Letter to the Editor
A patient with COVID-19 and anti-glomerular basement membrane disease
Un paciente con Covid-19 y enfermedad de la membrana basal anti glomerular
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Glomerulus with partial cellular crescent formation (C, hematoxylin–eosin stain), another glomerulus with extensive extracapillary proliferation filling the Bowman space and part of a tubule filled with a red blood cell cast (D, hematoxylin–eosin stain). Accompanying interstitial inflammation with abundance of eosinophils (E, hematoxylin–eosin stain). Immunofluorescence microscopy showing lineer IgG along the glomerular basement membrane (F).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Elderly patients and patients with co-morbidities such as hypertension, diabetes and heart disease are under risk of COVID-19.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune disease presenting with features of rapidly progressive glomerulonephritis and alveolar hemorrhage.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> It requires an aggressive immunosuppressive treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 80-year-old female patient with anti-GBM disease who had a fatal course after acquiring a severe COVID-19 infection under immunosuppressive treatment. She had well-controlled hypertension and presented with fever, dyspnea, hemoptysis and hematuria for the last five days. Her laboratory values were as follows: Creatinine (Cre): 6.0<span class="elsevierStyleHsp" style=""></span>mg/dL, blood urea nitrogen (BUN): 86.6<span class="elsevierStyleHsp" style=""></span>mg/dL, sodium (Na): 139 mEq/L, potassium (K): 3.6<span class="elsevierStyleHsp" style=""></span>mEq/L, uric acid (Ua): 12.6<span class="elsevierStyleHsp" style=""></span>mg/dL, albumin (alb): 3.1<span class="elsevierStyleHsp" style=""></span>g/dL, erythrocyte sedimentation rate (ESR): 64<span class="elsevierStyleHsp" style=""></span>mm/h, CRP: 14.8<span class="elsevierStyleHsp" style=""></span>mg/dL, BNP: 403<span class="elsevierStyleHsp" style=""></span>pg/mL, procalcitonin: 1.14<span class="elsevierStyleHsp" style=""></span>ng/mL. Urinalysis revealed 1226 erythrocytes/HPF and 86 leucocytes/HPF. 24-h proteinuria was 5.8<span class="elsevierStyleHsp" style=""></span>g/day. Echocardiography revealed normal left ventricular functions with an ejection fraction of 66% and pulmonary hypertension (pulmonary artery pressure: 60<span class="elsevierStyleHsp" style=""></span>mmHg).</p><p id="par0015" class="elsevierStylePara elsevierViewall">A non-contrast chest CT revealed alveolar hemorrhage and a suspicion of pneumonia. Nasopharyngeal swap for respiratory pathogens and PCR for COVID-19 was sent but there was no positivity. ANA, ANCA were negative, C3 and C4 levels were normal. However, testing for anti-GBM antibody was reported as positive.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Renal biopsy revealed a focal necrotizing extra-capillary proliferative glomerulonephritis and acute tubulointerstitial nephritis. Immunofluorescence microscopy showed presence of linear IgG along the glomerular basement membrane. A diagnosis of anti-GBM disease with a comment about supervening possible drug reaction was made (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">500<span class="elsevierStyleHsp" style=""></span>mg intravenous metylprednisolone (mps) for three days and 500<span class="elsevierStyleHsp" style=""></span>mg once a week cyclophosphamide treatment was started. She was discharged on oral mps treatment since there was no fever and progression in the infiltrations in the control CT imaging.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Three days after discharge, patient presented to the emergency service with tachypnea and hemoptysis. She was admitted to intensive care unit. A control chest CT showed similar findings with the previous ones (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Considering her hospitalization history during COVID-19 outbreak and CT findings, a control PCR for COVID-19 was sent which was reported as positives. She had leukocytosis with lymphopenia and high level of acute phase reactants.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Combination treatment of hydroxychloroquine and azithromycin was started. In the fifth day of treatment she had to be intubated and vasopressor treatment was started. Favipravir and intravenous immunoglobulin were added because of resistant COVID-19 infection. Patient underwent continuous renal replacement therapy due to severe oliguric acute kidney injury and died on the 14th day of hospitalization.</p><p id="par0045" class="elsevierStylePara elsevierViewall">This case report demonstrates a patient with anti-GBM disease who died in a short period of time after acquiring COVID-19 infection under immunosuppressive treatment. Although immunosuppressive treatment may theoretically complicate the course of an infectious disease,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> there is no firm evidence of increased complication for COVID-19 infections in patients under immunosuppressive treatment.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4–6</span></a> However, it is impossible to completely exclude any detrimental effect of immunosuppression for specific disorders such as anti-GBM disease on COVID-19 infection. The unfavorable clinical course of this patient may be related either to the immunosuppression or the primary disease affecting the lungs, as it is well known that patients with lung diseases are at increased risk.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The PCR test for COVID-19 is far from perfect as approximately 30% of the patients have an initial false-negative result.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> This creates a dilemma for the clinicians when encountering a patient who has or may have an alternative diagnosis requiring immunosuppression but also has some features of COVID-19 infection. In this particular patient, since the initial PCR for COVID-19 was negative, a prompt response to antibacterial treatment was observed and there was no progression in the control CT imaging we excluded COVID-19 during the initial hospitalization. However, when the patient presented with a more severe condition in the second admission, considering her previous hospitalization history in the same ward with COVID-19 positive patients and her severe lymphopenia a repeat PCR test for COVID-19 was ordered which was found positive. The patient was therefore considered as new onset COVID-19 infection under immunosuppressive treatment.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Another point that should be considered however is the potential direct pathogenetic effect of the COVID-19 infection on the kidneys. Anti-GBM disease is known to be associated with infectious triggers and to present as mini-epidemics concurrent with influenza outbreaks.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8–9</span></a> Considering reports of false negativity of patients at initial PCR testing there is thus the possibility that COVID-19 can be the causative factor of the anti-GBM disease. A Chinese study that examined post mortem renal biopsy findings in 26 COVID-19 infection cases however did not mention any cases with necrotizing extracapillary proliferative glomerulonephritis that could suggest possibility of anti-GBM renal disease.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Thus to date there is no known case of anti-GBM glomerulonephritis in a covid19 patient.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical approval</span><p id="par0060" class="elsevierStylePara elsevierViewall">The article does not contain any studies with human participants or animals performed by any of the authors.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Informed consent</span><p id="par0065" class="elsevierStylePara elsevierViewall">Since the patient that is described in the case report was died, her daughter has given consent for publication</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical approval" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Informed consent" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Funding" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interest" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1041 "Ancho" => 1674 "Tamanyo" => 320959 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Glomerulus with focal fibrinoid necrosis (A, hematoxylin-eosin), another glomerulus with fibrinoid necrosis, which can be seen as the pink argyrophobic area in the silver stain (B, Jones methenamine silver). Glomerulus with partial cellular crescent formation (C, hematoxylin–eosin stain), another glomerulus with extensive extracapillary proliferation filling the Bowman space and part of a tubule filled with a red blood cell cast (D, hematoxylin–eosin stain). Accompanying interstitial inflammation with abundance of eosinophils (E, hematoxylin–eosin stain). Immunofluorescence microscopy showing lineer IgG along the glomerular basement membrane (F).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 669 "Ancho" => 1067 "Tamanyo" => 85836 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Chest computerized tomography revealed anti-GBM disease but could not exclude accompanying infection.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 8 | 15 |
| 2024 October | 70 | 48 | 118 |
| 2024 September | 70 | 42 | 112 |
| 2024 August | 83 | 74 | 157 |
| 2024 July | 74 | 30 | 104 |
| 2024 June | 76 | 54 | 130 |
| 2024 May | 90 | 60 | 150 |
| 2024 April | 73 | 46 | 119 |
| 2024 March | 64 | 47 | 111 |
| 2024 February | 53 | 48 | 101 |
| 2024 January | 52 | 67 | 119 |
| 2023 December | 35 | 39 | 74 |
| 2023 November | 65 | 55 | 120 |
| 2023 October | 99 | 38 | 137 |
| 2023 September | 287 | 48 | 335 |
| 2023 August | 261 | 37 | 298 |
| 2023 July | 105 | 43 | 148 |
| 2023 June | 134 | 29 | 163 |
| 2023 May | 90 | 39 | 129 |
| 2023 April | 87 | 34 | 121 |
| 2023 March | 68 | 29 | 97 |
| 2023 February | 73 | 21 | 94 |
| 2023 January | 54 | 55 | 109 |
| 2022 December | 85 | 55 | 140 |
| 2022 November | 75 | 55 | 130 |
| 2022 October | 89 | 78 | 167 |
| 2022 September | 85 | 48 | 133 |
| 2022 August | 58 | 35 | 93 |
| 2022 July | 77 | 65 | 142 |
| 2022 June | 72 | 48 | 120 |
| 2022 May | 63 | 24 | 87 |
| 2022 April | 64 | 44 | 108 |
| 2022 March | 85 | 62 | 147 |
| 2022 February | 75 | 47 | 122 |
| 2022 January | 97 | 81 | 178 |
| 2021 December | 67 | 45 | 112 |
| 2021 November | 51 | 39 | 90 |
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