Understanding Long-Term COVID-19 Symptoms and Enhancing Recovery
Posted on by Walter J. Koroshetz, M.D., National Institute of Neurological Disorders and Stroke
We are in the third year of the COVID-19 pandemic, and across the world, most restrictions have lifted, and society is trying to get back to “normal.” But for many people—potentially millions globally—there is no getting back to normal just yet.
They are still living with the long-term effects of a COVID-19 infection, known as the post-acute sequelae of SARS-CoV-2 infection (PASC), including Long COVID. These people continue to experience debilitating fatigue, shortness of breath, pain, difficulty sleeping, racing heart rate, exercise intolerance, gastrointestinal and other symptoms, as well as cognitive problems that make it difficult to perform at work or school.
This is a public health issue that is in desperate need of answers. Research is essential to address the many puzzling aspects of Long COVID and guide us to effective responses that protect the nation’s long-term health.
For the past two years, NIH’s National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Allergy and Infectious Diseases (NIAID), and my National Institute of Neurological Disorders and Stroke (NINDS) along with several other NIH institutes and the office of the NIH Director, have been leading NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative, a national research program to understand PASC.
The initiative studies core questions such as why COVID-19 infections can have lingering effects, why new symptoms may develop, and what is the impact of SARS-CoV-2, the virus that causes COVID-19, on other diseases and conditions? Answering these fundamental questions will help to determine the underlying biologic basis of Long COVID. The answers will also help to tell us who is at risk for Long COVID and identify therapies to prevent or treat the condition.
The RECOVER initiative’s wide scope of research is also unprecedented. It is needed because Long COVID is so complex, and history indicates that similar post infectious conditions have defied definitive explanation or effective treatment. Indeed, those experiencing Long COVID report varying symptoms, making it highly unlikely that a single therapy will work for everyone, underscoring the need to pursue multiple therapeutic strategies.
To understand Long COVID fully, hundreds of RECOVER investigators are recruiting more than 17,000 adults (including pregnant people) and more than 18,000 children to take part in cohort studies. Hundreds of enrolling sites have been set up across the country. An autopsy research cohort will also provide further insight into how COVID-19 affects the body’s organs and tissues.
In addition, researchers will analyze electronic health records from millions of people to understand how Long COVID and its symptoms change over time. The RECOVER initiative is also utilizing consistent research protocols across all the study sites. The protocols have been carefully developed with input from patients and advocates, and they are designed to allow for consistent data collection, improve data sharing, and help to accelerate the pace of research.
From the very beginning, people suffering from Long COVID have been our partners in RECOVER. Patients and advocates have contributed important perspectives and provided valuable input into the master protocols and research plans.
Now, with RECOVER underway, individuals with Long COVID, their caregivers, and community members continue to serve a critical role in the Initiative. The National Community Engagement Group (NCEG) has been established to make certain that RECOVER meets the needs of all people affected by Long COVID. The RECOVER Patient and Community Engagement Strategy outlines all the approaches that RECOVER is using to engage with and gather input from individuals impacted by Long COVID.
The NIH recently made more than 40 awards to improve understanding of the underlying biology and pathology of Long COVID. There have already been several important findings published by RECOVER scientists.
For example, in a recent study published in the journal Lancet Digital Health, RECOVER investigators used machine learning to comb through electronic health records to look for signals that may predict whether someone has Long COVID [1]. As new findings, tools, and technologies continue to emerge that help advance our knowledge of the condition, the RECOVER Research Review (R3) Seminar Series will provide a forum for researchers and our partners with up-to-date information about Long COVID research.
It is important to note that post-viral conditions are not a new concept. Many, but not all, of the symptoms reported in Long COVID, including fatigue, post-exertional malaise, chronic musculoskeletal pain, sleep disorders, postural orthostatic tachycardia (POTS), and cognitive issues, overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
ME/CFS is a serious disease that can occur following infection and make people profoundly sick for decades. Like Long COVID, ME/CFS is a heterogenous condition that does not affect everybody in the same way, and the knowledge gained through research on Long COVID may also positively impact the understanding, treatment, and prevention of POTS, ME/CFS, and other chronic diseases.
Unlike other post-viral conditions, people who experience Long COVID were all infected by the same virus—albeit different variants—at a similar point in time. This creates a unique opportunity for RECOVER researchers to study post-viral conditions in real-time.
The opportunity enables scientists to study many people simultaneously while they are still infected to monitor their progress and recovery, and to try to understand why some individuals develop ongoing symptoms. A better understanding of the transition from acute to chronic disease may offer an opportunity to intervene, identify who is at risk of the transition, and develop therapies for people who experience symptoms long after the acute infection has resolved.
The RECOVER initiative will soon announce clinical trials, leveraging data from clinicians and patients in which symptom clusters were identified and can be targeted by various interventions. These trials will investigate therapies that are indicated for other non-COVID conditions and novel treatments for Long COVID.
Through extensive collaboration across the multiple NIH institutes and offices that contribute to the RECOVER effort, our hope is critical answers will emerge soon. These answers will help us to recognize the full range of outcomes and needs resulting from PASC and, most important, enable many people to make a full recovery from COVID-19. We are indebted to the over 10,000 subjects who have already enrolled in RECOVER. Their contributions and the hard work of the RECOVER investigators offer hope for the future to the millions still suffering from the pandemic.
Reference:
[1] Identifying who has long COVID in the USA: a machine learning approach using N3C data. Pfaff ER, Girvin AT, Bennett TD, Bhatia A, Brooks IM, Deer RR, Dekermanjian JP, Jolley SE, Kahn MG, Kostka K, McMurry JA, Moffitt R, Walden A, Chute CG, Haendel MA; N3C Consortium. Lancet Digit Health. 2022 Jul;4(7):e532-e541.
Links:
COVID-19 Research (NIH)
Long COVID (NIH)
RECOVER: Researching COVID to Enhance Recovery (NIH)
“NIH builds large nationwide study population of tens of thousands to support research on long-term effects of COVID-19,” NIH News Release, September 15, 2021.
Director’s Messages (National Institute of Neurological Disorders and Stroke/NIH)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 18th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.
Will ‘non vaccinated, Covid experienced, no long term symptoms’ people be put into this study to see if on a slim chance vaccinations contribute to long Covid?
I’m sure that vaccination status will be among the factors identified.
How can I join the Recover Program?
no mention of those who have totally lost their sense of taste or smell ; (
I would like to join Recover as a person with all the symptoms of Long Covid since Sept 24th, 2020. I have attempted to join NIH research groups at hospitals at Baylor and Mayo but was told because I live in Alaska they are not licensed to treat me.
Please tell me what the steps are to be included in Recover. It is lonely out here without a guide to live with this.
Hi Sandra, I am in the same predicament as you. I live here in Alaska as well and have been suffering with Long Covid beginning October 2021, after my Covid pneumonia diagnosis in September 2021. Prior to that I had what I believe was alpha Covid March 2020 and suffered major brain fog after that and to this day. I was Covid positive again in May 2022 and have not been able to recover from chronic fatigue, muscle malaise, and joint pain. I hope someone can help us up here in Alaska.
I have read reports of treatments of the auto response system of the body, will take care of most of the symptoms generated by Covid.
What reports? Where?
Like the article says we are 3 years into this and we still don’t have any clinical trials. Please can this be expedited
Agreed! What is the holdup? I signed up about 18 months ago, nothing…. Please help those of us suffering this debilitating disease.
As a clinician of Acupuncture I have treated a number of Long Covid patients successfully as well as authored an article with 2 case studies. I am not a researcher but would be happy to provide my clinical data/experience with patients to other researchers. Acupuncture definitely should be studied as an effective intervention for recovery from Long Covid.
We are a group of trauma-informed psychologists with an interest in the psychological aspects of the pandemic, including Long COVID. Previous research suggests that for serious medical illnesses of all types, there exists a bi-directional relationship between the biological and the psychological, such that one cannot meaningfully be studied in the absence of the other. Psychological stress and trauma is known to have an impact on the body, and the pandemic has been a source of stress for most people, and has resulted in trauma for others. Further, previous trauma can create an increased susceptibility and vulnerability to the effects of later trauma and this may be at play with Long COVID as well. Unfortunately, the major studies being done (and funded) on Long COVID have been strictly biologically-based and have not incorporated this important body of knowledge into their research designs. It seems imperative at this point to integrate trauma-informed psychologists into the investigation of Long COVID.
MaureenO’Reilly-Landry, Ph.D.
Patricia O’Gorman, Ph.D.
Co-chairs
Hospital, Health & Addictions working group
COVID Psychology Task Force
Trauma Division (Div. 56)
American Psychological Association
(est. by 14 divisions of the APA)
It appears that the COVID PsychologyTask Force of the APA is not familiar with a Sept. 2022 study just published in JAMA Psychiatry entitled “Associations of Depression, Anxiety, Worry, Perceived Stress and Loneliness Prior to Infection with Risk of Post-COVID-19 Conditions”. Here’s the link to this study with a cohort of 55,000 participants: 0.1001/jamapsychiatry.2022.2640. As someone who has recently recovered from Long COVID after two years of suffering with a plethora of symptoms, I always find it curious that when the medical profession can’t come up with a diagnosis or treatment of a malady, they conclude that there is something psychologically wrong with the patient. One of my brilliant UCLA specialists, a rheumatologist, decided to treat me similarly to a ME/CFS patient having a “biologically-based” response to a viral infection which was causing systemic inflammation. She focused on the vagus nerve which controls the parasympathetic nervous system. It accounted for just about every one of my debilitating symptoms. Prior to getting COVID-19, I was a healthy, fit person and while I’ve always been a big proponent of psychotherapy from which I’ve greatly benefited over the years, no amount of mindfulness meditation, talk therapy, and other psychologically-based modalities or medications were making a dent in my recovery. My team of Long COVID doctors believe that the physiology or biology of the virus can also cause psychological dysregulation. The only one in bunch who was out to lunch – the world-famous Long COVID psychiatrist who told me to accept my plight and that I may never recover. She blew the wind right out of my sails. I fired her. The study I mentioned above has some very striking flaws and my deep concern is that healthcare providers will jump to conclusions by misinterpreting or misusing these kinds of studies and lead patients in the wrong direction. Sometimes it truly does come down to treating the body and the mind will heal as well.
Thank you for your comment, as it provides an opportunity for me to clarify my own comment, and thank you also for your willingness to share your experiences publicly because it is essential that the patient experience be heard by medical scientists and clinicians. I am very aware of the impressive and extremely important study in JAMA and was elated to see that it had been done on such a large, if narrow, sample. However, I do believe an opportunity was missed by not drawing on previous psychological research on mind-body disorders. I share your concern that the results will be misconstrued and patients will be treated dismissively. However, I believe the best solution is for there to be a paradigm shift such that mind and body are understood by us all to be one inseparable unit.
At the time I got ill with the virus, I was in a burnout situation after working 60 to 80 hours consistently for 5 years in an extremely stressful sales environment for a corporate giant. The attitude was do whatever it takes to get it done. I was essentially always on, working from home, waking up and falling asleep with my laptop and colleagues and customers pressuring me was constant. I absolutely believe that I am having symptoms that deserve to be treated medically to save my career that I worked so hard for, but I do wonder if the anxiety from that burnout did make me vulnerable to the post viral syndrome.
Over reaction of immune system which destroys uninfected cells is the problem. Most antiviral medicines help mediate this reaction. Damaged organs need regenerative medicine so Phase 3 Clinical Trials of Stem Cells are needed. RMAT trials would give quick proof after so many Phase 1 & 2 Clinical Trials have shown safety and efficacy…
In regard to long COVID symptoms, you did not recognize the loss of taste and smell. I have had that condition as well as fatigue since December ,2020. At that point there were no vaccines available. I did have an infusion within 1 day of receiving two positive test results, both PCR. It is a difficult symptom to live with and dangerous as well. Please include that in your study.
Thank you
I just recovered from the virus. My theory is many of the long term neurological symptoms, whether it be headaches, dizziness, light headed, gastrointestinal discomfort, brain fog, are from a viral infection of the inner ear; a form of vestibular neuritis. I am fairly certain I was infected with the Omicron variant. There is a group of ENT’s at Harvard who are on the right path.
That is interesting and makes sense as I lost hearing in my left after having Covid and suffer from non-stop tennitus.
I experienced the symptoms of long COVID, never having had COVID 5 weeks after initial vaccination series (including being hospitalized).Then 9 months later had COVID and actually since then the symptoms are now 85% resolved. Never got boosted on MD recommendations. And yes, I submitted an initial report and FU report to VAERS. I’m a nurse and former clinical research monitor for over 39 years.
Could you possibly cooperate with the Million Veteran Program? They have 750,000 veterans with their DNA and all health care provided by the Veterans Administration, to research. They are looking at what is in your DNA,that makes one susceptible to certain diseases. If some have died from Covid, they may have the particular parts of DNA which are similar in all cases. Also which parts of the DNA show a tendency to which diseases, one symptom at a time.
THIS! …and specifically for ME/CFS.
Asking again for a study on long-covid with a loss of taste and smell. I have a gas stove and I have to constantly watch the burners so they don’t get tipped because I cannot even smell the putrid smell of propane. Also, if my dog gets sprayed by a skunk, I will not be able to smell that either. As far as taste goes, it is disgusting sitting at a table with everyone enjoying a meal that cannot be tasted or smelled. I had an MRI of my brain, which was an awful experience, and the ENT said there wasn’t anything related to covid on the scan. Do you have any idea what he may have missed in his findings of nothing? It would be helpful. I heard the vagus nerve may be injured from covid, there’s another start for your study of loss of taste and smell. Thank you for your consideration.
In a country where the culture makes someone irrelevant after the age of 50, imagine how much collective knowledge is lost in the workforce to be repeated by a younger generation. Negative data usually doesn’t get published. Given that the vast majority of clinical development ends up in failure and most do not look at literature that is older than a decade it’s the ultimate case of reinventing the wheel (yet again).
At one point, there was a distinction being made between PASC and Long-COVID. Now they seem to lumped together. Why?? They seem like two different problems.
PASC originally was described (to the best of my recollection) as symptoms persisting “longer than would be expected” following a viral illness such as lingering cough, difficulty breathing, tiring easily, loss of taste and smell. (Exactly how one determines “longer than would be expected” following a Novel virus is a mystery to me…and a discussion for another time…..). The general consensus seemed to be that whatever damage had been done to the body in the fight against the COVID virus would eventually subside or heal given time and proper support, just not as quickly “as expected”. From previous comments, it’s not clear to me how well that support is being given, especially regarding loss of taste/smell!!
Long-COVID, on the other hand, in my not very humble opinion and nearly 40 YEARS OF ENDURING ME/CFS, is that Long-COVID IS ME/CFS. Dr. Anthony Fauci was often (re)quoted as saying so – almost….. But not quite….. WHY????? WHY NOT????? These are the people who may or may not have had COVID at all or only mildly. Then suddenly they are desperately ill with the EXACT PATTERN (it’s all about the PATTERN) of symptoms that have been VERY CLEARLY DEFINED (though very poorly described) as ME/CFS.
IS ANYONE LOOKING AT THE POSSIBILITY THAT THE CAUSE OF ME/CFS (under whatever name, dating back to at least the 1940’s) is CAUSED BY A UNIQUE VIRUS (or other infectious agent) that prefers or needs to have a ride or camouflage of a different virus???? A sort of stealth virus. A virus that has yet to be ‘discovered’ or disentangled…imagine the professional prestige for the people who do find it!!!!!!!!
The repeated coincidence of outbreaks of ME/CFS (or its name at the time) COINCIDING with Polio; Epstein-Barr; influenzas; etc cannot be coincidence. The SIMPLEST ANSWER IS THAT THERE ARE TWO DIFFERENT AGENTS AT WORK. The convoluted contortions to explain how ME/CFS is one of many post-infections illnesses infuriates me. The idea that it is a “Process”; a “Conversion”; a long trip from point A to point B – when so, so many of us were healthy and active one day, and within hours become desperately, irrevocably, life-long ill – is completely non-sensical.
Polio gives you polio. People with Icelandic disease were described as having polio-like symptoms, but not really at all alike; abortive polio was a term…..as in, your clearly ill with something, it’s obviously not polio, we don’t know what is, but you’re not dead or paralyzed so let’s move on from this “difficult”, “Perplexing” “mysterious” ILLNESS. WHY????? Too many deeply rooted institutional problems to illuminate here…… (OR, a purposeful military cover-up???? Idk….after 40 years of no answers and minuscule research one starts to wonder……)
So, very long story short, if the government had put the same resources into ME/CFS back in 1950 as it did into cancer and then AIDS, Alzheimer’s, etc etc, we would likely know exactly what “Long-COVID” aka ME/CFS is and how to treat it in a TARGETED AND EFFECTIVE way, not just with scattered symptom relief that you are left to search out on your own, if you’re lucky enough to have some energy, help, and money to do the search and try the options (many of us doing this long before there was the internet!!!!!!).
AND IS ANYONE REACHING OUT TO THOSE OF US WHO BECAME ILL WITH ME/CFS IN the huge 1980’s OUTBREAK (it wasn’t caused by COVID-19!!!!!!!) AND ARE NOW 40 years older than when we got sick, and wondering how this will end????? HOPE for a cure in our lifetimes IS RUNNING VERY THIN!!!!!!!
Somebody should at least have the decency to reach out and start tracking how we decline and die (for those of us who are still clinging to what is left of our lives and ENDURING this EXCRUCIATINGLY LONG ignored, painful, lonely, and misunderstood ILLNESS.)
LOOK FOR THE REAL VIRUS!!!!!!!
FIND THE TARGETED TREATMENT!!!!!
CURE BY 2025!!!!!!!!
LOOK. FIND. CURE.
Yes to all of this. Now 80 diagnosed late 1990s w CFS soon after severe shingles. Never offered anti-virals. Diagnosed w Mesenteric Panniculitis. Now RA, Polymyalgia rheumatica and still only treated with standard protocol. Recurrent flares of one and another continually. Biologics iffy in my case due to side effects. Thank you Elizabeth.
Mary,
It does my heart a world of good to know that my words were heard and helpful. I’m glad you’re still fighting for answers and better care. So sorry it’s been so long…. Thank you so much for your reply! Sending you healing thoughts as best can,
Elizabeth
Thanks for the commentary, hope it does some good, not holding my breath. Nearly 2 years into Long Covid. Usual suspects as far as symptoms…. Fatigue, tinitus, fog, muscle aches, GI issues. It’s been a nightmare, really. Read book by Sarah Myhill on ME and CFS. She says Long Covid is the same, as does the last “specialist” I saw here in Charleston .
I had COVID in April 2020 and another women in my complex had it in March 2020. We were not hospitalized and had no breathing problems. My sickness was mainly in my nose/sinuses and in my throat, coughing, and related discomfort. I and she can smell but we have dysgeusia. We can taste sweet, salty, hot peppery things, sour, and vinegary things. We can not taste meat which I think means the umami taste is gone. I can taste mint; I don’t know if she can. One example: we can smell coffee but can not taste it. I have adjusted to appreciating textures of food. Prior to COVID I had a very good sense of smell and taste. Much of what I read is about loss of smell. What is known about post-COVID loss of taste and if long haulers regain taste. I think I have started to taste onion, which I could not after COVID.
I think I have long term covid. I had covid no shots. Just caught covid. The days I had it with fever only two days . But I have been going down hill sence , sleep, fog weakness in legs..
“Pregnant people” Would they be women by any chance?
Covid October 2020 before vaccines were available. Several times notified doctor that I felt foggy , tired … this July 2022 , labs found high lymphocytic markers , high cardio inflammation markers . I was not on prednisone for two months due to a ” blood infection ” . Awaiting lab retests. Covid had been building inflammation in my blood till I was exhausted. Unable to work , no energy/ stamina
@ > Rhonda: – I ask that you please post the results of your lab re-tests when you receive them. I’ve been tested by practically every known medical specialty w/negative results. What I have NOT had ordered is a full lab workup(??). Your post/answer may be what I need to convince my PCP to order one. Thanks much.
Long Covid and M.E., Myalgic Encephalomyelitis/cfs, need to be studied together since long term data for ME/cfs can be predictive of long term Covid, and biochemistries, diagnostics, treatments may be similar …