Showing posts sorted by relevance for query Sequelae COVID. Sort by date Show all posts
Showing posts sorted by relevance for query Sequelae COVID. Sort by date Show all posts

Wednesday, November 11, 2020

CDC: Late Sequelae of COVID-19 (Long COVID)

https://twitter.com/KartikSehgal_MD/status/1281695760879202304

#15,552

While the initial concerns with the COVID pandemic were handling acute illnesses and minimizing deaths, by early summer it had become apparent that some (perhaps many) COVID survivors were experiencing slow recoveries, and prolonged (and sometimes severe) sequelae. 

Some `recovered' patients have been left with lung, heart, or kidney damage while others have experienced lingering neurological manifestations ranging from relatively mild (headaches, dizziness, anosmia, mild confusion, etc.) to more profound (seizures, stupor, loss of consciousness, etc.) to potentially fatal (ischemic stroke, cerebral hemorrhage, muscle injury (rhabdomyolysis), etc.).

Some experts have suggested we may see huge increases in COVID-19 related heart failure and neurological diseases in the years ahead.

Emily A. Troyer, Jordan N. Kohn, and Suzi Hong 

Yesterday, in MMWR: Readmission Of COVID-19 Patients Within 2 Months Of Hospital Discharge, we looked at the likelihood of being readmitted to a hospital in the 60 days following release from a COVID diagnosis. 

While 3 weeks ago, in UK NIHR: Living With COVID-19 (Long COVID), we looked at the potential for many patients to develop a Post Viral Fatigue syndrome - similar to ME/CFS - that could cause permanent disability. 

The CDC has acknowledged these concerns in a number of MMWR & EID Journal articles, and by the following brief statement which has been on their COVID-19 website (Wayback Machine link) since September:

Long-Term Effects of COVID-19
Updated Sept. 16, 2020 

CDC is actively working to learn more about the whole range of short- and long-term health effects associated with COVID-19. As the pandemic unfolds, we are learning that many organs besides the lungs are affected by COVID-19 and there are many ways the infection can affect someone’s health.

One of the health effects that CDC is closely watching and working to understand relates to COVID-19 and the heart. Heart conditions associated with COVID-19 include inflammation and damage to the heart muscle itself, known as myocarditis, or inflammation of the covering of the heart, known as pericarditis. These conditions can occur by themselves or in combination. Heart damage may be an important part of severe disease and death from COVID-19, especially in older people with underlying illness. Heart damage like this might also explain some frequently reported long-term symptoms like shortness of breath, chest pain, and heart palpitations.

The risk of heart damage may not be limited to older and middle-aged adults. For example, young adults with COVID-19, including athletes, can also suffer from myocarditis. Severe heart damage has occurred in young, healthy people, but is rare. There may be more cases of mild effects of COVID-19 on the heart that can be diagnosed with special imaging tests, including in younger people with mild or minimal symptoms; however, the long-term significance of these mild effects on the heart are unknown. CDC will continue to assess and provide updates as new data emerge.
Yesterday, the CDC updated and expanded this statement and added a new web page addressing Late Sequelae of COVID-19:  

First the update. 

Updated Nov. 10, 2020

CDC is actively working to learn more about the whole range of short- and long-term health effects associated with COVID-19. As the pandemic unfolds, we are learning that many organs besides the lungs are affected by COVID-19 and there are many ways the infection can affect someone’s health.

While most persons with COVID-19 recover and return to normal health, some patients can have symptoms that can last for weeks or even months after recovery from acute illness. Even people who are not hospitalized and who have mild illness can experience persistent or late symptoms. Multi-year studies are underway to further investigate. CDC continues to work to identify how common these symptoms are, who is most likely to get them, and whether these symptoms eventually resolve.

The most commonly reported long-term symptoms include:
  • Fatigue
  • Shortness of breath
  • Cough
  • Joint pain
  • Chest pain
Other reported long-term symptoms include:
  • Difficulty with thinking and concentration (sometimes referred to as “brain fog”)
  • Depression
  • Muscle pain
  • Headache
  • Intermittent fever
  • Fast-beating or pounding heart (also known as heart palpitations)
More serious long-term complications appear to be less common but have been reported. These have been noted to affect different organ systems in the body. These include:
  • Cardiovascular: inflammation of the heart muscle
  • Respiratory: lung function abnormalities
  • Renal: acute kidney injury
  • Dermatologic: rash, hair loss
  • Neurological: smell and taste problems, sleep issues, difficulty with concentration, memory problems
  • Psychiatric: depression, anxiety, changes in mood
The long-term significance of these effects is not yet known. CDC will continue active investigation and provide updates as new data emerge, which can inform COVID-19 clinical care as well as the public health response to COVID-19.
 
Preventing COVID-19

The best way to prevent these long-term complications is to prevent COVID-19. The best strategies for preventing COVID-19 infection in youth and adults are to wear a mask in public places, stay at least 6 feet away from other people, frequently wash your hands, and avoid crowds and confined or poorly ventilated spaces.

Also published yesterday is the following review of what is currently known about the late sequelae of COVID-19. 
Late Sequelae of COVID-19
Updated Nov. 10, 2020

The identification of the novel coronavirus SARS-CoV-2 in December 2019 has led to a growing and continually evolving body of knowledge about the virus and the disease it causes, COVID-19.

In peer-reviewed literature and public discussion, persistent symptoms are being reported among COVID-19 survivors, including individuals who initially experience a mild acute illness. These persistent symptoms pose new challenges to patients, healthcare providers, and public health practitioners. The natural history of SARS-CoV-2 infection and COVID-19 is a current area of investigation, and the prevalence, type, duration, and severity of persistent symptoms following resolution of acute SARS-CoV-2 infection, as well as risk factors associated with their development, are currently being studied.

While older patients may have an increased risk for severe disease, young survivors, including those physically-fit prior to SARS-CoV-2 infection, have also reported symptoms months after acute illness (Assaf, Asthma UK and British Lung Foundation, Godlee). Research is underway to differentiate symptoms of a prolonged course of COVID-19 illness from sequelae following resolution of acute SARS-CoV-2 infection, achieve consensus on the time period at which to define the post-acute and long-term phases of COVID-19, and distinguish health effects exclusively related to infection with SARS-CoV-2 from consequences of procedures and treatments required for care of persons with severe disease of any etiology.

Characterization of the etiology and pathophysiology of late sequelae is underway, and may reflect organ damage from the acute infection phase (Ngai), manifestations of a persistent hyperinflammatory state (Yende, Tay), ongoing viral activity associated with a host viral reservoir (Hartley), or an inadequate antibody response (Wu). Factors in addition to acute disease that may further complicate the picture include physical deconditioning (Gemelli) at baseline or after a long disease course (Thornton), pre-COVID-19 comorbidities (O’Keefe), and psychological sequelae following a long or difficult disease course (Yende) as well as those relating to lifestyle changes due to the pandemic (Galea). Likely, the persistent sequelae of COVID-19 represent multiple syndromes resulting from distinct pathophysiological processes along the spectrum of disease.

Though there is limited information on late sequelae of COVID-19, reports of persistent symptoms in persons who recovered from acute COVID-19 illness have emerged (Tenforde, Carfi, Halpin, COVID Symptom Study, Greenlaugh, del Rio). The most commonly reported symptoms include fatigue, dyspnea, cough, arthralgia, and chest pain (Tenforde, Halpin, O’Keefe, Calfi, Assaf, Banda, Lambert). Other reported symptoms include cognitive impairment, depression, myalgia, headache, fever, and palpitations (Tenforde, Halpin, O’Keefe, Calfi, Assaf, Banda, Lambert). More serious complications appear to be less common but have been reported. These complications include:
  • Cardiovascular: myocardial inflammation, ventricular dysfunction (Sardari, Puntmann, Rajpal)
  • Respiratory: pulmonary function abnormalities (Huang, Zhao)
  • Renal: acute kidney injury (Peleg)
  • Dermatologic: rash, alopecia (Lambert)
  • Neurological: olfactory and gustatory dysfunction, sleep dysregulation, altered cognition, memory impairment (Otte, Paderno, Halpin, Lambert, Assaf, Banda)
  • Psychiatric: depression, anxiety, changes in mood(Halpin, Lambert, Singh)
Post-COVID-19 care centers are opening at academic medical centers in the United States, bringing together multidisciplinary teams to provide a comprehensive and coordinated treatment approach to COVID-19 aftercare. The National Institutes of Health have published interim guidelines for the medical management of COVID-19, including a section on persistent symptoms or illnesses after recovery from acute COVID-19. These guidelines will be updated as new information emerges.
Survivor support groups are connecting individuals, providing support, and sharing resources with survivors and others affected by COVID-19 (Body Politic, Survivor Corps). Multi-year studies will be crucial in elucidating longer-term sequelae. CDC continues active investigation into the full spectrum of COVID-19 to establish a more complete understanding of the natural history of SARS-CoV-2 infection and COVID-19 related illnesses, which can inform care strategies as well as the public health response to this virus.
Ongoing research
National Institutes of Health, National Institute of Allergy and Infectious Diseases. A longitudinal study of COVID-19 sequelae and immunity. https://clinicaltrials.gov/ct2/show/NCT04411147
University of California, San Francisco. Long-term impact of infection with novel coronavirus (COVID-19) (LIINC). https://clinicaltrials.gov/ct2/show/record/NCT04362150

This early acknowledgement of long-term impacts from COVID-19 is encouraging, and it hopefully means these patients will be treated better than the millions of ME/CFS, Post Lyme Disease Syndrome, and Gulf War Illness patients that have too often been marginalized and/or ignored by the medical system over the past few decades.

It is even possible that what we learn from Post-COVID Syndrome may aid in the treatment of these other illnesses.

While its burden may not become fully apparent for years, Long COVID is something that individuals, and society as a whole, will have to deal with long after the pandemic has ended. 

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Sunday, January 29, 2023

EID Journal: Postacute Sequelae of SARS-CoV-2 in University Setting


#17,260

While politicians and pundits argue over whether the COVID emergency has ended, we continue to see a steady stream of studies showing that COVID infection - and particularly reinfection - even when the resulting illness is mild, can lead to serious, even debilitating, sequelae. 

While many of these `Long COVID' symptoms are relatively mild, and often resolve over a period of weeks or months, Post-COVID sequelae can also include far more serious cardiovascular, renal, pulmonary, neurological, and endocrine disorders. 

As we discussed at some length on Friday in Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks, there is growing evidence linking viral illnesses (including COVID) to neurological manifestations and neurodegenerative diseases like Parkinson's and dementia. 

And nearly a year ago, in Nature: Long-term Cardiovascular Outcomes of COVID-19 by Yan Xie, Evan Xu, Benjamin Bowe & Ziyad Al-Aly we looked at a study that described long-term cardiac damage among COVID survivors. 

A few (of many) additional studies we've looked at over the past year include:



The Lancet: Neurological and Psychiatric Risk Trajectories After SARS-CoV-2 Infection

MMWR: Post–COVID-19 Symptoms and Conditions Among Children and Adolescents

Nature: Long COVID After Breakthrough SARS-CoV-2 Infection

BMJ: Elevated Risk Of Blood Clots Up To 6 Months After COVID Infection

Diabetologia: Incidence of Newly Diagnosed Diabetes After Covid-19

Beyond the individual impact of each of these post-COVID conditions is the collective cost to society as literally millions of people are disabled (either partially or fully), unable to work, and in dire need of medical and financial support. 

Our response in the past - most recently with ME/CFS and Chronic Lyme Disease - has been to ignore the problem, and even ridicule and marginalize the patient. But that becomes harder to do as the number of cases increases. 

While most people who are infected (or reinfected) with COVID won't develop serious sequelae, right now we don't know how big the impact will become over time.  

A little over a week ago, the AMA released a statement (see What doctors wish patients knew about COVID-19 reinfection) calling reinfection `problematic' and equating it to `. . . playing Russian roulette" with the virus.

All of which brings us to a new research article, published this week in the CDC's EID Journal, that looks at the incidence of `Long COVID' in a university setting (faculty and students), and finds that more than 1/3rd (36%) of those who tested positive for COVID reported some post-acute sequelae. 

Strikingly, this study cohort was quite young (median age 23), with most reporting no underlying health problems, and had never smoked.   

While follow-up surveys were limited to 30-days post-infection, not everyone could be contacted, and recall bias may have impacted the results, the incidence of self-reported sequelae in such a young and reportedly healthy cohort is concerning.  

I've only posted some excerpts from a much longer report, so follow the link to read it in its entirety.  I'll have a postscript after the break. 

Research
Postacute Sequelae of SARS-CoV-2 in University Setting

Megan Landry , Sydney Bornstein, Nitasha Nagaraj, Gary A. Sardon, Amanda Castel, Amita Vyas, Karen McDonnell, Mira Agneshwar, Alyson Wilkinson, and Lynn Goldman
Author affiliation: The George Washington University Milliken Institute School of Public Health, Washington DC, USA

Abstract

Postacute sequelae of SARS-CoV-2 infection, commonly known as long COVID, is estimated to affect 10% to 80% of COVID-19 survivors. We examined the prevalence and predictors of long COVID from a sample of 1,338 COVID-19 cases among university members in Washington, DC, USA, during July 2021‒March 2022. 

Cases were followed up after 30 days of the initial positive result with confidential electronic surveys including questions about long COVID. The prevalence of long COVID was 36%. 

Long COVID was more prevalent among those who had underlying conditions, who were not fully vaccinated, who were female, who were former/current smokers, who experienced acute COVID-19 symptoms, who reported higher symptom counts, who sought medical care, or who received antibody treatment. 

Understanding long COVID among university members is imperative to support persons who have ongoing symptoms and to strengthen existing services or make referrals to other services, such as mental health, exercise programs, or long-term health studies.


It is estimated that 1 in 3 Americans who have SARS-CoV-2 infection will experience symptoms related to postacute sequelae of SARS-CoV-2 (1), also referred to as long COVID (other terms include long-haul coronavirus disease, post–-COVID-19 conditions, or chronic COVID-19) (2). The length of time that a person must experience symptoms to be considered to have long COVID is not universally accepted; definitions range from 28 days to 6 months after acute SARS-CoV-2 infection (3–7). A recent World Health Organization working group used a Delphi process to conclude that “a post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis” (8).

Regardless of a universally agreed upon length of time a person must experience symptoms to be characterized as long COVID, this sequela has been suggested to be the “next national health disaster” (9), and because of discrepancies in symptoms and long-term effects on quality of life, there seem to be more questions than answers. Although long COVID manifests differently in each person, nearly 50 signs and symptoms have been linked to the condition (10).

The most common signs and symptoms are fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste, and diarrhea (11). Other reported signs and symptoms include cognitive impairment (known as brain fog), memory loss, palpitations, anxiety, sore throat, sleep disorders, runny nose, sneezing, hoarseness, ear pain, thoughts of self-harm and suicide, seizures, and bladder incontinence (8,11), as well as cardiac effects, such as myocardial inflammation (12).

Although some investigators have reported that long COVID occurs at rates that are independent of symptom severity (11–13), others have found long COVID is more common among patients hospitalized for COVID-19 or those who experienced moderate-to-severe symptoms (6,11,14–20). However, long COVID has been observed in patients who were asymptomatic (2) or only experienced mild symptoms, and it has been reported that symptoms can fluctuate or relapse (7–8,21–23). Furthermore, little is known about long COVID signs and symptoms and predictors on a college campus, where most of the population is young and healthy, but among whom potential complications of long COVID could be detrimental to academic learning and overall quality of life.

(SNIP)
Discussion

This study aimed to examine the prevalence and predictors of long COVID in a university community. This sample was unique in that it consisted of primarily young adults who had few underlying health conditions and otherwise were considered healthy. Regardless of initial symptoms, nearly 36% of COVID-19 survivors in this study reported experiencing symptoms consistent with long COVID.

That result is within ranges found in other studies reporting a prevalence of long COVID of anywhere from 10% to 80% among COVID-19 survivors (3–5,7,21,29–31). Our study also found an increased odds of reporting symptoms consistent with long COVID for each additional symptom reported during the initial infection. This finding is consistent with recent studies conducted with a high proportion of young adults that also found a higher number of acute symptoms during a COVID-19 infection predicted >1 long COVID symptom (32). Monitoring symptoms of initial cases could help identify persons at risk for long COVID.

Our study also found that persons who had the fewest previous COVID-19 vaccines and boosters were at higher risk for development of symptoms consistent with long COVID, supporting other investigations suggesting that vaccination is associated with reduced risk for long COVID (33–36). Many colleges and universities required the COVID-19 vaccine before the fall 2021 semester but offered reasonable medical/religious exemptions. Our results further highlight the need for routine short- and long-term follow-up for persons who test positive for COVID-19 while continuing to advocate and monitor for vaccine and booster adherence to published recommendations.

Although prevention efforts are needed for long COVID, the findings from this study support the need to ameliorate consequences of long COVID. Based on symptomatology, recovery strategies for long COVID include physical rehabilitation, management of preexisting conditions, mental health support, social services support, and exercise programs scaled to the ability of the patient (11,37). Because long COVID can greatly interfere with the ability to learn or work, classroom or job accommodations, such as modifying academic and workplace policies, flexible scheduling, changing workplace environment, enabling remote or alternative learning, and modifying job responsibilities, are recommended for those having long COVID.

(SNIP)

Future research avenues should consider following up with long COVID survivors/patients to assess long-term or long-lasting symptoms. Such analysis could explore the consequences of long COVID for 5‒10 years after the initial infection, especially to gain a better understanding of its effect on young, healthy populations. Follow-up could also occur with older populations to assess whether symptoms progress into retirement and to determine the cost of long-term care resulting from long COVID. Furthermore, research should continue to examine the effect vaccine booster doses have on long COVID symptoms. Such research is vital to clarifying long-term effects of long COVID and how universities can support those dealing with long COVID to promote health and wellness across campus communities.

Dr. Landry is the project director for the Campus COVID-19 Support Team at the George Washington University, Washington, DC. Her primary research interests are public health surveillance and maternal and child health.
          (Continue . . . )


There is little doubt that Post-COVID syndrome is real, and for a significant number of people, it can prove severe enough to cause permanent disability and even premature death.

The $64 question is how big of a problem this is going to become. And frankly, we don't know, and may not know for 5 or 10 years. 

But the early warning signs are there, and while everyone wants to move beyond the COVID emergency and treat COVID like `seasonal flu', we ignore them at our own peril. 

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Friday, April 09, 2021

CDC Update & UK Survey On `Post' or `Long' COVID Sequelae

 

#15,903

Pandemics, like wars, have a lot in common.  They both can exact a high toll in lives, disrupt economies, separate loved ones, and often leave behind a trail of broken and damaged survivors. Ironically, they both also tend to spark abrupt leaps in both science and medicine. 

While our COVID pandemic will eventually end, the ravages of this virus will continue in some of the survivors - perhaps for the rest of their lives - due to `Post' or `Long' COVID sequelae. 

We've been following these concerns for roughly a year, as evidenced by this blog (see JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease) published in April of 2020.  In the months that would follow we'd see mounting evidence of serious  - and sometimes permanent - lung, cardiac, kidney, or neurological damage due to COVID infection. 

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury


Eurosurveillance: Reduced Maximal Aerobic Capacity After COVID-19 In Young Adult Recruits

JASN: Acute Kidney Injury In Hospitalized Patients With COVID-19

Additionally, a growing number of `recovered' COVID cases have reported a wide spectrum of chronic, and often debilitating symptoms - such as fatigue, recurrent fevers, `brain fog', myalgias, etc. - that are highly reminiscent of ME/CFS - which has disabled and traumatized well over a million Americans over the past 3 decades (see NIH About CFS/ME).

The burden of COVID-19 on society, even after the pandemic has ended, is likely to be heavy and prolonged one. Hopefully we'll do better by these casualties of this pandemic than we have with those who have suffered from ME/CFS, Post-Lyme Syndrome, and other post-viral syndromes. 
 
One positive, early sign is that the CDC, the WHO, and other agencies have recognized and acknowledged that Post-COVID syndrome is real, although it may take years of study to understand it fully. 

Yesterday, the CDC updated their POST-COVID Conditions webpage for the first time since November 13th (see below), after which I'll have the results of a UK Nationwide poll - conducted by their Office of National Statistics - on the self-reported incidence of `Long COVID' in the UK as of Early March. 

Post-COVID Conditions
Updated Apr. 8, 2021

Although most people with COVID-19 get better within weeks to months of illness, some do not. CDC and experts around the world are working to learn more about short- and long-term health effects associated with COVID-19, who gets them, and why. CDC uses the term post-COVID conditions to describe health issues that persist more than four weeks after first being infected with the virus that causes COVID-19.

Experts do not know why or how often some people experience post-COVID conditions. Other infectious diseases can also cause longer-term symptoms for a variety of reasons. Some post-COVID conditions are likely to be similar to those seen in other infectious diseases, but others may be more specific to COVID-19. Some post-COVID conditions involve symptoms similar to those caused by other health problems. Scientists are actively investigating the causes of post-COVID conditions.

Types of Post-COVID Conditions

Long COVID

Long COVID is a range of symptoms that can last weeks or months after first being infected with the virus that causes COVID-19 or can appear weeks after infection. Long COVID can happen to anyone who has had COVID-19, even if the illness was mild, or they had no symptoms. People with long COVID report experiencing different combinations of the following symptoms:
  • Tiredness or fatigue
  • Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
  • Headache
  • Loss of smell or taste
  • Dizziness on standing
  • Fast-beating or pounding heart (also known as heart palpitations)
  • Chest pain
  • Difficulty breathing or shortness of breath
  • Cough
  • Joint or muscle pain
  • Depression or anxiety
  • Fever
  • Symptoms that get worse after physical or mental activities

Multiorgan Effects of COVID-19

Multiorgan effects can affect most, if not all, body systems including heart, lung, kidney, skin, and brain functions. Multiorgan effects can also include conditions that occur after COVID-19, like multisystem inflammatory syndrome (MIS) and autoimmune conditions. MIS is a condition where different body parts can become swollen. Autoimmune conditions happen when your immune system attacks healthy cells in your body by mistake, causing painful swelling in the affected parts of the body.

It is unknown how long multiorgan system effects might last and whether the effects could lead to chronic health conditions.

Effects of COVID-19 Treatment or Hospitalization

Post-COVID conditions also can include the longer-term effects of COVID-19 treatment or hospitalization. Some of these longer-term effects are similar to those related to hospitalization for other respiratory infections or other conditions.

Effects of COVID-19 treatment and hospitalization can also include post-intensive care syndrome (PICS), which refers to health effects that remain after a critical illness. These effects can include severe weakness and post-traumatic stress disorder (PTSD). PTSD involves long-term reactions to a very stressful event.

Treatment

There are ways to help manage post-COVID conditions, and many patients with these symptoms are getting better with time. If you think you have a post-COVID condition, talk to your healthcare provider about options for managing or treating your symptoms and resources for support. Post-COVID care clinics are opening at medical centers across the United States to address patient needs.

The best way to prevent these long-term complications is to prevent COVID-19
Important Ways to Slow the Spread of COVID-19

COVID-19 and Vaccination

CDC recommends that people be vaccinated regardless of whether they already had COVID-19. Learn more about vaccination.

Although media articles have reported that some people with long COVID say their symptoms improved after being vaccinated, studies are needed to determine the effects of vaccination on post-COVID conditions.

What CDC is Doing

CDC continues to work to identify how common these longer-term effects are, who is most likely to get them, and whether symptoms eventually resolve. Multi-year studies are underway to further investigate post-COVID conditions. These studies will help us better understand post-COVID conditions and understand how to treat patients with these longer-term effects.

(Continue . . . )


While perhaps more speculation than science at this time, there are concerns expressed by some researchers that hidden sequelae from COVID infection may not become apparent for 5 or 10 years. 

In the decade following the 1918 pandemic, the world saw an epidemic of neurological diseases like Encephalitis Lethargica and Parkinson's disease, and while a causal link to the pandemic has never been established, a viral infection is a likely culprit (see The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?)

Emily A. Troyer, Jordan N. Kohn, and Suzi Hong

Similarly, there are concerns that what appears to be minor heart damage today may, over time, progress into something more problematic. 

Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter?

Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
 
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575

For now, even the scope of the problem is difficult to gauge, and we've seen estimates of as few as 1 in 10 cases and as high as 1 in 3 cases reporting long-lasting symptoms following COVID infection.  

A recent large retrospective cohort study from the UK, published last week in The BMJ that fonds nearly 30% of patients hospitalized with COVID were rehospitalized within 140 days of release, and over 12% had died.  

Rates that were (respectively) 3.5 and 7.7 times higher than matched controls. 

But even non-hospitalized, mildly affected COVID cases report post-COVID syndrome.  In an attempt to quantify the impact of `Long COVID' the UK's ONS has published their first analysis of both a study group of more than 20,000 participants, and a nationwide poll, that suggest a high degree of long-lasting sequelae from COVID-19. 

The ONS estimates that more than 1 million residents are currently affected by Long COVID in the UK. I've only posted their summary, follow the link to read the analysis in full. 

Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 1 April 2021

Estimates of the prevalence of self-reported "long COVID", and the duration of ongoing symptoms following confirmed coronavirus infection, using UK Coronavirus (COVID-19) Infection Survey data to 6 March 2021.
Main points
  • Over the four-week period ending 6 March 2021, an estimated 1.1 million people in private households in the UK reported experiencing long COVID (symptoms persisting more than four weeks after the first suspected coronavirus (COVID-19) episode that are not explained by something else).
  • The estimates presented in this analysis relate to self-reported long COVID, as experienced by study participants, rather than clinically diagnosed ongoing symptomatic COVID-19 or post-COVID-19 syndrome. There is no universally agreed definition of long COVID, but it covers a broad range of symptoms such as fatigue, muscle pain, and difficulty concentrating.
  • Self-reported long COVID symptoms were adversely affecting the day-to-day activities of 674,000 people in private households in the UK, with 196,000 of these individuals reporting that their ability to undertake their day-to-day activities had been limited a lot.
  • Of people with self-reported long COVID, 697,000 first had (or suspected they had) COVID-19 at least 12 weeks previously, and 70,000 first had (or suspected they had) COVID-19 at least one year previously.
  • Prevalence rates of self-reported long COVID were greatest in people aged 35 to 69 years, females, those living in the most deprived areas, those working in health or social care, and those with a pre-existing, activity-limiting health condition; however, it is not possible to say whether these patterns are because of differences in the risk of coronavirus infection or susceptibility to experiencing long COVID following infection.
  • These estimates provide a measure of the prevalence of self-reported long COVID across the whole population, and reflect both the risk of being infected with coronavirus and the risk of developing long COVID following infection; to investigate the second of these components, we examined the duration of self-reported symptoms following confirmed infection.
  • Among a sample of over 20,000 study participants who tested positive for COVID-19 between 26 April 2020 and 6 March 2021, 13.7% continued to experience symptoms for at least 12 weeks. This was eight times higher than in a control group of participants who are unlikely to have had COVID-19, suggesting that the prevalence of ongoing symptoms following coronavirus infection is higher than in the general population.
(Continue . . . )

 

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Monday, June 19, 2023

Preprint: Inflammatory Profiles are Associated with Long COVID up to 6 Months After Illness Onset

 

Slide From June 17th, 2021 CDC COCA Call on `Post-COVID' Syndrome

#17,501

Although many people sill discount the risks, there is growing evidence that SARS-CoV-2 infection can lead to persistent - and sometimes permanent - sequelae, what is commonly called `Long COVID', Post-COVID Syndrome, or sometimes post-acute sequelae of COVID-19 (PASC). 

It doesn't happen to everyone, but estimates range (based on varying criteria) that anywhere between 10% and 50% of COVID survivors will experience some degree of lingering after-effects. 

While most eventually recover, for some this post-COVID sequelae can be both debilitating, and permanent.  There is also growing evidence that repeated infections with COVID increase the risks of Long COVID, disability, and death (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection).

Post-COVID sequelae may include cardiovascular, renal, pulmonary, neurological, and endocrine disorders. A few (of many) studies we've looked at over the past few months include:
Study: SARS-CoV-2 Infection and Viral Fusogens Cause Neuronal and Glial Fusion that Compromises Neuronal Activity

JAMA: Additional Evidence Of A Post-COVID/Diabetes Link
EID Journal: Postacute Sequelae of SARS-CoV-2 in University Setting

Nature: Long-term Cardiovascular Outcomes of COVID-19
The Lancet: Neurological and Psychiatric Risk Trajectories After SARS-CoV-2 Infection

MMWR: Post–COVID-19 Symptoms and Conditions Among Children and Adolescents

To this growing list of studies we have a preprint from the Netherlands's RECoVERED Study Group from the Public Health Service of Amsterdam and Amsterdam UMC, which finds links between long COVID and elevated inflammatory profiles (cytokines) following COVID illness. 

While they say immune dysregulation does not completely explain Long COVID, it appears to play an important role, and elevated Interleukin-1 beta levels were strongly predictive of ongoing PASC at 6 months.

Due to its length and technical nature I've only reproduced the abstract and few excerpts below.  Follow the link to read the report in its entirety. 

Inflammatory profiles are associated with long COVID up to 6 months after illness onset: a prospective cohort study of individuals with mild to critical COVID-19

Elke Wynberg,  Alvin X. Han, Hugo D.G. van Willigen, Anouk Verveen, Lisa van Pul, Irma Maurer, Ester M. van Leeuwen, Joost G. van den Aardweg, Menno D. de Jong, Pythia Nieuwkerk, Maria Prins, Neeltje A. Kootstra, Godelieve J. de Bree the RECoVERED Study Group
doi: https://doi.org/10.1101/2023.06.14.23291395        
Abstract

Background After initial COVID-19 disease, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC.

Methods RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after illness onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects.

Results 186/349 (53%) participants had ≥2 serum samples and were included. Of these, 101 (54%: 45/101[45%] female, median age 55 years [IQR=45-64]) reported PASC at 12 and 24 weeks after illness onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR=40-56]). PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks in the multivariate model. Early (0-4 week) IL-1β and BMI at illness onset were predictive of PASC at 24 weeks.

Conclusions Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among those individuals with reduced pulmonary function. Early IL-1β shows promise as predictors of PASC.

         (SNIP)

COVID-19 is associated with persistent elevation of pro-inflammatory cytokines

First, we determined how the levels of cytokines in the study participants with SARS-CoV-2 infection compared to the uninfected reference group. Within the first 4 weeks after symptom onset, levels of IP10, IL10, IL17, IL1β, IL6 and TNFα were significantly elevated among participants infected with SARS-CoV-2 compared to reference samples (Supplementary Figure S1; Supplementary Table S2). Levels of IL10, IL17, IL1β and IL6 also remained elevated up to 21-24 weeks after SARS-CoV-2 infection in study participants as compared to the reference group (Supplementary Figure S1). Cytokine correlation matrices are shown in Supplementary Figure S2. These data indicate the presence of immune dysregulation in study participants with COVID-19.

          (SNIP)

Conclusions

In summary, our study indicates that immune dysregulation does not single-handedly explain PASC as defined by self-reported symptoms. However, confirmation of PASC status with impaired pulmonary function as an objective measure revealed an association with raised pro-inflammatory cytokines, as previously reported in other studies. In addition, early raised IL1β levels were strongly predictive of ongoing PASC at 6 months in our analyses. Our findings therefore suggest that immune dysregulation plays an important role in the pathogenesis of ongoing symptoms in some individuals.

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There is little doubt that Post-COVID syndrome is real, and for an as-yet unquantified percentage of the population, it can prove severe enough to cause permanent disability and even premature death. 

The $64 question is how big of a problem this is going to become. 

Some experts have suggested we may see huge increases in COVID-19 related heart failure and neurological diseases in the years ahead.

Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575
 
Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms
Emily A. Troyer, Jordan N. Kohn, and Suzi Hong  

The truth is, we don't know, and may not know for another  5 or 10 years. 

But we continue to see the warning signs, and while everyone wants to move beyond the COVID emergency and treat COVID like `seasonal flu', we ignore them at our own peril.
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Friday, August 14, 2020

PAHO Epi Alert: Complications & Sequelae Of COVID-19

 

#15, 414

Very early on in our COVID-19 outbreak it was apparent that this emerging coronavirus did not carry the same level of lethality as MERS-CoV, SARS-CoV, or H5N1/H7N9 avian flu in humans. The Case Fatality Rate (CFR) - at least among healthy adults - was relatively low, albeit higher than seasonal flu. 

More concerning were the high communicability and attack rates, and the lengthy hospitalization stays and slow recoveries being reported. By the end of February it was apparent we were facing a high-morbidity/low-mortality pandemic. 

One that might kill 1% of those infected, but that could often require weeks or even months for many to recover from. Twenty-five weeks ago, in Pandemics Are More Than Just About The CFR, I warned about the danger of focusing too heavily on the number of deaths, while ignoring the other negative impacts of a high-morbidity contagion. 

Sadly, until recently the media has focused primarily on the grim daily death toll, while glossing over long recoveries and often - long-term health problems and/or disability - associated with SARS-CoV-2 infection. 

Some of the adverse outcomes reported among COVID-19 survivors include:

JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury


https://twitter.com/KartikSehgal_MD/status/1281695760879202304

Over the past few months, we've seen cardiologists and neurologists weigh in on the potential for seeing huge increases in COVID-19 related heart failure and neurological diseases, some that may not become fully apparent for years. 

Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
 
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575


Emily A. Troyer, Jordan N. Kohn, and Suzi Hong

And just over a month ago,  Dr. Anthony Fauci expressed concerns that many COVID patients are suffering from a post-viral syndrome - similar to ME/CFS - which has disabled and traumatized well over a million Americans over the past 3 decades (see NIH About CFS/ME). 

We are literally just scratching at the surface of the damage this pandemic virus has caused, and may cause going forward.  

And as we go into what is likely to be a chaotic and dangerous fall,  The Psychological Impact On 1st Responders & Frontline HCWs can't be brushed aside either.  After the limited 2015 MERS-CoV outbreak ins South Korea (see Study: Burnout & PTSD Among Nurses Working During A Large MERS-CoV Outbreak - Korea, 2015) half of all nurses reported PTSD symptoms.

Regardless of the death toll, we'll be living with the physical and psychological wounds of COVID-19 for years to come. 

All of which brings us to a 16-page PAHO (Pan American Health Organization) Epidemiological Alert on Complications and sequelae of COVID-19  released on August 12th.  Due to its length, I've only reproduced the introduction.  Follow the link to download and read it in its entirety. 

More than 7 months following the first report of novel coronavirus disease (COVID-19), knowledge of the complications and sequelae of this disease has increased substantially.

Through this alert, the Pan American Health Organization / World Health Organization (PAHO/WHO) urges Member States to keep health professionals informed as new information continues to become available in order to strengthen the timely detection and proper management of COVID-19 cases, complications, and sequelae.

Introduction

Between 10 July and 10 August 2020, an additional 4,433,115 cases of COVID-19, including 114,480 additional deaths, were reported in the Region of the Americas, for a cumulative total of 10,697,800 confirmed cases of COVID-19 including 390,849 deaths. This represents a relative increase of 64% in cases and 37% in deaths compared to the number of new cases and deaths reported during the previous 4-week period (12 June to 9 July). The highest proportion of new cases were reported in the United States of America (44%) and Brazil (30%), while the highest proportion of new deaths were reported in Brazil (29%), the United States of America (26%), and Mexico (17%).

More than 7 months following the notification of the first COVID-19 cases (Joint Report of the WHO and the Government of China in February 2020) (1), there have been advances in the knowledge of the disease, including but not limited to the source of infection; the pathogenesis and virulence of the virus; transmissibility; risk factors; effectiveness of prevention measures; surveillance; diagnosis; clinical management; and complications and sequelae, amongst others. However, there remain several gaps pertaining to these factors that still require contribution from the entire scientific community.

The intense transmission of COVID-19 in most of the countries and territories of the Americas, along with evidence generated from the scientific community, has increased our knowledge of several of these factors including those related to complications and sequelae from COVID-19.

Knowledge of these factors is necessary to improve and adjust the prevention and control strategies of the pandemic.

The following is a summary of the available evidence regarding complications and sequelae of COVID-19.
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The morbidity and sequelae associated with COVID-19 not only presents a serious challenge to our already stressed health care delivery system, it can negatively affect economic recovery, supply chains, and the overall functioning of society. 

Longer term, we'll have to figure out how to care for those left permanently damaged or disabled by this pandemic. 

While COVID-19 remains a relatively low-mortality pandemic, its overall impact on individuals, and society, are far from benign. 


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Tuesday, November 10, 2020

MMWR: Readmission Of COVID-19 Patients Within 2 Months Of Hospital Discharge

#15,549


COVID-19 has produced a relatively high morbidity - low mortality pandemic; and while several times deadlier than than seasonal flu, is has not been as lethal as might be expected from MERS-CoV, SARS, or avian H5N1, H5N6, or H7N9.  

This `good news' is tempered somewhat by numerous reports of slow recoveries and/or lingering illness among survivors.  Unlike influenza - which is primarily a pulmonary infection - COVID-19 appears to launch a more systemic attack (see Nature Med. Review: Extrapulmonary manifestations of COVID-19).


Although it still appears that most COVID cases experience a relatively mild and self-limiting illness, for months we've been following reports of chronic illness ( aka `Long COVID'), or sequelae related to the initial infection (see UK NIHR: Living With COVID-19 (Long COVID)).

Some past blogs include:
 
Eurosurveillance: Reduced Maximal Aerobic Capacity After COVID-19 In Young Adult Recruits

JASN: Acute Kidney Injury In Hospitalized Patients With COVID-19


JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury

The Lancet: Yet Another Study On Neurological Manifestations In Severe COVID-19 Patients

Over the past few months we've seen cardiologists and neurologists weigh in on the potential for seeing huge increases in COVID-19 related heart failure and neurological diseases, some that may not become fully apparent for years.
 
Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
 
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575
 

Emily A. Troyer, Jordan N. Kohn, and Suzi Hong


Not surprisingly, older patients, and those with comorbidities, are more likely to have a slower or more difficult recovery from COVID-19.  This isn't unique to COVID, of course. Any significant illness in a medically vulnerable patient can trigger a cascade of negative events requiring additional treatment. 

Yesterday the CDC's MMWR published a review of readmissions (within 60 days) of COVID cases discharged from hospitals between March and August, and found that 1 in 11 were readmitted to the same hospital within two months. 

While this doesn't capture all readmissions, or all significant sequelae in discharged (or never hospitalized) COVID cases, it does help illustrate the lingering health impacts of COVID-19, and the ongoing burden this may place on the healthcare delivery system. 

I've only posted excerpts from a much longer report, so follow the link to read it in its entirety. 

Characteristics of Hospitalized COVID-19 Patients Discharged and Experiencing Same-Hospital Readmission — United States, March–August 2020
Early Release / November 9, 2020 / 69
Amy M. Lavery, PhD1; Leigh Ellyn Preston, DrPH1; Jean Y. Ko, PhD1; Jennifer R. Chevinsky, MD1; Carla L. DeSisto, PhD1; Audrey F. Pennington, PhD1; Lyudmyla Kompaniyets, PhD1; S. Deblina Datta, MD1; Eleanor S. Click, MD, PhD1; Thomas Golden, MD1; Alyson B. Goodman, MD1; William R. Mac Kenzie, MD1; Tegan K. Boehmer, PhD1; Adi V. Gundlapalli, MD, PhD1 (View author affiliations)View suggested citation
Summary
What is already known about this topic?
Evidence suggests that potential health complications after COVID-19 illness might require ongoing clinical care.
What is added by this report?
After discharge from an initial COVID-19 hospitalization, 9% of patients were readmitted to the same hospital within 2 months of discharge. Multiple readmissions occurred in 1.6% of patients. Risk factors for readmission included age ≥65 years, presence of certain chronic conditions, hospitalization within the 3 months preceding the first COVID-19 hospitalization, and discharge to a skilled nursing facility or with home health care.

What are the implications for public health practice?

Understanding frequency of, and potential reasons for, readmission after a COVID-19 hospitalization can inform clinical practice, discharge disposition decisions, and public health priorities, such as health care resource planning.
(EXCERPT)
Among 126,137 unique patients with an index COVID-19 admission during March–July 2020, 15% died during the index hospitalization. Among the 106,543 (85%) surviving patients, 9% (9,504) were readmitted to the same hospital within 2 months of discharge through August 2020. More than a single readmission occurred among 1.6% of patients discharged after the index hospitalization. Readmissions occurred more often among patients discharged to a skilled nursing facility (SNF) (15%) or those needing home health care (12%) than among patients discharged to home or self-care (7%).
The odds of hospital readmission increased with age among persons aged ≥65 years, presence of certain chronic conditions, hospitalization within the 3 months preceding the index hospitalization, and if discharge from the index hospitalization was to a SNF or to home with health care assistance.
          (SNIP)


These results are comparable to those of recently published analyses, which found a similar group of chronic conditions to be significantly associated with hospital readmission (6,7) and could be explained by the complications of underlying conditions in the presence of COVID-19 (8), COVID-19 sequelae (3), or indirect effects of the COVID-19 pandemic (9). Although only a small proportion of patients discharged to home or self-care were readmitted, 7% returned to the hospital within a median of 7 days. One explanation for their readmission is that approximately two thirds of these 4,406 patients had one or more of the selected chronic conditions.
 
After hospitalization for COVID-19, the most common primary discharge diagnoses from hospital readmission were diseases of the circulatory, digestive, or respiratory systems. Future work will examine the detailed diagnoses recorded during readmissions to better understand COVID-19 sequelae or health conditions that require extended or ongoing care. 

 (Continue . . . )

 


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