Post COVID-19 Sequelae in Adults: A Review

Abstract

Post-COVID syndrome is a multisystem disorder that develops after an acute illness. Numerous studies of past respiratory virus pandemics have shown persistence of various symptoms, fatigue, shortness of breath, and cognitive dysfunction that are frequently mentioned. The research carried out use a systematic literature search, a systemic search of published was performed in the databases PubMed and ScienceDirect. To find papers search terms “Post COVID-19”, “SARS-Cov-2”, “Sequelae” and “Adult”. The online search performed between December 2022 to April 2023. The results from the 14 journals used in this study consisted of 9 journals with cohort studies, 3 journals cross sectionals, 2 journals systematic reviews. Fatigue was the most common sequelae (71,4%), shortness of breath (64,1%), anxiety/depression (35,7%), memory and attention deficits (21,4%), myalgia/joint pain (21,4%), Smell/taste disorders (21,4%), hair loss (14,2%), and (7,1%) weakness legs, pain when breathing, cough, tiresness, headaches, problems seeing or blurred vision, hyperhidrosis, insomnia, sore throat, rhinitis, diarrhoea, ageusia, impaired pulmonary function, abnormal CT findings including pulmonary fibrosis, incurred greater risk of heart failure. There are many Sequelae in post COVID-19 sufferers, this will affect the target organs in the body. Fatigue is the most reported sequelae.

INTRODUCTION

Patients who recover from SARS-CoV-2 infection experience various systemic and organ-specific health problems, which can last a long time and persist or appear only after recovering from infection (Heidemann et al., 2023). Defines a post-COVID-19 condition as a condition characterized by symptoms that usually appear within three months of the onset of acute SARS-CoV-2 infection, last at least two months, and have no alternative diagnosis (Heidemann et al., 2023; Soriano et al., 2022). Post-COVID syndrome is a multisystem disorder that develops after an acute illness. Numerous studies of past respiratory virus pandemics have shown persistence of various symptoms after an acute episode, it means that the post-COVID syndrome is not a new entity (Afrin et al., 2020), consequences lasting for longer than three months after infection are currently referred to as “post-COVID-19 syndrome” or “Long Covid” (Martino et al., 2022).

Among other things, Fatigue, shortness of breath, and cognitive dysfunction are among the long COVID symptoms that are frequently mentioned (Soriano et al., 2022). Additionally, COVID has been around connected to restrictions on daily activities and a lower quality of life (Martino et al., 2022). Persistent pulmonary illness, one of the post-COVID-19 sequelae, has recently attracted attention due to the possible ramifications for morbidity and mortality (Lopez-Leon et al., 2021). Following COVID-19, several symptoms or clinical aftereffects have been described. Most patients describe bothersome symptoms such fatigue, dyspnoea, cognitive impairment, sleep disruptions, muscle discomfort, attention issues, and headache (van der Sar-van der Brugge et al., 2021). There is no clear evidence suggesting the exact pathogenesis for the development of chronic post-COVID illness. One study shows the role of mast cell activation in developing long-term symptoms (Menges et al., 2021).

Several studies have investigated respiratory consequences after acute COVID-19 illness, reported lung survival differently abnormalities or functional impairment in up to 70% of cases patients at different follow-up times (Shah et al., 2022; Wu et al., 2021). However, current data suggest that the post-COVID-19 syndrome occurs not only in those with severe illness requiring hospitalization or in older adults with comorbidities, but also in young and previously healthy individuals with mildly illness person (Davis et al., 2021; Logue et al., 2021; Willi et al., 2021).

Previous research has provided a lot of insight into the symptoms of COVID-19 positive patients and following the recovery of COVID-19 cases, especially in countries serious case. However, systematic review of COVID-19 based on residual symptoms or sequelae after the patient is declared cured and symptoms persist in adults with long-term COVID-19 disease is still rare (Eiros et al., 2022). In this systematic review, we identify and summarize the original articles published data on the December 2022. Focus on historical data healthy adult people. Children and elderly exception.

METHODS

Using information from a literature search, A systemic search of published was performed in the databases PubMed and ELSEVIER (ScienceDirect). English literature course is offered. To find papers search terms include “Post COVID-19”, “SARS-Cov-2”, “Sequelae” and “Adult”. The online search performed between December 2022 to April 2023. A study that Discusses literature must full access. References found through systematic search will be included to Mendeley, a reference management tool. After the first deletion duplicates, reference files created and uploaded, Covidence online tools, non-profit screening, and support services systematic review process. Authority to resolve including children (under 18 years) or elderly people only (60) age and older) are not included. The purpose of this system review is focus on young people aged between 18 and 60, as they constitute most of the adult population. Other systematic reviews have looked at COVID-19 sequelae in the adult 18 and before 60 years. The study period including follow-up after recovery to normal and/or discharge from hospital. Animal, laboratory, or in vitro studies have been excluded. This paper focuses on sequelae in previously healthy individuals (Figure 1).

Figure 1. PRISMA Flow Diagram

RESULT

A total of 1085 references were retrieved during the search and imported into Mendeley where 358 duplicates were removed. Leaving 727 references for title and abstract screening. A total of 727 references were deemed irrelevant during the title and abstract screening 544 record exclude. Of the remaining 14 references, 12 references containing original data were finally included during the full text review (Supplement 1).

The results obtained from the 14 articles used in this study consisted of 9 articles with cohort studies, 3 articles with cross sectionals, 2 articles with systematic reviews. The most residual symptom reported in post-COVID-19 patients who have been declared cured is fatigue. 10 of 14 articles stated that fatigue was the most common sequelae in COVID-19 patients after recovery, namely fatigue (36.9% vs. 26.1%, 1.76) (Heidemann et al., 2023). Another study reported 233 (55%) participants reported symptoms of fatigue At six to eight months after COVID-19 recovery (Logue et al., 2021). The most common post-COVID-19 sequelae in the respiratory system was shortness of breath (23.0% vs. 9.5%, 3.46) (Afrin et al., 2020; Heidemann et al., 2023), and the 9 out of 14 studies reporting sequelae of COVID-19 were shortness of breath. 5 of 14 studies reported anxiety or depression, 3 of 14 studies reported memory and attention deficits, 3 of 14 studies reported myalgia/joint pain, 3 of 14 studies reported Smell/taste disorders, 2 of 14 studies reported hair loss and 1 of 14 studies reported weakness in legs, pain when breathing, cough, tiredness, headaches and problems seeing or blurred vision, hyperhidrosis, insomnia, sore throat, rhinitis, diarrhoea, ageusia, impaired pulmonary function, abnormal CT findings including pulmonary fibrosis, incurred greater risk of heart failure.

DISCUSSION

Some patients, regardless of disease severity, continue to have symptoms weeks and months after the onset of COVID-19 (Baig, 2021). Try to distinguish between “post-acute COVID-19” and “chronic COVID-19”, which can last more than 3 weeks and 12 weeks respectively after the first symptoms appear. We chose the term post-Covid syndrome instead of post-acute COVID-19 syndrome because symptoms persist for more than three months (Moldofsky & Patcai, 2011). SARS-CoV-2 can infect lung, heart, liver and kidney tissues, gastrointestinal mucosa, vascular endothelium, macrophages, T cells, and neurons. Therefore, in each affected organ, whether directly or indirectly, there is a possibility of persistent damage with specific sequelae. WHO recommends a recovery time of up to two weeks for mild illness and up to six weeks for severe illness (Eiros et al., 2022). Those with comorbidities reported post-COVID complications such as mobility problems, pain, anxiety, and depression, as well as more significant signs of dementia. In post-COVID-19 syndrome studies, relatively high rates of fatigue, dyspnoea, or physical intolerance, and psychological symptoms have been consistently documented in all studies (Logue et al., 2021). A longitudinal cohort consisting of 91% of participants with mild disease detected persistent symptoms in 33% of outpatients and 31% of hospitalized patients (Sudre et al., 2021). Studies with shorter follow-up (?2 months) reported higher frequency of acute symptoms such as cough, fever, and acute gastrointestinal symptoms, which might indicate persistent infection, 17–20 whereas studies with follow-up beyond 3 months reported fatigue, shortness of breath, and musculoskeletal symptoms more frequently (Mclaughlin et al., 2023).

The range of symptoms reported include those which may be related to direct lung damage, such as breathlessness, and those for which an underlying pathophysiological mechanism may be less clear such as fatigue, muscle pain and cognitive complaints. The latter group are also features of other post infectious syndromes and post intensive care syndrome, and may have a similar aetiology, such as infection triggered autoimmunity, dysautonomia or other mechanism (Davis et al., 2021) or some individuals, COVID-19 can cause symptoms that last for weeks or months after the infection has gone. Post-COVID conditions are being seen in a growing number of patients reporting a constellation of symptoms after SARS-CoV-2 infection that are persistent, debilitating, and have yet to be fully explained by known or measurable mechanisms (Todt et al., 2021). At 3 months, more than a quarter of our cohort reported feeling persistently more breathless than before the onset of COVID-19 symptoms. Previous studies had already identified dyspnoea as a frequent symptom among patients recovering from COVID-19 up to 6 months following hospital discharge (Badinlou et al., 2023).

There is evidence of chronic fatigue as a long-term consequence, particularly in people under 30 years of age, following outbreaks of influenza A (H1N1), SARS-CoV, Ebola virus and West Nile virus. In some of these cases, the diagnostic criteria for chronic fatigue syndrome were met (Eiros et al., 2022). Fatigue has been identified as one of the most common symptoms of post-COVID syndrome and among survivors of the 2003 SARS-CoV-1 pandemic (Afrin et al., 2020). The term “myalgic encephalomyelitis” is used to describe a broad-spectrum condition with symptoms such as fatigue, post exertional malaise, sleep disturbances, cognitive impairment, and non-provoked pain that persist for more than 6 months with substantial intensity and not completely explained by a medical condition (Lopez-Leon et al., 2021; Martino et al., 2022). It is a heterogeneous, multifactorial etiology involving immune, virologic, psychological, musculoskeletal, and endocrine factors. Nutritional deficiencies could be a major challenge in some patients who have poor oral intake due to debility, lack of taste and smell, and medication side-effects, leading to negative protein balance and a lack of nutrients essential to proper musculoskeletal functioning. These factors are augmented in the elderly with previously existing chronic health issues. Persistent low-grade neuroinflammation in a vulnerable population is a potential cause of chronic fatigue (Boddu et al., 2020).

Misinformation about inflammatory response pathways, particularly in the cytokine network, may be the underlying cause (Eiros et al., 2022). Findings regarding longer-term sequalae are similar to those from prior coronavirus outbreaks, with 40% of severe acute respiratory syndrome (SARS) survivors reporting chronic fatigue up to four years after infection. Similar chronic symptoms, in particular. fatigue, have been also described in other viral (e.g. Ebola virus, Epstein-Barr virus, Dengue virus), and bacterial (e.g. Borrelia burgdorferi) infections (Logue et al., 2021). Fatigue, persistent cough, exertional dyspnoea, and body discomfort or vertigo were seen in 28.3%, 2%, 6.7%, and 17.7% of cases, respectively, in our study. The underlying cause of fatigue is still largely unknown. Fatigue can be caused by changes in the immune system due to viral infections (Ackermann et al., 2020).

Post-COVID pathophysiologic changes that predispose to glucose intolerance are being actively investigated. Three prominent pathophysiologic mechanisms that have emerged relate to a heightened proinflammatory state, the role of angiotensin converting enzyme (ACE)-2 receptors, and pancreatic beta cell dysfunction (Boddu et al., 2020). As seen in the results section, abnormalities in pulmonary function were observed in the lung function examination (e.g. as decrease in aerobic capacity or reduction in diffusion capacity) as well as radiologically. Although many patients have fully recovered or are in the process of radiological and/or clinical recovery, it would not be surprising if residual pulmonary fibrosis persists. for a long time. This could also be a plausible explanation for why some patients experience shortness of breath even up to 12 weeks after admission (Eiros et al., 2022; Moldofsky & Patcai, 2011). The most frequently reported radiographic abnormalities at 6 and 12 months were opacities and reticular opacities. Although the proportion of patients with abnormalities is relatively high, a small number of lung parenchyma are often involved and, more importantly, abnormalities that are not suggestive of the fibrotic interstitial lung disease phenotype (Lopez-Leon et al., 2021).

Myocarditis, perimyocarditis and pericarditis were diagnosed as late as 11 weeks after symptom of infection onset (Mongioì et al., 2020). Our study revealed that 28.75% of patients, asymptomatic and symptomatic together, had a raised troponin level and it is assumed that this is owing to myocarditis, microangiopathy, myocardial infarction and cytokine storm (Kumar-M et al., 2020). Some authors believe that SARS-CoV-2 may cause long-term neurodegenerative diseases such as multiple sclerosis, Parkinson's disease, and narcolepsy in predisposed individuals (Mannan et al., 2021).

Nevertheless, research hypothesize a role of SARS-CoV-2 in pancreatic damage and subsequent development of diabetes, in hypothalamic-pituitary-adrenal axis dysfunction and adrenal insufficiency and in hypothalamic-pituitary-thyroid axis dysfunction with thyroid damage, as seen in SARS-CoV infection (Mannan et al., 2021). Endocrine perturbations stemming from pituitary malfunction, hypothyroidism or hypothalamic-pituitary-adrenal axis disruption might be potential components that delay or prevent post-COVID recovery (Greer et al., 2022; Lam et al., 2023). Additionally, there is emerging data that a scenario of insulinopenic hyperglycemia resembling type 1 diabetes (T1DM), possibly via immunologic pathways, might be associated with acute COVID-19 and its aftermath (Lam et al., 2023).

Elevated liver enzyme, alanine transaminase, was also found in 36.83 patients in this study, which is also consistent with many other review articles. SARS-CoV-2 has been shown to persist in the small intestine of 7 out of 14 people. Since the intestine is the largest lymphatic organ, virus particles remaining in the intestine can cause long-term effects (Rizvi et al., 2022).

A study have reported that respiratory failure caused by fibrosis, interstitial thickening and vascular abnormalities may still persist in COVID-19 survivors 12 months following their acute infections (Lopez-Leon et al., 2021). Despite the gradual improvement in pulmonary physiology and exercise capacity, persistent physiological and radiographic abnormalities may still persist 12 months beyond hospital discharge (Shah et al., 2022; van der Sar-van der Brugge et al., 2021; Wu et al., 2021).

Anosmia is a well-known symptom in COVID-19 patients which appears to be more common in women and improves with time. Anosmia’s pathophysiological mechanisms aren’t entirely known. Injury to the olfactory neuroepithelium is possible because SARS-CoV-2 accesses the nasal epithelium via the Angiotensin-converting enzyme-2 (ACE-2) receptor (Afrin et al., 2020). Impact of long COVID on daily activities, work and caring. Interestingly, both severity and frequency of neurological symptoms, including lack of attention, loss of smell, impaired sense of smell, loss of taste, impaired sense of taste, and loss of appetite, associated most strongly with negative mood. Previous research has found that a loss of taste and smell attributed to COVID-19 infection has strong detrimental impacts on psychological well-being and quality of life (Almas et al., 2022).

Persistent squeal lung injury can explain cough and respiratory difficulty. Detected shortness of breath and anosmia in the context of post-COVID syndrome may be attributed to SARS-CoV-2 path mechanism: vascular angiogenesis was observed at a higher frequency in the lungs of patients with COVID-19 when compared to individuals infected with influenza virus (Mowat & Agace, 2014). Hypertension, diabetes mellitus-II, chronic lung disease, and malignancies were the most common concomitant conditions before SARS-CoV-2 infection. They thus reflected the most common concomitant diseases in the general population (Afrin et al., 2020; Menges et al., 2021; Shah et al., 2022).

Post-COVID pathophysiologic changes that predispose to glucose intolerance are being actively investigated. Three important pathophysiological mechanisms have emerged involving increased inflammation, the role of angiotensin-converting enzyme (ACE)-2 receptors, and pancreatic beta-cell dysfunction (Afrin et al., 2020; Martino et al., 2022). The post-COVID pathophysiological changes that lead to glucose intolerance are under active investigation (Willi et al., 2021). Three prominent pathophysiologic mechanisms that have emerged relate to a heightened proinflammatory state, the role of angiotensin converting enzyme (ACE)-2 receptors, and pancreatic beta cell dysfunction (Sigfrid et al., 2021).

Like chronic fatigue syndrome, the etiology, and pathophysiology of neuropsychiatric symptoms in COVID-19 are multifactorial and unclear (Boddu et al., 2020). In a cohort of 355 patients in Bangladesh, and 143 patients in Italy, a cumulative 63% of the patients were screened positive in at least one of the domains evaluated for neuropsychiatric sequelae (depression, anxiety, insomnia, obsessive-compulsive disorders, etc.) Clinical depression and anxiety were reported in approximately 17% of patients following COVID-19 (Sigfrid et al., 2021; Sudre et al., 2021). Memory loss in the form of dementia and ageusia is also reported in a few studies, including cognitive impairment with or without fluctuations (Sigfrid et al., 2021).

In addition to highly complex health symptoms, organ-specific complications and the emergence of new chronic non-communicable diseases may be long-term consequences of SARS-CoV-2 infection, particularly in people with severe COVID-19 illness (van der Sar-van der Brugge et al., 2021; Wu et al., 2021).

CONCLUSIONS

Particular attention should be paid to residual multi-organ dysfunction, particularly persistent pulmonary impairment. function and inflammatory heart disease, as well as mental health and neurological sequelae including post-viral fatigue syndrome. There are many Sequelae in post COVID-19 sufferers, this will affect the target organs in the body. Fatigue is the most reported sequelae symptom.