REGISTRO DOI: 10.5281/zenodo.8045200
Sandro Pinheiro da Costa1
Maria Luiza Zoboli2
Breno Alves Ribeiro3
Raissa Alves de Araujo4
Ana Claudia Rodrigues da Silva5
Pedro Julien Salvarani Borges6
Deyvisson Luís Malta de Melo7
Irlane Silva Veras8
Lucas Amaral Cunha9
Rodrigo Daniel Zanoni10
Abstract
Studies have indicated that this condition is associated with an acute inflammatory process and thrombotic disorder, leading to public health and quality of life of patients. In this context, this work aims to carry out a comprehensive review of the importance of studying and recognizing the sequelae of long-term Covid, especially in relation to the inflammatory and thrombotic process. A systematic search was conducted in the main scientific databases, such as PubMed and Scopus, using terms related to Covid-19, sequelae, inflammation and thrombosis. Original studies, systematic reviews, and meta-analyses published between 2020 and 2023 were selected. The studies examined indicate that long-term Covid can affect a wide range of organ systems, including the respiratory, cardiovascular, immune, gastrointestinal, and musculoskeletal systems. Symptoms are associated with an acute inflammatory state, characterized by increased pro-inflammatory cytokines and immune system dysfunction. The thrombotic process is related to activation of the coagulation system and persistent inflammation, increasing the risk of cardiovascular events and long-term complications. Long Covid poses a significant clinical and epidemiological challenge. Early recognition and study of inflammatory and thrombotic sequelae are essential for a better understanding of this condition and for the development of appropriate management strategies. It is critical to establish long-term follow-up protocols for patients who have recovered from COVID-19 in order to identify and treat persistent complications early. In addition, additional research is needed to elucidate the phenomena underlying the long-term Covid sequelae in order to develop specific therapies and promote the rehabilitation of inpatients. Recognition and understanding of these sequels are critical to minimizing the impact of COVID-19 on global health and improving clinical patient outcomes.
Keywords: COVID-19; Covid long; Thrombotic Disorders; Inflammatory Process.
Abstracto
Los estudios han indicado que esta condición se asocia con un proceso inflamatorio agudo y un trastorno trombótico, lo que lleva a la salud pública y la calidad de vida de los pacientes. En este contexto, este trabajo pretende realizar una revisión exhaustiva de la importancia de estudiar y reconocer las secuelas de la Covid a largo plazo, especialmente en relación con el proceso inflamatorio y trombótico. Se realizó una búsqueda sistemática en las principales bases de datos científicas, como PubMed y Scopus, utilizando términos relacionados con Covid-19, secuelas, inflamación y trombosis. Se seleccionaron estudios originales, revisiones sistemáticas y metanálisis publicados entre 2020 y 2023. Los estudios examinados indican que el covid a largo plazo puede afectar una amplia gama de sistemas de órganos, incluidos los sistemas respiratorio, cardiovascular, inmunológico, gastrointestinal y musculoesquelético. Los síntomas se asocian con un estado inflamatorio agudo, caracterizado por un aumento de las citocinas proinflamatorias y una disfunción del sistema inmunitario. El proceso trombótico está relacionado con la activación del sistema de coagulación y la inflamación persistente, aumentando el riesgo de eventos cardiovasculares y complicaciones a largo plazo. Long Covid plantea un importante desafío clínico y epidemiológico. El reconocimiento temprano y el estudio de las secuelas inflamatorias y trombóticas son esenciales para una mejor comprensión de esta condición y para el desarrollo de estrategias de manejo adecuadas. Es fundamental establecer protocolos de seguimiento a largo plazo para los pacientes que se han recuperado de COVID-19 para identificar y tratar las complicaciones persistentes de manera temprana. Además, se necesita investigación adicional para dilucidar los fenómenos que subyacen a las secuelas a largo plazo de Covid para desarrollar terapias específicas y promover la rehabilitación de pacientes hospitalizados. El reconocimiento y la comprensión de estas secuelas son fundamentales para minimizar el impacto de la COVID-19 en la salud mundial y mejorar los resultados clínicos de los pacientes.
Palabras clave: COVID-19; Covid largo; trastornos trombóticos; Proceso inflamatorio.
1. Introduction
The Covid-19 pandemic has represented an unprecedented global challenge, affecting millions of people around the world. As understanding of the disease has evolved, it has been observed that infection with the SARS-CoV-2 virus can result in persistent symptoms and long-term complications known as “long-term Covid sequelae”. Among these sequelae, the infectious inflammatory process and thrombotic disorders have gained prominence due to their significant impact on the health and well-being of patients (LLITJOS et al., 2020).
The study and recognition of the long-term Covid sequelae, especially with regard to the inflammatory and thrombotic process, are extremely important. These complications can affect different body systems, causing debilitating symptoms and affecting the quality of life of affected individuals. Understanding the nature and severity of these sequelae is essential to provide adequate and targeted care to patients, in addition to promoting early identification and appropriate treatment of these complications (HARENBERG, FAVALORO, 2020).
The inflammatory process triggered by SARS-CoV-2 infection can result in an unregulated, persistent and harmful immune response to the body. This prolonged inflammation can affect several organs and systems, followed by symptoms such as persistent fatigue, dyspnea, musculoskeletal pain, cognitive and emotional disturbances, among others. Understanding the prolonged effects of the inflammatory process in long-term Covid is essential to develop therapeutic approaches and provide relief to hospitalized patients (CONNORS, LEVY, 2020).
Furthermore, an association has been observed between SARS-CoV-2 infection and an increased risk of thrombotic disorders, including deep vein thrombosis, pulmonary embolism, and vascular complications. Activation of the clotting system and chronic inflammation can contribute to the formation of blood clots, increasing the risk of cardiovascular events and long-term complications. Therefore, it is essential to investigate the thrombotic procedures involved in long Covid, in order to implement effective preventive and therapeutic strategies (LIPPI, PLEBANI, HENRY, 2020; TANG et al., 2020).
Given this context, the study and recognition of the sequelae of long-term Covid, especially related to the inflammatory and thrombotic process, are essential to provide a comprehensive and integrated approach in the care of elderly patients due to the disease. Understanding these persistent complications will enable the development of more effective interventions, effectively improving patients’ quality of life and looking forward to the global impact of this unprecedented pandemic.
2. Development
2.1 Methodology
The qualitative approach study reviewed the literature in question for a better understanding of the association of long-term Covid, inflammatory and thrombotic processes. It was decided to carry out a systematic review, defined as an instrument for obtaining, identifying, analyzing and summarizing the literature directed to the specific theme. It also allows for a comprehensive literature review, including discussions of methods and publication results. Articles, monographs, dissertations and books published on the subject were consulted, such as the Scielo, Science Direct, PubMed and Medline sites. To identify the study designs, the following terms Covid long, Thrombotic disorders and inflammatory process. The pre-selection of studies was based on reading the title and/or abstract and, when necessary, the full text. The search was scheduled for the period from January 2020 to May 2023.
The use of articles was analyzed in consensus, rejecting those that did not present specific data about the research. The articles were obtained based on studies of the pathophysiological mechanisms of the disease and its correlation with the aggravations and sequelae. Of the 2,658 articles analyzed, 2,627 were excluded from the research because they did not present specific content for carrying out the work and 31 presented essential data for carrying out the bibliographic survey. Data were reported following the recommendations of the JBI Manual for Evidence Synthesis and PRISMA for Scoping Reviews (PRISMA ScR) and initially presented through a flowchart recommended by PRISMA ScR to present the evidence search flow.
Next, tables will be presented with the information extracted from the included articles, taking into account the population, concept and context. From the analysis of the tables, graphs will be traced to present the correlations obtained in a didactic way. After presenting the data, they will be discussed in depth in order to list future research gaps and the limitations of the studies that will serve as a basis for further research focused on the analysis of this review.
3. Results and Discussion
After the selection process, 31 studies met the inclusion criteria. The study selection process is presented in a flowchart (Figure 1), according to PRISMA standards.
Figure 1. Flowchart with study steps adapted from Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA).
3.1 Disorders of hemostasis and the coagulation system of COVID-19
Coagulation abnormalities are common among patients with COVID-19, such as mild thrombocytopenia, elevated fibrinogen, lactate dehydrogenase (LDH), liver enzymes, D-dimer and fibrin degradation products (FDPs) are frequently reported (LIPPI, PLEBANI, HENRY, 2020; TANG et al., 2020). A slightly prolonged prothrombin time, shortening of activated partial thromboplastin time (aPTT) in early and prolonged aPTT in later stages of infection, increased Von Willebrand activity (vWF), vWF antigen, and FVIII levels are also described (LIPPI, FAVALORO, 2020; HARENBERG, FAVALORO, 2020).
The coagulopathy seen in COVID-19 differs from that seen in other infections and has been defined as “sepsis-induced coagulopathy”, characterized by increased levels of D-dimer and fibrinogen. This situation can evolve to disseminated intravascular coagulation, where prolonged PT, increased D-dimer, thrombocytopenia and hypofibrinogenemia are commonly reported (LIPPI, PLEBANI, 2020).
While COVID-19 was initially recognized as a respiratory illness, SARS-CoV-2 has the ability to damage multiple organ systems. The damage demonstrated in various tissues has been predominantly attributed to the immune-mediated response and inflammation, rather than the direct infection of cells by the virus. Disruption of the circulatory system includes endothelial dysfunction and subsequent downstream effects, as well as increased risks of deep vein thrombosis, pulmonary embolism, and bleeding events. Microclots detected in both acute and long-term COVID-19 contribute to thrombosis. Long-term changes in blood cell size and stiffness have also been found in long-term COVID, with the potential to affect oxygenation delivery. A lasting reduction in vascular density, specifically affecting small capillaries up to 18 months after infection (BOWLES et al., 2020). Changes in coagulation parameters are shown in Table 1.
Table 1: Changes in coagulation parameters in patients with COVID-19
| Parameters | Changes |
| Platelet Count | Slightly Diminished |
| Prothrombin Time | Slightly Prolonged |
| International Normalized Ratio | Slightly Increased |
| Aptt | Decreased First, Then Increased |
| Protein C | Increased |
| Protein S | Decreased |
| Antithrombin | Decreased |
| Factor VIII | Increased |
| Von Willebrand Factor Activity | Increased |
| Von Willebrand Factor Antigen | Increased |
| Factor XII | Decreased |
| Fibrinogen | Increased |
| Fibrin Degradation Products | Increased |
| Parameters | Changes |
| Platelet Count | Slightly Diminished |
| Prothrombin Time | Slightly Prolonged |
3.2 COVID-19 thrombotic disorders
Thrombosis plays a key role in clinical outcomes associated with COVID-19. There is increasing evidence to support the impact of thrombosis on disease worsening, tissue damage and deaths. The most plausible mechanism underlying the increased thrombosis in COVID-19 is due to an inflammatory reaction triggered by the infection itself, which results in damage to the microvascular system and causes abnormal activation of the coagulation system. These are followed by increased vascular inflammation and generation of excessive microthrombi (LLITJOS et al., 2020).
The most common thrombotic events seen during COVID-19 are venous thromboembolism and pulmonary microvascular thrombosis. However, thrombotic events can occur anywhere, including the cardiac, venous, or arterial systems. Recent studies have also shown that changes in coagulation parameters provide prognostic information in COVID-19 (WONG, LUI, SUNG, 2020; LLITJOS et al., 2020). Furthermore, thrombotic rather than embolic lung injuries were the leading cause of death in COVID-19. Venous thromboembolism (VTE) was determined in 69% of anticoagulated COVID-19 patients in intensive care units. Peripheral arterial thrombosis has also been reported in critically ill individuals with COVID-19. Cases of myocardial infarction associated with increased thrombosis have also been reported among patients with COVID-19 (HELMS etl., 2020; MESTRES et al., 2020; JANUZZI et al., 2020).
3.3 Inflammatory process in COVID-19
SARS-CoV-2 is found in different tissues, including alveolar epithelial cells, lung macrophages, hilar lymph nodes, spleen and testes. Inflammation plays an important role in disease progression and its clinical outcomes (TIAN et al., 2019). Inappropriate increase in inflammation causes a cytokine storm leading to diffuse alveolar damage, renal failure, myocarditis, central nervous system involvement and multiple organ failure, associated with poor clinical prognosis. ARORA, 2014). The infection causes a release of pro-inflammatory cytokines, associated with a systemic inflammatory response syndrome (SIRS) and accelerates cell death in the lungs, liver, heart, kidneys and adrenal parenchyma tissue (LIAO et al., 2002).
Cytokine storm is characterized by markedly increased levels of interleukins (ILs), primarily IL-6, IL-2, IL-7, granulocyte colony-stimulating factor, interferon-γ-induced protein (IP-10), chemoattractant protein of monocytes 1 (MCP-1), inflammatory macrophage protein 1 alpha (MIP1-a) and tumor necrosis factor (TNF)-alpha, which can promote lymphocyte apoptosis (AGGARWAL, GOLLAPUDI, GUPTA, 1999; PAMUKCU et al ., 2010). These cytokine levels have been shown to be increased in patients with severe COVID-19. Cytokine storm results in tissue damage, thrombotic microangiopathy, endotheliitis and endothelial dysfunction (SARZI-PUTTINI et al., 2020; JACKSON, DARBOUSSET, SCHOENWAELDER, 2019).
Monocytes and their tissue-derived macrophages are innate immune cells that interact with microbial threats by producing inflammatory cytokines. These cells eliminate pathogens and promote tissue repair. In addition to clearing infectious agents, monocytes play roles in atherosclerosis, angiogenesis, thrombosis, and tissue repair. An inadequate macrophage response can be harmful to the host (e.g., macrophage activation syndrome induced by severe infections, including COVID-19) (MERAD, MARTIN, 2020).
3.4 COVID-19: inflammatory disease related to thrombotic disorders
Disease severity has been linked to markers of clotting disorders and independently associated with the development of respiratory failure, hypoxia, and death. In more severe cases, SARS-CoV-2 induces an intensified inflammatory process (cytokine storm) that ultimately results in the activation of the coagulation cascade, which causes various thrombotic phenomena, compromising adequate blood supply to different organs. In addition, hemodynamic disturbances in coagulation can affect sensitive organs with hypoxia, including the myocardium, brain and lungs, compromising the maintenance of the patient’s physiological functions and potentially causing death (VEENSTRA et al., 2020).
The prothrombotic state is a major contributor to the diverse prognosis of severe COVID-19. The infection has been described as being associated with hypercoagulable states and thromboembolic events. These lead to limb ischemia, associated with neurological symptoms and complications, including stroke, macro and microthromboembolic activities (causing renal dysfunction) or infarction (TANG, LI, WANG, SUN, 2020).
Activation of the innate immune system and the discharge of large amounts of substances involved in the process of vascular inflammation also contribute to the aggressiveness of the infection. In the production of Angiotensin II (Ang II) and ACE2-R is massively expressed in arterial and venous endothelium. This creates an enabling environment that promotes intravascular clotting. Thus, the viral infection penetrates the vascular endothelium, reducing the density of hACE2-R receptors and generating a chain of events (result of the inflammatory action of Ang II) that induces a pro-adhesive environment for the aggregation and migration of macrophage inflammatory cells, leukocytes and lymphocytes (VINAYAGAM, SATTU, 2020; IBA, CONNORS, LEVY, 2020).
These produce interferon-gamma, TNF-alpha, IL-1, IL-6, and pro-fibrotic factors such as tissue factor, plasminogen activation factor-1, and von Willebrand factor. Due to these conditions, heparin and similar drugs have shown positive pharmacological effects on disseminated coagulation and vascular inflammation. In addition, they may have other non-anticoagulant and anti-inflammatory effects, being relevant in the clinical aspects of infected patients (VERNUCCIO et al., 2020). Therefore, several scientific studies have indicated that these properties may be involved with the following immunoinflammatory mechanisms.
a) binding to inflammatory cytokines,
b) inhibition of neutrophil chemotaxis and leukocyte migration,
c) neutralization of the positively charged peptide complement factor C5a; It is
d) sequestration of acute phase proteins.
Thus, heparin may decrease levels of inflammatory biomarkers. However, to prove these indications, further studies must be carried out. Infection usually involves the cardiovascular system studied that had evidence of myocardial injury, defined as the presence of elevated levels of biochemical markers on admission. These patients are generally elderly and have a higher prevalence of hypertension, diabetes mellitus, coronary artery disease and heart failure (VINAYAGAM, SATTU, 2020; VERNUCCIO et al., 2020).
Myocardial injury is associated with a greater need for mechanical ventilatory support and greater in-hospital mortality. Although the myocardium is an important organ for maintaining homeostasis, several other important organs are also involved, and the direct or indirect impact of the virus can affect the maintenance of blood pressure levels, blood clotting and, consequently, tissue oxygenation patterns (VERNUCCIO et al., 2020).
The symptoms described are among the main manifestations observed in lung tissue that can lead to acute failure of the cardiorespiratory system in critically ill patients. Although it was originally believed to be a syndrome characterized by acute lung injury and respiratory failure, the pathological description is characterized by an exacerbated cytokinemia, with consequent endothelial inflammation, microvascular thrombosis and multiple organ failure (VEENSTRA et al., 2020; TANG, LI, WANG, SUN, 2020).
3.5 Thrombotic and inflammatory complications of long-term COVID
Several studies have attempted to quantify the incidence of ongoing thrombosis in patients after discharge. Giannis and colleagues conducted a large-scale statistical analysis (n=4906) of major thromboembolic events in this population. The results showed that 76 patients (1.55%) were diagnosed with venous thromboembolism (VTE), including 44 deep vein thrombosis (0.90%), 42 pulmonary embolism (0.85%), 2 splanchnic vein thrombosis (0 .04%) and 3 other vein thrombosis (0.06%) ( Giannis et al., 2020 ). A study analyzing the serum metabolic profile of 75 previously diagnosed COVID-19 patients 2 months after discharge found that all patients had very high serum ferritin and D-dimer concentrations, and 73% had elevated erythrocyte sedimentation rate and CRP (PASINI et al., 2021).
Another study showed that plasma samples from long-term COVID (post-acute sequelae of COVID-19) still contain large amyloid deposits (microclots). Several inflammatory molecules were significantly increased both in the supernatant and trapped in the solubilized pellet deposits of Long COVID/PASC samples (PRETORIUS et al., 2021). A study measuring coagulation indicators 4 months after discharge from patients with COVID-19 found that patient samples increased the thrombin generating capacity and decreased the fibrinolytic potential of plasma, indicating sustained prothrombotic changes.
Overall, these studies have shown that persistent clotting abnormalities and thrombosis are common in long-term COVID. Other experiments have found that continuous activation of clotting can lead to abnormal functions in various organs. Postpulmonary thrombosis syndrome can manifest as persistent thrombosis and long-term functional limitation in long-term COVID, through pulmonary hypertension, embolism and fibrosis are characterized as common sequelae of the lungs (CARFÌ et al., 2020 ; CARUSO et al., 2021 ; CUETO-ROBLEDO et al., 2022), which may result in impaired function. Thus, the above data indicate that abnormal clotting is a common manifestation in long-term COVID, with prolonged activation of clotting, microvascular injury, and thrombosis leading to systemic damage in patients.
3.6 Post-COVID physiological mechanism hypothesis
After a severe primary infectious disease such as COVID-19, in which a systemic inflammatory response syndrome is predominant, a long-lasting compensatory anti-inflammatory response syndrome (RIC) occurs that leads to post-infectious immunosuppression. The goal of the RIC response is mirrored counter-regulation to Systemic Inflammatory Response Syndrome (SIRS), seeking to ameliorate the pro-inflammatory state, prevent maladaptive dysfunction of multiple organs and return to immune homeostasis (PRETORIUS et al., 2021).
Thus, multiple interaction factors are involved, seeking to ensure the homeostasis of pro- and anti-inflammatory responses. Thus, excessive inflammatory responses play a role in:
1) viral exposure or incubation,
2) presence/absence of comorbidities and
3)state of immunocompetence
They are characterized by excessive release of inflammatory cytokines called “cytokine storm”. This process results in the development of acute lung injury, acute respiratory distress syndrome, coagulopathy, hypotension, hypoperfusion, multiple organ failure and death (CARUSO et al., 2021; CUETO-ROBLEDO et al., 2022).
However, when the inflammatory response occurs through regulation of RIC, there may be modulation of the initial storm of hyperinflammatory cytokines and progression to SIRS, and may enter a stage of prolonged immunosuppression known as persistent inflammation, immunosuppression and catabolism syndrome that is observed after sepsis is one of the main hypothetical causes of persistent post-COVID syndrome (PASINI et al., 2021).
In support of this hypothesis, postseptic patients are prone to latent virus reactivation. Likewise, as with sepsis, patients with COVID-19 are at risk of developing secondary bacterial and fungal infections, highlighting the immunosuppression and dysregulation present (CARUSO et al., 2021).
3.7 Risk factors associated with COVID long
The main risk factors for the development of long-term COVID-19 are asthma, type 2 diabetes mellitus, obesity, pre-existing clinical depression, hypothyroidism, and patients who had severe COVID-19 that required hospitalization represent a greater number of symptoms during acute infection. Other risk factors for long-term COVID include the presence of symptoms during the acute phase such as shortness of breath (dyspnoea), fatigue, headaches, anosmia, myalgia. Several other contributing factors may increase the risk of developing long-term COVID, such as COVID-induced viral reactivation due to the presence of pre-existing antibodies at the time of infection and a high viral load of SARS-CoV-2 during acute infection (VINAYAGAM , SATTU, 2020; VERNUCCIO et al., 2020).
The case definition by the World Health Organization (WHO) states that long-term COVID can occur in individuals with a history of presumed or confirmed SARS-CoV-2 infection, usually three months after the onset of infection, with symptoms continuing for at least two months accompanied by the inability to explain the symptoms through an alternative diagnosis. Thus, many COVID-19 survivors report at least one or more virus-related symptoms that persisted for more than four weeks after initial diagnosis. Long COVID was observed in 54% of hospitalized and 34% of non-hospitalized COVID patients. Furthermore, the risk of developing Long COVID increases with each subsequent reinfection with SARS-CoV-2 (CUETO-ROBLEDO et al., 2022).
Common phenotypes of long-term COVID are fatigue, anosmnia/dysgeusia, respiratory (shortness of breath and cough), cardiovascular (major adverse cardiovascular events and arrhythmias), cognitive (cerebral confusion, impaired memory and concentration), neurological (headaches, dizziness , insomnia, daytime hyperactivity drowsiness and postural orthostatic tachycardia syndrome), psychiatric, musculoskeletal (myalgia, costochondritis and arthralgia), coagulopathy (deep venous thrombosis, pulmonary embolism and bleeding), dermatological (COVID fingers, hives and rashes) and gastrointestinal (diarrhea, abdominal pain and reflux) (VINAYAGAM , SATTU, 2020; VERNUCCIO et al., 2020).
3.8 The impact of vaccines on long-term COVID risk
In vaccinated patients with a COVID-19 outbreak episode, the first and second doses of vaccination were associated with reduced odds of requiring hospitalization or developing more than five symptoms within the first week of infection. For those who received two doses of vaccine, the chance of long-lasting symptoms (≥28 days) was significantly reduced compared to unvaccinated individuals (CUETO-ROBLEDO et al., 2022; VINAYAGAM , SATTU, 2020).
More persistent symptoms after acute COVID-19 have been reported less frequently in vaccinated individuals than in unvaccinated individuals. At-risk individuals remain highly susceptible to SARS-CoV-2 infection despite vaccination due to immunosenescence, multimorbidity (diabetes, hypertension, and obesity), and low socioeconomic status. However, vaccination in this vulnerable population is associated with a lower risk of mortality and a significantly lower risk of Long COVID (CUETO-ROBLEDO et al., 2022; VINAYAGAM , SATTU, 2020).
Notably, vaccination was observed to reduce the risk of prolonged COVID symptoms, such as sleep disturbances, myalgia, kidney damage, and cognitive deficits, in vaccinated subjects before or after acute infection. The likelihood of persistent prolonged COVID symptoms steadily decreases after vaccination, with a growing body of evidence suggesting that lasting improvements are seen after a second dose of vaccine. The impact of COVID-19 vaccination in people with long-COVID remains incomplete, with conflicting reports from existing studies.
3.9 Conclusion
The study for the recognition of long-term Covid sequelae, including the inflammatory and thrombotic process, which played a crucial role in understanding the long-term effects of this disease. Understanding the nature, severity, and procedures involving persistent complications is critical to providing physiological and targeted procedures aimed at minimizing adverse effects and improving patients’ quality of life.
Early recognition and proper diagnosis of long-term Covid sequelae are essential to effectively implement therapeutic and rehabilitation strategies. The identification of persistent symptoms and complications associated with the painful inflammatory process and thrombotic disorders allows for a multidisciplinary and individualized approach, aiming to reduce debilitating symptoms, promote recovery and minimize long-term sequelae.
The importance of studying and recognizing the after-effects of the long Covid, the inflammatory and thrombotic process transcends the clinician. These complications start in terms of public health, health policy and resource planning. A comprehensive understanding of these sequelae is critical to inform prevention, intervention and long-term management strategies, ensuring a more effective and sustainable approach to dealing with the challenges posed by the Covid-19 pandemic.
In short, the study and recognition of the long-term Covid sequelae, especially those related to the inflammatory and thrombotic process, are extremely important. Understanding these persistent complications allows us to improve patient care, develop more effective preventive strategies, and reduce the global impact of the pandemic. These efforts are essential to provide a fuller and more satisfactory recovery for affected individuals and to address the public health challenges arising from COVID-19.
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1Centro Universitário Serra dos Órgãos (UNIFESO), Teresópolis, Rio de Janeiro, Brasil.
2Centro Universitário do Planalto Central Apparecido dos Santos (UNICEPLAC), Gama, Brasilia, Brasil
3Universidade de Rio Verde (UniRV), Aparecida de Goiânia, Goiânia, Brasil
4Faculdade Ages, Jacobina, Bahia, Brasil
5Universidade do Estado de Mato Grosso (UNEMAT), Cáceres, Mato Grosso, Brasil
6Centro Universitário de Brasilia (UniCEUB), Brasília, Destrito Federal, Brasil
7Universidade de Pernambuco (UPE), Recife, Pernambuco, Brasil
8Faculdade Santa Terezinha (CEST), São Luís, Maranhão, Brasil
9Universidade Federal de Alagoas (UFAL), Maceió, Alagoas, Brasil
10Centro de Longevidade Irineu Mazutti, Sumaré, São Paulo