14), 1381. doi: 10.1001/jama.2020.17709. Retrieved from https://jamanetwork.com/journals/jama/fullarticle/2771111
  11. Doctors Begin to Crack COVID’s Mysterious Long-Term Effects. The Wall Street Journal. https://www.wsj.com/articles/doctors-begin-to-crack-covids-mysterious-long-term-effects-11604252961
  12. Garrigues, E., Janvier, P., Kherabi, Y., Le Bot, A., Hamon, A., & Gouze, H. et al. (2020). Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. Journal Of Infection. doi: 10.1016/j.jinf.2020.08.029. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445491/
  13. Sudre, C., Murray, B., Varsavsky, T., Graham, M., Penfold, R., & Bowyer, R. et al. (2020). Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App. doi: 10.1101/2020.10.19.20214494. Retrieved from https://www.medrxiv.org/content/10.1101/2020.10.19.20214494v1
  14. Sudre, C., Murray, B., Varsavsky, T., Graham, M., Penfold, R., & Bowyer, R. et al. (2020). Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App. doi: 10.1101/2020.10.19.20214494. Retrieved from https://www.medrxiv.org/content/10.1101/2020.10.19.20214494v1

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