Brief report
Multi-organ pathological findings associated with COVID-19 in postmortem needle core biopsies in four patients and a review of the current literature
Hallazgos patológicos multiorgánicos asociados a COVID-19 a través de biopsias con aguja gruesa postmortem y revisión de la literatura actual
Tais González Pessolani
, Marta Muñóz Fernández de Legaria, Margarita Elices Apellániz, Silvia Salinas Moreno, María del Mar Lorido Cortés, Sagrario García Sánchez
Corresponding author
Department of Pathology, Hospital Universitario Infanta Sofía, Madrid-Spain (Servicio de Anatomía Patológica, Hospital Universitario Infanta Sofía), Madrid, Spain
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A case report" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2429 "Ancho" => 2500 "Tamanyo" => 1112604 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Estudio inmunohistoquímico: (a) p40 (x100) que muestra negatividad para las células neoplásicas. (b) CK20 (x200). (c) CK7 (x100). (d) Sinaptofisina (x200). (e) INMS1 (x200). 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Consenso de expertos de la Sociedad Española de Endocrinologia y Nutrición y de la Sociedad Española de Anatomía Patológica" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "263" "paginaFinal" => "274" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Recommendations on the pathological report of pituitary tumors. A consensus of experts of the Spanish Society of Endocrinology and Nutrition and the Spanish Society of Pathology" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1644 "Ancho" => 3167 "Tamanyo" => 427426 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Propuesta de algoritmo diagnóstico de los subtipos de TNEH sobre la base de la determinación en un primer escalón de los FTH hipofisarios.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">PIT-1: factor de transcripción 1 específico de la hipófisis; T-PIT: el factor de transcripción t-box; SF-1: el factor esteroidogénico-1. ACTH: hormona corticotropa; GH: hormona del crecimiento; FSH: hormona foliculoestimulante; LH: hormona luteinizante; PRL: prolactina; TSH: hormona estimulante de la tiroides. Cg-A: cromogranina A.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Antonio Picó, Ignacio Aranda-López, Gemma Sesmilo, Óscar Toldos-González, Miguel A. Japón, Raúl M. Luque, Manel Puig-Domingo" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Antonio" "apellidos" => "Picó" ] 1 => array:2 [ "nombre" => "Ignacio" "apellidos" => "Aranda-López" ] 2 => array:2 [ "nombre" => "Gemma" "apellidos" => "Sesmilo" ] 3 => array:2 [ "nombre" => "Óscar" "apellidos" => "Toldos-González" ] 4 => array:2 [ "nombre" => "Miguel A." "apellidos" => "Japón" ] 5 => array:2 [ "nombre" => "Raúl M." "apellidos" => "Luque" ] 6 => array:2 [ "nombre" => "Manel" "apellidos" => "Puig-Domingo" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S169988552100009X?idApp=UINPBA00004N" "url" => "/16998855/0000005400000004/v1_202109180718/S169988552100009X/v1_202109180718/es/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Brief report</span>" "titulo" => "Multi-organ pathological findings associated with COVID-19 in postmortem needle core biopsies in four patients and a review of the current literature" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "275" "paginaFinal" => "280" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Tais González Pessolani, Marta Muñóz Fernández de Legaria, Margarita Elices Apellániz, Silvia Salinas Moreno, María del Mar Lorido Cortés, Sagrario García Sánchez" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Tais" "apellidos" => "González Pessolani" "email" => array:1 [ 0 => "taisgonzalez87@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Marta" "apellidos" => "Muñóz Fernández de Legaria" ] 2 => array:2 [ "nombre" => "Margarita" "apellidos" => "Elices Apellániz" ] 3 => array:2 [ "nombre" => "Silvia" "apellidos" => "Salinas Moreno" ] 4 => array:2 [ "nombre" => "María del Mar" "apellidos" => "Lorido Cortés" ] 5 => array:2 [ "nombre" => "Sagrario" "apellidos" => "García Sánchez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Pathology, Hospital Universitario Infanta Sofía, Madrid-Spain (Servicio de Anatomía Patológica, Hospital Universitario Infanta Sofía), Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hallazgos patológicos multiorgánicos asociados a COVID-19 a través de biopsias con aguja gruesa postmortem y revisión de la literatura actual" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1009 "Ancho" => 1500 "Tamanyo" => 612607 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Histological study of the lung: (a and b) lung parenchyma with diffuse thickening of alveolar walls by inflammatory infiltrate and fibrosis (DAD pattern, proliferative/fibrotic phase) (H&E stain, 2×); (c) lung parenchyma with DAD pattern and frequent associated alveolar hemorrhage (H&E stain, 2×); (d–f) Alveolar walls coated by reactive pneumocytes and thickened by increased cellularity and fibrosis. Note the numerous vascular microthrombi (head of arrow) (H&E stain, 20×).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Spain has become one of the epicenters of an unprecedented pandemic caused by Coronavirus disease 2019 (COVID-19) and is one of the countries with a higher coronavirus mortality rate. Many hypotheses have been proposed to explain the increase in fatalities but so far it remains largely an enigma. The underlying factors responsible for worldwide variations in mortality are poorly understood but may be related to genetic predisposition,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> access and quality of healthcare and prevalence of comorbidities.</p><p id="par0010" class="elsevierStylePara elsevierViewall">COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> It was first detected in December, 2019 in Wuhan (China) and declared a pandemic on March, 2020.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Only a few autopsy results have been reported to date. However, it is vital that we improve our understanding of this disease from every possible angle. Histopathological analysis of postmortem core needle biopsies (PMCNB) of target organs may shed light on the pathogenesis of the microorganism.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The lungs and the heart are amongst the organs most affected by COVID-19.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> In the lung, the typical pattern of injury described is diffuse alveolar damage (DAD),<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> a nonspecific pattern of interstitial pneumonia that evolves through phases (exudative, proliferative and fibrotic). It is characterized by hyaline membranes in the early stages and fibrosis in later stages.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> Interstitial lymphocytic infiltrates with predominant CD4-positive T cells<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">4–6</span></a> are commonly reported. Although some authors propose that, in severe infections, “acute fibrinous and organizing pneumonia (AFOP)” is the main pattern found, where intra-alveolar fibrin balls are seen without hyaline membranes,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> this diagnosis should be reserved for large samples so that the absence of DAD features can be confirmed.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> An important common finding is the presence of microvascular thrombi<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> and associated hemorrhage. Other findings include reactive pneumocytes and multinucleated giant cells (MGC). To our knowledge, no viral inclusions in association with this infection have been reported.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">4,9</span></a> In the heart, myocyte hypertrophy is a common finding, probably related to underlying conditions.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> A spectrum of mild interstitial chronic inflammation within the myocardium without necrosis to lymphocytic myocarditis with myonecrosis is also described.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> Further reports describe individual cell necrosis without associated inflammation.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Other organs known to be involved in this disease are the liver, spleen and kidney. In the liver, frequent sinusoidal dilatation with congestion, as well as steatosis, have been described, in addition to patchy hepatocytic necrosis and microvascular thrombi.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">9,11</span></a> In the spleen, lymphocytic depletion of the white pulp with a decrease or absence of lymphoid follicles is usually found.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> Acute tubular necrosis (ATN) is generally present in the kidney,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a> with glomerular capillary thrombi and vacuolization and dilatation of tubules<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> also being reported.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">Once the initial overloading of the hospital system due to the pandemic had abated, PMCNBs were performed on four cases of PCR-positive for COVID-19, between April and May 2020, at the Infanta Sofia Hospital in Madrid, Spain. The procedure was carried out with the previous consent of the first-degree relative of the deceased.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Six pathologists studied the samples using H&E, histochemical (Alcian blue and Masson for lungs; PAS-diastase, Masson, Reticulin and Perls Prussian blue for liver; PAS, Silver, Masson for kidney) and immunohistochemical stains (CD20, CD3, CD4 and CD8 for lungs; CD20, CD3 and CD23 for spleen). Lung tissue was sampled in all patients, as well as other organs such as heart, liver, spleen and kidney. Findings were compared with previously published reports.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical data and pathologic findings of the patients are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 1</span>(P1) was a 56-year-old male, native of Peru, ex-smoker with no concomitant diseases and with clinical diagnoses of COVID-19 pneumonia and respiratory failure. Lung, liver and spleen biopsies were sampled.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Lung parenchyma showed a DAD pattern in predominant proliferative/fibrotic phase, with many intra-alveolar fibrin balls. Moderate lymphocytic interstitial infiltrates with predominant CD8-positive T cells and frequent eosinophils were seen, both in the interstitial septa and inside the alveolar spaces. Numerous microvascular fibrin thrombi were noted, as well as reactive pneumocytes, MGC, intra-alveolar hemorrhage and edema.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Liver parenchyma showed moderate lymphocytic infiltrates in portal spaces and a microvascular fibrin thrombus. A focal area of lobular necrosis was also noted. Many hepatocytes had glycogenated nuclei and sinusoids were congested throughout.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Spleen parenchyma showed lymphocytic depletion of the white pulp with decreased/absent lymphoid follicles. Red splenic arteriolar hyalinosis was observed, with narrow lumens.</p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 2</span>(P2) was a 78-year-old male, hypertensive ex-smoker with type 2 diabetes mellitus, dyslipidemia, COPD and obstructive sleep apnea. His clinical diagnoses were COVID-19 pneumonia, respiratory infection by <span class="elsevierStyleItalic">S. maltohphilia</span>, bilateral pulmonary embolism, multi-organ failure and probable acute mesenteric ischemia (AMI). Lung, heart and kidney biopsies were sampled. Unfortunately, intestinal samples were not examined to rule out the clinical suspicion of AMI.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Lung parenchyma showed histologic signs of acute bronchopneumonia, with no features suggestive of DAD.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Heart parenchyma only showed myocyte hypertrophy.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Kidney parenchyma showed focal ATN and frequent vacuolization of the tubular epithelium. Vessels had moderate arteriolar hyalinosis and arteriosclerosis.</p><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 3</span>(P3) was a 78-year-old man with a history of dyslipidemia. His clinical diagnoses were COVID-19 pneumonia, respiratory and renal failure and probable respiratory infection by <span class="elsevierStyleItalic">A. fumigatus</span>. Lung, heart, liver and kidney were sampled.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Lung parenchyma showed features of DAD predominantly in the proliferative phase, with focal hyaline membranes. Fibrin intra-alveolar balls and moderate interstitial lymphocytic infiltrates with a slight predominance of CD8-positive T cells were present. Microvascular fibrin thrombi, as well as intra-alveolar edema, hemorrhage, reactive pneumocytes and MGC were also found. Furthermore, acute bronchopneumonia with numerous intra-alveolar neutrophils and fungal hyphae positive by Grocott's silver stain, was diagnosed.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Heart parenchyma showed myocyte hypertrophy and mild patchy inflammatory mixed infiltrate, without associated necrosis.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Liver parenchyma showed hepatocytes with frequent glycogenated nuclei. Mild cholestasis, a slight increase in intrahepatocytic iron (detected using Perls Prussian blue) and widespread sinusoidal congestion were also found.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Kidney parenchyma showed a fibrin thrombus in a glomerular capillary. There were occasional dilated tubules with diminished wall thickness and focal ATN. Mild arteriolar hyalinosis and moderate arterial arteriosclerosis were also present.</p><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 4</span>(P4) was a 57-year-old overweight, hypertensive male, native of Cuba, whose clinical diagnoses were COVID-19 pneumonia, respiratory and renal failure, catheter-related bacteriemia by <span class="elsevierStyleItalic">S. epidermidis</span> and candidemia by <span class="elsevierStyleItalic">C. parapsilosis</span>. Lung, heart and liver were sampled.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Lung parenchyma showed a DAD pattern predominantly in the proliferative/fibrotic phase, with frequent fibrin intra-alveolar balls. There were moderate foci of interstitial lymphocytic infiltrates with predominant CD8-positive T cells. Microvascular fibrin thrombi, common reactive pneumocytes, MGC and areas of alveolar hemorrhage were also present.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Heart parenchyma showed myocyte hypertrophy and focal areas of necrotic myocytes without associated inflammation. The sample included a medium-size artery with moderate to intense arteriosclerosis.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Liver parenchyma showed intense acute hepatitis, severe steatosis and widespread sinusoidal congestion. Some hepatocytes showed multinucleation and enlarged, bizarre nuclei.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discussion</span><p id="par0130" class="elsevierStylePara elsevierViewall">We report the histopathological findings of PMCNBs of four cases of COVID-19. To date, available data are scarce, however, it is crucial that the reason for the elevated mortality associated with COVID-19 in Spain be investigated. Although we are aware that our study is limited by the small number of cases, we hope that it will contribute to a better understanding of the disease.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Morphological manifestations generally fitted the profile described in previous reports.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a> Lung histology revealed a DAD pattern predominantly in a proliferative/fibrotic phase (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a and b), with frequent intra-alveolar fibrin balls and focal hyaline membranes in only one case (P3). Reactive pneumocytes, MGC, interstitial lymphocytic infiltrates, alveolar hemorrhage and edema (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c) were common, as well as microvascular fibrin thrombi (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>d–f). In all patients, cardiac histology showed some degree of myocyte hypertrophy, probably related to comorbidities, including hypertension. In one case (P3) there was mild interstitial chronic myocardial inflammation without associated necrosis, and in another case (P4) a focal area of acute myocardial infarct (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a) without inflammatory infiltrates, as in prior reports.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> Liver histology showed diffuse sinusoidal congestion and frequent hepatocytes with glycogenated nuclei (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>b). One case (P1) had a small area of hepatocellular necrosis and a portal microvascular fibrin thrombus (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>c). Another case (P4) showed intense steatosis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>d). In the only case in which spleen tissue had been biopsied (P1), histopathological findings similar to previous reports were seen, in the form of lymphocytic depletion of the white pulp and areas with diminished/absent lymphoid follicles<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>e). Kidney samples in one case (P3) showed vascular injury with a glomerular capillary thrombus (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>f), arteriolar hyalinosis and arteriosclerosis. Tubular injury was also frequently noted, with ATN in two cases (P2, P3) and widened tubular lumina with flattened epithelium in one case (P3) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>g).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Abnormalities were found in most of the organs sampled, mainly in the lungs. In contrast to previous reports, interstitial lymphocytic infiltrates were predominantly CD8-positive.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">4–6</span></a> One case (P1) showed frequent eosinophilic infiltrates. Although some authors report the presence of a few eosinophils,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> to the best of our knowledge, these cells are not a frequent finding in COVID-19 lungs. One case (P2) did not have a DAD pattern, but acute bronchopneumonia, probably related to <span class="elsevierStyleItalic">S. maltohphilia</span>. Another case (P3) had, as well as DAD, concomitant acute bronchopneumonia, probably related to <span class="elsevierStyleItalic">A.fumigatus</span>. In the liver, one case (P4) showed acute hepatitis, not typically associated with this disease and probably secondary to drug cytotoxicity. The same patient showed hepatocytes with multinucleation and enlarged bizarre nuclei (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>d); to our knowledge, an unreported feature. Kidney histology showed vacuolization of tubular epithelium in one case (P2) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>h), also probably in relation to drug therapy.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The present study also revealed two interesting clinical aspects. Both of the younger patients (P1, 56 and P4, 57 years-old) were Latin Americans (Peruvian and Cuban, respectively). Two previous studies have linked blood group A with a higher susceptibility to COVID-19 in comparison to blood group O, and suggested that this former blood group may be associated with coagulopathies related to this disease.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a> Three of our four patients had blood group A (P1: A+, P3: A− and P4: A+). Only one patient had blood group O- (P2)<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">15,16</span></a> and, interestingly, he had no features of DAD.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusion</span><p id="par0155" class="elsevierStylePara elsevierViewall">Although the study of PMCNB of patients dying of COVID-19 is not as complete as a full autopsy, it will further the understanding of the histopathology related to this highly lethal virus. Our study, albeit a small one with only four cases, correlates well with previously published reports, and highlights some interesting pathological findings. Therefore, we hope it will contribute in shedding some light on the nature of this microorganism, although further and larger histopathological series are urgently required.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare regarding this study.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1574366" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1418607" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1574365" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1418608" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack555996" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-06-13" "fechaAceptado" => "2020-09-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1418607" "palabras" => array:6 [ 0 => "Coronavirus" 1 => "COVID-19" 2 => "Pneumonia" 3 => "Histopathology" 4 => "Pathogenesis" 5 => "Microscopy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1418608" "palabras" => array:6 [ 0 => "Coronavirus" 1 => "COVID-19" 2 => "Neumonía" 3 => "Patología" 4 => "Patogénesis" 5 => "Microscopía" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Coronavirus disease 2019 (COVID-19) has spread worldwide, resulting in significant morbidity and mortality. Histopathological findings are essential in understanding its pathogenesis and we present our findings from postmortem core needle biopsies in an attempt to share information that may shed some light on this severe pandemic.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Different organ samples from four patients with PCR-confirmed COVID-19 at the Infanta Sofía Hospital (Madrid) were studied during the months of April and May, 2020 by six pathologists using routine stains, histochemistry and immunohistochemistry. Results were compared with other reported cases.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All patients had a clinical diagnosis of pneumonia and biopsies revealed lung damage in the majority. Heart, liver, spleen and kidney were also studied and abnormalities were found in all cases and are extensively described.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The histopathology of organs affected by COVID-19 is vital to the understanding of this disease and its sequelae.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de coronavirus 2019 (COVID-19) ha afectado de forma mundial causando intensa morbimortalidad. Los hallazgos patológicos son claves para entender su patogénesis. A través de biopsias con aguja gruesa postmortem, intentamos responder a las incógnitas que giran en torno a la severidad de esta infección.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Se enviaron muestras de cuatro pacientes COVID-19 positivos al servicio de Anatomía Patológica del Hospital Infanta Sofía (Madrid) en los meses de Abril y Mayo 2020. Se estudiaron a través de distintas técnicas y los resultados se compararon con la literatura, buscando similitudes y peculiaridades.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Todos los pacientes tenían un diagnóstico de neumonía. Las biopsias mostraron daño pulmonar en la mayoría. El resto de los órganos estudiados fueron: corazón, hígado, bazo y riñón. Se encontraron características distintivas en muchos, las cuales fueron descritas exhaustivamente.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En conclusión, el análisis microscópico de los órganos afectados por COVID-19 es importante para comprender ésta enfermedad y sus posibles consecuencias.</p></span>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1009 "Ancho" => 1500 "Tamanyo" => 612607 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Histological study of the lung: (a and b) lung parenchyma with diffuse thickening of alveolar walls by inflammatory infiltrate and fibrosis (DAD pattern, proliferative/fibrotic phase) (H&E stain, 2×); (c) lung parenchyma with DAD pattern and frequent associated alveolar hemorrhage (H&E stain, 2×); (d–f) Alveolar walls coated by reactive pneumocytes and thickened by increased cellularity and fibrosis. Note the numerous vascular microthrombi (head of arrow) (H&E stain, 20×).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 800 "Ancho" => 1500 "Tamanyo" => 454383 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Histological study of other organs: (a) heart myocardium with necrotic myocytes (H&E stain, 20×); (b) hepatocytes with frequent glycogenated nuclei (H&E stain, 20×); (c) portal vascular microthrombus (H&E stain, 20×); (d) Hepatocytes with intense steatosis and enlarged nuclei (H&E stain, 40×); (e) Spleen with lymphocytic depletion of the white pulp and diminished lymphoid follicles (H&E stain, 4×); (f) Glomerular capillary microthrombus (H&E stain, 20×); (g) Tubular dilatation with flattened epithelium (H&E stain, 20×); (h) Vacuolization of tubular epithelium (H&E stain, 20×).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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="elsevierStyleItalic">Sex</span> \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">Male \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">Male \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">Male \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">Male \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="elsevierStyleItalic">Age</span> \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">56 \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">78 \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">78 \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">57 \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="elsevierStyleItalic">Nationality</span> \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">Peruvian \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">Spanish \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">Spanish \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">Cuban \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="elsevierStyleItalic">Blood group</span> \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">A+ \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">O− \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">A− \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">A+ \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="elsevierStyleItalic">Clinical history</span> \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">Ex-smoker \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">Ex-smoker, HTA, DM, Dyslipidemia \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">Dyslipidemia \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">HTA, overweight \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="elsevierStyleItalic">Days with symptoms</span> \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">31 \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">41 \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">37 \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">43 \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="elsevierStyleItalic">Days in ICU</span> \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 \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 \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 \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 \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="5" 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="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Histopathological findings:</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>Lungs \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">• DAD (proliferative/fibrotic phase)• Microvascular fibrin thrombi• Eosinophilic infíltrates \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">Acute bronchopneumonia \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">• DAD with focal hyaline membranes (predominant proliferative phase)• Acute bronchopneumonia with fungal hyphae• Microvascular fibrin thrombi \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">• DAD (proliferative/fibrotic phase)• Microvascular thrombi \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>Heart \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"><span class="elsevierStyleItalic">Not sampled</span> \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">Myocyte hypertrophy \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">• Myocyte hypertrophy• Mild inflammatory infiltrates \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">• Myocyte hypertrophyFocal area of necrotic myocytes without associated inflammation• Moderate-intense arteriosclerosis \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>Liver \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">• Portal lymphocytic infiltrates• Focal lobular necrosis• Microvascular fibrin thrombus• Glycogenated nucleiSinusoidal congestion \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"><span class="elsevierStyleItalic">Not sampled</span> \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">• Mild cholestasisMild increase in intrahepatocytic iron• Sinusoidal congestion \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">• Intense acute hepatitisSevere steatosis• Multinucleated hepatocytes with bizarre nuclei \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>Spleen \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">• Intense lymphoid depletion• Decreased/absent lymphoid follicles• Red splenic arteriolar hyalinosis \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"><span class="elsevierStyleItalic">Not sampled</span> \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"><span class="elsevierStyleItalic">Not sampled</span> \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"><span class="elsevierStyleItalic">Not sampled</span> \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>Kidney \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"><span class="elsevierStyleItalic">Not sampled</span> \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">• Focal acute tubular necrosis• Vacuolization of tubular epithelium• Moderate arteriolar hyalinosis and arteriosclerosis \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">• Focal glomerular capillary thrombus• Focal acute tubular necrosis• Occasional dilated tubules with diminished walls• Mild arteriolar hyalinosis and moderate arteriosclerosis \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"><span class="elsevierStyleItalic">Not sampled</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2697746.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Clinical data and Pathological findings.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0085" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "COVID-19 Host Genetics Initiative" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41431-020-0636-6" "Revista" => array:6 [ "tituloSerie" => "Eur J Hum Genet" "fecha" => "2020" "volumen" => "28" "paginaInicial" => "715" "paginaFinal" => "718" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32404885" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0090" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. 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Lu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1101/2020.03.11.20031096" "Revista" => array:2 [ "tituloSerie" => "MedRxiv" "fecha" => "2020" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0160" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Testing the association between blood type and COVID-19 infection, intubation, and death" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Zietz" 1 => "N.P. Tatonetti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1101/2020.04.08.20058073" "Revista" => array:2 [ "tituloSerie" => "medRxiv" "fecha" => "2020" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack555996" "titulo" => "Acknowledgments" "texto" => "<p id="par0165" class="elsevierStylePara elsevierViewall">The authors would like to thank the head of the ICU service of Hospital Infanta Sofía, Miguel Angel González, for performing the PMCNBs and thus making this study possible, as well as Dr Alejandro Ayala from the University of Miami (USA) for his significant contribution.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/16998855/0000005400000004/v1_202109180718/S1699885520301008/v1_202109180718/en/main.assets" "Apartado" => array:4 [ "identificador" => "5740" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Artículos breves" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/16998855/0000005400000004/v1_202109180718/S1699885520301008/v1_202109180718/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699885520301008?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 44 | 4 | 48 |
| 2024 September | 127 | 2 | 129 |
| 2024 August | 67 | 8 | 75 |
| 2024 July | 64 | 11 | 75 |
| 2024 June | 48 | 6 | 54 |
| 2024 May | 54 | 6 | 60 |
| 2024 April | 87 | 3 | 90 |
| 2024 March | 108 | 15 | 123 |
| 2024 February | 96 | 8 | 104 |
| 2024 January | 192 | 17 | 209 |
| 2023 December | 96 | 18 | 114 |
| 2023 November | 123 | 20 | 143 |
| 2023 October | 164 | 20 | 184 |
| 2023 September | 86 | 6 | 92 |
| 2023 August | 86 | 9 | 95 |
| 2023 July | 79 | 14 | 93 |
| 2023 June | 131 | 10 | 141 |
| 2023 May | 159 | 12 | 171 |
| 2023 April | 83 | 8 | 91 |
| 2023 March | 56 | 6 | 62 |
| 2023 February | 73 | 15 | 88 |
| 2023 January | 72 | 9 | 81 |
| 2022 December | 80 | 13 | 93 |
| 2022 November | 83 | 16 | 99 |
| 2022 October | 70 | 20 | 90 |
| 2022 September | 59 | 19 | 78 |
| 2022 August | 81 | 14 | 95 |
| 2022 July | 64 | 18 | 82 |
| 2022 June | 69 | 20 | 89 |
| 2022 May | 78 | 27 | 105 |
| 2022 April | 84 | 29 | 113 |
| 2022 March | 126 | 37 | 163 |
| 2022 February | 98 | 22 | 120 |
| 2022 January | 114 | 21 | 135 |
| 2021 December | 106 | 30 | 136 |
| 2021 November | 111 | 40 | 151 |
| 2021 October | 228 | 73 | 301 |
| 2021 September | 222 | 64 | 286 |
| 2021 August | 23 | 24 | 47 |
| 2021 July | 21 | 21 | 42 |
| 2021 June | 28 | 22 | 50 |
| 2021 May | 50 | 46 | 96 |
| 2021 April | 546 | 171 | 717 |
| 2021 March | 144 | 53 | 197 |
| 2021 February | 58 | 50 | 108 |
| 2021 January | 35 | 30 | 65 |
| 2020 December | 59 | 44 | 103 |
| 2020 November | 11 | 31 | 42 |
| 2020 October | 0 | 9 | 9 |
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