STM_longcovid_translation.txt

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Long-lasting COVID-19 -
Consensus statement of the expert group appointed by STM on 31 December 2021
VN / 20672/2021



DRAFT 7.1.2022





Table of contents

Summary 3
Setting up an expert group 4
Definition of long-term COVID-19 4
Long-term COVID-19: epidemiology and indicators 5
Socio-economic impacts of long-term COVID-19 6
On the disease mechanisms of long-term COVID-19 7
Long-term COVID-19: clinical picture 7
Long-term COVID-19 in children and adolescents 12
COVID-19 Diagnostics, Immunity, and Long-Term COVID-19 13
Long-term COVID-19 and COVID-19 vaccines 14
Long-term COVID-19: treatment and rehabilitation 15
Information retrieval and consensus statement process
Composition of the expert group 17








Summary

WHO estimates and published prevalence figures from different countries
more than 100 million people will be infected with long-term COVID-19 by autumn 2021,
which poses a threat to public health worldwide, causing significant costs and suffering.
According to the national register maintained by the UK health authorities, around 2% of the total
population suffers from the symptoms of long-term COVID-19 based on self-reports, almost every second
the symptoms have lasted for more than a year, and in the majority of patients the symptoms interfere with everyday life or
reduce functional capacity. Hundreds of studies and millions have been published on the epidemiology of the disease
patient-based meta-analyzes. Several domestic investigations are also underway.

On 6 October 2021, the WHO defined long-term COVID-19 as follows:
“Long-term COVID-19 (long covid) usually occurs within 3 months of COVID-19 infection
in individuals with a probable or confirmed SARS-CoV-2 infection.
The symptoms of long-term COVID-19 last for at least 2 months and cannot be explained by an alternative
diagnosis. Common symptoms include fatigue, shortness of breath and cognitive impairment
dysfunction as well as many other symptoms that interfere with daily activities. Symptoms may
continue from acute COVID-19 disease or occur with a delay. Symptoms may also include waves or
recur over time. Long-term COVID for children may require a different definition. ” USA
according to the Center for Disease Control (CDC), the symptoms last for at least four
weeks, and the four main symptoms are difficulty breathing, exhaustion, decreased physical or
cognitive stress tolerance and difficulty concentrating, or brain fog.

Depending on the definition, long-term COVID-19 occurs in approximately one in two adults with SARS-CoV-2.
after infection and in about one in fifty children. The incidence is higher
after an illness requiring hospitalization, but the disease may also occur with asymptomatic or asymptomatic
after infection.
The mechanisms of the disease have so far been described as the infection of several organs by the SARS-COV-2 virus, and
results in prolonged inflammation, tissue damage, and impaired immune defense, which may include
associated with both coagulation and nervous system dysregulation. Significantly related to the disease
psychosocial stress can also affect symptom. Long-term effects of the disease
not known. Current mRNA vaccines reduce SARS-CoV-2 in patients with infection
risk of long-term COVID-19 and often have a beneficial effect on its symptoms.

Treatment of long-term COVID-19 is currently symptomatic and empirical. Multifactorial
multidisciplinary treatment and rehabilitation is recommended as an approach to the disease. Osana
the integration of primary health care and specialist care in welfare areas is likely to be present
better opportunities for health centers to form multidisciplinary Teams with extensive
competence.


3

Setting up an expert group

On 25 August 21, the Ministry of Social Affairs and Health set up an expert group to monitor
and to analyze nationally and internationally long-term COVID-19 or long covid syndrome
and, where appropriate, issue opinions and proposals for action
to support decision-making. The accumulated research data require national coordination and
joint analysis by experts in order to be able to react and take action
based on the right information and in a proportionate manner.
There are thousands of peer-reviewed studies of long-term COVID-19, with systematic
the search for information on the topic has produced more than 10,000 hits for the expert group. Expert group
has read the published literature and prepared reviews based on it as well as the first
domestic consensus vision, which will be updated during 2022.


Definition of long-term COVID-19

On October 6, 2021, the World Health Organization defined long-term covid as follows:

“Long-term COVID-19 (long covid) usually occurs within 3 months of COVID-19 infection
in individuals with a probable or confirmed SARS-CoV-2 infection.
The symptoms of long-term COVID-19 last for at least 2 months and cannot be explained by an alternative
diagnosis. Common symptoms include, in particular, fatigue, dyspnea, and cognitive impairment
as well as many other symptoms that interfere with daily activities. Symptoms may not begin until acute
COVID-19 disease or continue thereafter. Symptoms may also waves or recur over time
within. Long-term covid in children may require a different definition. ”

According to the WHO definition, the criteria include the onset of symptoms within 3 months of acute
The onset of COVID-19 infection and the duration of symptoms are at least 2 months and are unexplained.
The definition was introduced for consensus use by the generally accepted Delphi method and represents
global consensus opinion, not the outcome of the study. Symptoms should be limited
everyday life and ability to function. The diverse spectrum of the disease and the duration of the weeks are individual
most important for diagnosis rather than symptom. In the US, the CDC defines symptoms as the minimum duration
from the onset of an acute infection for 4 weeks. According to the CDC, the four main symptoms are difficulty breathing,
fatigue, impaired endurance of physical or cognitive exertion (PEM, post-exertional
malaise) and difficulty concentrating.

Several other terms have been used for prolonged symptoms after COVID-19 infection (e.g.
PACS = post-acute COVID-19 syndrome; PASC = post-acute sequelae of COVID-19; PCC = COVID-19 post
condition; Long COVID, long Haul COVID-19 ”). The expert group recommends in the first instance
to use the Finnish term “long-term COVID-19”.

The diagnostic code for the extended COVID-19 ICD-10 in 2021 is U09.9.
The diagnosis number should differentiate patients with microbiologically confirmed COVID-19
prolonged post-infection symptoms in those with microbiological confirmation of the disease
There is no COVID-19 disease. According to the WHO, a positive COVID-19 PCR test or an increase in antibodies is not
is not a prerequisite for a long-term diagnosis of COVID-19. Based on the nature of the syndrome
appropriate symptomatic diagnosis is recommended and a “causal diagnosis” would be an additional diagnosis.
For practical reasons, our working group considers it important that long-term COVID-19 could be
in the future to be classified as generally accepted based on the severity of the symptoms
4

criteria such as three levels of difficulty: 1) mild, 2) moderate,
restrictive) and 3) severe (severely restrictive).


Long-term COVID-19: epidemiology and indicators

Hundreds of studies and dozens of studies have been published on the incidence of long-term COVID-19 symptoms.
meta-analyzes. WHO estimates, the latest research findings and country-specific prevalence figures
it is estimated that more than 100 million people worldwide would be ill so far
long-term COVID-19 disease, and the number is growing rapidly. British health authorities
According to the national register maintained by the COVID-19, about 2% of the total population suffers from long-term COVID-19
based on self - reports, almost every second symptoms have persisted for more than a year, and
in the majority of patients, symptoms interfere with daily life or impair functioning.
Incidence rates vary widely between individual studies, depending on the incidence of COVID-19 infection.
severity, need for hospitalization, ventilator and intensive care, age group, symptoms
duration and number of cases and the associated disadvantages. Extremes are represented by children, for example
severe long-term symptoms in less than 1% of patients treated in hospital for more than 6 months
endured symptoms by up to 90%. For example, female gender and asthma are also risk factors
prolongation of symptoms like many long-term illnesses. On the other hand, young and basic health
become ill without demonstrable risk factors. Sudden loss of sense of smell is affected
epidemiological studies on a rather specific symptom not seen in other diseases
manifests as an acute symptom, especially if associated with hallucinations. Instead, the sense of smell
gradual deterioration is common in many long-term illnesses. Studies show symptoms
most often decrease over time, but some Finnish patients have already contracted almost 2
years and the long-term forecast is not yet known.

Extensive studies have shown that COVID-19 infection affects approximately 80% of patients on average
at least one prolonged symptom occurs more than 3 months after the onset of an acute illness and about 50
% have at least one symptom more than 6 months after the onset of an acute illness. The spectrum of symptoms is
large and include both subjective and objectively measurable symptoms. The most common symptom
more than 3 months after the onset of acute illness, fatigue, weakness or malaise (typically
post-exertional malaise, PEM), while abnormal breathing or chest pain and
Anxiety or depression are the most common symptoms after more than 6 months of acute illness.
illness. According to WHO criteria, symptoms should affect daily activities
essentially, but the syndrome may be wavy. Although prolonged symptoms are very
common, it is generally estimated that 10-20% of COVID-19 infected patients experience symptoms beyond 3 months of age.
in such a way that they have a significant effect on day-to-day operations and prolonged COVID-19
criteria are met.

According to extensive research evidence, more than 6 months have been produced by several studies and their meta-analyzes
the incidence of persistent symptoms appears to be halved. In all studies and their
in meta-analyzes, the incidence of symptoms has not decreased over time. Freshly advanced
in a meta-analysis of follow-up studies with a total of more than 250,000 mostly in hospital
treated patients with COVID-19, symptoms of long-term COVID-19 may occur in more than 50
% for the entire 6-month follow-up period. Symptoms are more common in patients treated in hospital
compared to those with the disease at home. Severity of the disease and especially of respiratory symptoms
initially correlate with the severity of long-lasting sequelae. Different
the prevalence of symptoms varies depending on the asymptomatic or even asymptomatic nature of the acute disease
compared to severe symptoms. On the other hand, a large proportion of those with mild illness at home
prolonged symptoms have been reported in adolescents for at least 6 months.

5

Based on meta-analyzes involving dozens of high-quality studies and millions of patients
the incidence of long-term symptoms ranges from 40 to 60%. No studies have been reported with them
the proportion of patients with only one symptom, so the incidence is likely to be lower if
cohorts are limited to multi-symptomatic patients. The number of symptoms is not systematic
reported, the median number of symptoms is sometimes reported. Despite the symptom, the majority
return to work or otherwise normal life. High prevalences in most
cross-sectional studies reflect bias in selection, as symptoms respond to questionnaires
more often than asymptomatic.

The latest meta-analyzes are based on follow-up studies, so they contain less
sources of error than cross-sectional cohorts. According to progressive follow-up studies, every second
A patient with COVID-19 infection will have long-lasting symptoms.

There are health authorities in different countries and also countless studies published on the subject
have so far used different definitions, which weakens the information
co-ordination and evaluation. Incidence figures will continue to be affected
variable definition of long-term COVID-19. Concerning the prevalence of long-term COVID-19
may be considered as a constraint on research and a potential source of bias
the following:
1. Variation in the definitions of long-term COVID-19.
2. There are few progressive follow-up studies, with the exception of the latest meta-analyzes.
3. Studies have been conducted and published in the midst of a pandemic, but in the current context or follow-up
the incidence may change.
4. Many studies involve patient sets without a control group. PCR negative
the use of patients as a control group is problematic because the patient may receive a false PCR test
negative result, the control group may include patients with long-term illness
COVID-19, on the other hand, in long-term COVID-19, the symptom may not depend on SARS-CoV-2
virological confirmation of infection.
5. Several cross-sectional studies have been carried out as questionnaires asking different questions
or they are conducted as self-reporting, in which case symptomatics can be expected to respond to surveys more frequently
than asymptomatic.
6. Publications do not generally cover patients with asymptomatic COVID-19 infection.
7. The target population and background population of the studies vary: hospitalized only, SARS
CoV-2-positive or the general population, so incidences are not directly comparable.
8. There are currently no data on the long-term morbidity of the Omikron variant.


Socio-economic effects of long-term COVID-19

The effect of long-term COVID-19 on health costs depends on the adverse effects of the symptoms,
their duration and number of patients. Chronic disease modeling has shown that
COVID-19 as an acute disease is only part of the SARS-Cov-2 virus and pandemic
disease burden, and more than half of the loss of quality-focused life years would result
long-term symptoms. According to the modeling applied to the recent Finnish population, the 2021
by the end, long-term COVID-19 would cause more than 15,000 lost in our country
quality-weighted life years (QALYs) in the coming years and decades. In children at the individual level
the cost may be higher, but long-term symptoms are much less common.



6

Disease mechanisms of long-term COVID-19

Our current understanding of the pathogenesis of long-term COVID-19 disease is based on more than a thousand
peer-reviewed research, some are congressional presentations or peer-reviewed, and new results
published daily. There are several underlying pathophysiological mechanisms that may occur
depend on the course of the acute illness and hereditary factors. So far, it has been confirmed that
vascular damage and blood clotting disorders are common after SARS-CoV-2 infection and
associated with long-term symptoms.

The SARS-CoV-2 virus infects a wide variety of tissues, leading directly to tissue destruction. As well as straight
viral infection and especially a strong immune response can damage tissues. Mixed
the entry of the virus into the walls of the blood vessels and the immune response damage the walls of the blood vessels
causing blood clots and lack of tissue oxygen. Lung, heart and nervous system function
associated symptom is associated with such organ damage as a result of viral infection. The SARS-CoV-2 virus can
infect both neurons and the supporting tissue of the nervous system, the latter most likely
explain most of the symptoms. The incidence of multiple neurological diseases increases with COVID-19 infection
after. There is indicative evidence that, for example, Alzheimer's disease and Parkinson's disease
the incidence increases after COVID-19 infection, but the mechanisms are not yet known.
Rare autoantibodies to the body's own structures are found in a number of cases
in patients with long-term COVID-19 and a high incidence of autoantibodies
more than after other viral infections. There are also indications that auto-antibodies
production continues after the acute phase, explaining prolonged symptoms.

Symptoms of long-term COVID-19 include dysregulation of the autonomic nervous system. Interference is transmitted
autoantibodies, followed by an inflammatory condition of the centers or ganglia of the autonomic nervous system,
autonomic nerve neuropathy or the effect of cytokines. Activated in severe coronavirus infection
strong cytokine-mediated inflammatory response.
Inflammations of cellular biological mechanisms, altered function of different cells and especially
The production of autoantibodies suggestive of autoimmune disease is apparently the predominant part of the symptoms
in the background. Slow tissue recovery after acute infection may prolong symptoms. Above
there is ample evidence of this, but the effects of different mechanisms and their
there is no adequate data on the prevalence in individual patients.


Long-term COVID-19: clinical picture

According to the WHO consensus, common manifestations of long-term COVID-19 are severe exhaustion,
dyspnoea and cognitive symptoms. Cognitive symptoms refer to e.g.
disorders of memory functions, brain data processing and learning. Some of the symptoms are new
occurring only after patients recovered from the acute phase of the disease, some of the initials continuing
unchanged from the onset of infection. Patients may experience intermittent fluctuations in symptoms
so that the symptoms may sometimes subside completely, but start again later, often
as a result of stress. For patients, the return of symptoms after a better period often produces large ones
disappointments. The spectrum of symptoms of long-term COVID-19 is diverse and of individual symptoms
reported incidence rates vary.

The largest meta-analyzes published in 2021 are based on a total of dozens of studies and more
million patients. The most common symptoms of long-term COVID-19, which occur in at least one
another patient has experienced fatigue and impaired stress tolerance, the next most common
sleep disorders, pain, headache, shortness of breath, difficulty concentrating and other cognitive disorders,
odor or taste disturbance and anxiety or depression.
7

The most common single symptom in patients with long-term COVID-19 is fatigue or decreased
stress tolerance experienced by at least half of these patients 3 months after the onset of infection.
The proportion of people with long-term symptoms has been higher than that of influenza and others
after respiratory infections. Cognitive symptoms tend to be more common in the elderly as well
hospitalized and in the intensive care unit than those in home care. The temporal course of different symptoms
can vary considerably, and pain is often the most prolonged symptom. There are several sleep disorders
in the study after COVID-19 infection, although not always
widely asked, and the psychosocial factors associated with the pandemic may also explain
increased sleep disturbances and fatigue. According to some studies, almost a third of the size
the population has suffered from poor quality sleep and fatigue during a pandemic.

Dyssautonomy, or disorders of the autonomic nervous system, is quite common.
Inappropriate increase in pulse level even under light stress and vertical position, ie
postural orthostatic tachycardia (POTS) and hypotension (orthostatic
hypotension) in the upright position are typical of dysautonomy, as well as gastrointestinal disturbances
(abdominal pain, diarrhea, constipation), disorders of temperature control (fever, sweating, frostbite)
and allergic symptoms. In patients with long-term COVID-19, symptoms are typically persistent,
often recurrent or prolonged, ranging from 20 to 70% in different studies.
between. If a mere increase in pulse level is considered a symptom of dysautonomy, dysautonomy occurs
in most patients.

COVID-19 infection is often associated with skin symptoms, which most often resolve but may
symptoms in a wavy long-lasting form. The more common chronic skin symptom is the so-called
COVID toes with changes in the toes resembling reddish cold nodules. Phenomenon
suspected to be associated with the presence of autoantibodies and small vessel obstructions. To many
diseases and COVID-19 infection are associated with hair loss. This is usually benign and
a reversible phenomenon that can last for months. In addition, patients have been described as long-term
skin infections and reactivation of herpes viruses.

Prolonged airway symptoms associated with pulmonary dysfunction and
abnormal lung imaging are common after COVID-19 infection,
are typically associated with a more severe acute infection and are often associated with significant
long-term harm.

The most common respiratory symptoms are decreased performance, difficulty breathing,
shortness of breath, feeling out of oxygen, mucus, cough and chest or breathing problems
pain. Prolonged symptoms may be due to several causes, such as those caused by an acute illness
lung damage, worsening of previous chronic lung disease, pulmonary vascular disease
coagulation disorders and other disorders of respiratory regulation. Anomalous
Musculoskeletal causes and dysautonomy have also been suggested as mechanisms of respiration.

In patients with mild disease, the objective findings in a clinical stress study are low and
hypoxia in the blood and tissues is rare, even with reduced stress tolerance.
Prolonged symptoms include shortness of breath, feeling out of oxygen, or pain associated with breathing
may also be explained by causes other than cardiac or pulmonary.

Patients who require hospitalization and especially intensive care are more likely to have measurable ones
abnormal findings related to lung structure or function. In patients with severe disease
decreased lung gas exchange capacity, decreased

oxygen uptake, lung volume depletion, and long - term imaging changes such as
connective tissue, especially after pneumonia. It has been observed in patients with mild disease
tendency to bronchoconstriction and changes in CT scan of the lungs.
Abnormal lung findings are present in up to half of hospitalized COVID-19 patients at 6 months of age.
and still about a third at 12 months of onset.
Pulmonary imaging findings have most often correlated with lung function test results and patient
with symptoms. Prolonged hypoxemia occurs, but abnormalities
lung function studies appear to be largely corrected at year follow-up.
Prolonged respiratory symptoms include age, female gender, severity of acute illness,
ventilator therapy and Finding blood clotting activity.

The first of the cardiac symptoms of COVID-19 infection is acute myocardial infarction,
which is present in 20-30% of hospitalized patients. Marker of myocardial injury
troponin is often elevated in the blood and the prognosis is worse in these patients. In some patients
troponin levels remain elevated for longer.
The mechanisms of myocardial infarction in COVID 19 patients include endothelial damage, small vessel
cytokine-mediated inflammatory reaction, severe hypoxia, sepsis, pulmonary embolism and
coronary thrombosis or coronary artery spasm.

According to meta-analyzes, typical cardiovascular events persist for more than 2 weeks after illness
symptoms include exertional respiration, shortness of breath, chest pain, and elevation
resting heart rate and rhythm disturbances, and slightly less commonly, vertical blood pressure
decrease or increase in pulse level. Cardiac imaging studies have shown the right ventricle
dilation, left ventricular contraction and diastolic dysfunction, in addition to
magnetic resonance imaging may indicate swelling, connective tissue, or inflammation
Findings.
Cardiovascular symptoms and findings also occur in patients who are ill
COVID-19 in home care, although they are more common in hospital. Prolonged
mechanisms of cardiovascular syndrome may include endothelial damage and microthrombosis, chronic
hypoxia, increased pulmonary arterial pressure and ventricular load. Dysfunction of the autonomic nervous system
can lead to harmful fluctuations in heart rate and blood pressure (POTS) without
heart disease.

Myocarditis, pericarditis, pulmonary embolism and increased pulmonary arterial pressure
instead, they are relatively rare findings associated with poorly predicted COVID-19 infection. Half
within one year of COVID-19 infection, patients have experienced more controls than controls
myocardial ischaemia and the need for coronary contrast media imaging; and
coronary artery procedures.

In the absence of long-term follow-up, it is not yet known whether cardiac magnetic resonance imaging
The observed change leads to myocardial infarction, heart failure or arrhythmias.
The effect of COVID-19 infection on the development of coronary heart disease should also be considered. Pandemic
causes a lack of treatment for chronic diseases, and is likely to worsen the isolation of those living
the condition of the patients.

COVID-19 infection is usually associated with significant activation of the coagulation system and is accelerated
especially during a serious illness leading to hospitalization. Coagulation disorder is
interact with local inflammatory vascular damage, and natural coagulation
regulatory mechanisms weaken as the disease progresses. Coagulation activity was already observed in the pandemic
leading to deep vein thrombosis, especially in hospitalized patients, and
pulmonary embolism, but also predisposing to arterial occlusion and organ damage. In some patients
coagulation activity continues, slowing the recovery phase and
9

related to symptom variation. In acute severe COVID-19 infection and lung injury (ARDS)
blood fibrinogen and fibrin breakdown products D-dimer levels are high, indicating
acceleration of coagulation. The finding is also seen without any detectable thrombosis as a reference
peripheral circulatory disorders. According to the latest research data, biomarkers of coagulation are common
also persisted in prolonged COVID-19, although the acute infection is no longer present
indication. Some patients may have a background of small coagulation associated with continuous coagulation activation
vascular occlusion, which has also been widely described in the peripheral circulation, including the brain.
There is an imbalance between the formation and dissolution of a blood clot. You can join the space
also hyperlipidemia.
The persistence of coagulation disorder favors targeted anticoagulant therapy,
from which research evidence is currently accumulating.

Intensive care is generally associated with sequelae in patients other than COVID-19, especially
associated with severe lung injury, and the independent contribution of COVID-19 to the incidence of
difficult to assess. Prolonged symptom may occur after COVID-19 leading to intensive care
multifactorial. In particular, symptoms of exhaustion and respiratory symptoms and Findings appear to be
more common in intensive care. In terms of cognitive performance, results vary
studies, and the deterioration may be partly explained by factors other than the acute phase
severity of the disease. In patients undergoing respiratory therapy after intensive care
The most common findings from long-term follow-up are restrictive respiratory function
decline, which is most often mild and resembles another cause in adults
Findings from long-term follow-up of patients with respiratory distress syndrome. In addition
even a significant reduction in diffusion capacity is common. Muscle weakness is an intensive treatment
after normal and affects physical performance. The majority are also evolving
malnutrition and muscle loss can be significant. In the acute phase, COVID-19 occurs in patients
also commonly confusion as an organic brain disorder. Insufficient after intensive care
one - third of patients experience anxiety, depression, pain, sleep disturbances, and
traumatic stress disorder, which may last longer than poor physical performance,
at least half a year.
At least four out of five people in intensive care feel that they have not fully recovered after 6 months
after hospitalization. The results of the long-term follow-up after a six-month follow-up period are still available
is expected.

The term Neurocovid has been used to describe the central
or peripheral nervous system dysfunction or disease. Possible symptoms of neurocovidide include
acute confusion, impaired consciousness, headache and peripheral nervous system damage
sensory disturbances and pain. There are no sequelae of neurological diseases that occur in the acute phase
generally classified as long-term COVID-19. The most common of the neurological diseases
are encephalopathy (= a brain disease that changes the structure or function of the brain) and
cerebrovascular disorders. Both are primarily associated with a severe form of infection that
requires intensive care unit care. There are also severe immune-mediated encephalitis (encephalitis)
reported, but not in Finland.
Inflammatory changes in the olfactory coil of the brain that explain the loss of sense of smell are also sometimes seen
in the acute phase of brain magnetic resonance imaging. The brain has been found in the UK
in a magnetic resonance imaging study after COVID-19 infection, mild brain tissue loss in the frontal lobe
imaging findings have been compared from the same patient previously prior to the onset of the pandemic
taken pictures. Neurological diseases are associated with long-term or permanent sequelae
particularly cerebrovascular disease and encephalopathy, which also increases the risk of disease
later memory impairment.

Cognitive impairment is one of the major neurological disorders of long-term COVID-19
10

or neuropsychiatric symptoms, and are the most significant workplace for patients in addition to fatigue
in terms of operational capacity. These disturbances in the information processing processes in the brain are manifested in memory,
learning, concentrating, thinking, perceiving, attentive, and problem-solving
as a deterioration. Brain fog is a popular term that usually refers to difficulty concentrating
and the slowness of data processing. Viral infections are known to cause cognitive symptoms,
and, for example, patients with SARS / MERS coronavirus infections
about 15% had problems with memory, alertness, concentration, and data processing.
Following COVID-19 infection, these symptoms are clearly more common (20-40%). Cognitive
In addition to exhaustion, functional disturbances are the most significant impairments in work and functional capacity
symptoms.

Based on neuropsychological studies and brain imaging findings, long-term exposure to COVID-19
cognitive symptoms suggest dysfunction of the forehead and scalp.
Typical
manifestations are ERP, attentiveness, fluency, memorization, memory
search and processing speed disturbances. Stress or pre-pandemic psychiatric symptoms no
alone explain these symptoms, nor the severity of the infection or hospitalization.
Cognitive symptoms are common for a few months after the onset of infection and occur
some more than six months later. There are indications that prolonged inflammation of the body
the way the defense system responds to the infection would also explain the cognitive symptoms. Cerebral
a PET scan measuring metabolism is seen about 3 months after illness
local disturbances of glucose metabolism. Severe exhaustion is often involved for more than six months
in persistent cognitive impairment, thus emphasizing a prolonged picture of the disease
to the initial stage. Exhaustion refers to the subjective difficulty of initiating or maintaining
involuntary activities and fatigue or reduced stress tolerance. As a symptom, it occurs
often concomitantly with muscle fatigue, somnolence, or depression.
On the other hand, the difficulty of finding words and the disturbances of attention and action control
also characteristic of chronic fatigue syndrome (CFS), where similar conditions may occur.
cognitive symptoms than in patients with long-term COVID-19.

Psychosocial stress can be reflected in the symptom in many ways. In the background of congestion
are e.g. anxiety related to illness, loss of function, or loss of life, social
isolation, traumatic treatment experiences, financial worries, and prolonged
somatic symptom. This type of stress can manifest as a psychiatric symptom, complicating
symptoms of long-term COVID-19 or slows rehabilitation.

The most serious infections leading to hospital and intensive care account for an estimated one in eight
in the patient so-called. traumatic stress disorder (PTSD). Its main symptoms are persistent,
anxiety-like hyperexcitability and memory of traumatic events
intrusion into consciousness in waking and asleep as well as distressing situations
avoidance, which can significantly limit life. Traumatic in the largest meta-analyzes
stress disorder has been rare.

The incidence of depressive or anxiety disorders after COVID-19 infection has been estimated to be approx
one and a half times higher than, for example, in people with the flu. About 17% of patients
received a diagnosis of anxiety and approximately 14% depression within six months
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infection in the United States. For depression, anxiety and stress disorder
the more severe the infection, the greater the risk of getting the disease. The biggest risk is
those in intensive care, followed by others in hospital and relatively the least in outpatient care
treated patients. The previous psychiatric diagnosis and female gender are associated with some
extensive studies suggest an increased risk of psychiatric disorders. Psychiatric symptoms
decreases with time, so that the symptom level is clearly higher than three to six months
follow-up.

In chronic fatigue syndrome (ME / CFS), long-term exhaustion syndrome of long-term COVID-19 is often
whereas the disease is associated with a six-fold increase in suicide rates compared with the general population,
but long-term COVID-19 is not known to be associated with increased suicide mortality.
Approximately 0.4% of patients develop psychosis after COVID-19 infection. Post-infection
Organic brain disease, especially when developing psychosis, must also be kept in mind
the possibility of autoantibody-mediated autoimmune encephalitis described in SARS-CoV-2
in connection with the infection.


Long-term COVID-19 in children and adolescents

The recent WHO definition of long-term COVID-19 does not apply to children and the symptoms of
commonly agreed case definition such as COVID-19 in adults with long-term syndrome.

Prolonged post-COVID-19 infection in children has been reported in several countries without further explanation
fatigue, shortness of breath, palpitations, difficulty concentrating, headache, dizziness,
muscle weakness, difficulty sleeping, joint pain, loss of sense of smell, weight loss and
sore throat. According to studies, the prevalence of prolonged symptoms is about 1-2% of patients.
Children and adolescents can sometimes suffer from prolonged anosmia, the only
as a symptom after COVID-19 infection. Intensive care is very common in children and adolescents
rare, and therefore the associated sequelae. Some suffer from prolonged symptoms
children and adolescents need assessment and care in specialist care. Not for children and young people
there is precise treatment for prolonged symptoms. For most children and young people
prolonged symptoms resolve within 3 to 6 months, but high-quality follow-up studies are not yet available.

The prevalence of long-term symptoms in children and adolescents after coronary infection has been evaluated, for example
in a high-quality progressive follow-up study in the UK, and at least
4% of PCR-positive children and adolescents (77/1734) experienced symptoms within one month.
The most common symptoms lasting at least a month were loss of sense of smell, headache, and fatigue.
1.8% of children and adolescents experienced symptoms for at least two months (25/1734). In the United Kingdom
in a national follow-up study of at least one symptom after coronary infection
0.7% of affected children under 12 years of age were continuously affected for 3 months, and symptoms
very rarely affected daily activities. Similar results have been published as well
In a study based on antibody testing from Switzerland.

At the national level, the impact of long-term COVID-19 in children is limited in some countries
has been so significant that special pediatric long covidium concentrators have been established
outpatient clinics. In the Netherlands, the national survey reported 89 patients with long-term symptoms
children and adolescents, and children and adolescents following a coronary infection requiring hospitalization in Sweden
one-fifth suffered from symptoms of long-term COVID-19. There is IapsiIIa in Finland

12

and adolescents have had very few prolonged symptoms of coronary infection so far
in specialist care.

Children and adolescents with long-term symptoms of COVID-19 will require medical attention for other causes.
and if the symptoms are detrimental to functioning and schooling, the child or
the young person should be evaluated in a specialist multidisciplinary team. For children and young people
prolonged symptoms appear to have a better prognosis than adults, there is research evidence e.g.
From Australia.

In addition, severe COVID-19 infection has been reported in children and adolescents
an inflammatory reaction (hyperinflammatory syndrome, MIS-C), which can be a life-threatening condition and
leads to intensive care, in Finland MIS-C cases have been reported in about 1 child for every 1,000 symptoms
per test-positive child during the first pandemic year in Finland. MIS-C patients recover
usually well after the sudden inflammatory reaction has been treated.


COVID-19 diagnostics, immunity, and long-term COVID-19

COVID-19 infection can be confirmed microbiologically either in the acute phase by detection of SARS-CoV-2
(usually from a nasopharyngeal sample by either a so-called PCR test or an antigen test) or by detection
subsequent antibody-mediated immunity to the SARS-CoV-2 virus, or
T cell immunity (blood test positive). Antibodies as well
The results of tests measuring T cell immunity usually remain positive for at least 6 months
after becoming ill with an acute illness. Antibody measurements can be used to differentiate the disease
of the immune response to vaccination (based on S-protein) by examining the immune response
against the viral core protein (N protein).

COVID-19 infection induces innate immunity and is antibody- and cell-mediated
activation of the immune response. The components of the patient's innate immune activation do not
however, reliably predict the development of prolonged COVID-19 syndrome. COVID-19 infection
can be detected by detecting or demonstrating SARS-CoV-2 virus from the patient’s upper respiratory tract
immune response to viral structural proteins. The virus can be detected by virus culture,
by the detection of viral antigens or by PCR testing to detect virus in a sample
RNA. PCR testing is the most sensitive method, and if the sample contains viral RNA, it is thus the safest
a test to diagnose COVID-19 infection or to show asymptomatic infection / infection. Also
antigen detection tests, the so-called home tests, are quite accurate, but their sensitivity
varies depending on the test compared to the sensitivity of the PCR test. Positive PCR test results
the rate drops rapidly and is mostly negative 3 weeks after the disease
from the beginning.

In the early stages of symptomatic COVID-19 infection (1 to 7 days), approximately 30% of patients have
and / or an IgA and / or IgM response to SARS-CoV-2. In the middle stages of the disease (8-15 days), the immune response
approximately 70%, and in the convalescent phase (15-21 days) in more than 90% and 3-4 weeks of
up to 96% of the onset. After one year, only about 50% have neutralizing antibodies to beta
delta variant. Some virus variants evade those formed against previous variants
protection. Only about 70-80% of patients with asymptomatic COVID-19 infection develop identifiable
the amount of antibodies and antibodies also disappear faster. In the absence of an antibody response, no
therefore, long-term COVID-19 due to previous SARS-CoV-2 virus infection cannot be ruled out.
disease. The same therefore applies to the PCR test if it has not been properly performed in the first place
during the days.


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Cell-mediated immunity is activated in patients with symptomatic infection and is maintained
measurable longer than antibodies, and 85% of IIa patients with asymptomatic infection may be
to measure SARS-CoV-2-specific immunity 9 to 12 months after infection.
However, measuring cell-mediated immunity is not suitable for extensive clinical use.
Lack of immunity does not completely rule out a previous COVID-19 infection, nor does long-term
COVID-19 can be associated with a typical immune response.

Differential diagnostics for the long-term COVID-19 are very diverse and pose a particular challenge
patient work and the selection of differential diagnostic tests, especially when
the patient develops new symptoms after recovery from an acute COVID-19 infection.
Co-morbidities of long-term COVID-19 disease and previous long-term disease
aggravation should be considered as a possible delayed effect of COVID-19 infection. On the other hand
in clear cases with a typical course of the disease, differential diagnosis may not be necessary
most often needed.

The patient's long-term illness, which may be affected by or from COVID-19 infection, should also be considered
even causes new comorbidities. Differential diagnostic tests may be considered
for example, CT scan of the lung, ultrasound examination of the heart, and impaired functioning
measurement by walking test, spirometry, spiroergometry, and cognition tests.
Following COVID-19 infection, coagulation may occur in laboratory tests (eg fibrinogen,
FVIII and D-dimer (FiDD) may be abnormally active and
inflammatory changes referring to small vessel and peripheral circulatory disorders.
Differential diagnosis of long-term COVID-19 should also take into account the worsening or
onset, thyroid disease, development of heart failure, renal function
deterioration, many autoimmune diseases, sleep apnea, memory disorders and psychiatric disorders.
With regard to the latter, it should be noted that the symptoms of prolonged COVID-19 in themselves
on a high-score scale measuring fatigue, anxiety, and depression.

The development of diagnostic tests for long-term COVID-19 has so far not been successful,
partly also because its causes and mechanisms are diverse and still poor
known. The diagnosis is still based on the clinical picture. However, it may be that
In the near future, it will be possible to find additional diagnostic tests, for example specific ones
demonstration of autoantibodies or a typical cytokine or coagulation profile.
As noted above, not all patients with long-term covidium can be shown
infected SARS-CoV-2 infection, so the need for specific diagnostic tests is obvious. WHO: n
according to the guidelines, missing virological evidence does not rule out long-term covidium.


Long-term COVID-19 and COVID-19 vaccines

Several effective vaccines with good protective efficacy have been developed against Covid-19 disease
against acute COVID-19 infection, and in particular against severe disease, based on and
randomized and blinded, controlled studies and real-life evidence.

There is less research data on the protective effect of vaccines against prolonged corona, as
randomized, blinded, placebo-controlled studies were no longer possible for ethical reasons
make. Research data on the prevention of long-term symptoms are based on population-based studies with
compared vaccinated to unvaccinated, based on subjects ’own report of prolonged
symptoms.

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A British study followed 971,504 adults. Two of the vaccine recipients were symptomatic
Patients with a COVID-19 infection caused by a British variant who received more than 28 days of
half less than unvaccinated. The coronary vaccine was investigated in the U.S. data
effect on the development of long-term symptoms in 240,648 subjects exposed to SARS-CoV-2 virus.
The pre-existing coronary vaccine significantly reduced the risk of long-term use
development of symptoms compared to unvaccinated, who are at risk of developing at least two
long-term symptoms were approximately 9-fold higher than those vaccinated. Prolonged symptoms
the likelihood of developing it was also reduced in cases where the vaccine had only been given
after exposure to coronavirus. In a British study, 900 long-term COVID-19s
patients were vaccinated and 56.7% had improvement in symptoms and 18.7% had worsening of symptoms.
after coronary vaccination. The effect of coronary vaccination was investigated in the French data
pre-existing symptoms of long-term COVID-19 in 910 patients, 60% of whom also had
set long covid diagnosis. After 120 days, 16.6% of patients in the vaccination group reported all
relief of symptoms of long-term COVID-19 in the non-vaccinated group was
7.5%, in addition, the effect of prolonged symptoms on life in the vaccination group was less than
in the control group.

Taking the vaccine is a very effective way to prevent the development of severe, acute COVID-19 disease.
If the person receiving the vaccine becomes a pass-through infection, then the likelihood of long-term symptoms
development is significantly lower than in unvaccinated patients. Long-term COVID-19
In the light of current knowledge, these symptoms do not preclude the use of a coronary vaccine, as
is associated with serious side effects, although some have experienced worsening of symptoms. It's possible that
administration of the vaccine as soon as possible after acute COVID-19 infection will reduce long-term exposure
the possibility of developing symptoms, but this requires further evidence.


Long-term COVID-19: treatment and rehabilitation

Long-term COVID-19 causes challenging, multifactorial dysfunctions affecting
both physical functioning, cognition and mental health.
For a multifactorial disease, a multidisciplinary approach is recommended in the treatment and
in rehabilitation.

Key elements of a multidisciplinary approach are access to rehabilitation services,
social security benefits, medicines to relieve symptoms, access to what is needed
programs based on specialist consultations and peer support.

Patients with long-term COVID-19 experience autonomic dysfunction, ie
dysautonomy. The cornerstones of the treatment of autonomic disorder are finding out the situation for the patient and
exercises that promote calming and rehabilitation of the nervous system.
First, the aim is to prevent a deterioration in general condition and thus a slowdown in recovery, or
exacerbation of symptoms. In long-term COVID-19, the prediction of dysautonomy is generally
good and at least 80% of patients recover, some with prolonged symptoms.

At least the following factors have been shown to be important in treatment and rehabilitation: dysautonomy
identified by properly directed research, avoiding a continuous cycle of research, physical
increasing activity individually and gradually, setting targets according to capacity,
fluid and salt balance is maintained, isometric muscle exercises are used, avoided
lying position, used if necessary

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compression clothing and use symptomatic medication if necessary. Medication for dyssautonomy
is based on the stabilization of autonomic nervous system responses and is generally best suited for this
a low-dose, long-acting beta-blocker.

Rehabilitation of patients with long-term COVID-19 can be supported by self-medication programs.
A self-care program implemented as a digital service can support stress management,
improving sleep and gradually increasing exercise. Self-care support may be provided
online therapies, such as HUS Online Therapy for Long-Term and Adverse Physical Symptoms
or Insomnia Online Therapy. In milder cases, mindfulness exercises may be helpful,
intended to manage stress and strengthen the function of the parasympathetic nervous system.

The share of long-term COVID-19 in primary health care, health centers and occupational health care
coordination and rehabilitation of patients with
In primary care, patients are often known for a long time, which promotes treatment
coordination. In occupational health care, rehabilitation can be supported through job modification,
time solutions and support measures for return to work.

Rehabilitation is multidisciplinary and the team may include a physiotherapist in addition to a doctor,
occupational therapist, nutritionist and speech therapist, social worker or psychologist. Patients can
provide careful and gradual physical strength training and aids.
Methods for coping with exhaustion, cognitive exercise programs,
for psychological problems, relaxation exercises, conscious Presence, sleep hygiene instructions,
lifestyle counseling and, if necessary, psychologist interventions such as psychotherapy. Psychic
Symptom rehabilitation is at its simplest by a primary care physician or nurse
supportive monitoring, but more severely symptomatic require a variety of psychotherapeutic and
Medicinal treatments.

Internationally, treatment recommendations emphasize the care provided by multidisciplinary teams and
the importance of rehabilitation. Because the methods of treatment and rehabilitation are at least to some extent
similar to, for example, the prolonged pain, sleep disturbance and fatigue problems of others
in the context of diseases, the pathways between primary care and specialist care, and
setting up integrative workgroups can be an option, here are some examples
from all over the world. Administrative and organizational reform as welfare areas start operating
could be a good time to start this work. As part of primary care and
the integration of specialist care in wellness areas could be in existing health centers
better opportunities to form multi-professional Teams with extensive expertise.


Information retrieval and consensus statement process

Systematic information searches were carried out from mid-September to early October 2021. Information search
carried out by Pia Pörtfors, an IT specialist from the Department of Health and Welfare. Information searches were performed
databases Medline (OVID), the Cochrane Library, and the Web of Science Core Collection and Cochrane
Library. In addition, larger common searches were searched in the WHO's daily updated COVID-19
information portal, which rakes information from many different databases and data sources (Scopus, Embase,
MedRXiv, Psycinfo, etc.). In scientific databases (Medline, Web of Science Core Collection,)
the search focused mainly on the title, abstract, and subject fields and the author
in the keyword field, which also uses free identifiers identified by the computer scientist and experts
search terms, as good as possible

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to achieve coverage. The working group was divided into sixteen subgroups, each with one
or several research perspectives to be worked on on the topic. The search strategy includes both the big picture
related searches and more thematic searches. Research areas of the working groups
twelve themes were identified from which information retrieval was conducted. Thematic and database specific
the information retrieval strategies and their results were stored on the working group's common Tiimer platform; and
the RefWorkso program was used for reference management. RSS feeds were created from data searches that
was also added to the RefWorks library RSS collection.
The data search has yielded a total of nearly 10,000 hits from the long-running COVID-19 when
duplicates have been removed and included more than 4,000 peer-reviewed studies.
Monitoring continues to be up to date.
As a result of the information searches, thematic literature reviews were prepared, which
with literature references serve as background material for this Consensus Statement. Literature reviews
for drafting, the expert group was divided into 12 themes and separate working groups produced by
the reviews and their conclusions have been discussed and approved at the joint meetings of the expert group.
To improve readability, the Consensus Statement is a summary that does not contain separate ones
literature reviews and not the literature references used in them, and it is written
in a common sense. This statement has been accepted by the whole group of experts, largely unanimously
and in some respects by a majority decision. The entire team of experts has participated as background material
preparation of effective literature reviews. At least so far, these reviews have not been prepared
using the methods of formal impression scores, as the scope and timing of the topic do not
enabled. The Consensus Statement will be updated as new information accumulates during 2022 with one or
multiple times.


Composition of the expert group

Professor Risto 0. Roine (TY) has chaired the expert group, the other members of the group
in alphabetical order are
Tiina Heliö, Chief Physician, Associate Professor of Cardiology (HUS, HY) Aki Hietaharju, Chief Physician,
Docent of Neurology (PSHP, TUNI) Pirta Hotulainen, Docent of Cell Biology (Minerva)
Johanna Hästbacka, Chief Physician, Docent of Intensive Care (HUS, HY) Ilkka Julkunen, Chief Physician,
Professor of Virology (VSSHP, TY)
Riitta Lassila, Chief Physician, Professor of Coagulation Diseases (HUS, HY) Helena Liira, Chief Physician,
docent (HUS, HY)
Jarmo Oksi, Chief Physician, Associate Professor of Internal Medicine and Professor of Infectious Diseases (VSSHP, TY) Seppo
Parkkila, Professor of Anatomy, Dean of Education (TUNI)
Markku Partinen, Professor (Terveystalo, HY) Markus Perola, Research Professor (THL)
Jere Reijula, Chief Physician, Specialist in Lung Diseases and Allergology, LT (HUS, HY)
Mika Rämet, Professor of Pediatrics (OY) and Experimental Immunology (Vaccine Research Center,
TUNI)
Terhi Tapiainen, Pediatric Infectious Diseases, Professor of Pediatrics (OYS, OY) Risto Vataja, LL
(PhD), Chief Physician, Line Director (HUS)







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