An overview of post COVID sequelae

Introduction

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most devastating infectious disease in recent times. SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO) [1], that initially started from Wuhan, China, and spread extremely rapidly, making its way to over 180 countries around the world. SARS-CoV-2 is an enveloped beta-coronavirus. There are seven species of beta-coronaviruses can cause human infections. Three out of these seven human infections, namely severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 are potentially fatal [2]. The angiotensin-converting enzyme 2 (ACE2) receptor in human cells acts as the functional receptor for SARS-CoV-2, facilitating its entry into the cell and plays a critical role in COVID-19 pathogenesis [3]. ACE2 receptor is abundantly expressed on smooth muscle cells and endothelia in virtually all organs [4] (Table 1).

Epidemiology

COVID-19 has been confirmed in 0.29 billion (290,642,746) individuals worldwide, with over 254,583,687 (88%) recovered cases. By January 3, 2022, 98.2% (3,42,95,407) of COVID-19 patients in India had recovered and had been declared discharged [5]. This group accounts for a sizable portion of the population. Recovery from COVID-19 is a global concern, as growing evidence shows a wide range of sequelae in patients who have returned to microbiological normalization after infection by SARS-CoV-2. Although most patients recover completely within a few weeks, some cases, including those who had mild disease, continue to experience symptoms known as “long hauler” symptoms of COVID-19 or post‐COVID syndrome after their initial recovery [6]. Long-term consequences of COVID-19 are widely documented, although the relative frequency of specific symptoms and diagnoses has yet to be determined [7, 8]. Post-Covid syndrome has been defined by the National Institute for Health and Care Excellence guideline [9], as signs and symptoms that appear during or after an infection consistent with COVID-19, that last for more than 12 weeks, and are not explained by another diagnosis (as shown in Figure 1). Furthermore, the recommendation emphasizes that many persons with post-COVID syndrome suffer from nonspecific symptoms like physical exhaustion, a persistently high fever, and psychological issues. In addition to the aforementioned post COVID syndrome, evidence is mounting indicating COVID sequelae lasting more than three weeks from the onset of first symptoms, which are referred as post-acute COVID-19 [10]. The implications of infection are currently being investigated as this is a newly discovered virus. There is currently no well defined clinical classification for post-COVID-19 symptoms, nor are there any well-defined therapeutic management guidelines. As the numbers of people recovering from COVID-19 are increasing, it is critical to gain a better knowledge of the healthcare difficulties that they are likely to encounter. COVID-19 is now known to be a multi-organ disease with a wide range of symptoms. There are increasing reports of persistent and extended sequelae after acute COVID-19, similar to post-acute viral symptoms observed in survivors of previous virulent coronavirus outbreaks [11].

Figure 1:

Definition of long and acute COVID-19.

An observational cohort study conducted in 38 hospitals of United States looked at the outcomes on 1,250 patients that have recovered from COVID-19. 6.7% of patients died over the study period, while 15.1% required re-admission. There were 32.6% of patients who had chronic symptoms, with 18.9% having new or exacerbated symptoms. The most prevalent symptom was dyspnea while walking up the stairs (22.9%), followed by cough (15.4%) and prolonged loss of taste and/or smell (13.1%) [12]. Similar findings have been observed from European studies like in an Italian study, at a mean follow-up of 60 days following the onset of the first symptom, 87.4% of 143 patients discharged from hospital who recovered from acute COVID-19 (referred to as the post-acute COVID-19) reported persistence of symptoms. The most commonly reported symptoms were fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%), and chest pain (21.7%), with 55% of patients continuing to experience three or more symptoms. In this study, 44.1% of patients had a deterioration in quality of life, as judged by the EuroQol visual analogue scale [13]. Another European research study conducted in 150 non-critical COVID-19 survivors in France reported that symptoms persisted in two-thirds of those who were followed for 60 days, with one-third reporting feeling worse than at the outset of acute COVID-19 [14]. Other studies had comparable results, including surveys of 100 COVID-19 survivors in the United Kingdom at 4–8 weeks post-discharge [15] and 120 patients discharged from hospital in France at 100 days after admission [16]. At the time of follow-up, fatigue, dyspnea, and psychological discomfort, such as post-traumatic stress disorder (PTSD), anxiety, depression, and concentration and sleep irregularities, were reported by 30% or more of the study participants. Long-term effects of COVID-19 were assessed in a prospective cohort study from Wuhan, China, using a full in-person evaluation of 1,733 patients at 6 months from onset of symptom (hereby referred to as the post-acute COVID-19 Chinese study) [17]. At least one symptom was recorded by the vast majority of patients (76%). Fatigue/muscular weakness was the most commonly reported symptom (63%), followed by sleep difficulties (26%), and anxiety/depression (23%). Another study in China looked at the effects of COVID-19 on patients three months after hospital discharged. This was a questionnaire-based study that answered questions on five elements of COVID-19 survivors’ symptoms: overall symptoms, respiratory symptoms, cardiovascular symptoms, psychosocial symptoms, and specific symptoms. After three months of discharge, general symptoms were seen in 49% of patients. Among general symptoms, fatigue was seen in 28% of patients. Respiratory symptoms were seen in 39% of patients in which post-activity shortness of breath, and chest distress was seen in 21 and 14% patients, respectively. Cardiovascular symptoms were seen in 13% of patients, and 22.7% of patients reported psychosocial symptoms [18].

These studies provide preliminary data that can be used to identify people who are at high risk of acquiring post-acute COVID-19. The presence or persistence of symptoms (such as dyspnea, fatigue/muscular weakness, and PTSD) in the post-acute COVID-19 setting, as well as a decrease in health-related quality of life scores, pulmonary function abnormalities, and radiographic abnormalities, have all been linked to the severity of illness during acute COVID-19 (measured, for example, by admission to an intensive care unit (ICU) and/or the need for non-invasive and/or invasive mechanical ventilation) [11]. Furthermore, Halpin et al. [15] discovered additional links between pre-existing respiratory disease, higher BMI, older age, and Black, Asian, and minority ethnic (BAME) and dyspnea after 4–8 weeks of follow-up. The post-acute COVID-19 Chinese study demonstrated sex differences, with women more likely to experience tiredness and anxiety/depression at 6 months follow-up, similar to SARS survivors [17]. Other comorbidities are well-known risk factors of increased COVID-19 severity and mortality, such as diabetes, obesity, chronic cardiovascular or kidney disease, cancer, and organ transplantation, but their link with post-acute COVID-19 outcomes in people who have recovered is still unknown. According to one study, matched by propensity score, 10% of COVID-19 cases had one new sequela and 4% had more than one new sequela requiring medical care within a 4-month period commencing 21 days after diagnosis. Compared to the uninfected 2020 group, these rates were higher by 2.9 percent (1 sequela) and 2 percent (>1 sequela); rates were higher by 0.7 percent and 1 percent, respectively, compared to the viral lower respiratory tract illness group. When compared to the 2020 uninfected group, COVID-19 cases had the highest hazard ratios (HR>2.5) for interstitial lung disease, encephalopathy, respiratory failure, pulmonary hypertension, hypercoagulability (deep venous thrombosis, pulmonary embolism), congestive heart failure, arrhythmia, memory disorder, and stroke. HRs peaked in the first month but remained significantly elevated for up to six months, particularly for fatigue, sleep apnea, diabetes, and hypertension, which all increased with age [19, 20]. Although SARS-CoV-2 primarily affects the respiratory system, COVID-19 appears to be a multisystem infection with both overt and subtle health implications, according to many investigations and interim findings [21, 22].

Nonspecific symptoms

There are emerging evidences that a significant number of COVID-19 convalescents experienced weariness weeks after the acute illness has passed. Post-infectious weariness has been found in a variety of viral illnesses months and even years following recovery. Chronic fatigue has been reported as a long-term effect of influenza A(H1N1) virus, SARS-CoV, Ebolavirus, and West Nile virus outbreaks, particularly in those younger than 30 years old. The diagnostic criteria for Chronic Fatigue Syndrome were met in some of these patients. The fundamental cause could be a miscommunication in the inflammatory response pathways, particularly cytokine networks [22]. A COVID-19 infection has been linked to an increased risk of developing a variety of cancers. Following a COVID-19 infection, the mitogen-activated protein kinase and janus kinase/signal transducers and activators of transcription pathways would be activated, resulting in enhanced carcinogenesis, as well as a compromised immune system following a cytokine storm [23].

Otorhinolaryngological sequelae of COVID-19 infection

The olfactory system is thought to act as a viral sensor after infection with SARS-CoV-2, alerting medical personnel to the presence of the disease. A large number of participants reported olfactory and gustatory impairment that did not improve or improved only moderately. The olfactory bulbs are critical in removing invading pathogens from this entry-prone interface early and quickly. Viral clearance is thought to be both rapid and robust, preventing post-mortem detection of virions in patients who have had a long hospital stay and time to autopsy. According to Imam et al. [24], COVID-19-related olfactory dysfunction follows a similar path to post-viral olfactory dysfunction seen in other viral infections such as influenza, rhinovirus, metapneumovirus, or parainfluenza virus. As a result, these adverse effects may become less noticeable over time [24].

Respiratory sequelae of COVID-19 infection

Many patients experience chronic respiratory symptoms weeks to months after being diagnosed with COVID-19. Endothelial and epithelial damage produced by monocyte and neutrophil invasion resulting in acute respiratory distress syndrome (ARDS) is mediated by both viral-dependent and viral-independent processes. The most commonly documented physiologic abnormality in post-acute COVID-19 is a decrease in diffusion capacity, which is directly related to the severity of acute sickness. The persistence of ground-glass opacities is the most common high-resolution lung computed tomography (CT) finding in post-acute COVID-19. Dyspnea, cough, oxygen dependency, difficulties weaning from mechanical ventilation or non-invasive ventilation, fibrotic lung alterations, decreased diffusion capacity, and decreased endurance are common pulmonary sequelae in patients with post-acute COVID-19 syndrome. In post-acute COVID-19, dyspnea is the most common pulmonary symptom (40–50% prevalence at 100 days). Because of shortness of breath, the average 6-min walking distance was significantly lower than the usual reference after a 6-month follow-up. At the 60-day follow-up, about 6% of patients still require supplementary oxygen [12]. At a 30-day follow-up post-discharge, about half of tracheostomy patients were successfully weaned off, according to research from Spain [25]. At a 6-month follow-up, around half of the patients have at least one abnormal CT chest finding (ground-glass opacity, fibrotic alterations).

Pathophysiology

Both viral-dependent (such as SARS-CoV-2 invasion of alveolar epithelial and endothelial cells) and viral-independent (such as immunological damage, including perivascular inflammation) mechanisms contribute to the breakdown of the endothelial–epithelial barrier, with monocyte and neutrophil invasion and extravasation of a protein-rich exudate into the alveolar space, as seen in other forms of ARDS [26]. In the COVID-19 patient`s autopsy report, all phases of diffuse alveolar damage have been described, with organized and localised fibroproliferative diffuse alveolar damage seen later in the disease course, comparable with other ARDS etiologies [27–30]. Cytokines like interleukin-6 (IL-6) and transforming growth factor-β, which have been linked to the development of pulmonary fibrosis and may predispose to bacterial colonization and infection, may trigger this fibrotic condition [31–36]. The histopathologic and single-cell RNA expression patterns in lung tissue were similar to end-stage pulmonary fibrosis without ongoing SARS-CoV-2 infection, suggesting that some people experience accelerated lung fibrosis after the active illness is resolved [37]. COVID-19 patients exhibit pulmonary vascular micro-thrombosis and macro-thrombosis at a rate of 20–30%, which is significantly greater than other critically sick patient populations (1–10%) [11, 37, 38].

Hematologic sequelae

Compared to consumption coagulopathy from disseminated intravascular coagulation (DIC), acute COVID-19 related thromboembolism is secondary to the hyperinflammatory and hypercoagulable state. Thromboembolism is disproportionately high in acute COVID-19 due to hypoxia, endothelial damage, platelet activation, and proinflammatory cytokines. In the post-COVID-19 phase, both the duration and intensity of this hyper-inflammatory state contribute to the risk of thrombotic events [39].

Pathophysiology

COVID-19-associated coagulopathy, unlike consumption coagulopathy associated with disseminated intravascular coagulation, is associated with a hyperinflammatory and hypercoagulable condition [40, 41]. This could explain why acute COVID-19 has a disproportionately high rate of thrombotic rather than bleeding consequences (20–30%) [42]. Endothelial injury, complement activation, platelet activation and platelet–leukocyte interactions, neutrophil extracellular traps, release of pro-inflammatory cytokines, disruption of normal coagulant pathways, and hypoxia are all part of the pathophysiology of thrombo-inflammation, which is similar to the pathophysiology of thrombotic microangiopathy syndromes. The duration and intensity of a hyperinflammatory state are likely associated to the risk of thrombotic problems in the post-acute COVID-19 phase, however, how long this last is still not known [43–49].

Cardiovascular sequelae

Cardiovascular consequences have been documented in asymptomatic COVID-19 patients as well as symptomatic COVID-19 patients. In most persons with Long Covid, the most common symptom is extreme weariness. Other symptoms in patients with cardiac sequelae include chest pain, dyspnea, and palpitations, to name a few. Up to 20–30% of patients with severe COVID-19 who are admitted to the hospital have cardiac involvement, as evidenced by high troponin levels, venous thromboembolism, heart failure, and arrhythmias. Troponin levels beyond a certain threshold have been linked to poor outcomes and greater in-hospital mortality in acutely symptomatic individuals. Increased cardiometabolic demands, myocardial fibrosis or scarring, chronic left ventricular dysfunction, heart failure, arrhythmias, inappropriate sinus tachycardia, and autonomic dysfunctions are all long-term consequences. At the 60 day follow-up, 20% of COVID-19 survivors complained chest pain. At the 60 day follow-up, 10% of COVID-19 survivors experienced palpitations. At six months after receiving COVID-19, 5 and 9% of patients experienced ongoing chest discomfort and palpitations, respectively. In one study, myocardial inflammation observed on cardiac MRI was found in up to 60% of patients more than 2 months following diagnosis. According to retrospective research, the risk of venous thromboembolism in the post-acute COVID-19 context is around 5%. The vast majority of patients with asymptomatic/mild COVID-19, on the other hand, do not have any significant consequences [50].

Pathophysiology

Direct viral invasion, downregulation of ACE-2, inflammation, and the immune response all impact the structural integrity of the myocardial, pericardium, and conduction system, prolonging cardiovascular sequelae in post-acute COVID-19. In 39 cases of COVID-19, autopsy examinations revealed virus in the cardiac tissue of 62.5% of victims [51]. The inflammatory response that follows may result in cardiomyocyte mortality and fibro-fatty displacement of desmosomal proteins that are required for cell-to-cell adhesion [52, 53]. As seen in long-term evaluations of SARS survivors, recovered patients have a continuously elevated cardiometabolic demand [54]. This may be linked to decreased cardiac reserve, corticosteroid use, and renin–angiotensin–aldosterone system dysregulation (RAAS). Re-entrant arrhythmia can be caused by myocardial fibrosis or scarring, as well as cardiomyopathy caused by viral infection [55]. COVID-19 may potentially contribute to arrhythmias by increasing catecholamine levels in response to cytokines such IL-6, IL-1, and tumour necrosis factor-b, which can prolong ventricular action potentials by regulating cardiomyocyte ion channel expression [56]. Adrenergic modulation has previously been linked to autonomic dysfunction during viral infection, resulting in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia [57]. Endomyocardial biopsy immunohistochemistry revealed significant intramyocardial inflammation with an increase in perforin-positive cells. The number of macrophages, T lymphocytes, and CD45R0 T memory cells have been found to be increased. The amount of cell adhesion molecules (CAM) such as CD 54/ICAM-1 have also seen to be increased [58].

Neuropsychiatric sequelae

The most common symptoms observed in people infected with post acute COVID are headache, anosmia, and myalgia. SARS-CoV-2 infection can damage the central nervous system and cause demyelinating lesions in the spine, which can lead to neuropsychiatric symptoms in the cognitive, emotional, behavioural, and perceptual domains. These neuropsychiatric symptoms, which include cerebrovascular, mental, and neuromuscular diseases, are common in elderly patients and those who have numerous comorbidities or are suffering from a severe illness. During the acute phase, both SARS and MERS are linked to delirium, depression, anxiety, memory loss, and sleeplessness. During the post-illness period, depression, sleeplessness, anxiety, memory loss, and sleep difficulties are common. Dementia, agitation, altered consciousness, and other neuropsychiatric symptoms, such as encephalopathy, encephalitis, depression, anxiety, and post-traumatic stress disorder, affect a large number of COVID-19 patients [59].

Pathophysiology

Direct viral infection, severe systemic inflammation, neuroinflammation, microvascular thrombosis, and neurodegeneration are some of the mechanisms that contribute to neuropathology in COVID-19 [60–62]. SARS-CoV-2 has been found to cause alterations in the brain parenchyma and arteries, potentially as a result of impacts on the blood–brain and blood–cerebrospinal fluid barriers, which drive inflammation in neurons, supporting cells, and the brain vasculature [63–65]. Furthermore, immunological activation levels are linked to cognitive and behavioural changes [66]. Inflammation (chronic low-level brain inflammation), together with a decreased ability to respond to novel antigens and an accumulation of memory T cells (hallmarks of immunosenescence in ageing and tissue injury, respectively) [67], may play a role in COVID-19’s long-term effects. Other theories include faulty lymphatic outflow from circumventricular organs, viral invasion in olfactory epithelial extracellular spaces, and passive diffusion and axonal transport across the olfactory complex. In patients with COVID-19, biomarkers of brain injury, such as higher neurofilament light chain levels in the peripheral blood, have been discovered, along with a more sustained increase in severe infections, implying the likelihood of more chronic neuronal impairment [68–71]. Deconditioning or Post-traumatic stress disorder (PTSD) may play a role in the development of post-COVID brain fog in critically ill COVID-19 patients. COVID-19 brain fog after mild COVID-19, on the other hand, suggests that dysautonomia may play a role. Finally, in the post-critical illness context, long-term cognitive impairment is well established, occurring in 20–40% of patients discharged from an ICU [72, 73].

Renal sequelae

Electrolyte disruption (especially hyperkalaemia) was the most common renal consequence, with a 12.5% incidence, followed by acute kidney injury (AKI) with an 11% incidence. AKI (adjusted hazard ratio (aHR), 1.94; 95% CI, 1.86–2.04), estimated glomerular filtration rate (eGFR) reduction 305 (aHR, 1.25; 955 CI, 1.14–1.37), eGFR decline 40% (aHR, 1.44; 95% CI, 1.37–1.51), eGFR decline 50% (aHR, 1.62; 95% CI, 1.51–1.74), end stage kidney disease (aHR, 2.96; 95% CI, 2.49) to (aHR, 1.66; 95% CI, 1.58–1.74). During hospitalisation, a significant number (20%) of severe COVID-19 patients who required intubation also required renal replacement therapy (RRT). Near discharge, the majority of them did not require dialysis. AKI requiring renal replacement therapy (RRT) occurs in 5% of all hospitalised patients and 20–31% of critically sick patients with acute COVID-19, particularly those who require mechanical ventilation. According to longer-term follow-up studies, patients who require RRT for severe AKI have a high death rate, with a survival probability of 0.46 at 60 days and rates of renal recovery of 84 percent among survivors [74–77].

Pathophysiology

SARS-CoV-2 has been isolated from renal tissue, and the most common finding in cases of COVID-19 renal biopsies and autopsy is acute tubular necrosis. COVID-19-associated nephropathy (COVAN) is a kind of focal segmental glomerulosclerosis that includes involution of the glomerular tuft as well as acute tubular damage. It is considered to occur in response to interferon and chemokine activation. SARS-association CoV-2’s with apolipoprotein L1 risk alleles suggests that, like the human immunodeficiency virus and other viruses, it functions as a second hit in vulnerable patients. Renal microcirculation thrombosis may possibly play a role in the development of renal damage [78–85].

Endocrine sequelae

Post-acute COVID-19 endocrine symptoms are caused by viral infection, inflammatory, and immunologic damage. Weeks after resolving acute COVID-19 symptoms, isolated case reports of diabetic ketoacidosis (DKA), subacute, and Hashimoto thyroiditis or Graves’ disease have been reported. Immobilization, steroid use, and vitamin D insufficiency during COVID-19 healing may all play a role in bone demineralization [86, 87].

Pathophysiology

In the post-acute COVID-19 scenario, endocrine symptoms could be the result of direct viral damage, immunological and inflammatory injury, as well as iatrogenic sequelae. Even if initially linked with DKA, pre-existing diabetes may become obvious during the acute phase of COVID-19 and may normally be treated long term with medicines other than insulin. There is no evidence that pancreatic cells are permanently damaged. Although some studies have found ACE2 and transmembrane serine protease (TMPRSS2; the protease involved in SARS-CoV-2 cell entry) expression in cells, the primary insulin production deficit is most likely mediated by inflammation or the infection stress response, as well as peripheral insulin resistance. There is currently no indication that COVID-19-related diabetes can be reversed after the acute phase, nor that the outcomes differ in COVID-19 long haulers. COVID-19 also shows that systemic inflammation, immobility, corticosteroid exposure, vitamin D deficiency, and cessation of antiresorptive or anabolic medications for osteoporosis are all risk factors for bone demineralization [88–90].

Gastrointestinal and hepatobiliary sequelae

In COVID-19 survivors, no significant gastrointestinal or hepatobiliary effects have been documented. COVID-19 exhibits prolonged viral faecal shedding, with viral ribonucleic acid detectable for an average of 28 days after the onset of SARS-CoV-2 infection symptoms and for an average of 11 days following negative respiratory samples [91–93]. COVID-19 has the potential to change the gut microbiota, favouring opportunistic infectious microbes while reducing beneficial commensals [94, 95]. The gut microbiota’s ability to influence the course of respiratory infections (gut–lung axis) has previously been observed in influenza and other respiratory diseases. Faecalibacterium prausnitzii, a butyrate-producing anaerobe associated with excellent health, was found to be inversely related to disease severity in COVID-19. COVID-19’s long-term effects on the gastrointestinal system, particularly post-infectious irritable bowel syndrome and dyspepsia, are now being studied [96–98].

Dermatologic sequelae

In an international investigation of 716 people with COVID-19, dermatologic manifestations of COVID-19 appeared after (64%) or concurrently with (15%) other acute COVID-19 symptoms, with an average latency of 7.9 days in adults from the time of upper respiratory symptoms to dermatologic findings. In the post-acute COVID-19 Chinese trial, only 3% of patients had a skin rash after 6 months. Hair loss was the most common dermatologic symptom, affecting roughly 20% of patients. Hair loss may be caused by telogen effluvium, which is caused by a viral infection or a stress response. Ongoing research could shed light on illness pathways involving the immune system or inflammation [99–101].

Multisystem inflammatory syndrome in children (MIS-C)

MIS-C is a new clinical entity defined by fever, multiorgan dysfunction, and elevated inflammatory markers in people under the age of 21 years who have recently or currently been infected with SARS-CoV-2. Complement activation, the production of autoantibodies (viral host mimicry), and excessive cytokines from T-cell stimulation are the most likely underlying mechanisms [102].

Pathology and pathophysiology

The emergence of MIS-C (which occurred about a month after peak COVID-19) and the fact that most patients are negative for acute infection but positive for antibodies suggest that MIS-C is the result of an abnormal acquired immune response rather than acute viral infection. Kawasaki disease and toxic shock syndrome may provide insights into the pathophysiology of MIS-C, with possible injury mechanisms related to immune complexes, complement activation, autoantibody formation through viral host mimicry, and massive cytokine release related to superantigen stimulation of T cells [102–104].

Reproductive system

Because the human testis expresses ACE2, an infection could result in potential testicular injury and male infertility [105, 106].

Nutrition and rehabilitation considerations

Like other critical illnesses, severe COVID-19 illness induces catabolic muscle loss, feeding difficulties, and fragility, all of which are linked to a higher risk of poor outcome. Malnutrition was found in 26–45% of COVID-19 patients in an Italian study using the Malnutrition Universal Screening Tool. Nutritional support protocols for patients (many of whom had respiratory discomfort, nausea, diarrhoea, and anorexia, resulting in a drop in food intake) are still being developed. All post-acute COVID-19 follow-up studies that included assessments of health-related quality of life and functional capacity measures, including the post-acute COVID-19 Chinese research, found severe deficits in these categories. Early rehabilitation therapies are being examined in ongoing clinical research due to the severity of the systemic inflammatory response associated with severe COVID-19 and the resulting weakness. They’ve been shown to be both safe and efficacious in critically ill patients with ARDS, as well as in preliminary COVID-19 investigations. Acute COVID-19 survivors require frequent assessment of swallowing function, nutritional condition, and functional independence in model COVID-19 rehabilitation units like those in Italy [11, 107–111].

Conclusion

Despite the fact that most immediate COVID-19 consequences in young, previously healthy adults are temporary, there are signs of long-term multi-organ involvement. The huge global burden of cases suggests that COVID-19 sequelae will most likely be a problem. Residual deficits in multi-organ function as well as mental health and neurological sequelae, such as post-viral fatigue syndrome, should be closely monitored. Further research to detect long-term structural and functional damage is need of the hour. Patients with post-viral fatigue syndrome and mental health issues could be followed up on a regular basis using questionnaires to track their progress. In general, follow-up study test batteries should be carefully constructed to detect subtle, long-term effects. Given the pandemic’s global scope, it’s clear that the healthcare demands of people suffering from COVID-19 complications will continue to rise for the foreseeable future. To meet this issue, current outpatient infrastructure will be leveraged, scalable healthcare models will be developed, and cross-disciplinary collaboration will be required for long-term mental and physical health of COVID-19 survivors.