SARS-CoV-2 identified by transmission electron microscopy in lymphoproliferative and ischaemic intestinal lesions of COVID-19 patients with acute abdominal pain: two case reports

Martín‐Cardona, Albert; Trull, Josep Lloreta; Albero-González, Raquel; Beser, Marta Paraira; Andújar, Xavier; Ruiz-Ramírez, Pablo; Tur-Martínez, Jaume; Ferrer, Carme; Izquierdo, José Ángel de Marcos; Pérez-Madrigal, Anna; González, Laura Goiburú; Perez, Jorge Espinós; Esteve, María

doi:10.1186/s12876-021-01905-3

Cited by 18 publications

(16 citation statements)

References 27 publications

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“…Our TEM study results are confirmed by the results of previously published works, revealing the presence of coronavirus virions mainly in vascular endothelial cells of the lungs [63], intestines [64,65], kidneys [66], heart [67], skin [68], brain [69], liver [70], pancreas [71]. Furthermore, the TEM data confirms the hypothesis about the critical role of endothelial dysfunction in the development of multiorgan failure and the fatal outcome of COVID-19 [72,73].…”

Section: Discussionsupporting

confidence: 90%

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Odilov

Волков

Абдуллаев

et al. 2021

Viruses

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Multi-organ failure is one of the common causes of fatal outcome in COVID-19 patients. However, the pathogenetic association of the SARS-CoV-2 viral load (VL) level with fatal dysfunctions of the lungs, liver, kidneys, heart, spleen and brain, as well as with the risk of death in COVID-19 patients remains poorly understood. SARS-CoV-2 VL in the lungs, heart, liver, kidneys, brain, spleen and lymph nodes have been measured by RT qPCR using the following formula: NSARS-CoV−2/NABL1 × 100. Dissemination of SARS-CoV-2 in 30.5% of cases was mono-organ, and in 63.9% of cases, it was multi-organ. The average SARS-CoV-2 VL in the exudative phase of diffuse alveolar damage (DAD) was 60 times higher than in the proliferative phase. The SARS-CoV-2 VL in the lungs ranged from 0 to 250,281 copies. The “pulmonary factors” of SARS-CoV-2 multi-organ dissemination are the high level of SARS-CoV-2 VL (≥4909) and the exudative phase of DAD. The frequency of SARS-CoV-2 dissemination to lymph nodes was 86.9%, heart–56.5%, spleen–52.2%, liver–47.8%, kidney–26%, and brain–13%. We found no link between the SARS-CoV-2 VL level in the liver, kidneys, and heart and the serum level of CPK, LDH, ALP, ALT, AST and Cr of COVID-19 patients. Isolated detection of SARS-CoV-2 RNA in the myocardium of COVID-19 patients who died from heart failure is possible. The pathogenesis of COVID-19-associated multi-organ failure requires further research in a larger cohort of patients.

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Section: Discussionsupporting

confidence: 90%

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Odilov

Волков

Абдуллаев

et al. 2021

Viruses

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“…In contrast, no viral signal was found in platelets from survivors. At the ultrastructural level, spherical crowned structures with a diameter of 50-80 nm and visible spikes at their periphery typical of SARS-CoV-2 [26][27][28][29][30] were detected inside non-survivor platelets (Fig. 1F and Figure S3D).…”

Section: Platelets From Covid-19 Non-survivors Harbor Sars-cov-2mentioning

confidence: 99%

Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19

Zhu

Real

Capron

et al. 2022

Cell. Mol. Life Sci.

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SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome. Platelets containing SARS-CoV-2 might originate from bone marrow and lung megakaryocytes (MKs), the platelet precursors, which were found infected by SARS-CoV-2 in COVID-19 autopsies. Accordingly, MKs undergoing shortened differentiation and expressing anti-viral IFITM1 and IFITM3 RNA as a sign of viral sensing were enriched in the circulation of deadly COVID-19. Infected MKs reach the lung concomitant with a specific MK-related cytokine storm rich in VEGF, PDGF and inflammatory molecules, anticipating fatal outcome. Lung macrophages capture SARS-CoV-2-containing platelets in vivo. The virus contained by platelets is infectious as capture of platelets carrying SARS-CoV-2 propagates infection to macrophages in vitro, in a process blocked by an anti-GPIIbIIIa drug. Altogether, platelets containing infectious SARS-CoV-2 alter COVID-19 pathogenesis and provide a powerful fatality marker. Clinical targeting of platelets might prevent viral spread, thrombus formation and exacerbated inflammation at once and increase survival in COVID-19.

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“…Several studies have reported persistent shedding of viral RNA for an extended period after the onset of acute symptoms, as well as the presence of viral RNA and/or antigen in the gastrointestinal tissues of convalescent patients ( 4 – 7 , 9 ). Nevertheless, we believe that these two cases are the first to report detected viral antigen and/or RNA in the tissues of patients with LC.…”

Section: Discussionmentioning

confidence: 99%

Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID

Goh

Lim

Fernaíndez³

et al. 2022

Front. Immunol.

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The World Health Organization has defined long COVID-19 (LC) as a condition that occurs in individuals with a history of SARS-CoV-2 infection who exhibit persistent symptoms after its acute phase that last for at least two months and cannot be explained by an alternative diagnosis. Since we had previously reported residual viral antigens in tissues of convalescent patients, we aimed to assess the presence of such antigens in long COVID tissues. Here, we established the presence of the residual virus in the appendix, skin, and breast tissues of 2 patients who exhibited LC symptoms 163 and 426 days after symptom onset. With multiplex immunohistochemistry, we detected viral nucleocapsid protein in all three tissues. The nucleocapsid protein was further observed to colocalize with macrophage marker CD68, suggesting that immune cells were direct targets of SARS-CoV-2. Additionally, using RNAscope, the presence of viral RNA was also detected. Our positive finding in the breast tissue is corroborated by the recent reports of immunocompromised patients experiencing LC symptoms and persistent viral replication. Overall, our findings and emerging LC studies raise the possibility that the gastrointestinal tract may function as a reservoir for SARS-CoV-2.

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SARS-CoV-2 identified by transmission electron microscopy in lymphoproliferative and ischaemic intestinal lesions of COVID-19 patients with acute abdominal pain: two case reports

Cited by 18 publications

References 27 publications

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19

Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID

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