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Long COVID – Just the Facts

The Food and Drug practice at ArentFox Schiff has received numerous inquiries from clients about long COVID, so we decided to ask our in-house scientist, Robert Edwards, Ph.D., Director of Regulatory Science, to prepare an Alert addressing many of the inquiries we have received. Dr. Edwards does this in a Frequently Asked Questions format below, but first, here is a summary of his Key Points.
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Key Points

  • Long COVID refers to symptoms – ongoing, new, or recurrent – that are present at least four weeks following infection.
  • Symptoms are numerous and diverse, and often include fatigue, “brain fog,” shortness of breath, and change in ability to taste or smell.
  • Diagnosis and treatment can be very challenging, and routine tests may appear normal, although MRI scans suggest some brain shrinkage.
  • Risk factors include hospitalization, prior severe COVID, lack of vaccination, pre-existing conditions, and even past infection with Epstein-Barr Virus.
  • Children, adolescents, and those who had mild infections or were asymptomatic are also at risk.
  • Risk is greater for females (1.4 to 2 times that for males), and increases with age.
  • General incidence of at least one symptom may be between 22% and 38% of COVID-19 survivors, and is higher in the previously hospitalized.
  • Incidence of long COVID after breakthrough infections in the vaccinated is lower than after infections in the unvaccinated.
  • Early post-infection vaccination may help lower the incidence of long COVID in some people.
  • The search for treatments is barely underway, but there are early indications certain antivirals may help relieve some symptoms.
  • Long COVID symptoms generally decrease over time, but may last for months or possibly even years in some people, and may be very debilitating.
  • Long COVID may be considered a disability under the ADA.
  • The White House has developed a major action plan for addressing long COVID.
  • Multiple studies of long COVID have been initiated under NIH’s RECOVER Initiative.
  • The current state of scientific and medical research on all the issues discussed below is such that statements like “the pandemic is behind us” are highly premature and should be discounted.

Frequently Asked Questions

What is the CDC’s Present Position on Long COVID?

On May 5, 2022, the Centers for Disease Control and Prevention (CDC) issued an updated guidance on long COVID.[1]  It also issued an updated report on current scientific investigations into long COVID, describing eight prospective, ongoing cohort studies. CDC defines long COVID as presenting symptoms at least four weeks after initial infection.[2] These symptoms of long COVID may persist for weeks, months, or even years.

What Are the Symptoms of Long COVID?

Possible symptoms of long COVID are numerous, heterogeneous and wide-ranging, potentially exceeding 200 in number, with the most common listed by CDC including the following:

  • General – tiredness or fatigue that interferes with daily life, and symptoms that worsen after physical or mental effort.
  • Neurological – “brain fog,” headache, sleep problems, change in taste/smell, depression or anxiety, lightheadedness when standing up, pins-and-needles.
  • Respiratory and heart – difficulty breathing, shortness of breath, cough, chest pain, heart palpitations.
  • Digestive – diarrhea, stomach pain.
  • Other – joint or muscle pain, rash, changes in menstrual cycles.

Since patients with long COVID may experience multiple symptoms, some of which could be due to other health conditions or may occur over different time periods, diagnosis and treatment are very difficult.  

CDC notes that symptoms of long COVID may be similar to those reported for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a hard-to-diagnose, highly debilitating illness that may render even the most mundane of everyday tasks highly challenging. Although ME/CFS itself is not yet listed among the symptoms of long COVID, it has been reported to appear in about 10% of cases following certain other microbial infections – Epstein-Barr virus, Ross River virus, and Q-fever.

Are There Tests for Long COVID?

No. There is presently no test to diagnose long COVID where routine clinical evaluations, blood tests, chest X-rays, and EKGs may appear normal. However, a recent major Oxford University study of brain MRI scans of generally older people before and after mostly mild COVID-19 infection showed significant changes in certain areas of the brain following infection (Douaud et al., Nature, March 2022); this work may provide clues to the origins of some of the reported neurological effects. Subjects were 51 to 81 years old; a total of 785 sets of “before and after” scans involved 401 subjects who tested positive between scans and 384 match-paired controls who had remained uninfected. On average, compared to the control group, the infected group showed:

  • Greater reduction in gray matter thickness in the orbitofrontal cortex and parahippocampus gyrus, areas associated with the sense of smell.
  • Greater tissue damage in areas connected with the primary olfactory cortex, also associated with the sense of smell.
  • Greater loss of gray matter and greater tissue damage in the insula, considered to be the area most associated with taste.
  • Greater decrease in whole-brain volume.
  • Atrophy in an area of the cerebellum associated with cognition, correlating with a greater decline in the ability to perform complex tasks observed in the infected group.

The normal annual rate of aging-related loss from the hippocampus – the region of the brain most associated with memory and learning – is 0.2% in middle age and 0.3% in later years. By way of comparison, this study revealed an additional 0.2% to 2% gray matter loss or damage as a result of COVID-19 infection.

Is There Any Proven Treatment?

Not at the present time. As noted above, investigating potential treatments is very challenging because of the wide range of possible symptoms. Ledford, in a recent article in Nature (April 2022), listed several potential treatments for specific types of symptoms that may result from a variety of causes – lingering viral reservoirs, autoimmunity, and tiny blood clots have all been proposed. Most such treatments are in small-scale clinical trials that may not give clear-cut answers because of their limited size. They include antivirals, immune-suppressing drugs, and a drug designed to reduce inflammation in blood vessels.

Outside of the clinical trial arena, Peluso et al. at the University of California San Francisco have just posted a non-peer-reviewed report on a very small number of case studies in which a 5-day treatment course of Pfizer’s antiviral therapy Paxlovid (nirmatrelvir) was provided to three long COVID patients, all in their 40s and all triple-vaccinated prior to infection (Research Square, May 9, 2022). The results were mixed: one male saw gradual improvement in symptoms, and one female saw sufficient improvement in her fatigue symptoms to allow her to resume daily activities, but a second male saw a recurrence of symptoms shortly after completing treatment. (Treatment could not continue beyond five days, since that is the limit of FDA’s Emergency Use Authorization for Paxlovid.) Subsequently, writing in The Lancet (May 24), Burki noted that the possible success of antivirals like Paxlovid in relieving long COVID symptoms may depend on whether those symptoms can be attributed to persistence of live virus rather than, for example, a dysregulated immune response. At this point, the search for potential treatments has far to go.

Who Might Develop Long COVID?

Anyone. Although long COVID is seen more frequently in those who experienced more severe forms of the initial infection, CDC emphasizes that people who had only a mild form of COVID-19, or were asymptomatic, may still develop symptoms of long COVID. It references a recent study that examined the effects of long COVID on those who had experienced only mild cases of COVID-19, but even in those cases, the authors stated that “the burden of persistent symptoms was significantly associated with poorer long-term health status, poorer quality of life, and psychological distress” (Han et al., Influenza and Other Respiratory Diseases, March 2022).

Furthermore, while long COVID is more common in adults, it also occurs in children and adolescents, as indicated by the results of a large cohort study in England that showed long COVID can be just as disabling in children and teenagers as it is in adults (Stephenson et al., The Lancet, February 2022).

What are the Possible Risk Factors?

CDC has developed the following list of those who may be more susceptible to developing long COVID, although it stresses that the list is not comprehensive:

  • Those who experienced more severe acute COVID-19, especially if hospitalized or admitted to the ICU.
  • Those with pre-existing health conditions.
  • The unvaccinated.
  • Those who experience multisystem inflammatory syndrome (MIS) during or after the initial illness.
  • Those affected by health inequities due to race, ethnicity, or disability.

A massive UK study of over 600,000 people using data from the REACT-2 database (discussed below) recently reported a similar list of risk factors for persistent symptoms at 12 weeks. Mutually adjusted for other variables, they were, in order of increasing importance: increasing age, smoking or vaping, healthcare work, female sex (discussed below), low income, obesity, moderate (as opposed to mild) symptoms during infection, severe symptoms, and (by far) hospitalization. Asian ethnicity was associated with about 15% lower risk than other ethnicities.

To underline the significance of prior hospitalization, preliminary data from a survey of more than 100,000 self-reporting COVID-19 survivors in a study announced in a 23andMe online blog on May 24 indicate that hospitalization appears to increase the risk of developing long COVID by a factor of ten. In addition, a history of depression or anxiety was associated with a two-fold risk of being diagnosed with long COVID.  

Meanwhile, a Seattle-based group recently published an in-depth study of potential biological factors in 209 mainly high-risk patients who had developed long-COVID symptoms 2-3 months after acute infection (Su et al., Cell, March 2022). In this group, 71% had originally been hospitalized, 30% had been admitted to the ICU, and 18% had been intubated and mechanically ventilated. Patients were studied at up to 3 time-points: initial diagnosis (T1), acute stage of infection (T2), and 2-3 months later (T3). The study identified four specific biological risk factors associated with symptoms of long COVID:

  • Pre-existing type 2 diabetes (22% of patients at T1)
  • SARS-CoV-2 RNAemia[3] (25% at T1)
  • Epstein-Barr virus (EBV) viremia[4] (14% at T1), indicating previous EBV infection
  • Specific auto-antibodies[5] (56% at T1 to 44% at T3), indicating possible autoimmune disease

Results suggest that it may be possible to link specific risk factors detected at initial diagnosis with specific long COVID symptoms, and so proactively try to treat and prevent such symptoms.

Unpublished data from the 23andMe study lend support to the Seattle findings. Thus, the presence of a cardiometabolic disease (which includes type 2 diabetes, as well as high blood pressure and coronary artery disease) was found to be associated with a 90% higher risk of long COVID, while 32% of those diagnosed with long COVID, compared to only about 20% of controls, had some type of autoimmune disease (which would be indicated by the presence of auto-antibodies in the blood).

Might There Be a Link between Long COVID and Previous Epstein-Barr Viral Infection?

Possibly. What appears particularly interesting from the Seattle study is the inclusion of EBV viremia – indicating a previous infection by EBV – as a risk factor for long COVID. Many people have been infected by EBV, the cause of infectious mononucleosis, most often as teens or young adults. Such an association between EBV and long COVID has also been studied by Gold et al. (Pathogens, June 2021), who investigated a group of 185 COVID-19 patients, of whom 56 (30%) developed long COVID symptoms. From a group of 30 with long COVID, 20 (67%) tested positive for EBV reactivation, compared with only 2/20 (10%) of uninfected control subjects. They raised the intriguing possibility that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of EBV reactivation induced by COVID-19 inflammation.

What is the Overall Incidence of Long COVID?

Estimates vary widely. For example, a large-scale review from Penn State of the COVID-19 literature published between December 2019 and March 2021 identified 57 studies addressing incidence of long COVID in over 250,000 survivors (Groff et al., JAMA Network Open, October 2021). The median proportion of survivors experiencing at least one symptom was between 54% and 55% at three time-points: 1 month, 2-5 months, and 6+ months. However, 79% of those subjects had originally been hospitalized, which would skew the results. In contrast, Malkova et al. (Pathogens, 2021) reviewed only the literature involving subjects who had been asymptomatic or had had mild infections, and reported an incidence of 30-60% across the 11 studies selected.

The UK’s massive Real-Time Assessment of Community Transmission-2 (REACT-2) study included the collection of COVID-19 data on over 500,000 people between September 2020 and February 2021. In a major analysis of the long COVID data, a total of 19.2% of the studied population reported a previous COVID-19 infection. At 12 weeks following initial infection, 37.7% of the previously infected reported one or more symptoms, and 17.5% reported three or more symptoms (Whitaker et al., Nature Communications, April 2022).

More than 26,000 (26%) of the 100,000 COVID-19 survivors from the new 23andMe study discussed above self-reported long COVID, although only about 7% had been formally diagnosed with it. A new CDC study published on May 24 (Bull-Otterson et al.) analyzed the records of more than 350,000 people diagnosed with COVID-19 from March 2020 to November 2021 and compared them to records of uninfected people over the same time frame; the CDC investigators concluded that at least one symptom attributable to long COVID developed in 22.2% of COVID-19 survivors, but this figure was somewhat age-dependent (see below).

What is the Effect of Prior Vaccination on Long COVID Following Breakthrough Infections?

It appears to be beneficial, although results vary. For example, a UK study of more than 8000 adults that followed cases from December 2020 to July 2021 (i.e., prior to Omicron and most Delta variant infections) found that the odds of developing long COVID symptoms following infection were approximately halved by receiving the second dose of a 2-dose vaccine compared to just a first dose (which appeared to have no effect on incidence of long COVID) prior to infection (Antonelli et al., The Lancet, January 2022).

A new study from the Department of Veterans Affairs (VA), just published on May 25, 2022, used the extensive medical records of the VA for the first nine months of 2021 (i.e., prior to the Omicron outbreak) to determine the effect of prior full vaccination on long COVID resulting from subsequent breakthrough infections (BTI) (Al-Aly et al., Nature). There were almost 34,000 participants in the BTI group with a positive COVID-19 test and a prior record of complete vaccination (as defined by the CDC[6]); there were almost 5 million in a contemporary control group with no record of a positive test. At six months after infection, survivors in the BTI group had an overall 50% increased risk of at least one symptom of long COVID compared with the uninfected control group. In comparison to controls, this represented an excess incidence of long COVID in about 12% of those with BTI at six months after infection. However, the results for those who had been hospitalized and those who had not were dramatically different. For those not hospitalized, the increased risk was 25%, and the excess incidence was 7.8%, while for those hospitalized, they were 195% increased risk and 33.4% excess incidence, and for those admitted to the ICU, they were 275% increased risk and 42.1% excess incidence.

On the positive side, prior vaccination still reduced the risk of long COVID, albeit modestly in cases of BTI. Compared to the second group of over 113,000 COVID-19 survivors with no history of vaccination, survivors in the BTI group had an overall 15% lower risk and a 4.4% lower incidence of at least one symptom. The range of symptoms appeared to be the same in both groups. The authors concluded that while vaccination may partially reduce the risks of long COVID, it should not be considered sufficient in itself, and other strategies to prevent breakthrough infections in the first place should remain a goal of public health policy.

What Effect does Prior Vaccination Have on Long COVID from Different Variants?

It varies, depending on the number of vaccine shots received. The following findings come from the UK Government’s latest (May 6 and June 1, 2022) reports on the prevalence of long COVID, and are based on information provided by approximately 2.0 million people (3.1% of the population) self-reporting long COVID:

  • For first infections among double-vaccinated adults, the odds of reporting symptoms 4-8 weeks later were almost 50% lower after Omicron BA.1 than after Delta (incidence 8.7% vs. 15.9%).
  • For first infections among triple-vaccinated adults:
    • There was no statistical difference between the two variants (incidence 8.0% for Omicron BA.1, 8.5% for Delta).
    • There was also no statistical difference in incidence between Omicron BA.2 (9.1%) and Delta (7.4%).
    • Incidence was about 22% higher for Omicron BA.2 than for BA.1 (9.3% vs. 7.8%).

Does Vaccination after Infection Help Prevent Long COVID?

Perhaps. There are indications that vaccination may help prevent the appearance of long COVID even when administered shortly after infection. A non-peer-reviewed study based on a retrospective analysis of the medical histories of about 240,000 COVID-19-infected subjects reported that unvaccinated patients who received a first COVID vaccination within four weeks following initial infection were 4-6 times less likely to go on to report multiple long COVID symptoms compared to those who remained unvaccinated (Simon et al., MedRxiv preprint, November 2021). Those who received a first dose 4-8 weeks after initial infection were three times less likely to report such symptoms.

How Does the Incidence of Long COVID Correlate with Gender and Age?

Incidence is greater in females. Data from the May and June 2022 UK Government reports on long COVID showed that self-reported cases appeared to be more prevalent in females than in males (58% to 42%, a 1.4:1 ratio). A very similar ratio was reported from the UK’s REACT-2 database. Although the new but as yet unpublished 23andMe study discussed above has just reported a much higher ratio among subjects diagnosed (not simply self-reported) with long COVID, with 78% being female, the comparison control group of COVID-19 survivors was not evenly split between the sexes, being 62% female, so the adjusted ratio is closer to 2:1.  

Also, incidence seems to increase with age. The new (May 24, 2022) CDC study discussed above reported that long COVID was somewhat age-dependent, with at least one symptom developing in 20.8% of the 18-64 age group and in 26.9% of the 65+ age group; those in the older age group were particularly at increased risk for neurological conditions and certain mental health conditions. The UK’s REACT-2 data calculated the risk in 10-year age groups; compared to a 55-64 year old reference group, people in the 18-24, 25-34, and 35-44 age groups were 30% to 36% less likely to develop long COVID, those 45-54 were only 15% less likely, while those 65-74 and 74+ were 16% and 19%, respectively, more likely.

How Long Might Long COVID Symptoms Last?

Possibly indefinitely in some people. While most patients’ symptoms slowly improve with time, for some people, symptoms may last months and potentially years and may result in disability, especially among those previously hospitalized; symptoms may even go away and later return. A variety of sources offer differing statistics as to the extent to which symptoms diminish with time, but they all indicate that long-term persistence affects a significant proportion of long COVID sufferers. For example, the data from the UK REACT-2 study indicated that the incidence of one or more symptoms fell from 100% down to 40% in males and 56% in females over the first four weeks after initial infection, followed by a further drop over the next eight weeks to symptoms in 31% males and 40% in females, and finally a much smaller drop over the next eight weeks (for a total of 20 weeks, the limit of the study) that still left 30% of males and 38% females with one or more lingering symptoms. Nevertheless, the incidence of 3 or more symptoms remaining after 20 weeks was substantially lower, at about 8% in males and 15% in females. The latest UK Government report (June 1, 2022) on 2.2m people (3.1% of the population) self-reporting long COVID examines a longer time-span; it estimates that 72% had one or more symptoms at least 12 weeks after infection, 42% at least one year after infection, and 19% at least two years after infection.

The 23andMe data indicate that symptoms remain past 12 months in at least 10% of those with long COVID, with the most prevalent symptoms being brain fog, fatigue, and shortness of breath. The number of long COVID participants who reported brain fog fell from 41% at three months to 19% at 12 months; over the same time period, fatigue fell from 34% to 17%, and shortness of breath from 29% to 14%.

The Institute for Health Metrics and Evaluation (IHME) is a research center at the University of Washington in Seattle that investigates the global health burden of diseases, including long COVID. According to a recent article by Else in Nature (May 19, 2022), IHME’s unpublished data suggest that in 2020-2021 an estimated 4.6 million people in the US had symptoms that persisted for at least three months. IHME has assigned symptoms to three general categories: fatigue, cognitive problems, and ongoing respiratory issues. More than 85% of cases of long COVID resulted from a COVID-19 infection that did not require hospitalization. For those with only a mild infection, IHME’s modeling suggests that about 5% of women and 2% of men still had symptoms after six months; those figures increase to 26% and 15%, respectively, for those who were hospitalized, and to 42% and 27% for those treated in an ICU.

Since the pandemic has only been with us since early 2020, it is difficult to predict the persistence of long Covid beyond 1-2 years. A newly published cohort study from a hospital in Wuhan, China, provides data on 1192 previously hospitalized patients over the longest available time period, since Wuhan is where COVID-19 first appeared (Huang et al., The Lancet, May 2022). The study characterizes the health outcomes and recovery status of these survivors for two years following initial COVID-19 infection. Although survivors saw gradual improvements in their physical and mental health over this period, and most returned to their original work, the incidence of residual symptoms remained fairly high, with 55% reporting at least one symptom at two years (down from 68% at six months); survivors had markedly worse health than the uninfected control population. After two years, 31% still reported fatigue or muscle weakness, and 31% reported sleep difficulties (the most commonly reported symptoms regardless of initial disease severity) compared to 5% and 14%, respectively, among controls. Dyspnea (shortness of breath) had dropped from 26% at six months to 14% at two years, while anxiety or depression had dropped from 23% to 12%.

How Debilitating is Long COVID?

It can be very debilitating. The June 1 UK Government report noted that long COVID symptoms adversely affected day-to-day activities of 1.4m (71%) of the 2.0 million self-reporting subjects, with 20% reporting that their ability to undertake day-to-day activities had been “limited a lot.” Fatigue was the most common symptom (55%), followed by shortness of breath (32%), cough (23%), and muscle ache (23%). Compared to the May report, fatigue was up (from 51%), and cough and muscle ache had replaced the loss of sense of smell (26%) and difficulty concentrating (23%) among the top four persistent symptoms.

Has the World Seen Similar Phenomena Following Previous Viral Epidemics?

Yes. Long-term persistence of symptoms following infection does not appear to be unique to COVID-19. An article by Spinney in the journal Nature (February 2022) looked at the historical record for other viral pandemics and epidemics, and described the appearance of encephalitis lethargica (EL) or “sleepy sickness,” often leading to a Parkinson-like disease, that followed infection during the 1918-19 outbreak of the so-called Spanish influenza; recurrence of symptoms decades after infection from the polio epidemics that regularly appeared in the US and Europe until the mid-1950s; and the recently recognized “post-Ebola” syndrome affecting the heart, brain, eyes, and joints following infection by the Ebola virus.

Is Long COVID Covered under the Americans with Disabilities Act?

Yes. As indicated in the CDC update, long COVID can be considered a disability under Title I of the Americans with Disabilities Act (ADA). The Office for Civil Rights of the Department of Health & Human Services (HHS) and the Civil Rights Division of the Department of Justice jointly issued a Guidance on this issue in July 2021. The Guidance also explains that long COVID can be a disability under Titles II (dealing with state and local government services) and III (dealing with public accommodations and commercial facilities) of the ADA as well as Section 504 of the Rehabilitation Act of 1973 and Section 1557 of the Patient Protection and Affordable Care Act if an individual, as a result of long COVID, has a physical or mental impairment that substantially limits one or more of the major life activities of such individual (“actual disability”). The Guidance discusses the terms “major life activities” and “substantially limits,” and provides examples of substantial limitations of major life activities as a result of long COVID. It also discusses the rights of qualifying individuals, and the federal resources that are available.  

The Equal Employment Opportunity Commission has issued technical assistance on how long COVID and other COVID-related conditions can constitute disabilities under Title I of the ADA and Section 501 of the Rehabilitation Act, which cover employment. For further information on the ADA aspects of long COVID – and indeed the ADA aspects of COVID itself – please contact the Labor and Employment attorneys at ArentFox Schiff.

Has the Biden Administration Responded to the Long COVID Issue?

Yes. On April 5, 2022, the White House issued a Memorandum from President Biden to the heads of the Executive Departments and Agencies summarizing the challenges presented by long COVID, and setting out the Government’s response to those challenges, to be coordinated by the Secretary of HHS. It includes organization of the Government-wide response, preparation of a report outlining the services and mechanisms of support for individuals suffering from long COVID, and development of a National Action Plan to be built upon existing research efforts. Simultaneously, the White House issued a Fact Sheet detailing the Administration’s “Whole-of-Government Effort to Prevent, Detect and Treat Long COVID.” Action items include:

  • Delivering high-quality care for individuals experiencing Long COVID.
    • Launching Centers of Excellence and promoting evidence-based care models.
    • Expanding and strengthening Long COVID clinics.
    • Promoting provider education and clinical support.
    • Bolstering health insurance coverage for Long COVID care.
  • Making services and supports available for individuals experiencing Long COVID.
    • Raising awareness of Long COVID as a potential cause of disability.
    • Translating research into inclusive disability policy.
    • Connecting people with the resources they need.
    • Strengthening support for workers experiencing Long COVID.
  • Advancing the nation’s understanding of Long COVID.
    • Launching the first-ever National Research Action Plan on Long COVID. 
    • Accelerating enrollment into the RECOVER Initiative.
    • Making further investments to advance Long COVID research and surveillance.
    • Leveraging the power of federal data.
    • Identifying workplace interventions that help keep individuals connected.

The RECOVER (Researching COVID to Enhance Recovery) Initiative referred to above was launched by NIH in 2021 to learn more about the incidence of long COVID by funding large-scale studies of tens of thousands of subjects across the nation. An award of $470m was made to New York University, which in turn is making multiple sub-awards to multiple researchers and institutions. In making the parent award, NIH stated:

Studies will include adult, pregnant, and pediatric populations; enroll patients during the acute as well as post-acute phases of the SARS-CoV-2 infection; evaluate tissue pathology; analyze data from millions of electronic health records; and use mobile health technologies, such as smartphone apps and wearable devices, which will gather real-world data in real-time. Together, these studies are expected to provide insights over the coming months into many important questions, including the incidence and prevalence of long-term effects from SARS-CoV-2 infection, the range of symptoms, underlying causes, risk factors, outcomes, and potential strategies for treatment and prevention.

Thus, future data from the RECOVER Initiative should provide more definitive answers to many of the questions discussed above.

Conclusions

The threat of any of a wide range of persistent and potentially debilitating symptoms following a COVID-19 infection is very real and not to be taken lightly. Long COVID symptoms can appear following any COVID-19 infection, regardless of vaccination status, age, identity of variant, severity of initial infection, or even asymptomatic infection. Diagnosis is challenging, and generally accepted treatment is virtually non-existent at this time. Much research and data-gathering remain to be done, and even the most recently published reports may be based on older and possibly outdated data gathered during pre-Omicron waves. In the meantime, wishful thinking that “the pandemic is behind us” should be seriously questioned or disregarded entirely, as should the trope that most recent infections, especially from the Omicron variants, are “no big deal” or “no worse than the flu.” Even if an initial infection is mild or asymptomatic, the available data indicate that no survivor is safe from the apparent randomness of long COVID, although taking full advantage of available vaccine boosters and maintaining established precautions will help reduce the risk by avoiding infection in the first place.


[1] Long COVID is also known as post-COVID, or referred to in the medical literature as “post-acute sequelae of SARS CoV-2 infection” or “post-acute COVID syndrome” (PASC).
[2] Other sources, such as the World Health Organization, may use later starting points of up to 12 weeks.
[3] The detection of RNA from the SARS-CoV-2 virus in the blood, e.g., by PCR test. Assays dropped 2-fold by T2, and were barely detectable at T3.
[4] EBV viremia is the detection of Epstein-Barr virus DNA in the blood. Assays dropped 3-fold by T2, and were barely detectable at T3.
[5] Defined as an antibody produced by the immune system that is directed against one or more of the individual’s own proteins (in contrast to an anti-SARS antibody). Many autoimmune diseases are caused by such autoantibodies.
[6] Two doses of Pfizer or Moderna vaccine or one dose of J&J/Janssen vaccine.

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