Long COVID

Last updated

Long COVID
Other namesLong-haul COVID, post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19 (PASC), chronic COVID syndrome [1]
Symptoms Highly varied, including post-exertional malaise (symptoms worsen with effort), fatigue, muscle pain, shortness of breath, chest pain and cognitive dysfunction ("brain fog") [2]
DurationWeeks to years, possibly lifelong [3]
Causes COVID-19 infection
Risk factors Female sex, age, obesity, asthma, more severe COVID-19 infection [4]
Frequency50–70% of hospitalised COVID-19 cases, 10–30% of non-hospitalised cases, and 10–12% of vaccinated cases [3]

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial period of COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. [3] The World Health Organization defines long COVID as starting three months after the initial COVID-19 infection, but other agencies define it as starting at four weeks after the initial infection. [2]

Contents

Long COVID is characterised by a large number of symptoms that sometimes disappear and then reappear. Commonly reported symptoms of long COVID are fatigue, memory problems, shortness of breath, and sleep disorder. [5] [4] [6] Several other symptoms, including headaches, mental health issues, loss of smell or taste, muscle weakness, fever, and cognitive dysfunction may also present. [5] [6] Symptoms often get worse after mental or physical effort, a process called post-exertional malaise. [5] There is a large overlap in symptoms with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). [2]

The causes of long COVID are not yet fully understood. Hypotheses include lasting damage to organs and blood vessels, problems with blood clotting, neurological dysfunction, persistent virus or a reactivation of latent viruses and autoimmunity. [3] Diagnosis of long COVID is based on (suspected or confirmed) COVID-19 infection or symptomsand by excluding alternative diagnoses. [7] [8]

Estimates of the prevalence of long COVID vary based on definition, population studied, time period studied, and methodology, generally ranging between 5% and 50%. [9] Prevalence is less after vaccination. [10] Risk factors are higher age, female sex, having asthma, and a more severe initial COVID-19 infection. [4] As of 2023, there are no validated effective treatments. [3] [5] Management of long COVID depends on symptoms. Rest is recommended for fatigue and pacing for post-exertional malaise. People with severe symptoms or those who were in intensive care may require care from a team of specialists. [11] Most people with symptoms at 4 weeks recover by 12 weeks. Recovery is slower (or plateaus) for those still ill at 12 weeks. [11] For a subset of people, for instance those meeting the criteria for ME/CFS, symptoms are expected to be lifelong. [3]

Globally, over 400 million people have experienced long COVID. Long COVID may be responsible for a loss of 1% of world GDP. [12]

Classification and terminology

Long COVID is a patient-created term coined early in the pandemic by those suffering from long-term symptoms. [13] [14] While long COVID is the most prevalent name, the terms long-haul COVID, post-COVID-19 syndrome, post-COVID-19 condition, [1] [15] post-acute sequelae of COVID-19 (PASC), and chronic COVID syndrome are also in use. [5]

Long COVID may not be a single disease or syndrome. It could be an umbrella term including permanent organ damage, post-intensive care syndrome, post-viral fatigue syndrome and post-COVID syndrome. [2]

Long COVID has been referred to by the scientific community as "Post-Acute Sequelae of SARS-CoV-2 infection (PASC)". [16] These terms are synonyms and are often used interchangeably. [17] [18] [19] [20] [21] Both terms refer to the range of symptoms that continue for weeks or even months after the acute phase of the SARS-CoV-2 infection. [16] [20]

Clinical case definitions

There are multiple definitions of long COVID, depending on country and institution. The most accepted is the World Health Organization (WHO) definition. [22]

The definitions differ in when long COVID starts, and how long persistent symptoms must have lasted. [22] For instance, the WHO puts the onset of long COVID at three months post-infection, if there have been at least two months of persistent symptoms. [1] [15] In contrast, the US Centers for Disease Control and Prevention (CDC) puts the onset of "Post-COVID Conditions" at four weeks "to emphasize the importance of initial clinical evaluation and supportive care during the initial 4 to 12 weeks after acute COVID-19" [7] According to National Institutes of Health (NIH), postacute sequalae of SARS-CoV-2 (PASC) refers to ongoing, relapsing, or new symptoms, or other health effects that occur four or more weeks after the acute phase of SARS-CoV-2 infection. [16]

The British National Institute for Health and Care Excellence (NICE) divides long COVID into two categories: [23]

The case definitions specify symptom onset and development. For instance, the WHO definition indicates that "symptoms might be new onset following initial recovery or persist from the initial illness. Symptoms may also fluctuate or relapse over time." [1]

The NICE and WHO definition further require the exclusion of alternative diagnoses. [22]

Specifically for children, a group of experts from UCL Great Ormond Street Institute of Child Health Population in the UK and from other institutions in the UK defines post–COVID-19 condition as a condition characterized by at least one physical symptom persisting for a minimum of 12 weeks after initial confirmed infection, unexplained by an alternative diagnosis, affecting everyday functioning, and may fluctuate or relapse over time. [16]

Many symptoms have similar severity in long COVID and ME/CFS Similar degrees of ME-CFS and long Covid symptoms.webp
Many symptoms have similar severity in long COVID and ME/CFS

Long COVID is a post-acute infection syndrome (PAIS) and shares similarities with other such syndromes. [24] For instance, there are similarities with post-Ebola syndrome and aftereffects of the chikungunya virus. These conditions may have similar pathophysiology to long COVID. [24] [25]

Long COVID has many symptoms in common with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and research estimates half of people with long COVID meet ME/CFS diagnostic criteria. [26] Like long COVID, ME/CFS is often triggered by infections, and some biological changes overlap. [27] [2] Dysautonomia and postural orthostatic tachycardia syndrome (POTS) are also potential shared aspects of long COVID and ME/CFS. [2]

Signs and symptoms

There are over 50 long-term effects of COVID-19, including those that are symptoms of long COVID. The image shows the symptoms along with their estimated prevalence. Around 80% of people have at least one overall effect beyond two weeks following infection. Long-term effects of COVID-19.webp
There are over 50 long-term effects of COVID-19, including those that are symptoms of long COVID. The image shows the symptoms along with their estimated prevalence. Around 80% of people have at least one overall effect beyond two weeks following infection.
External videos
Nuvola apps kaboodle.svg "Long Covid: A parallel pandemic", Akiko Iwasaki and others, Knowable Magazine , 8 August 2022.

There is a large set of symptoms associated with long COVID, impacting many different organs and body systems. Long COVID symptoms can differ significantly from person to person. [2] Symptom severity ranges from mild to incapacitating. [29]

Common symptoms reported in studies include fatigue, muscle pain, shortness of breath, chest pain, cognitive dysfunction ("brain fog") and post-exertional malaise (symptoms worsen after activity). [2] This symptom worsening typically occurs 12 to 48 hours after activity and can be triggered by either mental or physical effort. It lasts between days and weeks. [7]

Although long COVID is less common in children and adolescents, they can experience serious symptoms and long-term adverse health effects, including serious mental health impacts related to persistent COVID-19 symptoms. [30] The most common symptoms in children are persistent fever, sore throat, problems with sleep, muscle weakness, fatigue, loss of smell or distorted smell, and anxiety. [31] [32] Most children with long COVID experience three or more symptoms. [32]

Neurological symptoms

Common neurological symptoms in long COVID are difficulty concentrating, cognitive impairment and headaches. [3] [6] People also frequently experience loss of taste and loss of smell. [6]

Some people with long COVID experience dysautonomia, a malfunction of the central nervous system. [33] People with dysautonomia may experience palpitations and tachycardia (raised heart rate) after minor effort or upon standing up. This can be associated with dizziness and nausea. If the heart rate is raised by 30 beats per minute or more after continuous standing, this is described as postural orthostatic tachycardia syndrome. [34]

In terms of mental health, people with long COVID often experience sleep difficulties. [6] Depression and anxiety levels are raised in the first two months after infection, but return to normal afterwards. [35] This was in contrast to other neurological symptoms, such as brain fog and seizures, which lasted at least two years. [3]

Lungs, heart and digestive system

Difficulty breathing is the second-most common symptom of long COVID. [36] People can also experience a persistent cough. [6] Less frequently, people with long COVID experience diarrhea and nausea. [6]

In the cardiovascular system, effort intolerance and chest pain occur often in people with long COVID. [6] People are at increased risk of stroke, pulmonary embolism and myocardial infarction after recovering from an acute COVID infection, but there is disagreement as to whether this should be seen as part of long COVID or not. [2]

Reproductive system

In the female reproductive system, long COVID may disrupt fertility, the menstrual cycle, menopause, gonadal function, and ovarian sufficiency. [37] Exacerbation of other long COVID symptoms around menstruation has also been documented. [37]

Other symptoms

Joint pain and muscle pain are frequently reported as symptoms of long COVID. [6] Some people experience hair loss and skin rashes. [38] People are at increased risk of type I and II diabetes after recovering from acute COVID. [2]

Subgroups

Because the symptom combinations of long COVID vary significantly from person to person, one approach to researching the condition is to define subgroups or clusters of long-haulers. This would allow for more targeted clinical care. [2]

Causes and mechanisms

Possible causes of long COVID Long Covid possible causes.webp
Possible causes of long COVID

The causes of long COVID are not yet fully understood. It is likely that there is no single cause, but instead multiple, and possibly overlapping, mechanisms that all contribute to the development of long COVID. [3] Organ damage from the acute infection can explain a part of the symptoms, but long COVID is also observed in people where organ damage seems to be absent. [39] Several hypotheses have been put forward explaining long COVID, including: [3]

Further hypotheses include a dysfunction of the mitochondria and the cellular energy system, [40] persistent systemic inflammation, and the persistence of SARS-COV-19 antigens. [41]

Pathophysiology

Organ damage from the acute infection may explain symptoms in some people with long COVID. Radiological tests such as lung MRIs often show up as normal even for people who show clear desaturation (lowered blood oxygen level) after mild exercise. Other tests, such as a dual-energy CT scan, do show perfusion defects in a subset of people with respiratory symptoms. Imaging of the heart show contradictory results. Imaging of brains show changes after COVID infection, even if this has not been studied in relation to long COVID. For instance, some show a smaller olfactory bulb, a brain region associated with smell. [2]

In a subset of people with long COVID, there is evidence that SARS-COV-2 remains in the body after the acute infection. [42] This evidence comes from biopsies, studies of blood plasma, and by the indirect immune effects of persistent virus. Viral DNA or proteins have been found months to a year after acute infection in various studies. A small study demonstrated viral RNA up to nearly two years after an acute infection in people with long COVID. Persistent virus has also been found in people without long COVID, but at a lower rate. [43] Persistent virus could lead to symptoms via possible effects on coagulation and via microbiome and neuroimmune abnormalities. [44]

During or after acute COVID infection, various dormant viruses can become reactivated. For instance, SARS-COV-2 can reactivate the Epstein-Barr virus, the virus that is responsible for infectious mononucleosis. This virus lies dormant in most people. There is some evidence of a relationship between its reactivation and long COVID. A correlation was also found between reactivation of endogenous retroviruses and severity of active COVID-19. [45]

Autoimmunity is another potential cause of long COVID. Some studies report auto-antibodies (antibodies directed against an individual's own proteins) in people with long COVID, but they are not found in all studies. [41] Autoantibodies are often induced during acute COVID, with a moderate relationship to disease severity. Evidence from electronic health care records show that people develop auto-immune diseases, such as lupus and rheumatoid arthritis, more frequently after a COVID-19 infection, compared to controls. [2]

Issues with increased blood clotting are another potential driver of long COVID development. During acute infection, there is direct damage to the linings of blood vessels (endothelial damage), [2] and the risk of thrombosis-related diseases stays elevated longer-term after infection. Issues with blood clotting can include hyperactive platelets and microclots. These microclots may induce oxygen shortage (hypoxia) in tissues. [42] The clotting may potentially be driven by autoantibodies. [2]

Several studies suggest that brain penetration of serum components and cytokines as derived from breakdowns to the integrity of the blood–brain barrier could contribute to the neurological manifestations of Long Covid. [46]

Risk factors

Women are more at risk than men. [4] Age has been identified as another risk factor, with older people seemingly more at risk. [4] This is also true for children, with older children at a higher risk than younger children. [22] Most diagnoses of long COVID are in the 36–50 age bracket. [3] Risks of developing long COVID are also higher for people with lower incomes, people with fewer years of education and those from disadvantaged ethnic groups. [22] [42] People who smoke also have a higher risk of developing long COVID. [22]

Various health issues raise the risk of long COVID. For instance, people with obesity more often report long COVID. [4] Asthma and chronic obstructive pulmonary disease are also risk factors. [22] [4] In terms of mental health, depression and anxiety raise risks. [22]

Finally, characteristics of the acute infection play a role in developing long COVID. People who experience a larger number of symptoms during the acute infection are more likely to develop long COVID, as well as people who require hospitalisation. [4] Finally, long COVID risks may have been higher with the SARS-CoV2 Delta variant compared to the Omicron variant. The higher infection rate from the Omicron variant means that it is still responsible for a large group of long-haulers. [22]

Diagnosis

There are no standardised tests to determine if symptoms persisting after COVID-19 infection are due to long COVID. [5] [8] Diagnosis is based on a history of suspected or confirmed COVID-19 symptoms, and by considering and ruling out alternative diagnoses. [7] [8] Diagnosis of long COVID can be challenging because of the wide range of symptoms people with long COVID may display. [8]

Early diagnostic criteria of long COVID required a laboratory-confirmed COVID-19 infection, but current criteria do not require this anymore, given that people may not get tested during the acute infection. [8] For instance, people who develop long COVID after asymptomatic infection would have little reason to get tested. [7] Furthermore, tests for COVID are not foolproof, and can come back negative. [7] False negatives are more common for children, women and people with a low viral load. [3]

There are diagnostic tools available for some elements of long COVID, such as the tilt table test for POTS and MRI scans to test for cardiovascular impairment. Routine tests offered in standard care often come back normal. [3]

Prevention

Preventing a COVID-19 infection is the most effective way to prevent long COVID, for instance by improving ventilation, avoiding contact with people who test positive for COVID, washing hands, and wearing a properly-fitted N95 mask. [47] Treatment during the acute phase may also reduce the risk of long COVID. [5]

COVID-19 vaccination reduces the risk of long COVID. Receiving three doses of a COVID-19 vaccine can offer 69% effectiveness against long COVID, while two doses can provide 37% efficacy, for those who had not been infected with COVID-19 before. [48] [49] An analysis involving more than 20 million adults found that vaccinated people had a lower risk of long COVID compared with those who had not received a COVID-19 vaccine; they were also protective of blood clots and heart failure. [50] [51] [52]

Treatment

Center for Post-COVID Care at Mount Sinai's Union Square offices in New York City. Center for Post-COVID Care.jpg
Center for Post-COVID Care at Mount Sinai's Union Square offices in New York City.

As of 2023 there are no established effective treatments for long COVID, [3] however several countries and medical organizations have produced guidelines on managing long COVID for clinicians and the public. [5] [53] [54]

People with long COVID may need care within several clinical disciplines for long-term monitoring or intervention of ongoing symptoms, and to implement social services, physical therapy, or mental health care. [54] In some countries, such as the UK and Germany, specialised long COVID outpatient clinics have been established to assess individual cases for the extent of surveillance and treatment needed. [55] Primary care physicians should provide the first assessment of people with long COVID symptoms, leading to specialist referrals for more complex long COVID symptoms. [54] [55]

Management of long COVID depends on symptoms. [5] Rest, planning and prioritising are advised for people with fatigue. People who get post-exertional malaise may benefit from activity management with pacing. People with allergic-type symptoms, such as skin rashes, may benefit from antihistamines. [11] Those with autonomic dysfunction may benefit from increased intake of fluids, electrolytes and compression garments. [11]

Long-term follow-up of people with long COVID involves outcome reports from the people themselves to assess the impact on their quality of life, especially for those who were not hospitalised and receiving regular clinical follow-up. [54] [55] Digital technologies, such as videoconferencing, are being implemented between primary care physicians and people with long COVID as part of long-term monitoring. [54]

Prognosis

Around two in three with symptoms at four weeks are expected to recover fully by week twelve. [11] However, the prognosis varies by person, and some may find symptoms worsen within the first three months. [7] Recovery after twelve weeks is variable: some people plateau, whilst others see a slow recovery. [11]

The prognosis also varies by symptom: neurological symptoms may have a delayed onset, and some get worse over time. Symptoms of the gut and lungs are more likely to reduce over time. Pain in muscles and joints seems worse at 2 years than at 1 year after infection. If people meet the diagnostic criteria for ME/CFS or for dysautonomia, their symptoms are likely to be lifelong. [3]

Epidemiology

Long COVID's prevalence varies by age and gender in the United States US long COVID demographics.jpg
Long COVID's prevalence varies by age and gender in the United States

Estimates of the prevalence of long COVID vary widely. The estimates depend on the definition of long COVID, the population studied, [4] as well as a number of other methodological differences, such as whether a comparable cohort of individuals without COVID-19 were included, [56] what kinds of symptoms are considered representative of long COVID, [56] and whether long COVID is assessed through a review of symptoms, through self-report of long COVID status, or some other method. [57]

In general, estimates of long COVID incidence based on statistically random sampling of the population are much lower than those based on certified infection, which has a tendency to skew towards more serious cases (including over-representation of hospitalized patients). Further, since incidence appears to be correlated with severity of infection, it is lower in vaccinated groups, on reinfection and during the omicron era, meaning that the time when data was recorded is important. For example, the UK's Office for National Statistics reported [58] in February 2023 (based on random sampling) that "2.4% of adults and 0.6% of children and young people reported long COVID following a second COVID-19 infection".

By the end of 2023, roughly 400 million people had or have had long COVID. This may be a conservative estimate, as it is based on studies counting those with specific long COVID symptoms only, and not counting those who developed long COVID after an asymptomatic infection. While hospitalised people have higher risks of getting long COVID, most long-haulers had a mild infection and were able to recover from the acute infection at home. [12]

An April 2022 meta-analysis estimated that the pooled incidence of post-COVID conditions after infection was 43%, with estimates ranging between 9% and 81%. People who had been hospitalised with COVID saw a higher prevalence of 54%, while 34% of nonhospitalised people developed long COVID after acute infection. [4] However, a more recent (April 2024) meta-analysis [59] estimated a pooled incidence of 9%.

In the United States in June 2023, 6% of the population indicated having long COVID, as defined as symptoms that last for 3 months or more. [60] This percentage had stayed stable since January that year, but was a decrease compared to June 2022. [60] Of people who had had a prior COVID infection, 11% indicated having long COVID. A quarter of those reported significant limitation in activity. [60] A study by the Medical Expenditure Panel Survey estimated that nearly 18 million people — had suffered from long COVID as of 2023, building on a study sponsored by the Agency for Healthcare Research and Quality. [61]

In a large population cohort study in Scotland, 42% of respondents said they had not fully recovered after 6 to 18 months after catching COVID, and 6% indicated they had not recovered at all. The risk of long COVID was associated with disease severity; people with asymptomatic infection did not have increased risk of long COVID symptoms compared to people who had never been infected. Those that had been hospitalised had 4.6 times higher odds of no recovery compared to nonhospitalised people. [62]

Long COVID is less common in children and adolescents than in adults. [63] Around 16% of children and adolescents develop long COVID following infection. [31]

Society and culture

Patient community and activism

Early in the pandemic, official guidance made a distinction between those with mild illness who did not require hospitalisation, and those with severe illness which did require hospitalisation. The typical recovery time for those with mild illness was said to be around two weeks [64] and media attention was mostly focused on those with a severe infection. Patients with long-lasting systems after a mild infection started to describe their symptoms on Twitter and blogs, [65] challenging official assumptions. [14]

The term long COVID was reportedly first used in May 2020 as a hashtag on Twitter by Elisa Perego, a health and disability researcher at University College London. [13] [14] A month later, #LongCovid became a popular hashtag, alongside hashtags from non-English budding communities (for instance, #AprèsJ20 in French, and #koronaoire in Finnish). [14]

Experiences shared online filled a gap in knowledge in how the media talked about the pandemic. [65] Via the media, the knowledge reached governments and health officials, making long COVID "the first illness created through patients finding one another on Twitter". [14]

Some people experiencing long COVID have formed community care networks and support groups on social media websites. [55] [66] Internationally, there are several long COVID advocacy groups. [54] [67] [68] [14] Clinical advice on self-management and online healthcare programs are used to support people with long COVID. [55]

Stigma and discrimination

Many people with long COVID have difficulty accessing appropriate healthcare. The severity of their symptoms may be disbelieved, they may be subject to unsympathetic care, and their symptoms may not be investigated properly or may be falsely attributed to anxiety. [69] [54] People with long COVID may be misdiagnosed with mental disorders. Anxiety and depression questionnaires not designed for people with medical conditions can contribute to this; for example, a questionnaire may assume fatigue is due to depression or that palpitations are due to anxiety, even if explained by another condition like ME/CFS or POTS. [3]

The impact of long COVID on people's ability to work is large. Estimates vary on how many people are out of work, or work reduced hours because of long COVID. For those with mild or moderate disease, between 12% and 23% had had long periods of absence or remained absent from work at 3 to 7 months. The share of people working adjusted hours or tasks after mild or moderate COVID, was around 8% to 45% after three to eight months. [70] The percentage of people returning to work after hospitalisation was lower. [70] Return to work after hospitalisation differed by country. In China and the US a higher percentage went back to work. In the US this could be partially explained by a lack of paid sick leave for some workers. [71] The Institute for Fiscal Studies studied labour impacts of long COVID in the UK in 2021. They concluded that of people who worked before contracting long COVID, one in ten had stopped working. Most of them were on sick leave rather than unemployed. [72]

Economic impacts

The OECD estimates that 3 million people have left the work force due to long COVID in OECD countries. Only counting lost wages, this would amount to an economic loss of 141 billion USD. When taking into account reduced quality of life as well, yearly economics costs due to long COVID were estimated to be between $864 billion and $1.04 trillion USD. This does not include health care costs. [73] As a share of global GDP, impacts are estimated to be between 0.5% and 2.3%. [12]

A recent study estimated that long COVID contributes to global economic cost of about $1 trillion a year for the 400 million afflicted. [74] [75]

Research

As long COVID is a novel condition, there are many open questions. Research is ongoing in many areas, including developing more accurate diagnostic criteria, refining estimates of its likelihood, identifying risk factors, gathering data for its impact on daily life, discovering which populations face barriers to adequate care, and learning how much protection vaccination provides. [76] [77]

Many experimental and repurposed drugs are being investigated as possible treatments for different aspects of long COVID. [3] [78] These include the anti-inflammatory colchicine, the anticoagulant rivaroxaban, the antihistamines famotidine and loratadine, various immune-modulating drugs, and the experimental aptamer compound BC-007 (Rovunaptabin). [2] [3]

In 2021, the US National Institutes of Health started funding the RECOVER Initiative, backed by $1.15 billion over four years, [79] to identify the causes, prevention and treatment of long COVID. [29] In 2023, the Office of Long COVID Research and Practice was created to coordinate research across US government agencies. [80] At the same time, RECOVER announced which clinical trials it will fund: these include a trial of Paxlovid against potential persistent infection, one for sleep disorder, one for cognitive impairment and one for problems with the autonomic nervous system. [81]

In a survey of over 3,700 people in the UK with long COVID, fatigue was the strongest predictor of poor everyday functioning, with depression and brain fog also being linked. Some 20% of those surveyed reported being unable to work. [82] [83]

See also

Related Research Articles

<span class="mw-page-title-main">SARS</span> Disease caused by severe acute respiratory syndrome coronavirus

Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the virus SARS-CoV-1, the first identified strain of the SARS-related coronavirus. The first known cases occurred in November 2002, and the syndrome caused the 2002–2004 SARS outbreak. In the 2010s, Chinese scientists traced the virus through the intermediary of Asian palm civets to cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan.

<span class="mw-page-title-main">Seroconversion</span> Development of specific antibodies in the blood serum as a result of infection or immunization

In immunology, seroconversion is the development of specific antibodies in the blood serum as a result of infection or immunization, including vaccination. During infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but the antibody is absent. During seroconversion, the antibody is present but not yet detectable. After seroconversion, the antibody is detectable by standard techniques and remains detectable unless the individual seroreverts, in a phenomenon called seroreversion, or loss of antibody detectability, which can occur due to weakening of the immune system or decreasing antibody concentrations over time. Seroconversion refers the production of specific antibodies against specific antigens, meaning that a single infection could cause multiple waves of seroconversion against different antigens. Similarly, a single antigen could cause multiple waves of seroconversion with different classes of antibodies. For example, most antigens prompt seroconversion for the IgM class of antibodies first, and subsequently the IgG class.

<span class="mw-page-title-main">Postural orthostatic tachycardia syndrome</span> Abnormally high heart rate after a postural change

Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by an abnormally large increase in heart rate upon sitting up or standing. POTS is a disorder of the autonomic nervous system that can lead to a variety of symptoms, including lightheadedness, brain fog, blurred vision, weakness, fatigue, headaches, heart palpitations, exercise intolerance, nausea, diminished concentration, tremulousness (shaking), syncope (fainting), coldness or pain in the extremities, numbness or tingling in the extremities, chest pain, and shortness of breath. Other conditions associated with POTS include myalgic encephalomyelitis/chronic fatigue syndrome, migraine headaches, Ehlers–Danlos syndrome, asthma, autoimmune disease, vasovagal syncope, and mast cell activation syndrome. POTS symptoms may be treated with lifestyle changes such as increasing fluid, electrolyte, and salt intake, wearing compression stockings, gentler and slow postural changes, avoiding prolonged bedrest, medication, and physical therapy.

A sequela is a pathological condition resulting from a disease, injury, therapy, or other trauma. Derived from the Latin word meaning "sequel", it is used in the medical field to mean a complication or condition following a prior illness or disease.

<span class="mw-page-title-main">W. Ian Lipkin</span> Professor, microbiologist, epidemiologist

Walter Ian Lipkin is the John Snow Professor of Epidemiology at the Mailman School of Public Health at Columbia University and a professor of Neurology and Pathology at the College of Physicians and Surgeons at Columbia University. He is also director of the Center for Infection and Immunity, an academic laboratory for microbe hunting in acute and chronic diseases. Lipkin is internationally recognized for his work with West Nile virus, SARS and COVID-19.

<span class="mw-page-title-main">Myalgic encephalomyelitis/chronic fatigue syndrome</span> Chronic medical condition

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling chronic illness. People with ME/CFS experience profound fatigue that does not go away with rest, sleep issues, and problems with memory or concentration. Further common symptoms include dizziness, nausea and pain. The hallmark symptom is a worsening of the illness which starts hours to days after minor physical or mental activity. This "crash" can last from hours or days to several months.

<span class="mw-page-title-main">MERS</span> Viral respiratory infection

Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by Middle East respiratory syndrome–related coronavirus (MERS-CoV). Symptoms may range from none, to mild, to severe depending on age and risk level. Typical symptoms include fever, cough, diarrhea, and shortness of breath. The disease is typically more severe in those with other health problems.

<span class="mw-page-title-main">Post-Ebola virus syndrome</span> Sequelae following recovery from Ebola virus disease

Post-Ebola virus syndrome is a post-viral syndrome affecting those who have recovered from infection with Ebola. Symptoms include joint and muscle pain, eye problems, including blindness, various neurological problems, and other ailments, sometimes so severe that the person is unable to work. Although similar symptoms had been reported following previous outbreaks in the last 20 years, health professionals began using the term in 2014 when referring to a constellation of symptoms seen in people who had recovered from an acute attack of Ebola disease.

<span class="mw-page-title-main">Post-exertional malaise</span> Worsening of symptoms with activity

Post-exertional malaise (PEM), sometimes referred to as post-exertional symptom exacerbation (PESE) or post-exertional neuroimmune exhaustion (PENE), is a worsening of symptoms that occurs after minimal exertion. It is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and common in long COVID and fibromyalgia. PEM is often severe enough to be disabling, and is triggered by ordinary activities that healthy people tolerate. Typically, it begins 12–48 hours after the activity that triggers it, and lasts for days, but this is highly variable and may persist much longer. Management of PEM is symptom-based, and patients are recommended to pace their activities to avoid triggering PEM.

<span class="mw-page-title-main">COVID-19</span> Contagious disease caused by SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. The first known case was identified in Wuhan, China, in December 2019. Most scientists believe the SARS-CoV-2 virus entered into human populations through natural zoonosis, similar to the SARS-CoV-1 and MERS-CoV outbreaks, and consistent with other pandemics in human history. Social and environmental factors including climate change, natural ecosystem destruction and wildlife trade increased the likelihood of such zoonotic spillover. The disease quickly spread worldwide, resulting in the COVID-19 pandemic.

<span class="mw-page-title-main">Symptoms of COVID-19</span>

The symptoms of COVID-19 are variable depending on the type of variant contracted, ranging from mild symptoms to a potentially fatal illness. Common symptoms include coughing, fever, loss of smell (anosmia) and taste (ageusia), with less common ones including headaches, nasal congestion and runny nose, muscle pain, sore throat, diarrhea, eye irritation, and toes swelling or turning purple, and in moderate to severe cases, breathing difficulties. People with the COVID-19 infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; and a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, or throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of symptomatic cases.

<span class="mw-page-title-main">Multisystem inflammatory syndrome in children</span> Disease of children; pediatric comorbidity from COVID-19

Multisystem inflammatory syndrome in children (MIS-C), or paediatric inflammatory multisystem syndrome, or systemic inflammatory syndrome in COVID-19 (SISCoV), is a rare systemic illness involving persistent fever and extreme inflammation following exposure to SARS-CoV-2, the virus responsible for COVID-19. Studies suggest that MIS-C occurred in 31.6 out of 100,000 people under 21 who were infected with COVID-19. MIS-C has also been monitored as a potential, rare pediatric adverse event following COVID-19 vaccination. Research suggests that COVID-19 vaccination lowers the risk of MIS-C, and in cases where symptoms develop after vaccine, is likely extremely rare or related to factors like recent exposure to COVID-19. It can rapidly lead to medical emergencies such as insufficient blood flow around the body. Failure of one or more organs can occur. A warning sign is unexplained persistent fever with severe symptoms following exposure to COVID-19. Prompt referral to paediatric specialists is essential, and families need to seek urgent medical assistance. Most affected children will need intensive care.

<span class="mw-page-title-main">Impact of the COVID-19 pandemic on other health issues</span> Health consequences of outbreak beyond the COVID-19 disease itself

The COVID-19 pandemic has had many impacts on global health beyond those caused by the COVID-19 disease itself. It has led to a reduction in hospital visits for other reasons. There have been 38 per cent fewer hospital visits for heart attack symptoms in the United States and 40 per cent fewer in Spain. The head of cardiology at the University of Arizona said, "My worry is some of these people are dying at home because they're too scared to go to the hospital." There is also concern that people with strokes and appendicitis are not seeking timely treatment. Shortages of medical supplies have impacted people with various conditions.

The treatment and management of COVID-19 combines both supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support as needed, and a growing list of approved medications. Highly effective vaccines have reduced mortality related to SARS-CoV-2; however, for those awaiting vaccination, as well as for the estimated millions of immunocompromised persons who are unlikely to respond robustly to vaccination, treatment remains important. Some people may experience persistent symptoms or disability after recovery from the infection, known as long COVID, but there is still limited information on the best management and rehabilitation for this condition.

<span class="mw-page-title-main">Transmission of COVID-19</span> Mechanisms that spread coronavirus disease 2019

The transmission of COVID-19 is the passing of coronavirus disease 2019 from person to person. COVID-19 is mainly transmitted when people breathe in air contaminated by droplets/aerosols and small airborne particles containing the virus. Infected people exhale those particles as they breathe, talk, cough, sneeze, or sing. Transmission is more likely the closer people are. However, infection can occur over longer distances, particularly indoors.

<span class="mw-page-title-main">Impact of the COVID-19 pandemic on neurological, psychological and other mental health outcomes</span>

There is increasing evidence suggesting that COVID-19 causes both acute and chronic neurologicalor psychological symptoms. Caregivers of COVID-19 patients also show a higher than average prevalence of mental health concerns. These symptoms result from multiple different factors.

Ziyad Al-Aly is an American physician and clinical epidemiologist who is currently Director of the Clinical Epidemiology Center and Chief of the Research and Development at the Veterans Affairs St. Louis Health Care System. He is also a clinical epidemiologist at Washington University in St. Louis. He has led multiple studies on long covid and its sequelae.

Post-acute infection syndromes (PAISs) or post-infectious syndromes are medical conditions characterized by symptoms attributed to a prior infection. While it is commonly assumed that people either recover or die from infections, long-term symptoms—or sequelae—are a possible outcome as well. Examples include long COVID, Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and post-Ebola virus syndrome. Common symptoms include post-exertional malaise (PEM), severe fatigue, neurocognitive symptoms, flu-like symptoms, and pain. The pathology of most of these conditions is not understood and management is generally symptomatic.

Amy Proal is an American microbiologist who studies the effects of bacterial, fungal, and viral pathogens on human health at the molecular level. She is one of the founders of PolyBio Research Foundation, a company investigating the basis of chronic infection-associated illnesses, and currently serves on the company's board of directors. She has recently been noted for her work investigating the causes of long covid.

Carmen Scheibenbogen is a German immunologist who is the acting director of the Institute for Medical Immunology of the Charité university hospital in Berlin. She specialises in hematology, oncology and immunology. She leads the Outpatient Clinic for Immunodeficiency and the Fatigue Centre at the Charité hospital. She is one of the few doctors specialised in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Germany, and also researches long COVID.

References

  1. 1 2 3 4 Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV (April 2022). "A clinical case definition of post-COVID-19 condition by a Delphi consensus". The Lancet. Infectious Diseases. 22 (4): e102–e107. doi:10.1016/S1473-3099(21)00703-9. PMC   8691845 . PMID   34951953.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Altmann DM, Whettlock EM, Liu S, Arachchillage DJ, Boyton RJ (July 2023). "The immunology of long COVID". Nature Reviews. Immunology. 23 (10): 618–634. doi: 10.1038/s41577-023-00904-7 . PMID   37433988. S2CID   259831825.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Davis HE, McCorkell L, Vogel JM, Topol EJ (March 2023). "Long COVID: major findings, mechanisms and recommendations". Nature Reviews. Microbiology. 21 (3): 133–146. doi:10.1038/s41579-022-00846-2. PMC   9839201 . PMID   36639608.
  4. 1 2 3 4 5 6 7 8 9 10 Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B (November 2022). "Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review". The Journal of Infectious Diseases. 226 (9): 1593–1607. doi:10.1093/infdis/jiac136. PMC   9047189 . PMID   35429399.
  5. 1 2 3 4 5 6 7 8 9 "Long COVID or post-COVID conditions". Centers for Disease Control and Prevention, US Department of Health and Human Services. 20 July 2023. Archived from the original on 14 January 2022. Retrieved 23 July 2023.
  6. 1 2 3 4 5 6 7 8 9 Alkodaymi MS, Omrani OA, Fawzy NA, Shaar BA, Almamlouk R, Riaz M, et al. (May 2022). "Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis". Clinical Microbiology and Infection. 28 (5): 657–666. doi:10.1016/j.cmi.2022.01.014. PMC   8812092 . PMID   35124265.
  7. 1 2 3 4 5 6 7 "Post-COVID Conditions: Information for Healthcare Providers". Centers for Disease Control and Prevention . 16 December 2022. Archived from the original on 12 August 2023. Retrieved 10 August 2023.
  8. 1 2 3 4 5 Srikanth S, Boulos JR, Dover T, Boccuto L, Dean D (September 2023). "Identification and diagnosis of long COVID-19: A scoping review". Progress in Biophysics and Molecular Biology. 182: 1–7. doi:10.1016/j.pbiomolbio.2023.04.008. PMC   10176974 . PMID   37182545.
  9. Ledford H (June 2022). "How common is long COVID? Why studies give different answers". Nature. 606 (7916): 852–853. Bibcode:2022Natur.606..852L. doi: 10.1038/d41586-022-01702-2 . PMID   35725828. S2CID   249887289.
  10. Byambasuren O, Stehlik P, Clark J, Alcorn K, Glasziou P (2023). "Effect of covid-19 vaccination on long covid: systematic review". BMJ Medicine. 2 (1): e000385. doi:10.1136/bmjmed-2022-000385. PMC   9978692 . PMID   36936268.
  11. 1 2 3 4 5 6 Greenhalgh T, Sivan M, Delaney B, Evans R, Milne R (September 2022). "Long covid-an update for primary care". BMJ. 378: e072117. doi: 10.1136/bmj-2022-072117 . PMID   36137612. S2CID   252406968.
  12. 1 2 3 Al-Aly Z, Davis H, McCorkell L, Soares L, Wulf-Hanson S, Iwasaki A, et al. (9 August 2024). "Long COVID science, research and policy". Nature Medicine. 30 (8): 2148–2164. doi: 10.1038/s41591-024-03173-6 . ISSN   1078-8956. PMID   39122965.
  13. 1 2 Perego E, Callard F, Stras L, Melville-Johannesson B, Pope R, Alwan N (1 October 2020). "Why we need to keep using the patient made term 'Long Covid'". The BMJ. Archived from the original on 4 October 2020. Retrieved 18 October 2020.
  14. 1 2 3 4 5 6 Callard F, Perego E (January 2021). "How and why patients made Long Covid". Social Science & Medicine. 268: 113426. doi:10.1016/j.socscimed.2020.113426. PMC   7539940 . PMID   33199035.
  15. 1 2 "A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021". World Health Organization. 6 October 2021. Archived from the original on 23 April 2022. Retrieved 7 January 2022.
  16. 1 2 3 4 Rao S, Gross RS, Mohandas S, Stein CR, Case A, Dreyer B, et al. (2024). "Postacute Sequelae of SARS-CoV-2 in Children". Pediatrics. 153 (3). doi:10.1542/peds.2023-062570. PMC  10904902. PMID   38321938.
  17. Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB (2023). "Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)". eLife. 12. doi: 10.7554/eLife.86002 . PMC   10032659 . PMID   36947108.
  18. "NIH experts discuss post-acute COVID-19". National Institutes of Health (NIH). 13 April 2021. Archived from the original on 1 April 2024. Retrieved 26 March 2024.
  19. Yomogida K, Zhu S, Rubino F, Figueroa W, Balanji N, Holman E (2021). "Post-Acute Sequelae of SARS-CoV-2 Infection Among Adults Aged ≥18 Years — Long Beach, California, April 1–December 10, 2020". MMWR. Morbidity and Mortality Weekly Report. 70 (37): 1274–1277. doi:10.15585/mmwr.mm7037a2. PMC   8445372 . PMID   34529639. Archived from the original on 26 March 2024. Retrieved 26 March 2024.
  20. 1 2 Proal AD, Vanelzakker MB (2021). "Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms". Frontiers in Microbiology. 12. doi: 10.3389/fmicb.2021.698169 . PMC   8260991 . PMID   34248921.
  21. Solan M (1 July 2022). "Answers to questions about long COVID". Harvard Health Publishing. Archived from the original on 26 March 2024. Retrieved 26 March 2024.
  22. 1 2 3 4 5 6 7 8 9 Su S, Zhao Y, Zeng N, Liu X, Zheng Y, Sun J, et al. (July 2023). "Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update". Molecular Psychiatry. 28 (10): 4056–4069. doi:10.1038/s41380-023-02171-3. PMID   37491461. S2CID   260163143.
  23. "COVID-19 rapid guideline: managing the long-term effects of COVID-19". National Institute for Health and Care Excellence . 11 November 2021. p. 5. Archived from the original on 2 August 2023. Retrieved 9 September 2023.
  24. 1 2 Choutka J, Jansari V, Hornig M, Iwasaki A (May 2022). "Unexplained post-acute infection syndromes". Nature Medicine. 28 (5): 911–923. doi: 10.1038/s41591-022-01810-6 . PMID   35585196. S2CID   248889597.
  25. Brodin P (January 2021). "Immune determinants of COVID-19 disease presentation and severity". Nature Medicine. 27 (1): 28–33. doi: 10.1038/s41591-020-01202-8 . PMID   33442016.
  26. Grach SL, Seltzer J, Chon TY, Ganesh R (October 2023). "Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Mayo Clinic Proceedings. 98 (10): 1544–1551. doi: 10.1016/j.mayocp.2023.07.032 . PMID   37793728. S2CID   263665180.
  27. Komaroff AL, Lipkin WI (2 June 2023). "ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature". Frontiers in Medicine. 10. doi: 10.3389/fmed.2023.1187163 . ISSN   2296-858X. PMC   10278546 . PMID   37342500.
  28. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. (August 2021). "More than 50 long-term effects of COVID-19: a systematic review and meta-analysis". Scientific Reports. 11 (1): 16144. Bibcode:2021NatSR..1116144L. doi:10.1038/s41598-021-95565-8. PMC   8352980 . PMID   34373540.
  29. 1 2 "NIH launches new initiative to study 'Long COVID'". National Institutes of Health (NIH). 23 February 2021. Archived from the original on 13 May 2021. Retrieved 23 February 2021.
  30. Messiah SE, Francis J, Weerakoon S, Mathew MS, Shaikh S, Veeraswamy A, et al. (21 September 2023). "Persistent symptoms and conditions among children and adolescents hospitalised with COVID-19 illness: a qualitative study". BMJ Open. 13 (9): e069073. doi:10.1136/bmjopen-2022-069073. PMC   10514629 . PMID   37734886.
  31. 1 2 Jiang L, Li X, Nie J, Tang K, Bhutta ZA (August 2023). "A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population". Pediatrics. 152 (2). doi:10.1542/peds.2022-060351. PMC   10389775 . PMID   37476923.
  32. 1 2 Behnood S, Newlands F, O'Mahoney L, Takeda A, Haghighat Ghahfarokhi M, Bennett SD, et al. (2023). "A systematic review and meta-analysis conducted by UCL Great Ormond Street Institute of Child in collaboration with the World Health Organization". A clinical case definition for post covid-19 condition in children and adolescents by expert consensus. World Health Organization. p. 25. Archived from the original on 13 August 2023. Retrieved 13 August 2023.
  33. Stefanou MI, Palaiodimou L, Bakola E, Smyrnis N, Papadopoulou M, Paraskevas GP, et al. (2022). "Neurological manifestations of long-COVID syndrome: a narrative review". Therapeutic Advances in Chronic Disease. 13: 20406223221076890. doi:10.1177/20406223221076890. PMC   8859684 . PMID   35198136.
  34. Espinosa-Gonzalez AB, Master H, Gall N, Halpin S, Rogers N, Greenhalgh T (February 2023). "Orthostatic tachycardia after covid-19". BMJ (Clinical Research Ed.). 380: e073488. doi: 10.1136/bmj-2022-073488 . PMID   36828559. S2CID   257103171.
  35. Gonjilashvili A, Tatishvili S (February 2024). "The interplay between Sars-Cov-2 infection related cardiovascular diseases and depression. Common mechanisms, shared symptoms". Am Heart J Plus. 38: 100364. doi:10.1016/j.ahjo.2024.100364. PMC   10945907 . PMID   38510743.
  36. Healey Q, Sheikh A, Daines L, Vasileiou E (May 2022). "Symptoms and signs of long COVID: A rapid review and meta-analysis". Journal of Global Health. 12: 05014. doi:10.7189/jogh.12.05014. PMC   9125197 . PMID   35596571.
  37. 1 2 Pollack B, von Saltza E, McCorkell L, Santos L, Hultman A, Cohen AK, et al. (2023). "Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review". Frontiers in Rehabilitation Sciences. 4. doi: 10.3389/fresc.2023.1122673 . ISSN   2673-6861. PMC   10208411 . PMID   37234076.
  38. "COVID-19 rapid guideline: managing the long-term effects of COVID-19". National Institute for Health and Care Excellence . 11 November 2021. p. 100. Archived from the original on 2 August 2023. Retrieved 9 September 2023.
  39. Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, et al. (December 2022). "Pathophysiology and mechanism of long COVID: a comprehensive review". Annals of Medicine. 54 (1): 1473–1487. doi:10.1080/07853890.2022.2076901. PMC   9132392 . PMID   35594336.
  40. Astin R, Banerjee A, Baker MR, Dani M, Ford E, Hull JH, et al. (January 2023). "Long COVID: mechanisms, risk factors and recovery". Experimental Physiology. 108 (1): 12–27. doi: 10.1113/EP090802 . PMC   10103775 . PMID   36412084. S2CID   253760439.
  41. 1 2 Perumal R, Shunmugam L, Naidoo K, Wilkins D, Garzino-Demo A, Brechot C, et al. (June 2023). "Biological mechanisms underpinning the development of long COVID". iScience. 26 (6): 106935. Bibcode:2023iSci...26j6935P. doi:10.1016/j.isci.2023.106935. PMC   10193768 . PMID   37265584.
  42. 1 2 3 Turner S, Khan MA, Putrino D, Woodcock A, Kell DB, Pretorius E (June 2023). "Long COVID: pathophysiological factors and abnormalities of coagulation". Trends in Endocrinology and Metabolism. 34 (6). Pathophysiology of Long COVID: 321–344. doi:10.1016/j.tem.2023.03.002. PMC   10113134 . PMID   37080828.
  43. Proal AD, VanElzakker MB, Aleman S, Bach K, Boribong BP, Buggert M, et al. (September 2023). "SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)" (PDF). Nature Immunology. 24 (10). SARS-CoV-2 reservoir in PASC. doi: 10.1038/s41590-023-01601-2 . PMID   37667052. S2CID   261527320.
  44. Proal AD, VanElzakker MB, Aleman S, Bach K, Boribong BP, Buggert M, et al. (September 2023). "SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)" (PDF). Nature Immunology. 24 (10). Mechanisms of disease. doi: 10.1038/s41590-023-01601-2 . PMID   37667052. S2CID   261527320. Archived (PDF) from the original on 28 April 2024. Retrieved 28 April 2024.
  45. Chen B, Julg B, Mohandas S, Bradfute SB (May 2023). "Viral persistence, reactivation, and mechanisms of long COVID". eLife. 12. doi: 10.7554/eLife.86015 . PMC   10159620 . PMID   37140960.
  46. Greene C, Connolly R, Brennan D, Laffan A, O'Keeffe E, Zaporojan L, et al. (March 2024). "Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment". Nature Neuroscience. 27 (3): 421–432. doi:10.1038/s41593-024-01576-9. PMC   10917679 . PMID   38388736.
  47. CDC (6 July 2023). "COVID-19 and Your Health". Centers for Disease Control and Prevention. Archived from the original on 26 February 2020. Retrieved 3 September 2023.
  48. Van Beusekom M (13 October 2023). "Review estimates 69% 3-dose vaccine efficacy against long COVID". University of Minnesota. Archived from the original on 15 October 2023. Retrieved 15 October 2023.
  49. Marra AR, Kobayashi T, Callado GY, Pardo I, Gutfreund MC, Hsieh MK, et al. (2023). "The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research". Antimicrobial Stewardship & Healthcare Epidemiology. 3 (1): e168. doi: 10.1017/ash.2023.447 . ISSN   2732-494X. PMC   10644173 . PMID   38028898. S2CID   263909710.
  50. Català M, Mercadé-Besora N, Kolde R, Trinh NT, Roel E, Burn E, et al. (1 March 2024). "The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia". The Lancet Respiratory Medicine. 12 (3): 225–236. doi: 10.1016/s2213-2600(23)00414-9 . ISSN   2213-2600. PMID   38219763.
  51. "Vaccines reduce the risk of long COVID". NIHR Evidence. 24 July 2024. doi: 10.3310/nihrevidence_63203 .
  52. Mercadé-Besora N, Li X, Kolde R, Trinh NT, Sanchez-Santos MT, Man WY, et al. (1 May 2024). "The role of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complications". Heart. 110 (9): 635–643. doi:10.1136/heartjnl-2023-323483. ISSN   1355-6037. PMC   11041555 . PMID   38471729.
  53. "COVID-19 rapid guideline: managing the long-term effects of COVID-19". National Institute for Health and Care Excellence . 11 November 2021. Archived from the original on 2 August 2023. Retrieved 9 September 2023.
  54. 1 2 3 4 5 6 7 Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, et al. (September 2021). "Symptoms, complications and management of long COVID: a review". Journal of the Royal Society of Medicine. 114 (9): 428–442. doi:10.1177/01410768211032850. PMC   8450986 . PMID   34265229.
  55. 1 2 3 4 5 Wolf S, Zechmeister-Koss I, Erdös J (August 2022). "Possible long COVID healthcare pathways: a scoping review". BMC Health Services Research. 22 (1): 1076. doi: 10.1186/s12913-022-08384-6 . PMC   9396575 . PMID   35999605.
  56. 1 2 Nasserie T, Hittle M, Goodman SN (26 May 2021). "Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review". JAMA Network Open. 4 (5): e2111417. doi:10.1001/jamanetworkopen.2021.11417. ISSN   2574-3805. PMC   8155823 . PMID   34037731. Archived from the original on 28 April 2024. Retrieved 8 April 2024.
  57. "Technical article: Updated estimates of the prevalence of post-acute symptoms among people with coronavirus (COVID-19) in the UK - Office for National Statistics". www.ons.gov.uk. 16 September 2021. Archived from the original on 8 April 2024. Retrieved 8 April 2024.
  58. "New-onset, self-reported long COVID after coronavirus (COVID-19) reinfection in the UK: 23 February 2023". 23 February 2023.
  59. "New research examines the risk of developing Long Covid". 25 April 2024.
  60. 1 2 3 Ford ND, Slaughter D, Edwards D, Dalton A, Perrine C, Vahratian A, et al. (August 2023). "Long COVID and Significant Activity Limitation Among Adults, by Age – United States, June 1–13, 2022, to June 7–19, 2023". MMWR. Morbidity and Mortality Weekly Report. 72 (32): 866–870. doi:10.15585/mmwr.mm7232a3. PMC   10415000 . PMID   37561665.
  61. McMahan I (15 July 2024). "About 7 percent of U.S. adults have had long covid, report says". The Washington Post.
  62. Hastie CE, Lowe DJ, McAuley A, Winter AJ, Mills NL, Black C, et al. (October 2022). "Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study". Nature Communications. 13 (1): 5663. Bibcode:2022NatCo..13.5663H. doi:10.1038/s41467-022-33415-5. PMC   9556711 . PMID   36224173.
  63. Zheng YB, Zeng N, Yuan K, Tian SS, Yang YB, Gao N, et al. (May 2023). "Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review". Journal of Infection and Public Health. 16 (5): 660–672. doi:10.1016/j.jiph.2023.03.005. PMC   9990879 . PMID   36931142.
  64. Rushforth A, Ladds E, Wieringa S, Taylor S, Husain L, Greenhalgh T (October 2021). "Long Covid – The illness narratives". Social Science & Medicine. 286: 114326. doi:10.1016/j.socscimed.2021.114326. hdl: 10044/1/91206 . PMID   34425522. S2CID   237281271.
  65. 1 2 Roth PH, Gadebusch-Bondio M (January 2022). "The contested meaning of "long COVID" – Patients, doctors, and the politics of subjective evidence". Social Science & Medicine. 292: 114619. doi:10.1016/j.socscimed.2021.114619. PMC   8629766 . PMID   34906823.
  66. Witvliet MG (27 November 2020). "Here's how it feels when COVID-19 symptoms last for months". PBS NewsHour. Archived from the original on 29 November 2020. Retrieved 29 November 2020.
  67. Macnamara K. "The Covid 'longhaulers' behind a global patient movement". AFP. Archived from the original on 4 February 2021. Retrieved 30 January 2021.
  68. "Patient-Led Research Collaborative for Long COVID". Patient Led Research Collaborative. Archived from the original on 10 January 2022. Retrieved 8 January 2022.
  69. Hossain MM, Das J, Rahman F, Nesa F, Hossain P, Islam AM, et al. (16 February 2023). Canzan F (ed.). "Living with "long COVID": A systematic review and meta-synthesis of qualitative evidence". PLOS ONE. 18 (2): e0281884. Bibcode:2023PLoSO..1881884H. doi: 10.1371/journal.pone.0281884 . PMC   9934341 . PMID   36795701.
  70. 1 2 Nittas V, Gao M, West EA, Ballouz T, Menges D, Wulf Hanson S, et al. (2022). "Long COVID Through a Public Health Lens: An Umbrella Review". Public Health Reviews. 43: 1604501. doi: 10.3389/phrs.2022.1604501 . PMC   8963488 . PMID   35359614.
  71. Gualano MR, Rossi MF, Borrelli I, Santoro PE, Amantea C, Daniele A, et al. (1 January 2022). "Returning to work and the impact of post COVID-19 condition: A systematic review". Work. 73 (2): 405–413. doi: 10.3233/WOR-220103 . PMID   35938280. S2CID   251293637.
  72. Waters T, Wernham T (2022). Long COVID and the labour market (PDF). The Institute for Fiscal Studies. pp. 10–11. ISBN   978-1-80103-079-3. Archived (PDF) from the original on 5 August 2023. Retrieved 5 August 2023.
  73. Gonzalez AE, Suzuki E (13 June 2024). The impacts of long COVID across OECD countries (Report). OECD Health Working Papers. Paris: OECD. doi:10.1787/8bd08383-en.
  74. Belluck P (9 August 2024). "About 400 Million People Worldwide Have Had Long Covid, Researchers Say". The New York Times. ISSN   0362-4331 . Retrieved 23 August 2024.
  75. Al-Aly Z, Davis H, McCorkell L, Soares L, Wulf-Hanson S, Iwasaki A, et al. (August 2024). "Long COVID science, research and policy. Nat Med". Nature Medicine. 30 (8): 2148–2164. doi:10.1038/s41591-024-03173-6. PMID   39122965.
  76. "Post-COVID Conditions". Centers for Disease Control and Prevention. 16 December 2022. Archived from the original on 14 January 2022. Retrieved 7 June 2023.
  77. Montani D, Savale L, Noel N, Meyrignac O, Colle R, Gasnier M, et al. (March 2022). "Post-acute COVID-19 syndrome". European Respiratory Review. 31 (163): 210185. doi:10.1183/16000617.0185-2021. PMC   8924706 . PMID   35264409.
  78. Buonsenso D (2023). "Pharmacological trials for long COVID: first light at the end of the tunnel". The Lancet. Regional Health – Europe. 24: 100544. doi:10.1016/j.lanepe.2022.100544. ISSN   2666-7762. PMC   9647474 . PMID   36407125.
  79. Subbaraman N (March 2021). "US health agency will invest $1 billion to investigate 'long COVID'". Nature. 591 (7850): 356. Bibcode:2021Natur.591..356S. doi: 10.1038/d41586-021-00586-y . PMID   33664445. S2CID   232123730.
  80. Cohrs R (31 July 2023). "NIH begins long-delayed clinical trials for long Covid, announces new research office". STAT. Archived from the original on 31 July 2023. Retrieved 31 July 2023.
  81. Kozlov M (August 2023). "NIH launches trials for long COVID treatments: what scientists think". Nature. doi:10.1038/d41586-023-02472-1. PMID   37528203. S2CID   260375952.
  82. Walker S, Goodfellow H, Pookarnjanamorakot P, Murray E, Bindman J, Blandford A, et al. (1 June 2023). "Impact of fatigue as the primary determinant of functional limitations among patients with post-COVID-19 syndrome: a cross-sectional observational study". BMJ Open. 13 (6): e069217. doi: 10.1136/bmjopen-2022-069217 . ISSN   2044-6055. PMC   10335413 . PMID   37286327.
  83. "Long COVID: fatigue predicts poor everyday functioning". UK National Institute for Health and Care Research. 23 November 2023. doi:10.3310/nihrevidence_60359. Archived from the original on 4 December 2023. Retrieved 4 December 2023.

Further reading

General

Books

Journal articles