Long COVID’s daunting toll seen in study of pandemic’s earliest patients

Authors: Melissa Healy   6 hrs ago

COVID-19 patients in Wuhan were among the pandemic’s first victims, and a comprehensive new study finds that a year after shaking the coronavirus, survivors were more likely than their uninfected peers to suffer from mobility problems, pain or discomfort, anxiety and depression.

detailed accounting of 1,276 people hospitalized for COVID-19 in the pandemic’s opening months reveals that a full year later, almost half continued to report at least one lingering health problem that is now considered a symptom of “long COVID.”

One out of five said they had continued fatigue and/or muscle weakness, and 17% said they were still experiencing sleep difficulties. Just over one in four said they were suffering anxiety or depression in the wake of their bout with the SARS-CoV-2 virus.

For the growing number of patients who identify themselves as COVID “long haulers,” the new accounting offers cause for optimism — and concern. The period from six to 12 months after infection brought improvement for many. But most patients struggling with symptoms at the six-month mark were not yet well six months later.

The findings, catalogued by a team of Chinese researchers, were published late Thursday in the medical journal Lancet.

“This is not good news,” said David Putrino, a rehabilitation specialist who works with COVID long haulers at Mount Sinai Hospital in New York. “If you run the numbers here, about one-third of the group that had persistent symptoms are getting better after 12 months, while two-thirds are not.”

Putrino also called the findings a “wake-up call” to public health officials that even when the pandemic is over — a distant enough prospect in the midst of a fourth wave of infections — its downstream consequences will not be.

“We’re going to need resources for many years to come to deal with these patients,” he said.

There will be a lot of them. More than 87,000 COVID-19 patients are being hospitalized each day in the United States, and 2.7 million have receiving hospital care in the past year alone.

The half who contend with persistent symptoms will show up in doctors’ offices with clusters of vague and perplexing complaints including brain fog, heart palpitations, pain and exhaustion. And despite emerging evidence that time and specialized treatment can help many to improve, few will have the wherewithal to spend months in intensive rehabilitation for their symptoms, Putrino said.

An editorial published alongside the new study noted that only 0.4% of COVID long haulers are receiving rehabilitative treatment for their symptoms.

Even as scientists puzzle over the common biological mechanisms of long COVID’s diverse symptoms, healthcare providers “must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualised, patient-oriented goals, with an appropriately trained workforce,” Lancet’s editors wrote.

The new research also offered some glimmers of hope.

When the study’s COVID-19 patients were examined at six months, 68% said they had at least one of 15 symptoms considered hallmarks of long COVID, which is also known as Post-Acute Sequelae of COVID, or PASC. At one year, 49% were still afflicted by at least one of those symptoms.

The proportion of patients with ongoing muscle weakness and fatigue dropped from 52% to 20% during that time. Patients experiencing loss of smell dropped from 11% to 4%, and those afflicted with sleep problems fell from 27% to 17%. The 22% who reported hair loss at six months dwindled to 11% a full year out.

At the same time, the numbers of patients reporting breathing difficulties saw a slight increase, rising from 26% at six months to 30% after a year. Likewise, patients who reported new depression or anxiety increased from 23% to 26% during that period.

Study co-author Xiaoying Gu from the China-Japan Friendship Hospital in Beijing said the slight uptick in anxiety and depression was, like all of long COVID’s symptoms, hard to explain.

The psychiatric symptoms “could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it,” he said. “Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health or loss of employment associated with illness.”

Patients who required mechanical ventilation were more likely than those with less severe illness to have measurable lung impairment and abnormal chest X-rays at both six and 12 months.

But in the tally of more subjective long COVID symptoms, the difference between the most severely ill and those who required no supplemental oxygen at all was very small.

That finding underscores the fact that even patients who are only mildly ill are at risk of developing a range of persistent symptoms.

Of the study population’s 479 patients who held jobs when the pandemic struck, 88% had returned to work a year after their illness. Most of the 57 who did not return said they either could not or were unwilling to do the tasks required of them.

The findings from the Wuhan patients also tracked with the widespread observation that persistent post-COVID infection symptoms are more common in women than in men. Women who had been hospitalized for COVID-19 were twice as likely as their male counterparts to report depression or anxiety 12 months later. In addition, they were close to three times as likely to show evidence of impaired lung function, and 43% more likely to report symptoms of fatigue and muscle weakness.

All of the study’s participants were treated at a single hospital in Wuhan, where reports of a mysterious new form of pneumonia first surfaced in December 2019. The researchers followed a large group of patients sickened in the first five months that the outbreak.

That makes the Lancet report one of the earliest and largest accounts of lingering COVID-19 symptoms to be tallied and vetted by other researchers, and the only one to compare such patients to a group of uninfected peers matched on a wide range of demographic and health attributes.

One thing is already clear, the journal editors noted: “Long COVID is a modern medical challenge of the first order.”

This story originally appeared in Los Angeles Times.

Meningoencephalitis associated with COVID-19: a systematic review

Authors: Ritwick Mondal 1Upasana Ganguly 1Shramana Deb 2Gourav Shome 3Subhasish Pramanik 1Deebya Bandyopadhyay 1Durjoy Lahiri 4

Abstract

With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes “SARS-COV-2,” “COVID-19,” and “meningoencephalitis.” All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analyzing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33367960/

Here’s what we know so far about the long-term symptoms ofCOVID-19

July 26, 2020 3.56pm EDT

We’re now all too familiar with the common symptoms of COVID-19: a fever, dry cough and fatigue. Some people also experience aches and pains, a sore throat, and loss of taste or smell.

Sufferers with mild illness might expect to get better after a few weeks. But there’s mounting evidence this isn’t the case, and COVID-19 may leave a long-lasting impression on its victims – not just the most severely affected or the elderly and frail.

It’s not just an infection of the lungs

On the surface, COVID-19 is a lung disease. The SARS-CoV-2 coronavirus infects cells of the respiratory tract and can cause life-threatening pneumonia.

However, the full range of symptoms affects multiple parts of the body. An app that records daily symptoms developed at King’s College London has tracked the progress of more than 4 million COVID-19 patients in the United Kingdom, Sweden and the United States.

Besides the well-described symptoms of fever, cough and loss of smell are other effects, including fatigue, rash, headache, abdominal pain and diarrhoea. People who develop more severe forms of the disease also report confusion, severe muscle pains, cough and shortness of breath.

About 20% of those infected with COVID-19 require hospitalisation to treat their pneumonia, and many need assistance with oxygen. In about 5% of cases the pneumonia becomes so severe patients are admitted to intensive care for breathing support.

It trips the immune system

People with severe COVID-19 seem to show an altered immune response even in the disease’s early stages. They have fewer circulating immune cells, which fail to efficiently control the virus, and instead suffer an exaggerated inflammatory response (the “cytokine storm”).

This is increasingly recognised as one of the main factors that makes the disease so serious in some patients. Suppressing this exaggerated response with the immunosuppressant dexamethasone remains the only treatment that reduces death rates in those who require oxygen support or intensive care.


Read more: Dexamethasone: the cheap, old and boring drug that’s a potential coronavirus treatment


Patients with severe COVID-19 describe a far more complex range of symptoms than would normally be seen with pneumonia alone. This can include brain inflammation (encephalitis), causing confusion and reduced consciousness. Up to 6% of severe sufferers may have a stroke.

Pathology studies and autopsies of patients who died from COVID-19 reveal the expected features of severe pneumonia or acute respiratory distress syndrome (ARDS), with extensive inflammation and scarring. ARDS occurs when there’s sudden and widespread inflammation in the lungs, resulting in shortness of breath and blueish skin.

Uniquely, however, they also reveal the virus seems to directly cause inflammation of the small capillaries or blood vessels, not just in the lungs but in multiple organs, leading to blood clots and damage to the kidney and heart.

Persistent symptoms ‘deeply frustrating’

Anyone with a severe disease would be expected to suffer long-lasting consequences. But COVID-19 seems to have persistent symptoms even in those with milder forms of the illness.

Social media is replete with stories of survivors afflicted by ongoing symptoms. Support groups have emerged on Slack and Facebook hosting thousands of people, some still suffering more than 60 days after infection. They call themselves “long-termers” or “long-haulers”.

One of the most well-known sufferers is Paul Garner, an infectious disease specialist at the Liverpool School of Tropical Medicine in the UK. He was infected in late March and his symptoms continue. In a blog post published by the British Medical Journal he describes having a:

…muggy head, upset stomach, tinnitus (ringing in the ears), pins and needles, breathlessness, dizziness and arthritis in the hands.

These symptoms have waxed and waned but not yet resolved. He says this is:

…deeply frustrating. A lot of people start doubting themselves… Their partners wonder if there is something psychologically wrong with them.

So far, only one peer-reviewed study has reported results on the long-term symptoms of COVID-19 infection: a single group of 143 survivors from Rome. Most of them did not need hospitalization and all were assessed at least 60 days after infection. They reported a worsened quality of life in 44.1% of cases, including symptoms of persistent fatigue (53.1%), breathlessness (43.4%), joint pain (27.3%), and chest pain (21.7%).

Post-acute COVID-19 syndrome

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

Main

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for coronavirus disease 2019 (COVID-19), has caused morbidity and mortality at an unprecedented scale globally1. Scientific and clinical evidence is evolving on the subacute and long-term effects of COVID-19, which can affect multiple organ systems2. Early reports suggest residual effects of SARS-CoV-2 infection, such as fatigue, dyspnea, chest pain, cognitive disturbances, arthralgia and decline in quality of life3,4,5. Cellular damage, a robust innate immune response with inflammatory cytokine production, and a pro-coagulant state induced by SARS-CoV-2 infection may contribute to these sequelae6,7,8. Survivors of previous coronavirus infections, including the SARS epidemic of 2003 and the Middle East respiratory syndrome (MERS) outbreak of 2012, have demonstrated a similar constellation of persistent symptoms, reinforcing concern for clinically significant sequelae of COVID-19 (refs. 9,10,11,12,13,14,15).

Systematic study of sequelae after recovery from acute COVID-19 is needed to develop an evidence-based multidisciplinary team approach for caring for these patients, and to inform research priorities. A comprehensive understanding of patient care needs beyond the acute phase will help in the development of infrastructure for COVID-19 clinics that will be equipped to provide integrated multispecialty care in the outpatient setting. While the definition of the post-acute COVID-19 timeline is evolving, it has been suggested to include persistence of symptoms or development of sequelae beyond 3 or 4 weeks from the onset of acute symptoms of COVID-19 (refs. 16,17), as replication-competent SARS-CoV-2 has not been isolated after 3 weeks18. For the purpose of this review, we defined post-acute COVID-19 as persistent symptoms and/or delayed or long-term complications of SARS-CoV-2 infection beyond 4 weeks from the onset of symptoms (Fig. 1). Based on recent literature, it is further divided into two categories: (1) subacute or ongoing symptomatic COVID-19, which includes symptoms and abnormalities present from 4–12 weeks beyond acute COVID-19; and (2) chronic or post-COVID-19 syndrome, which includes symptoms and abnormalities persisting or present beyond 12 weeks of the onset of acute COVID-19 and not attributable to alternative diagnoses17,19. Herein, we summarize the epidemiology and organ-specific sequelae of post-acute COVID-19 and address management considerations for the interdisciplinary comprehensive care of these patients in COVID-19 clinics 

For More Information: https://www.nature.com/articles/s41591-021-01283-z

Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)—A Systemic Review and Comparison of Clinical Presentation and Symptomatology

Authors: Timothy L. Wong* and Danielle J. Weitzer

Abstract

Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness—myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.

1. Introduction

Coronavirus disease 2019 (COVID-19), a highly contagious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), was declared a pandemic by the World Health Organization in March 2020 [1]. As of 7 March 2021, there are over 100 million cumulative cases, with over 2.5 million deaths worldwide [2]. Within the United States alone, there have been almost 30 million cumulative cases, with over half a million deaths as of mid-March [3].

In terms of clinical profile and disease symptomatology, individuals afflicted with COVID-19 vary greatly in terms of clinical presentation [4,5]. While some individuals remain asymptomatic, others experience symptoms generally associated with other viral respiratory diseases, such as fever, cough, dyspnea, headache, and sore throat [6,7,8]. During the acute phase of COVID-19, various other systemic impacts including gastrointestinal, renal, hepatological, rheumatological, and neurological symptoms and complications have been reported [9,10]. While there continues to be significant public concern and research centered around the acute course and presentation of COVID-19, there is increasing public and academic interest in the chronic sequelae of the disease [11,12,13].

There is currently no uniform terminology for this so-called long COVID [14], or, as it has also been termed, long-haul COVID-19 [15,16], post-COVID syndrome [17], chronic COVID syndrome [18], and more recently, post-acute sequelae of SARS-COV-2 infection (PASC) [19]. There is no established case definition or diagnostic criteria, but some have suggested long COVID as being defined by persistent signs and symptoms more than four weeks after initial infection with SARS-COV-2 [20,21]. Research into the prevalence of long COVID is ongoing, but one study has estimated that over 87% of COVID patients continue to experience at least one symptom, two months after COVID symptom onset [22]. The risk for developing long COVID does not appear to be correlated with the severity of acute illness [23]. The etiologies of long COVID are uncertain, with some linking it to autoimmune condition or hyperinflammatory states after resolution of acute COVID [24,25,26].

The characteristics and mysterious nature of long COVID led some to suggest a connection to a debilitating but lesser-known chronic medical condition: myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [27,28,29]. ME/CFS is a long-term complicated illness characterized by at least six months of fatigue and exhaustion. This illness is estimated to account for USD 18–51 billion dollars in economic costs. In total, 2.5 million Americans suffer from chronic fatigue syndrome, with one quarter of those diagnosed being house or bed bound [30]. Within the general population, the prevalence of chronic fatigue ranges between ten and forty percent. Despite this, due to a lack in diagnostic testing without consistent and established treatments, there has been disputes regarding the actual existence of chronic fatigue syndrome. As the diagnosis is mostly based upon patient’s subjective feedback, this has sparked stigma that has led to dismissive behaviors in the medical community. The misconception regarding chronic fatigue syndrome may have been started because of how it was initially characterized. For example, early reports of chronic fatigue were described as a derogatory term known as the Yuppie Flu, which initially characterized the illness among young workers, with the implication of individuals trying to get out of their job responsibilities. However, since this time, the illness has come to be understood to rather affect a broader array of populations, but with a predominance of women being more affected than men [31]. To better understand this illness, improved knowledge of the research and definitions surrounding the illness is needed.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145228/

Recovered COVID Patients Suffering ‘Significant Cognitive Deficits’ According To Large-Scale UK Study

Over 190 million people have officially contracted SARS-CoV-2, the virus which causes Covid-19. Of that, the vast majority have recovered – while up to one-third reportedly suffer from lingering symptoms of varying severity, known as ‘long covid.’

Common complaints include a lack of smell and taste, as well as “brain fog” – in which sufferers often complain of ongoing confusion, lack of focus, and migraines – well after they’ve ‘recovered’ from the disease.

Last week, The Independent reported that Covid-19 may accelerate the onset of Alzheimer’s disease in patients suffering from neurological symptoms, while another study noted in the report found that coronavirus patients “are more susceptible to long-term memory and thinking problems.”

Last September, a study offered the first clear evidence that Covid-19 ‘hijacks’ brain cells to make copies of itself – starving nearby cells of oxygen. The same researchers found last July that some Covid-19 patients have developed serious neurological complications, including nerve damage.

For More Information: http://wp.cov19longhaulfoundation.org/wp-admin/post.php?post=1508&action=edit

Chronic Fatigue May Be Long-Term Effect of COVID

Authors: Carolyn Crist

A large number of people who contract the coronavirus don’t fully recover in a few weeks, and many of them are experiencing chronic fatigue.

More than a third of those who have tested positive for COVID-19 and have symptoms don’t feel like they’re back to normal, even weeks later, according to a new CDC report.

“COVID-19 can result in prolonged illness, even among young adults without underlying chronic medical conditions,” the CDC COVID-19 Response Team wrote.

About 35% of people surveyed for the study said they weren’t back to their “usual state of health,” according to the report. Among those between ages 18-34 without prior chronic medical conditions, one in five said they hadn’t completely recovered.

Scientists are beginning to study whether the coronavirus may create post-viral issues such as myalgic encephalomyelitis, which is also known as chronic fatigue syndrome. Common symptoms include brain fog, fatigue, pain, immune issues, and malaise after exercise.

Those who are experiencing long-term symptoms after contracting the coronavirus — called the “COVID long-haulers” — are beginning to talk about the months-long issues they’ve had, according to CNN.

Tens of thousands of people have joined online support groups on social media, private chat channels and special interest websites, where they can talk about their symptoms and what to do as they recover.

For More Information: https://www.webmd.com/lung/news/20200809/chronic-fatigue-may-be-long-term-effect-of-covid

Long-Term Brain Disorders in Post Covid-19 Neurological Syndrome (PCNS) Patient

Authors: Domenico Nuzzo,1,2,* Gaetano Cambula,3 Ignazio Bacile,3 Manfredi Rizzo,4 Massimo Galia,5 Paola Mangiapane,6 Pasquale Picone,1,2 Daniela Giacomazza,7 and Luca Scalisi8,9,*

In the recent pandemic disease, called COVID-19, the role of neurologists and neurobiologists represents a chance to study key features of brain infection and deepen neurological manifestations of COVID-19 and other coronavirus infections. In fact, many studies suggest brain damage during infection and persistent neurological symptoms after COVID-19 infection. Reverse transcription PCR test, antibody tests, Computed Tomography (CT) of the lung, and Magnetic Resonance (MR) of the brain of the patient were periodically performed during this case report for eight months after infection. The aim of this article is to describe the prolonged neurological clinical consequences related to COVID-19. We believe it is clinically clear that we can define a post-acute COVID-19 neurological syndrome. Therefore, in patients after a severe clinical condition of COVID-19, a deepening of persistent neurological signs is necessary.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066611/

Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue

Authors: Theoharis C Theoharides 1 2 3 4 5Christos Cholevas 5Konstantinos Polyzoidis 5Antonios Politis 6

COVID‐19 leads to severe respiratory problems, but also to long‐COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long‐COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250989/

COVID-19 ‘brain fog’ inspires search for causes and treatments

Authors: Kelly Servick

The true prevalence of cognitive problems in COVID-19 survivors is elusive, and the underlying causes of lingering symptoms are the subject of ongoing studies. But it’s now clear that trouble thinking, concentrating, and remembering can be among the most debilitating “long-haul” symptoms and can persist for months. As more and more people seek help to overcome their brain fog at clinics set up for post–COVID-19 care, researchers and physicians are turning to treatments developed for stroke and traumatic brain injuries. And a few are setting out to test cognitive training video games they hope will expand the reach of therapy.

“Even if it’s a fairly small percentage [of survivors] who report cognitive problems, the number of overall people in that category … represents a tremendous problem,” says James Jackson, a clinical psychologist at the Vanderbilt University School of Medicine’s ICU Recovery Center, where Furr will participate in a support group for COVID-19 long haulers.

For More Information: https://www.sciencemag.org/news/2021/04/covid-19-brain-fog-inspires-search-causes-and-treatments