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        "titulo" => "Consecuencias cl&#237;nicas&#44; radiol&#243;gicas y funcionales a corto y largo plazo de la COVID-19"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Acute&#44; short- and long-term effects of COVID-19 on multiple organ systems&#46; Clinical manifestations a patient might experience at a specific stage of COVID-19&#46; eGFR&#58; estimated glomerular filtration rate&#59; PTSD&#58; post-traumatic stress disorder&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Coronavirus disease of 2019 &#40;COVID-19&#41; has strained the medical infrastructure&#44; personnel and resources worldwide&#46; The burden continues to increase amid the emergence of new variants and the progressively waning immunity after global vaccine roll-out&#46; According to the latest statistics&#44; the total number of laboratory-confirmed cases of COVID-19 has exceeded 0&#46;4 billion globally&#44;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">1</span></a> despite the dramatically improved rate of survival&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although a certain number of patients ultimately developed severe or critical illness&#44; symptoms gradually resolved among most patients at convalescence&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#8211;4</span></a> The number of patients who recover from COVID-19 will continue to increase considerably in the next foreseeable future&#46; This constitutes a pressing need for caring a massive population which has not been fully characterized previously&#46; Not all patients achieved complete remission of symptoms&#44; radiologic findings and pulmonary function despite a prolonged convalescence phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;3&#44;5&#8211;11</span></a> The consequences contributed to the ongoing suffering from physiologic dysfunction and the impaired quality-of-life which markedly dampened the overall well-being&#46; Given the overwhelming tasks of disease prevention and control&#44; global research efforts have characterized the clinical presentations at disease onset or during hospital admission&#44; to identify the prognostic factors and disease phenotypes&#44; to design and validate rapid diagnostic tests&#44; and to verify the effects of therapeutic interventions and vaccines&#46; Recent studies have documented the manifestations of consequences which ranged from respiratory to systemic &#40;including psychological&#41; disorders&#44;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">12</span></a> with the follow-up duration ranging from 3&#160;months to 1&#160;year&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#8211;5&#44;10&#44;11&#44;13&#8211;17</span></a> In light of the variable study designs and research focus&#44; there remains a considerable knowledge gap in the understanding of the magnitude and heterogeneity of the consequences of COVID-19&#44; particularly in the era when the medical focus has been shifted from the diagnosis and treatment to the rehabilitation&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Exploring the spectrum of consequences among patients recovered from COVID-19 might help characterize the residual disease burden and identify the major predictors of adverse outcomes&#44; which have important implications to the early diagnosis and accelerate the development of novel interventions&#46; Here&#44; we review the major manifestations of short- and long-term consequences&#44; highlighting the clinical characteristics and predictors of having any consequences&#46; We also summarize the latest clinical interventions and elaborate the important future research directions&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical characteristics at acute phase</span><p id="par0020" class="elsevierStylePara elsevierViewall">Airborne droplets or virus-laden materials were the dominant sources of infection&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">18</span></a> After acquisition of virus&#44; common symptoms which consisted of fever&#44; cough&#44; fatigue&#44; dyspnea&#44; sore throat and headache typically occurred after the median incubation period of 4&#160;days&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> However&#44;<span class="elsevierStyleHsp" style=""></span>&#62;50&#37; of patients remained afebrile on hospital admissions and developed fever thereafter&#46; Gastrointestinal symptoms&#44; such as loss of appetite&#44; nausea and vomiting&#44; were less common as compared with those in patients with avian influenza&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">20</span></a> Neurological manifestations &#40;e&#46;g&#46;&#44; myalgia&#44; encephalopathy&#44; dysgeusia and anosmia&#41; were specific to aid in the diagnosis although appearing less common&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">21</span></a> Few patients developed autoimmune disorders&#44; including haemolytic anemia&#44;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">22</span></a> immune thrombocytopenia&#44;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">23</span></a> Guillain-Barre syndrome&#44;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">24</span></a> and Kawasaki disease-like syndrome in children&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">25</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">On laboratory examination&#44; the most common manifestations consisted of lymphopenia&#44; elevated C-reactive protein and elevated liver enzymes&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> These manifestations have important clinical implications for prognosis&#46; Lymphopenia &#40;seen in &#8764;85&#37; of patients&#41;&#44; has been associated with the risk of progression to critical illness and death&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> Several radiologic manifestations on chest X-ray or computed tomography &#40;CT&#41;&#44; such as ground-glass opacity&#44; pulmonary infiltration&#44; and consolidation usually developed at later stages of progression&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">26</span></a> The radiologic abnormality&#44; albeit rapidly evolving during progression&#44;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">26</span></a> could be readily detected at early stages among most patients and continued to persist&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> Lung function findings regarding airflow limitation and lung volumes were usually unremarkable&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">27</span></a> By contrast&#44; diffusing capacity impairment and reduced exercise tolerance were more specific to reflect functional impairment of COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">The path of disease progression</span><p id="par0030" class="elsevierStylePara elsevierViewall">Although approximately 85&#37; of patients developed mild diseases&#44;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> the risk of progression to critical illness &#40;e&#46;g&#46;&#44; severe pneumonia&#44; acute respiratory distress syndrome&#44; sepsis&#44; multisystem organ failure&#41; or death among the remaining patients could not be underestimated&#46; Older age&#44; greater symptom burdens&#44; severe hypoxemia&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">29</span></a> and comorbidities &#40;e&#46;g&#46;&#44; hypertension&#44; diabetes&#44; heart disease&#44; chronic obstructive pulmonary disease&#41; have been associated with a worse outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">30</span></a> Furthermore&#44; certain chest radiologic<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">31</span></a> and laboratory parameters &#40;e&#46;g&#46;&#44; decreased CD3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#44; CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#44; and CD8<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T cell count&#44; higher neutrophil-to-lymphocyte and neutrophil-to-CD8<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T cell ratio&#41; might provide prognostic implications&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">32</span></a> Prevention of progression to critical illness or death has been the core mission of the clinical management&#44; because the severity of illness correlated negatively with the likelihood of&#44; and the time needed for&#44; clinical recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Short- and long-term consequences</span><p id="par0035" class="elsevierStylePara elsevierViewall">Although the symptoms or signs of COVID-19 ultimately resolved among the majority of patients&#44; some suffered from persistent or new-onset symptoms and conditions which have been described as &#8220;long COVID&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">34</span></a> The definition is continuously evolving&#44; although a new consensus definition for &#8220;post COVID-19 condition&#8221; has recently been proposed&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">35</span></a> A commonly accepted concept refers long COVID to the symptoms that continue or develop after acute COVID-19 infection which cannot be explained by an alternative diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">36</span></a> However&#44; this could be seen in many COVID-19 survivors<span class="elsevierStyleHsp" style=""></span>&#62;6 months after recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">37</span></a> Thus&#44; we summarize the short- &#40;4 to 12 weeks after disease onset&#41; and long-term &#40;12 weeks to 1&#160;year or longer&#41; consequences of COVID-19 according to the ongoing symptomatic and post COVID-19 syndrome stages below&#44; as proposed by the UK National Institute for Health and Care Excellence guideline&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">36</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Short-term consequences</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Symptoms and signs&#58;</span> At 4-12 weeks after the initial symptom onset&#44; a considerable proportion of patients reported residual symptoms such as cough &#40;2&#37;-40&#46;3&#37;&#41;&#44; dyspnea &#40;5&#46;5&#37;-91&#46;5&#37;&#41;&#44; chest pain &#40;0&#46;2&#37;-42&#37;&#41;&#44; sputum production &#40;&#60;10&#37;&#41;&#44; cognitive impairment &#40;17&#37;-28&#46;3&#37;&#41;&#44; and fatigue &#40;17&#37;-84&#46;8&#37;&#41;&#44; while fever might persist for a couple of weeks without secondary infection &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">37&#8211;40</span></a> Over 60&#37; of patients reported amelioration of olfactory and&#47;or gustatory dysfunction within the first 2&#160;months &#40;with the percentage decreasing to 40&#37; and 20&#37;&#44; respectively&#41;&#44; followed by a slower rate of recovery thereafter&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">41</span></a> Psychological disorders &#40;e&#46;g&#46;&#44; post-traumatic stress disorder &#91;PTSD&#93;&#41; occurred in 24&#46;5&#37; of survivors at 1&#160;month after discharge and in 22&#46;4&#37; of patients at 3&#160;month follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">42</span></a> Insomnia&#44; anxiety and depression could still be identified at 3&#160;months&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">42</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chest radiologic findings&#58;</span> Chest radiologic abnormalities could be identified in<span class="elsevierStyleHsp" style=""></span>&#62;75&#37; of patients at initial presentation<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> and could persist at convalescence&#46; Ground-glass opacification &#40;GGO&#41; was highly prevalent at discharge &#40;99&#46;5&#37;&#41; but was only detected among 37&#46;3&#37; of patients at 3 months&#46; However&#44; consolidation and crazy-paving pattern might have resolved at hospital discharge&#46; At 1 month after discharge&#44; GGO &#40;42&#46;4&#37;&#44; 37&#46;5&#37;&#41; and reticular pattern &#40;22&#46;0&#37;&#44; 47&#46;5&#37;&#41; were most common in patients with mild and severe COVID-19&#46; These figures decreased to 29&#46;7&#37; and 28&#46;3&#37; for GGO and 13&#46;0&#37; and 36&#46;7&#37; for reticular patterns at 3&#160;months&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">43</span></a> By contrast&#44; parenchymal bands&#44; thickening of adjacent pleura and reticular lesions persisted in 34&#46;4&#37;&#44; 13&#46;9&#37;&#44; and 14&#46;8&#37; of patients at 3&#160;months&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">44</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Lung function abnormality&#58;</span> Although occurring in a small proportion of patients during acute phase&#44; pulmonary function remained abnormal in the early post-acute phase especially in patients with severe COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0765"><span class="elsevierStyleSup">45&#44;46</span></a> Reduced diffusing capacity&#44; seen in 10-20&#37; of patients at presentation&#44; could substantially improve at 3 month in patients with severe COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0770"><span class="elsevierStyleSup">46&#8211;48</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Systemic complications&#58;</span> COVID-19 conferred notable adverse impacts on multiple organ systems&#44; whose function was progressively normalized in the short term&#46; Cardiovascular complications included myocarditis&#44; myocardial infarction&#44; heart failure&#44; cardiogenic shock and arrhythmia&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">49</span></a> COVID-19 appeared to be associated with persistent cardiac injury after recovery&#44; particularly subclinical myocardial injury in the short term and diastolic dysfunction in the long term&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">50</span></a> Despite the high incidence at acute phase&#44;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> acute kidney injury could be generally resolved within 3 weeks without renal replacement therapy among patients with non-severe COVID-19&#59;<a class="elsevierStyleCrossRefs" href="#bib0795"><span class="elsevierStyleSup">51&#44;52</span></a> new-onset chronic kidney disease was unusual but could relapse after discharge&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">3&#44;53</span></a> Acute liver injury or hepatitis occurred in few patients only and resolved during the acute phase among patients with non-critical illness&#44; with minor impacts on long-term outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0690"><span class="elsevierStyleSup">30&#44;54&#44;55</span></a> Thyroid function might be impaired at acute phase in approximately 13&#46;5&#37; of patients and could be normalized within 2 months&#46;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">56</span></a> Hypercoagulability &#40;e&#46;g&#46;&#44; venous and arterial thromboses&#41; was common at acute phase&#44; especially in patients with severe or critical illness&#44;<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">57</span></a> but the incidence of venous thromboembolism fell to below 5&#37; in the post-acute phase&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">38</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Short-term mortality&#58;</span> Although most patients with COVID-19 had asymptomatic or mild-to-moderate illnesses&#44; findings from the initial outbreak indicated the fatality rate of approximately 1&#46;4&#37; in mainland China&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">19</span></a> Findings from Spain have also lent support to these earlier observations&#46; In a multicenter Spanish cohort of 12&#44;126 patients&#44; the mortality rate was 12&#46;5&#37; for non-hospitalized patients&#44; 29&#46;8&#37; in hospitalized patients and 38&#46;8&#37; in patients admitted to the intensive care unit&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">58</span></a> The key predictors of short-term mortality consisted of the age over 50&#44; obesity&#44; cardiac diseases&#44; fever&#44; dyspnea&#44; lung infiltration&#44; lymphopenia&#44; D-dimer levels above 1000 ng&#47;mL&#44; and requirement of mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">58</span></a> When taking into account the impact of the underlying diseases&#44; in particular the chronic respiratory diseases&#44; another multicenter Spanish cohort study of 5847 hospitalized patients with COVID-19 revealed a significantly higher 30-day mortality rate in patients with prior lung diseases than those without &#40;29&#46;5&#37; vs&#46; 17&#46;9&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">59</span></a> The study also revealed a more impressive 30-day mortality rate &#40;approximately 40&#37;&#41; in patients with pre-existing COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">59</span></a> Both studies&#44; however&#44; concurred that a greater age and higher D-dimer levels were associated with a significantly elevated risk of short-term death&#46;<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">58&#44;59</span></a> Patients aged greater than 60 years were at a particularly high risk of death at the short term&#44; with the overall in-hospital mortality rate of 23&#46;5&#37; in a retrospective single-center study in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">60</span></a> Among these elderly patients&#44; those with malignancy&#44; chronic liver diseases&#44; obesity and diabetes had an increased mortality risk despite the adjustment with the age&#46;<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">62</span></a> These studies have provided the scientific rationale for rapid identification of patients at risk of death and the implementation of more intensive therapeutic management&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Medium- to long-term consequences</span><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Symptoms and signs&#58;</span> At week 12 and thereafter&#44; symptoms or signs progressively waned but could still fluctuate over time&#46; Some patients reported residual symptoms for up to 6 months or longer&#44; especially those with severe COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">3&#44;61</span></a> Cough lasted for 6&#160;months or longer in 20&#37; of patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">62</span></a> which might be associated with pulmonary fibrotic changes&#46;<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">63</span></a> Breathlessness could persist for up to 1&#160;year&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">2</span></a> Chest pain or tightness was reported in approximately 15&#46;8&#37; of patients over 1 year&#46;<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">64</span></a> Systemic symptoms such as fatigue persisted for 12 months among 10-60&#46;8&#37; of patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;58&#44;64&#8211;68</span></a> which might be associated with the accentuated systemic inflammatory response and psychological disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">68</span></a> Persistent taste and smell disorders have been reported at 6 months &#40;7&#37; and 11&#37;&#44; respectively&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">3</span></a> although recovered progressively thereafter&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">2</span></a> Albeit less commonly reported&#44; arthralgia and myalgia could persist for over 6 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;69&#8211;71</span></a> Hair loss was reported in<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37; of patients at 6 months while decreased to 11&#37; at 1 year&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">2</span></a> Neurological disorders &#40;e&#46;g&#46; sleep disorder&#44; headache&#44; dizziness&#41; persisted with minor improvement for 1&#160;year&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;62&#44;71</span></a> Noticeably&#44; 27&#37; of patients suffered from sleep disorder at 6&#160;months and 17&#37; still had insomnia at 1&#160;year&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">2</span></a> Cognitive impairment was reported to be persistent&#44; the magnitude of which fluctuated from 4 months to 1 year&#44; and was more prevalent in patients with severe COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">62&#44;72&#8211;75</span></a> COVID-19 imposed a considerable burden on psychology&#46; More than 20&#37; of patients suffered from PTSD at 1 year or longer&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">76</span></a> Anxiety and&#47;or depression was reported in approximately 23&#37; of patients at 6&#160;months and 26&#37; at 12&#160;months&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;62&#44;76</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Chest radiologic findings&#58;</span> During recovery&#44; GGO and interstitial fibrotic changes remained common&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;44&#44;53</span></a> More than 60&#37; of patients with mild or moderate COVID-19 ultimately had resolved radiologic abnormalities&#46; However&#44; GGO and fibrotic changes could persist while consolidation was rare on chest CT at 1 year follow-up&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;77</span></a> Furthermore&#44; the disease severity was associated with the magnitude of chest CT manifestations&#46; At 3&#160;months&#44; pulmonary structural abnormalities were highly prevalent &#40;up to 80&#46;7&#37;&#41; in patients hospitalized in the intensive care unit due to ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">78</span></a> Radiologic abnormalities persisted in 20&#37; of patients with severe COVID-19 who did not require mechanical ventilation at 12 months&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">79</span></a> Compared with patients who had completely resolved&#44; a significantly higher proportion of patients diagnosed as having severe pneumonia and acute respiratory distress syndrome at the initial presentation had residual radiologic abnormality at 1 year&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">44</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Lung function abnormality&#58;</span> Restrictive and obstructive patterns and impaired diffusing capacity were common in COVID-19 survivors&#44;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">80</span></a> although improved considerably in non-critical survivors within 3 months&#46;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">47</span></a> The improvement of diffusing capacity&#44; however&#44; seemed to slow down at 6 months&#46; For up to 12 months&#44; impaired diffusing capacity was identified in 20-30&#37; of patients who had moderate COVID-19&#44; whose prevalence remained constant since month 6&#46; By contrast&#44; impaired diffusing capacity could be found in approximately 54&#37; of patients with critical illness at 1&#160;year&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">2</span></a> In patients who had initially suffered from severe COVID-19 but did not require mechanical ventilation&#44; impaired pulmonary function improved gradually over 1&#160;year&#44; with females having a higher risk of the ongoing impairment as compared with males&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">79</span></a> Impaired diffusing capacity could persist for a longer period&#44; for instance&#44; up to 18&#160;months after discharge&#44; among 57&#46;92&#37; of survivors with more severe disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0770"><span class="elsevierStyleSup">46&#44;81</span></a> Reduced exercise capacity was another important characteristic lung function change among survivors&#44;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">37</span></a> which improved gradually since month&#160;3 in patients with severe COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">79</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Systemic complications&#58;</span> As mentioned above&#44; most systemic complications appeared to be transient&#46; However&#44; the estimated glomerular filtration rate decreased in 35&#37; of patients after 6 months&#44; 13&#37; of which was categorized as the new-onset reduction of glomerular filtration rate despite the normal renal function at COVID-19 onset&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">3</span></a> At 6 months&#44; hyperglycemia persisted in<span class="elsevierStyleHsp" style=""></span>&#62;30&#37; of patients who experienced new-onset hyperglycemia during the hospitalization&#46;<a class="elsevierStyleCrossRef" href="#bib0950"><span class="elsevierStyleSup">82</span></a> A cohort study reported new-onset diabetes in 3&#46;3&#37; out of 1733 patients at 6&#160;months&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">3</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Functional abnormality&#58;</span> The magnitude of improvement depended considerably on the initial disease severity&#46; Most patients with severe illness reported a failure of recovery in physical activity at 6 months&#46;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">83</span></a> 45&#37; of hospitalized survivors exhibited limitations on daily living activities at 7 months &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">84</span></a> The health care workers with severe COVID-19 showed improvement in functional fitness within 1&#160;year&#44; and rigorous intervention might be considered for accelerating the pulmonary rehabilitation &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">85</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Medium- and long-term mortality&#58;</span> The adverse impact of COVID-19 on the mortality risk extended to the long terms&#46; In a cross-sectional study conducted in France&#44; the mortality rate was 62&#46;5&#37; during the intensive care unit stay and increased to 72&#46;1&#37; to month 6 among patients aged greater than 80 years who were receiving mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">86</span></a> At 1 year&#44; patients treated with corticosteroids had a markedly higher mortality rate as compared with those not &#40;50&#46;0&#37; vs&#46; 21&#46;0&#37;&#41;&#44; although the data interpretation was limited by the small sample sizes&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">87</span></a> A study conducted in Italy has also demonstrated a markedly higher mortality rate among hospitalized patients with COVID-19 than those without &#40;48&#46;4&#37; vs&#46; 33&#46;9&#37;&#41; at 1&#160;year&#46;<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">88</span></a> The 1-year mortality rate was also higher in non-hospitalized emergency room visitors with COVID-19 than those without &#40;18&#46;0&#37; vs&#46; 8&#46;7&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">88</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Future research perspective</span><p id="par0095" class="elsevierStylePara elsevierViewall">The continuously evolving global pandemic has elicited an unprecedented challenge for healthcare workers&#44; policy makers and the public&#46; Current research has outlined the clinical spectrum of the consequences&#44; but this would surely benefit from the in-depth mechanistic insights which would unveil the biologic pathways that contribute to the ongoing disorders&#46; Continuous profiling of the cytokine and chemokine expression levels within the lower airways &#40;e&#46;g&#46;&#44; induced sputum&#41; or peripheral blood will help understand the dynamics of residual inflammatory responses&#46; The combination of chest imaging with high-resolution CT or functional magnetic resonance imaging with isotopes and lung function assessment &#40;e&#46;g&#46;&#44; lung volume&#44; diffusing capacity&#44; exercise capacity&#41; will provide clinicians an indispensable avenue for tracking the trend of changes in pulmonary functional abnormality&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">7&#8211;9&#44;17&#44;89</span></a> Further extension of the clinical observation is needed to reveal the long-term impact &#40;e&#46;g&#46;&#44; 3-5 years&#41; on symptom perception&#44; lung function &#40;particularly the exercise capacity&#41;&#44; radiological characteristics&#44; quality-of-life and psychology&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">10&#44;11&#44;16&#44;90</span></a> This will help reveal the duration of recovery of individual symptoms which would normally take&#44; and determine the optimal timing for evaluating the magnitude of recovery and defining complete or partial recovery&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Few intervention strategies have been proposed to accelerate recovery&#44; with pulmonary rehabilitation demonstrating some promising findings&#46;<a class="elsevierStyleCrossRefs" href="#bib0995"><span class="elsevierStyleSup">91&#44;92</span></a> Anti-inflammatory medications or biologics might have a role in antagonizing the residual inflammation&#44; especially when taking into account the pulmonary &#40;e&#46;g&#46;&#44; cough&#44; sputum production&#41; and systemic manifestations &#40;e&#46;g&#46;&#44; fatigue&#41;&#46; There also lacks a crystal-clear indication for the population which would benefit most from therapeutic interventions after discharge&#46; Whether non-pharmaceutical interventions are superior to drug therapy for improving the functional well-being &#40;e&#46;g&#46;&#44; exercise capacity&#41; merits further investigations from the personalized interventions&#46; It would be important to address the optimal duration of such interventions should they be proven effective&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Previous studies have indicated a strong immune protective effect against acquiring re-infections among the COVID-19 rehabilitees&#46;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">93</span></a> The natural immunity has constituted the front line which prevents from being susceptible&#46; However&#44; approximately 4&#37; of patients were susceptible to re-infections with the precise mechanisms not fully explored&#46;<a class="elsevierStyleCrossRefs" href="#bib1005"><span class="elsevierStyleSup">93&#8211;95</span></a> Despite the formation of pan-sarbecovirus antibodies&#44;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">96</span></a> it remains unclear whether COVID-19 survivors would be immune to other coronavirus&#46; Continuous follow-up might help delineate whether re-infections were caused by the waning immunity alone&#44; the underlying immunodeficiency&#44; or emerging variants evading the established immunity&#46; A minority of patients were tested continuously RNA-positive or re-positive after discharge which might not necessarily reflect prolonged viral shedding&#46;<a class="elsevierStyleCrossRefs" href="#bib1025"><span class="elsevierStyleSup">97&#44;98</span></a> A work-up with the government&#44; epidemiologists and clinicians will help ascertain the true infectivity of COVID-19 survivors by gathering the information of the dynamic nucleic acid assays monitoring&#44; enforcing symptom monitoring of patients and close contacts&#44; and integrating multiple laboratory tests &#40;e&#46;g&#46;&#44; viral culture&#44; high-throughput sequencing&#41;&#46; This will be important for redefining the community-based prevention measures&#44; since no existing study has disclosed the infectivity of COVID-19 survivors who were discharged after having at least two consecutive RNA-negative laboratory test findings&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="par0110" class="elsevierStylePara elsevierViewall">The world has come across a tough period when COVID-19 resulted in an overwhelming burden&#46; Thanks to the efforts of the medical and scientific communities&#44; the rapid deployment of effective vaccines and accelerated development of repurposed and novel medications&#44; most patients have either partially or completely recovered from COVID-19&#46; Although many questions remain unanswered&#44; we keep optimistic that the ongoing efforts will better characterize the trajectory of clinical recovery and unveil new interventions which would promote recovery&#46; The goal of enabling a better recovery would ultimately be realized for most COVID-19 rehabilitees&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Support statement</span><p id="par0115" class="elsevierStylePara elsevierViewall">This work was supported by Guangzhou Institute for Respiratory Health Open Project &#40;funded by China Evergrande Group&#41; - Project No&#46; 2020GIRHHMS09 and 2020GIRHHMS19 &#40;Prof&#46; Guan&#41; and the Open Project of the State Key Laboratory of Respiratory Disease &#40;SKLRD-OP-201909&#41; &#40;Dr&#46; Gao&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Author contributions</span><p id="par0120" class="elsevierStylePara elsevierViewall">Yang Gao&#44; Wei-quan Liang&#44; Yi-ran Li&#44; Jian-xing He&#44; and Wei-jie Guan drafted the manuscript&#59; Wei-jie Guan&#44; and Jian-xing He critically revised the manuscript&#46; All authors have approved the final submission&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declared no conflict of interest with any financial organization regarding the material discussed in the manuscript&#46;</p></span></span>"
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          "titulo" => "Keywords"
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          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Clinical characteristics at acute phase"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "The path of disease progression"
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        7 => array:3 [
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          "titulo" => "Short- and long-term consequences"
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            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Short-term consequences"
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            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Medium- to long-term consequences"
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        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Future research perspective"
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          "titulo" => "Conflicts of interest"
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        13 => array:2 [
          "identificador" => "xack606125"
          "titulo" => "Acknowledgment"
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        14 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2022-02-22"
    "fechaAceptado" => "2022-03-04"
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          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:7 [
            0 => "COVID-19"
            1 => "Long COVID"
            2 => "Recovery"
            3 => "Symptom"
            4 => "Intervention"
            5 => "Radiology"
            6 => "Psychology"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:7 [
            0 => "COVID-19"
            1 => "COVID persistente"
            2 => "Recuperaci&#243;n"
            3 => "S&#237;ntomas"
            4 => "Intervenci&#243;n"
            5 => "Radiolog&#237;a"
            6 => "Psicolog&#237;a"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">As with the rapid increase of the number of patients who have recovered from COVID-19 globally&#44; there needs to be a major shift of the focus from rapid pathogen detection&#44; treatment and prevention to the promotion of better recovery&#46; Notwithstanding the scarcity of our understandings&#44; recent studies have unraveled a plethora of pulmonary and systemic consequences which require medical attention&#46; These consequences remained as of the end of follow-up which ranged from 1 month to 1 year&#46; Here&#44; we review the consequences of COVID-19 in terms of the residual symptoms&#44; radiological and functional manifestations&#44; and identify the potential risk factors that contribute to a prolonged recovery&#46; We also summarize the benefits of clinical interventions &#40;particularly the pulmonary rehabilitation program&#41;&#44; and address several undetermined concerns and key future research directions&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Como consecuencia del r&#225;pido aumento del n&#250;mero de pacientes que se han recuperado de la COVID-19 en todo el mundo&#44; es necesario cambiar el enfoque de la detecci&#243;n r&#225;pida del pat&#243;geno&#44; el tratamiento y la prevenci&#243;n para promover una mejor recuperaci&#243;n&#46; A pesar de la escasez de nuestros conocimientos&#44; estudios recientes han desvelado una pl&#233;tora de consecuencias pulmonares y sist&#233;micas que requieren atenci&#243;n m&#233;dica&#46; Estas consecuencias se mantienen al final del seguimiento&#44; que oscila entre 1 mes y 1 a&#241;o&#46; Aqu&#237; se hace una revisi&#243;n de las consecuencias de la COVID-19 en t&#233;rminos de s&#237;ntomas residuales y manifestaciones radiol&#243;gicas y funcionales y se identifican los posibles factores de riesgo que contribuyen a una recuperaci&#243;n demorada&#46; Tambi&#233;n se resumen los beneficios de las intervenciones cl&#237;nicas &#40;en particular el programa de rehabilitaci&#243;n pulmonar&#41; y se abordan varias preocupaciones no resueltas y direcciones clave de investigaci&#243;n futura&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Yang Gao&#44; Wei-quan Liang&#44; and Yi-ran Li contributed equally to the work&#46; Jian-xing He and Wei-jie Guan contributed equally to the work&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Acute&#44; short- and long-term effects of COVID-19 on multiple organ systems&#46; Clinical manifestations a patient might experience at a specific stage of COVID-19&#46; eGFR&#58; estimated glomerular filtration rate&#59; PTSD&#58; post-traumatic stress disorder&#46;</p>"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abnormalities reported within 4-12 weeks<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">53&#44;75&#44;99-104</span></a>&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Abnormalities reported at 6 months<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;3&#44;63&#44;70&#44;74&#44;83&#44;100&#44;105-107</span></a>&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abnormalities reported at 12 months or longer <a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">2&#44;46&#44;61&#44;62&#44;64&#8211;67&#44;72&#44;108</span></a>&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1 year or longer&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Patients with at least 1 symptom</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">37&#46;0-81&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">45&#46;0-60&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&#46;0-85&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyspnea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&#46;9-42&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chest pain&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;2-42&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0-21&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0-15&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0-40&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;1-24&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;0-29&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hair loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;3-28&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5-26&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;0-36&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anxiety or depression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3-45&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;39-26&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3-42&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sleep disorder &#40;e&#46;g&#46; insomnia&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;6-53&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;42-35&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;7-43&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Impaired memory or poor concentration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;1-41&#46;0&#37; &#40;up to several months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Less common symptoms</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Joint pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;6-27&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;0-33&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;8-32&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6-61&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0-26&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;3-17&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Myalgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;5-26&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0-38&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;0-27&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anosmia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7-10&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3-18&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;3-26&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ageusia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5-10&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;0-13&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;4-30&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Post-traumatic syndrome disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;2-28&#46;0&#37; &#40;up to several months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sputum production&#44; weight loss&#44; sweating&#44; skin rash&#44; sore throat&#44; edema of lower limbs&#44; palpitation&#44; diarrhea&#44; constipation&#44; nausea&#44; decreased appetite&#44; abdominal pain&#44; dizziness&#44; anorexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>10&#37; &#40;up to several months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>5&#37; &#40;up to several weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Proportion of patients with persistent symptoms at the short and long terms&#46;</p>"
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      "titulo" => "References"
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          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "1"
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                0 => array:1 [
                  "referenciaCompleta" => "WHO Coronavirus &#40;COVID-19&#41; Dashboard&#46; 2021&#46; Accessed Feb 21st&#44; 2022&#46;"
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              ]
            ]
            1 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "1-year outcomes in hospital survivors with COVID-19&#58; a longitudinal cohort study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(21)01755-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2021"
                        "volumen" => "398"
                        "paginaInicial" => "747"
                        "paginaFinal" => "758"
                        "link" => array:1 [ …1]
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              "identificador" => "bib0555"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "6-month consequences of COVID-19 in patients discharged from hospital&#58; a cohort study"
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                        0 => array:2 [ …2]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(20)32656-8"
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                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2021"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The characteristics of 527 discharged COVID-19 patients undergoing long-term follow-up in China"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijid.2021.01.064"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Infect Dis&#46;"
                        "fecha" => "2021"
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