Main Sequelae after Covid-19 in Adults

Introduction: During the pandemic, evidence emerged of patients with debilitating symptoms that persisted for weeks and even months after the diagnosis of COVID-19, a fact that is of great concern to the medical community. Objective: To assess the available evidence of the main sequelae of COVID-19 affecting previously healthy adults.


Introduction
Corona viruses are a family of viruses that cause illnesses ranging from the common cold to more serious illnesses such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) [1].The virus causing the pandemic was named as SARS-CoV-2.This new coronavirus generated a disease known as COVID-19, being the agent of a series of cases of pneumonia in the city of Wuhan (China).Until recently, there was no concrete information about the mechanism of action on the disease and, even today, there are no unquestionable measures of effectiveness for the clinical management of cases of human infection with SARS-CoV-2, with many details still to be clarified.The virus has shown to be highly transmissible and causes an acute respiratory syndrome that ranges from mild cases -around 80% -to very severe cases with respiratory failure -between 5% and 10% of cases.Its lethality varies, mainly, according to the age group and associated clinical conditions [2].
During the pandemic, evidence emerged of patients with debilitating symptoms that persisted for weeks and even months after a diagnosis of COVID-19, a fact that is of great concern to the medical community.When observing the size of groups such as the so-called "longhaulersCOVID" on social media, it is estimated that the members of such groups add up to thousands of people [3][4].Several small studies followed recovered cases of COVID-19, with a special focus on severe cases.However, an evidence-based systematic review of the long-term sequelae of COVID-19 in previously healthy adults is needed [3].This review aims to assess the available evidence of the main sequelae of COVID-19 affecting previously healthy adults.

Methods
This study constitutes a systematic review, classified as exploratory and descriptive.The elaboration of the research was bibliographical research in electronic databases on methods associated with RSL (Systematic Literature Review) and SMARTER applications (Simple Multi-Attribute Rating Technique using Exploiting Rankings).The work carried out is qualitative and quantitative.Qualitative data analysis was performed intuitively and inductively during the survey of the theoretical framework.It is also quantitative using the multicriteria method.In addition, there is also a numerical experimental study in order to simulate an article selection situation based on the observed criteria.Based on bibliographical research, located in the following databases: US National Library of Medicine (Pub Med), Scientific Electronic Library on-line (SCIELO), Latin American Caribbean Health Sciences Information System (LILACS), Science Direct (Elsevier) and Embase.Complementarily, searches were carried out based on bibliographical references of studies that relevantly addressed the topic on the Google Scholar search platform.
The search in the databases was carried out using the terminologies registered in the Health Sciences Descriptors created by the Virtual Health Library developed from the Medical Subject Headings of the US National Library of Medicine, which allows the use of common terminology in Portuguese, English and Spanish.The present study sought to investigate the literature on post-covid sequelae in previously healthy people.For this purpose, the descriptors "COVID-19", "coronavirus disease 2019", "SARS-CoV-2", "sequelae" were used, initially in English, and in a complementary way in Spanish and Portuguese.
As a tool to support the decision in the selection and prioritization of articles, a set of criteria were considered essential to represent the state of the art of the subject object of the research.This method has the following characteristics: (i) rigorous logic allows acceptance of the method as a decision support tool; (ii) simple to understand and apply with easily interpreted results.References from selected papers were also searched for other documents of potential interest.Once qualified for full-text evaluation, articles were included in the qualitative review if they met the following inclusion criteria: a) they contained data on Covid sequelae; b) Covid-19.Articles were excluded if they were reports, banners or conference abstracts.There was no review of confidential health information and the study was noninterventional.Therefore, ethics committee approval was not required.To theIn the end, the result obtained totaled 38 articles that contemplated the desired characteristics for the study.
Three independent researchers extracted data from articles that met the inclusion criteria and recorded them in a "Data Extraction Form" generated in Microsoft Excel on the main post-COVID-19 sequelae in adult subjects.From this form, the authors and year of publication, country, type of study (design), study title, sample size (n) and conclusion of the study, shown below in (

Results
A comprehensive systematic search of the literature yielded a total of 4495 articles referring to the main post-covid sequelae in adult patients.Of these, 302 studies were excluded due to overlapping data.From there, we choose the SMARTER method (Simple Multi-Attribute Rating Technique using Exploiting Rankings).393articles were suitable for full-text screening and 99 articles were included for data extraction, of which 61 were excluded by the exclusion criteria, making 38 articles eligible that were included for systematic review.In (Figure 1), we describe the strategy for selecting articles on the topic in question.

Discussion
A study carried out by [21], observed that a subset of individuals with COVID-19 may develop a chronic condition that persists long after the initial presentation, with cognitive slowing, prominent fatigue, and symptoms of autonomic impairment, such as exaggerated postural tachycardia, episodic hyperadrenergic spikes, and orthostatic intolerance.The study entitled "Clinical Sequelae of COVID-19 Survivors in Wuhan, China" conducted by [34],demonstrated that clinical sequelae were common, including general symptoms (49.6%), respiratory symptoms (39%), cardiovascular symptoms (13%), psychosocial symptoms (22.7%) and alopecia (28.6%).The study was carried out with 538 survivors, of which 54.4% were women, with a median age of 52 years and the time from discharge to the first follow-up was an average of 97 days.
Many patients who were diagnosed with the disease ended up not recovering completely, in some cases the symptoms continue to persist, and sometimes increase and sometimes decrease [16][17][18].It is believed that around 10% of patients who have had Covid-19 and have mild symptoms will eventually become long-term carriers [14][15][16][17][18]. Patients who have more severe comorbidities or infections with the SARS-CoV-2 virus are those who have a higher incidence of persistent symptoms [18][19][20].Although no time period has been established to be identified as persistent symptoms, it is acceptable to say that symptoms that last more than 3 to 4 weeks post diagnosis, and more than six weeks in the case of critical illness, are mild, moderate or severe, it can be considered that they are persistente [18].Although post-acute sequelae are still not well understood, some people have multiple affected systems that can persist for several months, which ultimately impairs quality of life [14][18] [36].Recovered patients, but with serious complications such as respiratory failure, post-acute thrombosis and cardiac and vascular damage, tend to increase the possibility of future morbidity and mortality.Cohort studies that have investigated these complications are still very limited, for this reason these studies have focused especially on complications that lead to readmission, rather than evaluating post-acute complications [36].The study carried [5], suggested that Covid-16 infection increases the risk of 6-month mortality.
A study of patients hospitalized for severe post-Covid sequelae showed that they are at greater risk of new hospitalizations than patients who had mild covid.However, in the study it was not clear whether the severe infection increases the risk of mortality in 12 months after the previous episode and there is still a lack of data regarding post-acute sequelae in young patients compared to older patients [36].
Several studies have demonstrated and spoken these days about post Covid sequels.Among these sequels we can mention:
A study carried out by [23], demonstrated that cardiovascular complications were arrhythmia (10%; ectopic atrial beat n = 10; ventricular arrhythmias n = 2; atrial fibrillation n = 4), followed by venous thromboembolism (VTE, 8%), hemodynamic instability (defined mainly by hypotension and also the need for pharmacological support with intravenous noradrenaline), deep vein thrombosis (DVT, 2%) and pericarditis (1%).The autonomic nervous system can also be affected by virial diseases, and orthostatic hypotension may be present together with tachycardia in response to changes in position, running the risk of presenting injury due to vasovagal syncope.These symptoms should be well evaluated to rule out other etiologies.Guidance for these patients must be well placed to control symptoms and avoid injuries .
The available vaccines herald a new phase in the pandemic with a reduction in serious infections and mortality, but it also comes with a lot of concern about their safety, due to the reports of several cases and registry data that have reported myocarditis as a side effect of vaccination against COVID-19 [10].The complexity of acute cardiovascular diseases caused by SARS-CoV-2 infection is already being well described nowadays, with arrhythmia, myocardial injury, acute coronary syndrome and heart failure as the main ones.Complications that in the long term may require chronic cardiovascular care [33].

Mental health sequelae
Because it is still uncertain, long-term Covid leaves patients feeling helpless about controlling their symptoms .Truck drivers went through an interview and said they were frustrated by the lack of assistance from both family members and health professionals [16].People who before the event were considered healthy and independent, have difficulties with their activities of daily living and have difficulties or have been unable to work because of the symptoms and their limited endurance [17][18].A cohort study carried out with anonymous data from electronic health records in 54 health institutions in the USA, demonstrated a 5.8% increase in the incidence of psychiatric illnesses, diagnosed 14 to 90 days after diagnosis of the illness, compared to the control group that 2.5 to 3.4% received a new psychiatric diagnosis [32].
These alterations have several etiologies, as a vast number of stressors appeared during the pandemic, such as social and financial isolation and fear and uncertainty regarding the SARS-CoV-2 infection [11].Acute psychiatric symptoms in patients who had the disease was reported in several studies and that at least 35% of patients demonstrated symptoms of depression and anxiety [15][27].

Musculoskeletal sequelae
Guillain-Barré syndrome (GBS) is a demyelinating polyneuropathy,Acquired nervous system disorder, probably autoimmune in nature, marked by loss of myelin sheath and tendon reflexes, which has been reported with symptoms appearing 3 to 4 weeks after the onset of COVID symptoms, as well asMiller-Fisher syndrome which is a variant of GBS.On magnetic resonance, GBS and its variants demonstrate hyper signal intensity, increase and mild to moderate contrast enhancement of nerve roots/plexuses and cauda equina [25][13], conducted a review study entitled "What might COVID-19 patients experience after recovery?".In this research, twenty-three studies demonstrated musculoskeletal symptoms in Covid-19 survivors, including myalgia and joint pain, which lasted from 35 days to 3 months after discharge.Twelve studies reported that patients experienced fatigue.

Table 1 :
Studies reporting the main sequelae after Covid-19 in adult individuals *ND -nothing described