Transbronchial biopsies’ histopathological findings leading to successful late steroid therapy in Covid-19 acute respiratory failure

Klein, Francisco; Soriano, Juan Calderón; Anfuso, Melany Berdiñas; Ruiz, Victoria; Perazzo, María; Paladini, Hugo; Vigliano, Alejandra; Ossés, Juan; Löwenstein, Pedro R.; Vigliano, Carlos; Cáneva, Jorge

doi:10.1007/s00428-020-02975-6

Cited by 4 publications

(5 citation statements)

References 14 publications

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“…These works have found characteristic findings in the lungs of patients with severe COVID‐19 such as diffuse alveolar damage, microthrombi, massive inflammatory infiltration, and increased megakaryocytes. Additional works examining biopsy specimens in symptomatic patients have found similar histopathologic alternations, including acute lung injury, interstitial pneumonia, type II pneumocyte hyperplasia, and septal thickening 11–13 …”

Section: Discussionmentioning

confidence: 91%

“…Additional works examining biopsy specimens in symptomatic patients have found similar histopathologic alternations, including acute lung injury, interstitial pneumonia, type II pneumocyte hyperplasia, and septal thickening. 11 , 12 , 13 …”

Section: Discussionmentioning

confidence: 99%

“…Autopsy series, transplantation pneumonectomy specimens, and cancer resection specimens have provided only a single time point for examination, and were heavily biased toward patients with severe disease. 7-10 These works have found characteristic findings in the lungs of patients with severe COVID-19 such as diffuse alveolar damage, microthrombi, massive inflammatory infiltration, and increased megakaryocytes.Additional works examining biopsy specimens in symptomatic patients have found similar histopathologic alternations, including acute lung injury, interstitial pneumonia, type II pneumocyte hyperplasia, and septal thickening [11][12][13]. Another work reported serial lung biopsies in a lung transplant recipient during and following hospitalization for severe SARS-CoV-2 infection and found diffuse alveolar damage, a lymphocytic and eosinophilic immune infiltrate, and fibrin clusters in the alveoli at the time of diagnosis 14.…”

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confidence: 88%

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Evolution of pathological findings in surveillance biopsies of lung transplant recipients infected with SARS‐CoV‐2

Wein

Liu

Lin

2022

Transplant Infectious Dis

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Background Previous reports of coronavirus disease 2019 (COVID‐19) following lung transplantation generally described a grim prognosis, but these were anecdotal case series of symptomatic patients. A systematic study of the outcomes and pathology of SARS‐CoV‐2 infection in a large cohort of lung transplant patients is lacking. Methods To determine the histopathologic evolution of COVID‐19 in lung transplant recipients, we identified all patients who underwent surveillance transbronchial biopsies at our institution, tested positive for SARS‐CoV‐2, and had multiple pathology specimens available for evaluation. Histology was reviewed and immunofluorescence for SARS‐CoV‐2 nucleocapsid protein was performed. Results Ten patients met inclusion criteria. Half (5/10) had incidental diagnosis on routine respiratory pathogen testing at the time of transbronchial biopsy. Six patients were hospitalized, with three requiring intensive care unit (ICU) admission. One patient died. Two specimens showed new onset International Society for Heart and Lung Transplantation (ISHLT) Grade A2 rejection at or following diagnosis. One patient developed bronchiolitis obliterans 111 days following diagnosis and 1 year post transplant. Two patients had organizing pneumonia at diagnosis and three patients showed evolving lung injury following diagnosis. The SARS‐CoV‐2 nucleocapsid protein was detected in a subset of samples at diagnosis and up to 111 days following diagnosis. Conclusions Overall, the pathology of SARS‐CoV‐2 infection in lung transplant patients is varied, ranging from no pathologic alterations to organizing pneumonia and lung injury. The pathology findings did not necessarily correlate with clinical acuity, as one patient admitted to the ICU had normal pathology. These findings may be generalizable to non‐transplant patients and require more follow‐up regarding long‐term outcomes.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 88%

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Evolution of pathological findings in surveillance biopsies of lung transplant recipients infected with SARS‐CoV‐2

Wein

Liu

Lin

2022

Transplant Infectious Dis

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“… 3 Although inferences can be made from clinical investigations such as peripheral blood sampling, post-mortem tissue analysis provides an unparalleled snapshot of tissue architecture, cellular constituencies, and cell gene-expression profiles, function, and interactions at the time of death. Several alternative approaches to tissue sampling in severe COVID-19 include mini-thoracotomy and transbronchial biopsy; 4 , 5 however, these methods are anatomically limited and not without risk. Analysis of explanted lung tissue from recipients of lung transplants after COVID-19 is hampered by low numbers and the picture is dominated by an advanced fibrotic disease stage.…”

Section: Introductionmentioning

confidence: 99%

Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19

Milross

Majó

Cooper

et al. 2022

The Lancet Respiratory Medicine

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The lungs are the main site that is affected in severe COVID-19, and post-mortem lung tissue provides crucial insights into the pathophysiology of severe disease. From basic histology to state-of-the-art multiparameter digital pathology technologies, post-mortem lung tissue provides snapshots of tissue architecture, and resident and inflammatory cell phenotypes and composition at the time of death. Contrary to early assumptions that COVID-19 in the lungs is a uniform disease, post-mortem findings have established a high degree of disease heterogeneity. Classic diffuse alveolar damage represents just one phenotype, with disease divisible by early and late progression as well as by pathophysiological process. A distinct lung tissue state occurs with secondary infection; extrapulmonary causes of death might also originate from a pathological process in the lungs linked to microthrombosis. This heterogeneity of COVID-19 lung disease must be recognised in the management of patients and in the development of novel treatment strategies.

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“…Most histopathological documentation has originated from autopsy reports [ 2 ], and recently, explanted lungs of lung transplant patients [ 3 ]. In a recent report, we have been able to show the histopathological evolution through sequential in-vivo transbronchial biopsies in an immunocompetent patient [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Evidence of Continued CD4+ and CD8+ T Cell Activity After SARS-COV-2 Clearance in a Late COVID-19 Pneumonia Heart Transplant Patient

Klein¹,

Renedo²,

Vigliano³

2022

Cureus

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We have studied an unvaccinated heart transplant 64-year-old patient admitted for low-grade fever, dry cough, general malaise, and bilateral interstitial infiltrates, after two months of a diagnosis of coronavirus disease 2019 (COVID-19) bilateral pneumonia. A bronchoalveolar lavage and transbronchial biopsy were performed. Bacterial, mycotic and viral infections were ruled out including repeated reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diffuse thickening of alveolar septa with fibrosis and infiltration of lymphocytes and macrophages into the alveolar septa with aggregates of CD4 + and CD8 + T cells with positive immunolabelling for granzyme B were observed, indicating a continuing cytotoxic process that might have induced proliferation and fibrosis. An intense ongoing immunopathological cellular reaction, potentially triggered by SARS-CoV-2 overcoming the anti-inflammatory and immunomodulatory effects of the immunosuppressive drugs is suggested by these findings, opening to debate the usual approach of minimizing immunosuppression after COVID-19 in transplant patients when presence of SARS-CoV-2 has been ruled out.

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Transbronchial biopsies’ histopathological findings leading to successful late steroid therapy in Covid-19 acute respiratory failure

Cited by 4 publications

References 14 publications

Evolution of pathological findings in surveillance biopsies of lung transplant recipients infected with SARS‐CoV‐2

Evolution of pathological findings in surveillance biopsies of lung transplant recipients infected with SARS‐CoV‐2

Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19

Evidence of Continued CD4+ and CD8+ T Cell Activity After SARS-COV-2 Clearance in a Late COVID-19 Pneumonia Heart Transplant Patient

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