Coping With the “Long-Haul” of COVID-19: More Research, Treatments Needed

Chloroquine and Hydroxychloroquine maybe an alternative to fight against Covid-19 while scientists are doing research for a vaccine
Patients with "long COVID" have described a wide array of ongoing, unpredictable impairments in physical, cognitive, emotional, and occupational functioning.

As the 1-year mark of the COVID-19 pandemic approaches, individuals with enduring impairment have become a focus of increasing attention. The term “long COVID” has been used to refer to the estimated 10% of patients with persistent symptoms lasting several weeks or more following acute infection.1

These COVID-19 “long haulers,” including cases ranging from mild to severe, have described a wide array of ongoing, unpredictable impairments in physical, cognitive, emotional, and occupational functioning.1 Many patients experience serious effects; for example, preliminary study results suggest that roughly two-thirds of patients incur organ damage.2 A group of clinicians in the United Kingdom with long COVID have reported new-onset diabetes, cardiovascular disease, and interstitial lung disease, among other effects and conditions, since the time of their infection. 2

Recovering From Long COVID-19

In an observational cohort study published in January 2021 in the Journal of General Internal Medicine, researchers from the New York University Grossman School of Medicine in New York City examined the nature of long-term COVID-19 recovery in patients who had been hospitalized with severe symptoms. They administered validated survey instruments to assess the health status of adult patients, both before and after infection, who had required at least 6 liters of oxygen on admission and were discharged a median of 37 days prior to study enrollment.3

Of the 152 patients who completed the survey (median age, 62 years; 37% women), 74% had experienced shortness of breath within the previous week, according to scores on the PROMIS® Dyspnea Characteristics instrument (median score 3 out of 10 [IQR, 0-5]) compared with 31% prior to COVID-19 infection [(0; IQR, 0-1), P <.001]. In addition, 35.1% of patients who were not oxygen-dependent prior to infection required home oxygen after discharge, and 13.5% of these individuals remained oxygen-dependent at the time of the study survey.3

On the PROMIS Global Health-10 instrument, participants’ general health scores were worse approximately 1 month after infection (3 out of 5; interquartile range [IQR], 2-4) compared with baseline (4; IQR, 3-5), and their summary t scores in the physical and mental health domains declined from 54.3 (standard deviation [SD], 9.3) and 54.3 (SD, 7.8) to 43.8 (SD, 9.3) and 47.3 (SD, 9.3), respectively (P <.001 for both).3

“Patients with severe COVID-19 disease typically experience sequelae affecting their respiratory status, physical health, and mental health for at least several weeks after hospital discharge,” the authors concluded.3

Despite these proliferating reports, individuals with long COVID — including many healthcare providers who have collectively written about the topic — have stated that their concerns were often doubted or dismissed by their clinicians.1,2 Numerous post-COVID-19 clinics have begun to emerge across the country and world with the aim of providing specialized, multidisciplinary care to these patients.4-6

Long-Term Effects of Influenza vs Long COVID

The recognition of long-term effects of COVID-19 has also renewed interest in previous reports describing the long-term effects of influenza infection.7 For example, a 2017 study of 56 influenza A (H7N9) survivors found that “pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS [acute respiratory distress syndrome], however long-term lung disability and psychological impairment … persisted at 2 years after discharge from the hospital.”8

We interviewed the following experts to learn more about long COVID, including similarities and differences compared with the long-term effects observed in patients with influenza: Christian Sandrock, MD, MPH, FCCP, director of critical care, professor of medicine, and vice chair for quality and safety at the University of California, Davis, in Sacramento; and Himali Weerahandi, MD, MPH, assistant professor in the department of medicine and the department of population health at NYU Grossman School of Medicine, and coauthor of the 2021 study described above.3

What is known or suspected thus far about the long-term effects of COVID-19?

Dr Sandrock: We know that some people have symptoms for a long time, and some will have them for about 180 days or more.1,2 It appears that the risk factors for experiencing these syndromes are an ICU [intensive care unit] stay, prior depression, prior anxiety, and obesity. Other than an ICU stay with mechanical ventilation, the severity of illness does not portend that a patient will have persistent symptoms.

Dr Weerahandi: Our studies, along with others, demonstrate that some survivors of severe COVID-19 may experience a constellation of symptoms including shortness of breath, fatigue, and cognitive issues that can last weeks and even months after the acute illness. It is unclear whether these sequelae are related to the virus SARS-CoV-2 itself, a postviral syndrome, or complications related to hospitalization such as deconditioning from prolonged hospital stays or post-intensive care syndrome.

How do these effects appear to compare to the long-term effects of influenza?

Dr Sandrock: The long-term effects are very different between influenza and COVID-19. In COVID-19, effects may include fatigue, lethargy, brain fog, chest pain, hypoxemia, skin changes, depression, anxiety, and loss of smell.1 Influenza does not have a long-term component unless a patient ends up in the ICU, and then the overlap of mental health disease and shortness of breath is the same.

However, it is much higher in COVID-19 — approximately 50% based on available data.9,10 Now, for influenza, this is harder — we have run numbers and feel that 0.5% of patients with influenza have complications. Regarding long-term complications, it is more of a guess, sadly. We do not have solid numbers for influenza, but they are much less given the lower rates of severe complications.

Dr Weerahandi: In a small number of people, influenza can cause serious illness, including ARDS. Some patients who have had ARDS can experience respiratory and psychological sequelae even more than a year after their illness. However, most patients who have been infected with influenza do not experience long-term effects such as these, because most of these patients do not experience the degree of respiratory failure that we are seeing with COVID-19. COVID-19 is much more likely to cause ARDS than influenza and has impacted so many people this year that we should be very concerned about the long-term effects of COVID-19.

Dr Sandrock, how are COVID “long haulers” being cared for at the UC Davis Post-COVID-19 Clinic

Dr Sandrock: We are doing testing and documenting the deficits, and then we develop a comprehensive plan of recovery that includes sleep improvement, mental health support, nutrition, anticoagulation if needed, and neuropsychiatric testing. We have a large group, from ENT [ear/nose/throat] to neurology, available to support patients.

But the main thing is that we treat this as a real syndrome and affirm that people are not “crazy” and “just need more rest.”  Treatment is still unknown overall, but it is clear that the approach should be multifaceted and will need further research.

What are some of the key recommendations for clinicians treating these patients? 

Dr Weerahandi: Most expert opinion-based recommendations on patients with “long COVID-19” recommend medical evaluation to potentially identify a more specific cause of this syndrome and addressing the specific symptoms patients are experiencing. For example, patients with persistent shortness of breath may need to be referred to pulmonary rehabilitation, and patients experiencing depression or anxiety may need referral to mental health services.

What are the most pressing remaining needs in terms of research or policy?

Dr Sandrock: We need to figure out what pathology drives long-term symptoms, who is at risk, what treatments work, and what the best treatments are for all the different effects, such as brain fog and hypoxemia.

Dr Weerahandi: The next step is to develop and test tailored rehabilitation interventions so we can build an evidence-based approach to facilitate these patients’ functional recovery. In addition, policy to support these patients during this time of compromised physical and mental health is important to consider. Last year, The Families First Coronavirus Response Act created an emergency paid sick leave program in states that previously had no paid sick leave requirement.11

However, while other parts of this particular legislation have been extended to March of this year, the requirement that employers provide sick leave to their employees expired at the end of December. Right now, the Biden administration has introduced a new large piece of legislation, the American Rescue Plan.12 Part of this legislation includes plans to reinstate this requirement and expand paid sick and family leave to the end of September.


1. Ladds E, Rushforth A, Wieringa S, et al. Persistent symptoms after Covid-19: qualitative study of 114 “long Covid” patients and draft quality principles for services. BMC Health Serv Res. 2020;20(1):1144. doi:10.1186/s12913-020-06001-y

2. Gorna R, MacDermott N, Rayner C, et al. Long COVID guidelines need to reflect lived experience. Lancet. 2021;397(10273):455-457.

3. Weerahandi H, Hochman KA, Simon E, et al. Post-discharge health status and symptoms in patients with severe COVID-19. J Gen Intern Med. Published online January 14, 2021. doi:10.1007/s11606-020-06338-4

4. Weiner S. Post-COVID-19 clinics help survivors recover. Association of American Medical Colleges. Published August 25, 2020. Accessed February 26, 2021.

5. Loria K. People with lingering coronavirus symptoms are turning to post-COVID clinics. Consumer Reports. Published January 28, 2021. Accessed February 26, 2021.

6. Lutchmansingh DD, Knauert MP, Antin-Ozerkis DE, et al. A clinic blueprint for post-coronavirus disease 2019 RECOVERY: learning from the past, looking to the future. Chest. Published online November 4, 2020. doi:10.1016/j.chest.2020.10.067

7. Honigsbaum M, Krishnan L. Taking pandemic sequelae seriously: from the Russian influenza to COVID-19 long-haulers. Lancet. 2020;396(10260):1389-1391.

8. Chen J, Wu J, Hao S, et al. Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection. Sci Rep. 2017;7(1):17275.

9. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232.

10. Logue JK, Franko NM, McCulloch DJ, et al. Sequelae in adults at 6 months after COVID-19 infection. JAMA Netw Open. Published online February 19, 2021. doi:10.1001/jamanetworkopen.2021.0830

11. US Department of Labor. Families First Coronavirus Response Act: Employer Paid Leave Requirements. Accessed online February 22, 2021.

12. The White House. President Biden Announces American Rescue Plan. Accessed online February 22, 2021.