Current issues of post-covid syndrome consequences

Key words: Background . The World

The World Health Organization (WHO) has confirmed the outbreak of a new viral infection caused by the SARS-CoV-2 virus and defined it as a global pandemic.According to the WHO, there have been 766,440,796 confirmed cases of COVID-19 worldwide as of May 17, 2023, including 6932591 fatal cases [1].In Ukraine, there were 5544969 (13.5%) patients with COVID-19 as of May 23, 2023, of whom 112,271 (2.0%) died, 5417188 (97.7%) recovered [2].
More than 4 years have passed since the beginning of the COVID-19 pandemic.During this period, sufficient experience has been accumulated regarding definition and detection of the virus, pathogenesis of the disease, nature of clinical manifestations, strategies of non-specific and specific treatment, etc.However, the world experience in researching this problem leaves many unsolved issues.For example, in the fight against acute and severe forms of COVID-19 infection in patients who required urgent and subsequent intensive care, there was no time to track the consequences of the patients' condition after discharge from the hospital until their full recovery.
Recently, complications have been increasingly reported in patients with COVID-19, while the clinical symptoms of the long-term course of this disease overlap, acquiring signs different from acute manifestations of the infection, and may persist in patients after reconvalescence for several weeks/months, causing a number of additional problems [3].
The main risk factors for the long-term course of the disease are concomitant pathology, severity of the acute phase of infection, duration of hospitalization and type of intensive care, post-infectious hyperinflammatory status, and the degree of fibroproliferative changes in various organs [4].However, even to the present day, the issue of prolonged COVID-19 infection and pathophysiological mechanisms of organ dysfunction resulting from it have not been sufficiently studied [5,6].
The rationale for the introduction of the concept of post-COVID syndrome is determined by a significant prevalence of asthenic, cognitive and autonomic disorders in those who have suffered from COVID-19, their high incidence that exceeds that in patients who have suffered from other infectious diseases, as well as a significant decrease in the quality of life of patients [7,8].
Objective.To evaluate the current state of the problem of post-COVID-19 syndrome, particularly in oncological patients.
Next, the sources were systematized by specific areas, i.e., issues related to post-Covid, in particular the mechanisms and pathogenesis of its development; treatment features, including cancer patients; longterm consequences in patients, etc. Duplicate publications were excluded from the selected set of papers.Further, abstracts and full texts of the selected articles were studied to assess the current state of the problem of post-COVID-19 syndrome, in particular, in cancer patients.

Definition of terms
Discussing such an important issue as post-COVID syndrome, it is necessary to focus first on the terminology, the interpretation of which is controversial.Thus, today there are such concepts as «post-COVID», «post-COVID syndrome» (PASC), «long-COVID», «acute COVID», «chronic COVID», etc.
The National Institute for Health and Care Excellence (NICE; UK) in its Guidelines for the long-term outcomes of COVID-19 defines post-COVID-19 syndrome as a combination of persistent physical, cognitive and/or psychological symptoms that last more than 12 weeks after the disease and are not explained by an alternative diagnosis [9][10][11].The definitions of persistent post-COVID-19 syndrome, chronic COVID-19 syndrome, or post-acute COVID-19 syndrome partially coincide but are not consistent between different researchers [5,6].The systematization of the main concepts is shown in Table 2.
Based on the available researches, it seems that the difference between post-COVID-19 and long-COVID-19 is almost undetectable.But discussions on this issue continue.Indeed, a study [17] suggests keeping the simplified terminology based solely on the time limit (i.e., less than or more than 12 weeks) to determine whether COVID-19 can become chronic and to see if the scientific community can develop a diagnostic strategy that will help to differentiate between post-viral phase symptoms that may disappear over time or aberrant immune and possibly hemostatic reactions that may persist for a long time and become worse.The signs of post-COVID syndrome can be divided into several groups: -Disturbance of general health, manifested in the form of general weakness, sharp decrease in tolerance to physical exertion, disturbance of vital functions, in particular insomnia or excessive drowsiness, sleep inversion (wakefulness at night, daytime sleep), myalgias and severe muscle weakness, due to a significant loss of protein mass during the acute period of infection and its slow recovery as a result of metabolic disorders.
-Disturbances of the emotional and volitional sphere: depression and anxiety, melancholy, depressed mood, unstable emotional state, mood fluctuations, low level of self-control, panic attacks.
-Neurologic manifestations: nausea, dizziness, intense recurrent headache in the form of migraine.There may be a disturbance in thermoregulation in the form of prolonged subfebrile hyperthermia (37-37.5 degrees), or a decrease of temperature to 36 degrees with chills, mainly in the evening.A frequent neurological manifestation of post-COVID syndrome can be visual impairment, brain fog, and photophobia.Disorders of skin sensitivity in the form of paresthesias, «goosebumps», burning sensation, skin tingling.Impaired sense of smell and taste may be observed for a long time.

World Health
Organization's [13] Український радіологічний та онкологічний журнал.-Cardiovascular disorders predominate in patients with a pre-COVID history of these diseases.In the post-COVID syndrome, blood pressure fluctuations, postural orthostatic tachycardia syndrome, and orthostatic collapse may be observed.
So, researchers are currently investigating which categories of patients are more likely to develop long-term COVID-19 and why.

Some views on the pathogenesis
of post-covid syndrome Post-covid sequelae of SARS-CoV-2 (PASC), also known as post-covid syndrome, is defined as a combination of signs and symptoms that persist for several weeks or months after initial infection with SARS-CoV-2.PASC causes damage to a variety of different organs and systems, including lungs, brain, cardiovascular system, as well as the kidneys and neuromuscular system [22].
According to the group of researchers from 12 institutions in Italy and the United Kingdom [22], the pathogenesis of PASC is complex and multifactorial.Available findings indicate that SARS-CoV-2 shedding and persistence in various organs, reactivation and response to unrelated viruses such as Epstein-Barr virus infection (EBV), autoimmunity, and uncontrolled inflammation are the main factors in the development of PASC.The relative importance of pathogenic pathways may differ in different tissues and organs.There is some evidence that vaccination, in addition to protection against the disease, reduces PASC after infection invasion, although its actual impact remains to be established.Post-covid syndrome is a serious problem for healthcare systems, and the study of pathogenic mechanisms may provide a pathway to targeted preventive and therapeutic approaches.It was found that PASC is the most common consequence of acute SARS-CoV-2 infection, affecting more than 10% of patients with various signs and symptoms in a large number of organs and systems.The most common manifestations of PASC, in addition to lung dysfunction, include neurocognitive changes; changes in cardiovascular function and increased risk of acute cardiac pathology, and fast fatigue.
The pathogenesis of PASC has been thoroughly studied in several systematic international researches with meta-analysis [22][23][24][25][26][27][28] involving research centers from Italy, Germany, the United Kingdom, the United States, Indonesia, Saudi Arabia, and others.They conclude that the pathogenesis of PASC is multifactorial and includes viral shedding and persistence in various organs; activation and response to unrelated viruses (e.g., EBV); autoimmunity; and uncontrolled inflammation.
The mechanisms of PASC pathogenesis can be classified into five main groups: persistence of SARS-CoV-2; reactivation of other viruses, including EBV; virus-induced autoimmunity; persistent tissue damage and inflammation caused by the immune response [29]; formation of microthrombi in the vascular bed of various tissues, etc (tab.3).
Thus, a group of researchers from India, Navami K., Sijina K.P., Rajanikant G.K. [39] established that the pathological condition was accompanied by damage to several organs and systems, which confirmed the theory of the formation of multiorgan damage due to COVID-19.Cancer, neurological disorders, liver disease, cardiovascular disease, lung disease, and hy-Український радіологічний та онкологічний журнал.2023 Another study by Y. López-Hernández, J.J. Oropeza-Valdez, D.A. García Lopez et al. (Mexico) proved that there is a link between metabolic disorders and clinical symptoms [40], where sterols, bile acids, isoprenoids, and fatty esters were predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients.They identified several types of phosphatidylcholines and sphingomyelins that were found at higher levels in post-COVID-19 patients compared to the control group.A paired analysis (comparison of patients with active infection and 2 years after recovery) revealed 170 regulatory dysfunctions of diagnostic and therapeutic markers based on cell signaling pathways.
Although the pathophysiologic mechanisms of the post-COVID-19 syndrome are currently unclear, there are studies describing systemic inflammatory or autoimmune phenomenon after remission of COVID-19 infection in some patients [4].This suggests the existence of molecular and cellular immune abnormalities, most likely caused by the initial strong immune response of the host to the viral infection in the form of three overlapping conditions: secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome, and cytokine release syndrome, consistent with various classical autoimmune diseases.
In conclusion, it is important to mention that there are several mechanisms responsible for PASC: inflammation, immune activation, viral persistence, activation of latent viruses, endothelial dysfunction, impaired response to physical activity, and severe deterioration of the heart condition after viral infection.

Main symptoms of post-COVID-19
Although the clinical course of COVID-19 in its acute phase is now well defined, its late phase is less clear, characterized by a heterogeneous series of sequlae affecting various organs and systems, particularly the cardiovascular system, which follow the acute episode or occur after its resolution.This syndrome, which is now identified by the new acronym «PASC» (post-acute sequlae of SARS-CoV-2 infection), has been officially recognized by various scientific societies and international organizations.The World Health Organization defines PASC, distinguishing it from «prolonged symptomatic COVID-19», as a condition that occurs several weeks after infection, persists for at least 8 weeks, and cannot be explained by alternative diagnoses [41].
There are several mechanisms responsible for PASC: inflammation, immune activation, viral persistence, activation of latent viruses, endothelial dysfunction, abnormal response to exercise, and severe deterioration of the heart after viral infection.The key symptoms of PASC are palpitations, exertional dyspnea, chest pain, exercise intolerance and postural orthostatic tachycardia syndrome, orthostatic hypotension, or, use of such drugs as beta-blockers, non-dihydropyridine calcium channel blockers, ivabradine, and fludrocortisone among some individuals [42].
symptoms is often explained by the presence of certain comorbid conditions -obesity, hypertension, diabetes mellitus, etc.
The manifestations of post-COVID syndrome are systematized in the study [42], where the authors distinguished: 1) residual symptoms and 2) organ dysfunction after acute COVID-19, as well as 3) new symptoms that develop after initial asymptomatic or mild infection.The first two categories can be combined with each other.

Огляд літератури
Literature review concentration) [43].In their opinion, these results require a more thorough study.

Different syndromes in the post-COVID period
Some studies have shown that patients may develop various syndromes in the post-COVID period after hospitalization and treatment.In general, the covid syndrome is defined as a multisystem inflammatory syndrome (MIS) during or after COVID-19.But researchers have identified many types of it.
Postural Orthostatic Tachycardia Syndrome (POTS) is the most commonly occurring multisystem disorder characterized by abnormal autonomic response to upright position, which causes orthostatic intolerance and excessive tachycardia without hypotension [44].POTS develops within 6-8 months after infection.Pronounced symptoms of POTS include fatigue, orthostatic intolerance, tachycardia, and cognitive impairment.Detailed mechanisms of POTS after COVID-19 are not fully studied.However, various hypotheses have been put forward, including the development of autoantibodies against autonomic nerve fibers, direct toxic effects of SARS-CoV-2, or secondary stimulation of the sympathetic nervous system due to the infection [45][46][47].
Post-intensive care syndrome (PICS) is also defined as health disorders after hospitalization in the intensive care unit that may persist after a patient is discharged from the hospital.These effects may include muscle weakness, difficulty thinking and judging, and symptoms of post-traumatic stress disorder (PTSD), long-term reaction to a very stressful episode.Although PICS is not specific to SARS-CoV-2 infection, it may occur and contribute to the development of long-term COVID-19 in patients.For people experiencing PICS after a COVID-19 diagnosis, it is difficult to determine whether these health problems are caused by the serious illness, the virus itself, or a combination of the both [48].
A particular place is occupied by vaccine-induced immune thrombotic thrombocytopenia (VITT), which was discovered about two years ago, at the beginning of the SARS-CoV-2 vaccination campaign, as a rare but life-threatening complication of adenovirus vector vaccines.Vaccine-induced thrombotic immune thrombocytopenia, also known as thrombosis with thrombocytopenia syndrome, is a catastrophic and life-threatening reaction to coronavirus vaccines that occurs disproportionately in response to vaccination with the non-replicated adenovirus (AV) vaccine vector.The mechanism of VITT is not well understood, and it is not clear why VITT cases are prevalent during AV vaccination [49,50].
It is also important to study the neurological syndrome.Since the virus is neurotropic, meaning that it enters the nervous system through the olfactory receptors in the upper nasal concha, it can directly damage brain structures such as the limbic system, hypothalamus, cerebellum, respiratory center, and others.Damage of such a large nerve as the vagus causes a variety of symptoms and also determines their fluctuating nature.This disorder is associated with an imbalance of two systems -parasympathetic and sympathetic, with the та погана концентрація уваги) [43].На їх думку ці результати потребують подальшого більш досконалого вивчення.

Огляд літератури
Literature review dominance of the latter, resulting in heart rate problems, orthostatic tachycardia, sleep problems, symptoms of panic attacks, as well as anxiety disorders and cerebro-asthenic syndrome [51,52].
Covid-19 appears to be a risk factor for deep vein thrombosis, pulmonary embolism and bleeding [53], coagulopathies (disorders of the blood clotting system), possibly related to amyloid fibrin microclots [54], which persist long after initial infection.Changes (decreased thickness) in the cerebral cortex as a consequence of Covid-19 infection have been observed in specific areas, mostly related to olfactory sensitivity, but it is not known whether such changes will remain over time.
Recent data from Wuhan show that Covid-19 survivors still had more widespread symptoms and more problems related to pain or discomfort, as well as anxiety or depression over 2 years than in control groups [55].

Post-COVID in cancer patients
In the context of the coronavirus pandemic, patients with malignant tumors fall into a special risk group.
These studies address several aspects.First, it is an assessment of the risk of progression and occurrence of oncological diseases in the post-COVID period, in particular due to the interruption and reduction of diagnostic and treatment programs during the pandemic.Secondly, optimization of the process of organization of oncological care in the post-COVID period.Thirdly, assessment of the level of complications and mortality of cancer patients with COVID-19.
The following features of the course of COVID-19 in cancer patients can be distinguished [56][57][58][59]: -high susceptibility to COVID-19 due to the systemic immunosuppressive condition caused by malignancies and stages of specialized treatment [56,57]; -higher rates of COVID-specific mortality.Mortality in the group of cancer patients with confirmed coronavirus infection is 7.6%; -high risk of development of severe forms of COVID-19 (about 33%) [56,58]; -high rate of hospitalization in intensive care units and the need for artificial lung ventilation [57].
Показано, що особи із запальними або імунодефіцитними захворюваннями, такими як рак, більш схильні до розвитку гострого респіраторного дистрессиндрому (ГРДС) і мають більш високі показники смертності [60] and immunosuppression contribute to the creation of an optimal microenvironment for oncogenesis, initiation and immune evasion of malignant cells, tumor progression and metastasis, as well as cancer recurrence.According to other studies [61,62], it has been observed that patients showed an increase in the antigen-specific response of CD4+ cells to the S-protein of SARS-CoV2 with a prolonged T-cell response and increased expression of T-lymphocytes, which indicates their depletion.Higher levels of proinflammatory cytokines (IL-17, IL-2) were found.Oncological pathology and therapy influence the level of proinflammatory cytokines, some cytokines (IL-1, IL-6) probably play a role in oncogenesis and development of residual inflammation in the affected organs.Such patients with impaired immune responses caused by underlying disease present an additive risk of developing long-term COVID-19 [61,62].
In the view of Monroy-Iglesias M.J. et al [63], more than half of cancer patients suffer long-term sequelae after COVID-19.A group of authors of the multicenter study involving 28 institutions first determined that in a mostly unvaccinated population, post-COVID-19 syndrome can affect a significant proportion of patients with non-metastatic cancer and persistent COVID-19 symptoms for more than 12 months [63].Among the prevailing types of oncological pathology accompanied by long-term COVID-19 are breast cancer (BC), lung cancer (LC), and CNS cancer.The researchers suggested that several factors contribute to the prolongation of the consequences of infection in cancer patients.For example, cancer causes a disruption of the autophagy processes, resulting in the accumulation of unfolded proteins in tissues, cellular stress and inflammation.In combination with defects of autophagy in the cancer pathology, viral proteins are accumulated, leading to a potential prolongation of the viral load [61].
Regarding the health status of cancer patients who have suffered from covid infection, a group of authors in their study [64] reported the most common symptoms (312 cancer patients) as follows: fatigue, sleep disturbances, myalgia, gastrointestinal disorders, headache, taste and smell alterations.In 60% of patients, long-term symptoms persisted from 7 to 14 months after diagnosis.The researchers have suggested a theory that attributes the pathogenesis of the infection to the interaction of the viral spike-like protein with ACE2.The men have higher expression of the protein and, as a result, more severe course of the acute form of COVID-19.Women are more susceptible to long-term sequelae of the infection [64].
The ESMO guidelines distinguish groups at high risk of COVID-19 infection and severe complications among the patients with oncological diseases [67,68]: -patients receiving chemotherapy or who have received it within the last three months -patients receiving radiation therapy; -patients who have undergone bone marrow transplantation in the last 6 months, as well as those receiving immunosuppressive therapy; -patients with oncohematologic diseases.Breast cancer occupies a special place among the patients with oncologic pathology during and after the pandemic, for several reasons: -BC is the leading oncological pathology among the female population, so the risk of infection is higher in women with BC, considering their number; -The «peak» of the BC incidence falls on women over 60 years of age, and this is the age cohort of patients with a high risk of developing complications and death from COVID-19; -unlike the majority of other solid tumors, the treatment of cervical cancer is practically always complex, patients need not only surgical treatment but also polychemotherapy and radiation therapy.This approach requires frequent visits to oncology clinics and increases the risk of coronavirus infection; -unlike most solid tumors, treatment of aggressive subtypes, even in the early stages, requires adjuvant/ neoadjuvant chemotherapy, which causes immunosuppression.
Thus, the combination of factors such as advanced age, presence of concomitant somatic diseases, active antiblastoma therapy, and necessity of frequent inpatient treatment at oncology centers creates prerequisites for a more severe post-COVID-19 course in cancer patients [69].

Radiological diagnostics
The pandemic has led to multiple changes in all areas, including the diagnosis of complications in cancer patients with COVID.
More than 60% of people who have had COVID still have various abnormal changes in their lungsdoctors detect them on X-rays, CT scans, and MRIs of the chest.These abnormalities are not always accompanied by any obvious symptoms.However, approximately every third person with post-covid syndrome complains of shortness of breath, and every tenth person complains of persistent cough.Most researchers consider CT examination to be the most informative [70].
In the field of radiological diagnostics, some advances have been made in CT and MRI [70][71][72][73].Thus, M.I.Linnik et al [74], based on CT data, reported the most common typical complications of pneumonia of coronavirus etiology: progression of viral pneumonia, occurrence of bronchial obstructive syndrome, aggravation of concomitant chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA), develop-Український радіологічний та онкологічний журнал.2023 [76,77].Special attention should be given to the differential diagnosis of radiographic symptoms of communityacquired pneumonia of viral etiology (COVID-19) and bronchoalveolar cancer.The latter is a rare primary malignant epithelial lung tumor: it makes up 2 to 9% of all primary forms of lung cancer, and 3 to 4% of non-small cell lung cancer [78].Bronchoalveolar cancer is a peripheral tumor, usually nonmucinous, rarely mucinous or mixed, tending to form extensive pneumonia-like and disseminated forms of lung diseases [78].Therefore, radiological signs of former bronchoalveolar cancer based on standard examination of images are very similar to typical CT criteria for pneumonia of viral etiology (COVID-19): -bilateral location of inflammatory changes, mainly lower lobular, peripheral and perivascular; -numerous «ground glass» pneumonitis-type opacities of various shapes and sizes; -reticular changes: the «crazy-paving» symptom, areas of consolidation, perilobular seals; -consolidation symptom.However, comparative studies of lung CT findings 6 and 12 months after COVID-19 are quite controversial.For example, in the study [79], the authors report the presence of idiopathic interstitial pneumonia, in particular, diffusion capacity disorder was the most common pathology (95%), and the incidence of restrictive pulmonary dysfunction was lower in 12-month studies than in 6-month studies.At the follow-up chest CT scan, the overall prevalence of persistent opacities such as ground glass and pulmonary fibrosis was 32%.At the same time, their prevalence did not decrease over time.A significant number of COVID-19 survivors have been diagnosed with various pulmonary complications as a part of post-COVID-19, the prevalence of which did not decrease up to 1 year after the initial infection.A relationship between severity of acute COVID-19 and the risk of pulmonary complications in the post-COVID-19 period was also found, which, according to the authors, requires a more thorough examination of the lungs of these patients.Other researchers evaluating pulmonary pneumonia one year after hospitalization showed on CT that residual lung abnormalities were rare and without signs of fibrosis [79].
In this regard, it is worth to mention the work of Palazzuoli A. et al [83], which solved the difficult problem of differential diagnosis between acute respiratory syndrome associated with COVID-19, distress syndrome and acute heart failure, as they have the same symptoms (shortness of breath and fatigue).Sometimes a patient can suffer from both acute respiratory distress syndrome (ARDS) and acute heart failure (AHF), which increases the complexity of differentiation.The method of differentiation is based on the comparison of differences in the history, clinical manifestations, additional examinations, and laboratory results.These data, along with others, were systematized and presented in Table 5 [80].
Several studies using contrast-enhanced and dual-energy CT have evaluated pulmonary vascular perfusion deficit in case of the acute lung disease caused by COVID-19.However, an ability of CT methods to assess perfusion deficits in the capillaries of the microcirculatory bed may be limited, especially in the absence of structural abnormalities on CT [84].Alternatively, lung function is assessed using a hyperpolarized xenon-129 (129Xe) inhalation MRI, which allows to track the passage of xenon by oxygen absorption in the lungs using spectroscopic imaging.This method was recently introduced in China [85] for a better understanding of the pathophysiology of acute COVID-19 lung disease after hospital discharge.It also revealed a regional physiological deficiency of gas exchange in patients with dyspnea after COVID-19, despite the absence of structural abnormalities on CT.Matheson A.M. et al [86] demonstrated abnormalities of the absorption of dissolved xenon by red blood cells in capillaries, which, in their opinion, is associated with the signs of «pruning» of small vessels.This study was conducted in the group of patients with PACS.The gas exchange parameters of MR spectroscopy using xenon-129 and indicators of vascular density on CT were abnormal and associated with pulmonary function tests, as well as with symptoms of dyspnea and limited physical activity.
Hence, due to the increased risk of complications in the post-COVID period, researchers recommend continuous diagnostic monitoring of patients who have been ill, especially those over 60 years old.
Український радіологічний та онкологічний журнал.2023 Influence of the COVID-19 pandemic on the treatment of cancer (radiation therapy and chemotherapy) Assessing the impact of the pandemic on the outcomes and adaptation of radiotherapy and chemo therapy to these conditions, it should be noted that there are very few publications regarding particular outcomes.Therefore, we will consider this problem in general, as it is known that the outcomes depend on the treatment strategy.
It should also be taken into account that many cancer patients were unable to receive timely specific treatment, as medical facilities canceled or postponed surgeries and other procedures, including chemotherapy and radiation therapy, during lockdown [87].The coronavirus pandemic resulted in restrictions to access the health care system and its temporary reorganization, with large quantitative resources being spent on the treatment of patients with COVID-19.Due to this temporary suspension of screening programs, diagnosis and treatment of oncological diseases were significantly slowed down, affecting the quality and availability of oncological services.This situation with a decrease in the number of cancer patients has been observed in  [93].
Today, the efforts of researchers from all over the world are focused on investigating the consequences of the coronavirus pandemic, its impact on the treatment of cancer patients, in particular the organization of radiation therapy (RT).Most studies regarding the impact of the pandemic were based on surveys of radiation therapy services in leading high-income countries [89][90][91][92].In Brazil, radiotherapy services submit monthly data to the public health database (DATA-SUS), which is necessary to assess changes in radiotherapy treatment outcomes before, during, and after the COVID-19 pandemic [93].Thus, the impact of COVID-19 on the activity of the RT was not consistent.Moraes F.Y. et al. determined a significant increase in the intensity of treatment of bone and brain metastases, and a decrease for prostate cancer.At the same time, the intensity of RT for some tumor types increased during the vaccination period compared to the pre-vaccination period.Primary tumors, depending on the screening, such as prostate, breast, and lung cancer, showed reduced intensity even after vaccination [93].
The group of researchers Pérez E.M. et al. report an increase in the intensity of BC RT in 2022.Despite a slight decrease in adjuvant BC RT within 2 years after the pandemic compared to 2019, in 2022, an increase of 18.8% was observed, which is associated with the expansion of diagnostic procedures under the screening program [94].
Due to the fact that low-dose RT reduces chronic internal inflammation, its administration for pneumonia in patients with COVID-19 has begun to grow rapidly.It is important that low-dose therapy is available in most countries, in contrast to COVID-19 drugs, which are available only in developed countries [95][96][97][98][99]. Spanish researchers emphasize the benefits of low-dose RT in patients with COVID-19 pneumonia, as it is associated with a partial increase in serum PON1 activity one week after the beginning of irradiation and an increase in TGF-β1 concentration after 24 hours [100].At the same time, some authors are cautious about the use of this technology and do not recommend its routine implementation for the treatment of patients with moderate and severe COVID-19, as it is not known whether SARS-CoV-2 alters the response to irradiation and the risk associated with radiation exposure [101].
Thus, considering the impact of RT, particularly low-dose RT, on various body tissues both immediate and in the long-term period after irradiation, published results have been presented on the mechanisms of this impact in patients with COVID-19 [102].The p53 signaling pathway was found to be impaired, while mRNA levels of p53, ATM, and CHK2 were lower in patients with COVID-19.Several key p53 target genes involved in cell cycle arrest, apoptosis, and p53 feedback inhibition were activated in patients with COVID-19, while other p53 target genes were inhibited.This dysregulation has functional consequences, as the transcription of p53-dependent genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 hours after ex vivo X-ray irradiation at both low (100 mGy) and Український радіологічний та онкологічний журнал.2023 It has also been shown that plasma SARS-CoV-2 RNA is probably associated with the worst prognosis of COVID-19.In the study [103], which examined plasma RNA in patients with COVID-19 receiving low-dose radiotherapy, disappointing results were obtained regarding plasma SARS-CoV-2 viremia 24 hours before RT.They were strongly associated with increased mortality after treatment, which generally reduces the success of treatment.
Speaking about the impact of RT on patients with COVID-19, we cannot ignore oncology patients, for whom the radiation regimen has also being changed during the pandemic.For instance, radiotherapy has become more often performed in hypofractionation mode, in particular for the treatment of colorectal cancer and breast cancer, to reduce the time of use of the linear accelerator and limit the radiation exposure of patients/ staff.Thus, the number of fractions for treatment was reduced to 40 Gy in 8 fractions instead of 10, and 50 Gy in 15 fractions instead of 55 Gy in 20 fractions [104].
Another study compared acute toxicity between conventional fractionated radiation therapy and hypofractionated radiation therapy among the patients who underwent organ-preserving surgery or mastectomy followed by RT of the breast or chest and regional nodes.It was shown that moderate hypofractionation had lower rates of acute toxicity without any changes in the quality of life [105].
In Spain in 2020, during the Covid-19 pandemic, oncology practice with the use of multimodality proton radiation therapy for the most common types of cancer was revised to improve the treatment efficiency and minimize risks for patients.In 2020-2021, seven research projects funded from the state budget were launched at the The University Clinic of Navarra (Clinica Universidad de Navarra, Madrid, Spain), and preliminary data on proton therapy under the control of molecular imaging for brain tumors and post-radiation characteristics of blood biomarkers were presented [106].
In addition, radiologists believe that such treatment has serious side effects: low-dose radiation therapy may reduce inflammation, but it also affects the B-and T-cells of the immune system, which are extremely important in the fight against coronavirus.
There is still a lack of research on antiblastoma therapy for patients with COVID-19.
Unfortunately, the mortality rate from covid infection in patients undergoing chemotherapy treatment, especially after immunotherapy, is quite high.The highest risk category is the elderly with concomitant pathology [68].Patients with low levels of immunoresistance after chemotherapy treatment, especially those with lung cancer, often have the same pulmonary symptoms as those with COVID-19 infection, which makes their treatment more difficult.Along with lung cancer, the category of patients with hematologic oncologic disorders caused by deep immunosuppressive therapy is also at high risk [107].
The negative impact of the COVID-19 pandemic on perioperative BC chemotherapy was also reported in comparison with the periods before and after the COVID-19 pandemic [111].Hence, most researchers believe that cancer progression during delayed oncological care will affect the long-term survival of patients.More than a half of cancer patients experience long-term consequences after the initial diagnosis of COVID-19.That is why further research on these issues is required [112,113].In addition, the overlap of cancer-related symptoms and symptoms of long-term COVID is another major challenge for oncologists in the future.логічну патологію унаслідок глибокої імуносупресивної терапії [107].
Assessing the current state of the problem of post-COVID syndrome, most researchers believe that cancer progression during the delays in oncological services will affect the long-term survival of patients, and the overlap of cancer-related symptoms and symptoms of long-term COVID is another major challenge for the future.In the future, it is necessary to study specific sequelae in cancer patients who have had COVID more thoroughly and to improve radiotherapy and chemotherapy technologies based on the detected changes in the human body.

Table 1 .
Distribution of publications in digital resources