BIBLIOMETRIC REVIEW
LIMA, Marcelo Henrique Vaz de [1], SANTOS, Lara Verardo Gomes dos [2], BORGES, Juliana Julien Salvarani [3], ALVES, Ítalo Corino [4], MACHADO, Gabriele Rodrigues [5], CARVALHO, Fernando César Ribeiro de [6], PALINSKI, Jane da Rosa [7]
LIMA, Marcelo Henrique Vaz de. et al. COVID-19 among elderly patients: epidemiology, pathogenesis and treatment. Revista Científica Multidisciplinar Núcleo do Conhecimento. Year. 07, Ed. 03, Vol. 03, pp. 160-173. March 2022. ISSN: 2448-0959, Access link: https://www.nucleodoconhecimento.com.br/health/pathogenesis-and-treatment
ABSTRACT
Since February 2020, Brazil has been suffering from the pandemic caused by COVID-19. Because it is a new disease, further studies and analyzes are needed to better understand and deal with this problem. Although the Coronavirus has a manifestation similar to a flu-like process, it has an intense dissemination, revealing itself in a serious way in the majority of the elderly, having a negative prognosis in the face of senile individuals with chronic diseases. In a country with extensive territorial dimensions such as Brazil, the presentation of this pathogen can occur differently depending on age, the presence of comorbidities and the sanitary conditions of the population, constituting a disease of relevant scientific interest, due to the lack of therapy curative, nor vaccination coverage. From the perception of how severe cases affect the elderly, the need arose to understand: what are the epidemiological, pathogenic characteristics and possible treatments for cases of COVID-19 among elderly patients? In this sense, an epidemiological, descriptive, retrospective, bibliographical study was conducted, aiming to analyze the behavior and repercussions of this microorganism in the context of individuals over 60 years of age and, for this purpose, it is worth noting that a theoretical incursion was carried out in published regency publications from 2019 on the subject. Concluding, in view of the senile population, that COVID-19 has pathophysiological manifestations similar to those of countries already affected and that the management of this condition has been internalized in Brazil, like in other countries, with the use of combined antivirals, thrombolytic drugs , anti-inflammatories and mechanical ventilation with positive pressure.
Keywords: COVID-19, Epidemiology, Pathogenesis, Treatment, Elderly.
1. INTRODUCTION
As can be seen from the lesson by Rothan and Byrareddy (2020), Coronavirus 19 is an enveloped RNA virus with a positive single strand that primarily attacks the respiratory system and has the “spike” protein, which favors its anchorage in the plasma membrane of the host cell, allowing the facilitation of endocytosis by lipoxidation of this membrane, giving this virus a formidable invasive power, using, after invasion, the cellular machinery to translate and transcribe its own genetic material, giving rise to new viral specimens that , after maturing, break the cell and infect sites with a predilection for the respiratory system, in addition to eliciting a severe immune response in some individuals.
The first cases date from December 2019, which occurred in the city of Wuhan, when hospitalized patients presented with fever, dyspnea and computed tomography with bilateral image of expansion of the bronchial web in the multifocal “ground-glass” pattern, and since then there have been viral spread to other regions of China and Asia, with cases being reported even in the United States of America on January 30, 2020, during the care of a patient from the hot zones of the initial epicenter of COVID-19 (ROTHAN and BYRAREDDY, 2020).
After the exponential growth of contamination by the Coronavirus, it was noticed that most of the patients treated, in the nosocomial environment, were over 70 years old and, among those who died, about 50% were over 83 years old. The viral pneumonic manifestation in this public was not expressed by a spectrum of typical signs such as fever, cough and dyspnea, in most cases, revealing itself by pathognomonic asymptomatology or being confused with typical signs associated with nosological processes resulting from senility such as delirium and fatigue. However, persistent diarrhea was one of the unusual incidental findings that was linked to COVID-19, as taught (NGUYEN et al., 2020).
In addition, older age demonstrates an association with a negative prognosis, showing that the loss of functional reserve combined with the senile inefficiency of the immune system can serve as negative predictors for the more intense evolution of the Severe Acute Respiratory Distress Syndrome caused by the Coronavirus, increasing the lethality of this viral agent (NGUYEN et al., 2020). In this sense, understanding the manifestations of this microorganism in the Brazilian senile population is an imperative need from the point of view of health protection.
It is urgent to point out that, in certain cases, taking into account atypical and non-specific manifestations of elderly patients, SARS-COVID-19 may not be satisfactorily diagnosed, precipitating a state of severe health degradation, specifically in the case of the elderly, due to presentations atypical features of Severe Acute Respiratory Syndrome which, in some cases, are revealed to have a rather suggestive symptomatological repertoire (TAY and HARWOOD, 2020).
That said, due to the real threat to life caused by this virus, it is necessary to better understand its transmission and infection processes. In this sense, this subject was approached through the following topics, in such a way that it was possible, not only to organize the main elements of this theme, but also to understand the manifestation of COVID-19 in the Brazilian territory, especially, in the face of patients in a state of senility.
Based on the arguments presented, this article aims to analyze the behavior and repercussions of this microorganism in individuals over 60 years of age, to answer the following question: what are the epidemiological, pathogenic characteristics and possible treatments for cases of COVID-19? 19 among elderly patients? To achieve the desired results, the following processes were adopted: Describe how it emerged and what were the initial concepts about the etiology and pathogenesis of COVID-19 in the elderly; describe and understand the epidemiology in the context of COVID-19 in the senile population, and list the possibilities of approaching and managing COVID-19 in senility.
2. METHODS
An epidemiological, retrospective and bibliographic study was conducted on October 1, 2020, from which an incursion into the theoretical repertoire on COVID-19 was carried out, searching especially through the use of Boolean operators the words: COVID-19, EPIDEMIOLOGY, AGENT ETIOLOGICAL, PATHOGENESIS and ELDERLY in the databases of NCBI, SCIELO, PUBMED, CLINICALTRIALS and RESEARCHGATE, both in Portuguese and in English. About 167 articles were found, of which, after reading their abstracts, only 24 were used.
In terms of inclusion criteria, only articles published between 2020 and 2021 on the topic of COVID-19 among the elderly were accepted, strictly with regard to the pathology, epidemiology and treatment of COVID-19, including those aimed at the elderly public , and an article on viral epidemiology dated 2005, which addresses the epidemiological evolution of viral diseases arising from the coronavirus, especially SARS and MERS. It should be noted that most of the articles originated from Chinese authors, in view of the great impact of COVID-19 in that country, with articles focusing on: etiology/epidemiology, pathogenesis and management of COVID-19 being accepted.
As for the issue of risks, this work presented a minimum risk because it is an article based on a bibliographic review, and it was not necessary to implement the Term of Free and Informed Consent – TCLE[8], nor to activate the local and national research ethics committees, since this scientific piece did not act directly with humans, but through documentary bibliographic analysis.
It is worth mentioning that the financing was implemented with resources from the authors themselves and that the only figure of the work, located on page 08, was extracted from material on which there is no limitation by copyright, since it is a manual issued by the Ministry of Brazilian health.
3. RESULTS
3.1 ETIOLOGY AND PATHOGENESIS OF COVID-19 IN THE ELDERLY
In terms of results, the analyzed literature indicates that the positive single-stranded RNA viral etiological agent attacks the host cell membrane through an anchoring mechanism favored by the “spike” protein, which allows the virus to adhere to the surface of the host cell and start its attack, lipo oxidizing, which allows its penetration into the cytoplasm. After that, the cellular machinery will be hijacked and forced to work for the virus, translating its RNA and retranscribing it, in order to produce viral clones that will be made available, after maturation, to the bloodstream, in order to infect other cells, maintaining the infection process (ROTHAN and BYRAREDDY, 2020; CHAN et al., 2020).
With regard to the symptomatological issue of COVID-19, the virus remains latent for 5 days and evolution to death occurs between the sixth and forty-first day, with the 14th day being the median of this process, which is aggravated in the age group over seventy years old. It is worth mentioning that the most common symptoms were fever, dry cough, fatigue, dyspnea, headache, lymphopenia and persistent diarrhea with a characteristic tomographic pattern of “ground-glass” bilaterally in the lungs, with a severe immune response that, in young patients, was demobilized between the 6th and 21st day of infection (ROTHAN and BYRAREDDY, 2020).
As for the pathogenesis, the presentation of COVID-19 in the laboratory context was associated with leukopenia, an increase in C-Reactive protein indicators, with a severe rate of erythrocyte sedimentation and D-dimer, indicating that there is a significant inflammatory action with the participation of pro-inflammatory cytokines in a stormy and acute way with the presence of various interleukins, alpha tumor necrosis factor and gamma interferon (ROTHAN and BYRAREDDY, 2020).
According to Niu et al. (2020), the elderly make up the group with the highest incidence of infected people, with symptoms that do not follow a regular pattern. However, the presence of fever, dry cough, dyspnea, persistent diarrhea and tiredness were the most frequently perceived conditions in the patients’ repertoire of symptoms, with fatality in 8.3% of positive cases, indicating that lethality grows proportionally with the subject’s age and the presence of cardiovascular, metabolic and immunological comorbidities.
According to a study conducted by Ruan et al. (2020), 68 patients admitted to Jin Yin-tan Hospital and Tongji Hospital, who had the severe form of COVID-19, had advanced age and pre-existing diseases as important predictors, so that 53% of them died due to respiratory failure, 7% died from fulminant myocarditis, indicating that chronic diseases of the cardiovascular and respiratory systems can influence the severe outcome of COVID-19, showing that the senile population with comorbidities is more susceptible to death in the case of this infection.
Also, according to Ruan et al. (2020), patients aged between 56 and 75 years are at greater risk of developing the severe form of COVID-19, having severely altered laboratory parameters, such as Cardiac Troponin, Myoglobin and C-Reactive Protein, which refer to the Syndrome of Cytokine Storm, triggering a severe immune response, which may be associated with the escalation of severe symptoms in the patients surveyed.
In a study conducted by Luo et al. (2020), patients admitted to a Chinese hospital had similar symptoms, such as itchy eyes, such as that derived from viral conjunctivitis, continuous fever, tiredness, dry cough and dyspnea, revealing that pulmonary impairment is common and, not infrequently, the affects bilaterally, and may progress to acute respiratory failure, which may precipitate the death of the subject being evaluated.
Opal et al. (2005) corroborate the thesis that the elderly may be more vulnerable to COVID-19, explaining that this occurs as a result of both innate and acquired immune decline, revealing defects in the functionality of T and B Lymphocytes and in the modulation of the secretion of pro-inflammatory cytokines , which causes a severe procoagulant state in the elderly, precipitating occlusive diseases, notably in the myocardium and lung parenchyma, which is corroborated by Fauci et al. (2020).
In Brazil, this symptomatological repertoire seems to be repeated, being more pronounced in patients with comorbidities and the elderly, in such a way that preventive actions, consistent with social isolation, are indicated to mitigate the exposure of elderly and chronic patients to the possibility of viral contagion, a since the escalation of symptoms in the public in question can follow a very severe logic and with a restricted and severe prognosis (SCHUCHMANN et al., 2020).
Still in line with Schuchmann et al. (2020), COVID-19 has no predilection for age group, gender or ethnicity, indistinctly infecting any individual who comes into contact with the microorganism , precipitating an infectious state that can escalate to a plausible risk of death, with social isolation being a measure of useful viral coping, especially in the context of preserving the service capacity of the Unified Health System – SUS[9].
In fact, COVID-19 can reach the contaminated individual systemically, producing microthrombi, which may lead to the appearance of thrombosis with a potentially ischemic lesion, leading to organ failure of the target reached by the thrombus (NEGRI et al., 2020). In this sense, prevention, even in this preliminary moment when there is no medication or vaccine, is still prevention through the quarantine of the contaminated public involved in this context.
That said, due to the morbidity and mortality presented by COVID-19, Brazil has carried out the National Contingency Plan, in order to promote attention against this pathogen in all spheres of government, regionalizing health strategies and offering locally the service, in order to monitor and articulate coping measures and allocation of financial resources (CRODA et al., 2020).
3.2 EPIDEMIOLOGY OF COVID-19 IN THE SENIL POPULATION
In line with the data obtained (BRASIL, 2020), the epidemiological tracing of COVID-19 in the country indicates that the first confirmed case was on February 26, 2020, duly identified, with individual monitoring of the infected person and their social relationships. However, more than 60 days after the first case, the country has registered more than 61,888 confirmed cases and 4,205 deaths due to complications linked to COVID-19.
According to Croda et al. (2020), the number of cases of COVID-19 in Brazil is vast, with an exponential growth, both of new contaminations and of severe forms of the disease, constituting causes for the resurgence of this process the presence of young and elderly adults with comorbidities and co-infections that accelerate the degradation of the health of the infected person, accentuating the most serious manifestations of COVID-19.
Therefore, making an epidemiological retrospective of the natural history of this disease, the viral etiological agent can be transmitted by droplets and aerosols, so that the proximity between subjects favors the contagion and dissemination of this disease. Until the 7th day, the viremic period occurs in which the subject incubates this microorganism, being diagnosed only via PCR; after the 8th day, a blood drop from a finger prick can already be captured to assess IGM antibodies for the Coronavirus, not ruling out the possibility of a “false negative” until the 10th day, when the subject has symptoms, but the test has not yet captured the presence of viral antibodies (BRASIL, 2020).
After the 14th day of infection, if the subject has been hospitalized on the 8th day, it is possible that the complications evolve to death, with an average hospitalization period of 9 to 17 days until hospital discharge in case of survival, indicating that the follow-up of the acute cases in the post-pathogenic period is important for the final outcome of the disease in the search for a positive prognosis and hospital discharge with the avoidance of deaths.
Thus, knowledge of the epidemiological manifestation allows knowing how this viral etiological agent acts and how its pathogenesis develops, in order to avoid the exponential propagation and the severe escalation of the symptomatology during the course of this disease; in addition, the natural course of this disease has the potential to aggravate the clinical condition of patients with comorbidities, which is a relevant public health condition in the world context (GUAN et al., 2020).
3.3 APPROACH AND MANAGEMENT OF COVID-19 IN SENILITY
According to Rothan and Byrareddy (2020) and Deng and Peng (2020), in view of the lack of a drug capable of eliminating this viral agent, initially, social isolation measures were proposed in order to contain the spread of contagion, avoiding the escalation of severe conditions at the same time, demanding very specific hospital care, notably, through hospitalization with intensive care and mechanical ventilation in the most serious cases.
In the context of pharmacological therapy, known antiviral drugs were used, such as nucleoside analogues and viral protease inhibitors, namely: Oseltamivir 75 mg twice daily IV, Lopinavir 500 mg IV, Ritonavir 500 mg IV, and Ganciclovir 0.25 g for 3-14 days associated with Chloroquine, demonstrating efficacy, but without explaining the drug interaction. In addition, Remdesivir has shown great promise, attenuating the speed of viral replication (ROTHAN and BYRAREDDY, 2020; MAHASE, 2020).
Velavan and Meyer (2020) stated that therapy with humanized CCR5 antagonist monoclonal antibodies obtained encouraging results, constituting an alternative for the management of COVID-19, taking into account the passive immunization caused by this antibody, which favors an immune response within of adequacy parameters, avoiding tissue damage due to immune hypermobilization, a conclusion reiterated in the study by Ji et al. (2020).
Fengcai (2020), at the Wuhan Institute of Biotechnology, began a study on April 12, 2020 to test the efficacy of a recombinant vaccine against COVID-19, co-opting 108 individuals who received specific antibodies against the “spike” protein, which is still in phase II of the clinical trial, awaiting the collection of results and verification of the advent of passive immunization brought about by this vaccine drug.
Xian (2020), at the Medical University of Wenzhou, on February 16, 2020, started the phase II clinical trial in which Bromhexine combined with recombinant human Interferon alpha-2B is being administered in the face of COVID-19, which is still under analysis and data collection, but with encouraging preliminary analyzes for the management of this disease with reduced hospitalization time and avoidance of serious effects on the respiratory system.
In Brazil, Negri et al. (2020) are implementing the use of antiembolism therapy via administration of Heparin in low doses for up to 10 days, allowing to attenuate the incidence of Acute Myocardial Infarctions due to coronary thromboembolization, having been tested in 27 patients with COVID-19 in a way randomized and double-blind study, whose outcome eliminated death in 100% of the patients surveyed, during the period of hospitalization due to cardiovascular complications.
4. DISCUSSION
In Brazil, the clinical presentation of COVID-19 is proving to be similar to that of other countries. However, the heterogeneity of individuals and the hospital condition differ, especially when checking the availability of medical instruments for the management of this disease, such as the surplus of mechanical ventilators and intensive care professionals to manage them (BRASIL, 2020).
Bearing in mind that the entire research process was developed around the intention of answering the etiological, pathogenic and epidemiological characteristics of COVID-19 in elderly patients, as well as observing possible treatments for such cases, the entire discussion above has the purpose of in order to provide adequate answers to these questions.
As for the etiology, viral genetic sequencing made it possible to attest that viral strains of COVID-19 have already mutated, expressing a major public health problem, since the viral component changes its conformation at a disproportionate speed, compared to the initial strains of January of 2020, demanding adaptation of attending physicians to more contemporary strains of this pathogen, especially in terms of therapeutic approach (GRUBAUGH; PETRONE; HOLMES, 2020).
With regard to pathogenesis and epidemiology, the pathognomonic presentation of COVID-19 in Brazil has been similar to that of other countries, notably, with regard to the escalation of symptoms in elderly individuals and those with comorbidities, deserving social isolation strategies to avoid exponential contagion and the advent of severe symptoms in multiple individuals simultaneously (CRODA, 2020).
In the context of approaching and managing this disease in Brazil, in an experimental way, drug therapy has been carried out through the use of broad-spectrum antivirals coupled with heparinizing antithrombotic therapy, which has shown promising results from the point of view attenuation of deaths due to Acute Myocardial Infarction caused by coronary embolism (NEGRI et al., 2020), following what has already been discovered by several Chinese researchers (NIU et al., 2020), since there is no specific therapy for the elderly, applying Combined antiviral, anti-inflammatory pharmacology and positive pressure mechanical ventilation are used for patients with severe escalation of symptoms in any age group.
5. FINAL CONSIDERATIONS
COVID-19 is a disease of great international repercussion, with multisystemic aggression endowed with severe morbi and mortality, giving rise to the need for further research and greater investments, notably in prevention. In Brazil, this nosological entity has a predilection for vulnerable individuals from an organic point of view and the elderly, with a higher incidence in large cities with an ICU hospitalization rate of 5% of individuals, with a significant need for preventive behavior that can be made possible by through horizontal social isolation and, in severe cases, social confinement, so that individuals in the risk range, such as the elderly and vulnerable, are protected (BRASIL, 2020).
Therefore, returning to the guiding question of this compendium, it is correct to state that, in epidemiological terms, COVID-19 has a predilection for senile subjects, imposing greater preventive care against contagion in this public, notably, social isolation and the offer of vaccine immunogenic therapy.
Still evoking the central problem of this work, it was possible to understand the etiological path, the pathogenesis already known around COVID-19 and the potential treatment strategies that were consigned in the lessons of Lei et al. (2020), who demonstrated that this disease process can be overcome through the advent and application of vaccine therapy. In addition, it is necessary to keep the population in social isolation in the face of ICU occupancy rates above 85%, in order to avoid disruption in the provision of health services. On the other hand, the treatment routes consist of attenuating the immune-mediated inflammatory response, in order to lessen the phlogotic effects capable of causing negative consequences such as thrombosis, ischemia and other conditions.
Finally, this study had limitations, since, although the theoretical repertoire can be applied in Brazil, it is still necessary to monitor the therapeutics applied worldwide, in order to adapt care with COVID-19 in the country, deserving new studies in other pharmacological perspectives, revealing that the present article potentially addressed the objectives, but still lacks new perspectives and clinical protocols.
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APPENDIX – FOOTNOTE
8. Termo de Consentimento Livre e Esclarecido (TCLE).
9. Sistema Único de Saúde (SUS).
[1] Master in Psychology, Specialist in Public Health, Graduated in Law, Medical Student. ORCID: 0000-0002-7574-6478.
[2] Medical Academy. ORCID: 0000-0002-1143-7019.
[3] Pharmacist graduated in Pharmacy and Biochemistry, Medical Student. ORCID: 0000-0003-1040-6357.
[4] Graduated in Pharmacy, Medical Student. ORCID: 0000-0001-6805-2681.
[5] Graduated in Nutrition, Medical Student. ORCID: 0000-0002-4178-0061.
[6] Graduated in Law, Medical Student. ORCID: 0000-0001-6758-1725.
[7] Advisor. ORCID: 0000-0001-6624-8963.
Submitted: December, 2021.
Approved: March, 2022.
