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Introduction: We report a case of a 67 year old lady with an acute drop in conscious level whilst on a transatlantic flight. She had a background history of TII DM and recent mild COVID. Past surgical history of a gastric bypass, at which time a CXR had incidentally shown a bulla, with no underlying respiratory symptoms, or history of COPD. Method(s): On arrival in the emergency department, her GCS was 7/15, and she required immediate intubation. Non-contrast CT head showed multiple tiny gas locules in keeping with air emboli. CT Chest, Abdo, Pelvis showed an 88mm bulla within the left lung lingula with a bronchus and many large pulmonary vessels running on its edge. Result(s): It was thought the change in air pressure during the flight caused a communication to open between the bulla and the pulmonary circulation resulting in the release of air emboli. Conclusion(s): She required ITU admission for 8 days. After initial stabilisation she was stepped down to HASU. Neurologically she was dysphagic, dysarthric, quadriplegic and GCS 14 due to confusion. MRI whole spine ruled out spinal cord pathology. Repeat CT head showed air initially present had completely resorbed leaving multifocal, small areas of cortical and subcortical ischaemia in both cerebral hemispheres. MRI head confirmed innumerable small early subacute embolic ischaemic infarcts across multiple vascular distributions.
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The pathophysiology behind Coronavirus Disease-2019 (COVID-19) has remained blur even after more than two years of onset of the pandemic. Apart from pulmonary parenchymal involvement, widespread vascular thrombosis affecting both pulmonary and extra-pulmonary systems has also been seen to contribute to COVID-19 associated morbidity. This vascular manifestation often remains undiagnosed due to non specific and varied symptoms that range from asymptomatic detection to life threatening presentations. A series of six COVID-19 positive (three male and three female) cases who presented with thrombosis of pulmonary, coronary and cerebral vessels despite being on thromboprophylaxis are reported herein. The age of patients ranged from 32 to 80 years. Out of six patients, three had comorbidities. The most common complication was Pulmonary Thromboembolism (PTE, n=3) followed by Brain infarct (n=2) and Myocardial Infarction (MI, n=1). Out of three patients with PTE, one patient had concurrent Deep Vein Thrombosis (DVT). All patients were managed as per guidelines issued by the Ministry of Health and Family Welfare for severe COVID-19 disease. Out of six patients, three patients died and three were discharged. The series highlights the need for high index of suspicion on the part of the treating physician that could aid in early detection and successful management of this potentially fatal condition.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.
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The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected — asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki–Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. Сo-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome. © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected — asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki–Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. Сo-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome.
ABSTRACT
The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected - asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki-Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. So-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
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Background: Coagulopathy and inflammation are hallmarks of COVID-19 and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19. Mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. Aim(s): In this study, we aimed to investigate a possible role of NETs-driven coagulation factor XII (FXII) activation in COVID-19- related thrombo-inflammation. Method(s): We performed comprehensive proteomics and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We compared FXII and DNase1 activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced FXII activation using a chromogenic substrate assay. Result(s): FXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients over controls. Active FXII (FXIIa) was increased in plasma of COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII activation in COVID-19. Accumulation of NETs in COVID-19 was at least in parts due to impaired DNA clearance by extracellular DNases. In plasma from COVID-19 patients, DNase1 substitution improved NET dissolution and reduced FXII activation in vitro. Conclusion(s): Collectively, our study shows that the NETs/FXIIa axis contributes to procoagulant and proinflammatory reactions in COVID-19. Targeting NETs and FXIIa may offer a potential therapeutic strategy for interfering with the COVID-19 lung pathology.
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Background: PAI-1 plays a key role in a wide range of physiological and pathological processes, including coagulation, fibrinolysis, inflammation. Aim(s): The aim was to estimate the prognostic role of PAI-1 on admission in hospitalized patients with confirmed COVID-19 pneumonia. Method(s): We observed 2 groups: Main -85 patients (age -59 (52;65) years, men -45 (52.9%)), hospitalized with pneumonia on the background of laboratory-confirmed (PCR) COVID-19;Control -25 healthy volunteers (age -50.0 (35;65) years, men -13 (52.0%)). General analysis, determination of PAI-1 (Human PAI-1 ELISA Kit, Elabscience) performed at admission before starting of anticoagulant treatment, autopsy data, statistical analysis. Result(s): At admission the level of PAI-1 in Main group was in 60 times higher than in Control group (6.1 [0.15;18] ng/ml versus 0.1 [0.09;0.11] ng/ml, p=0.000). Despite the adequate treatment 12 patients died from COOVID-19 pneumonia. Maximal levels of PAI-1 were in died patients. ROC analysis shows the powerful reliable connection between increased level of PAI-1 higher than 20.6 ng/ml at admission and COVID-19 mortality (Fig.1) (OR = 219;CI = 95% (7.7056 to 6224.1404);p = 0.0016). Autopsy shown a lot of fibrin clots in lung vessels, which proves the theory that problem in fibrinolysis plays the crucial role in thrombogenesis in COVID-19. Fig.2 demonstrates histological section of the artery of medium caliber, branching of the pulmonary artery, in horizontal projection, a fragment of vascular endothelial integrity violation was isolated, the arrow indicates a pale pink non-nuclear mass in the form of threads -fibrin clot. Conclusion(s): 1) problem in fibrinolysis plays the crucial role in thrombogenesis in COVID-19;2) increased level of PAI-1 at admission more than 20 ng/l is associated with 200-times higher risk of mortality. (Figure Presented).
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SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Inhaled nitric oxide (iNO) is a potent vasodilator of pulmonary vasculature improving perfusion to ventilated alveoli in ARDS and other lung pathologies. During the pandemic, intensivists turned to iNO as “salvage” therapy in COVID-19 patients. Rationale was driven by vasodilatory effect and antiviral properties despite lack of evidence of clear benefit even in patients without COVID. We hypothesized that iNO would provide reduced increases in pulmonary perfusion and subsequent gas exchange improvement in COVID-19 patients due to extensive endothelial damage and coagulopathy throughout the pulmonary vasculature. METHODS: Our IRB exempt analysis examined patients hospitalized with and without COVID-19 from January 2020 to September 2021 who received at least 24h of invasive mechanical ventilation with iNO (15-20ppm). Effectiveness outcomes were PaO2/FIO2 ratio(PFR), PEEP/CPAP level, and PaCO2 serially measured and observed up to 24 hours prior to initiation of iNO and for up to 120h post iNO administration. Data were statistically controlled for age, sex, race, time to initiation of therapy and COVID-19 directed treatment. RESULTS: From January 2020 and September 2021, 42 patients were admitted to the ICU and received invasive mechanical ventilation and iNO. Results are sequenced as ARDS COVID-negative, ARDS COVID-positive, viral pneumonia COVID-negative, viral-pneumonia COVID-positive. Patient n = 8/14/6/14. Median age was 56/55/63/62 years. Demographics split 64-62% male vs 36-38% female in ARDS without/with COVID, 50%/83% male vs 50%/17% female in viral pneumonia without/with COVID. Racial distribution resulted 75%/93%/86%/83% White vs 25%/0%/17%/14% Black. Other races constituted less than 7% of patient total in any category. PFR delta from -24h to +120h post-iNO = +35/+35/+41/+22. PEEP/CPAP delta from -24h to +120h = -4/-1/-3/-2. PaCO2 delta mmHg from -24h to +120h = -21/-23/-9/-13. Median Hospital LOS = 26/26.5/17/19 days. Median ICU LOS = 15.8/19.0/13.8/17.6 days. Hospital mortality = 100% across all 4 subgroups. CONCLUSIONS: ARDS patients with or without COVID showed similar rates of PFR response to iNO, however viral pneumonia patients with COVID exhibited a blunted PFR response vs those without COVID. No statistically significant difference was observed with respect to PEEP/CPAP levels, PaCO2 mmHg, hospital or ICU LOS, or mortality. CLINICAL IMPLICATIONS: Our findings suggest that the presence of COVID-19 did not significantly inhibit response to iNO in ARDS or other viral pneumonia patients. Further evaluation of other indirect markers of gas exchange could provide further evidence of responsiveness. DISCLOSURES: No relevant relationships by Katherine Burns No relevant relationships by Karen Hamad No relevant relationships by Bobby Malik No relevant relationships by Richard Walo Jr No relevant relationships by Wilhelmine Wiese-Rometsch No relevant relationships by Stephanie Williams
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SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: As the coronavirus pandemic continues to burden the global health care system, strong associations have emerged with hypercoagulability. Recent reports of Covid-19 support both venous and arterial thromboembolism, thus coagulopathy emerging as one of the most severe sequelae of the disease, which has also been associated with poorer outcomes. CASE PRESENTATION: A 71-year-old female with a past medical history of hypertension, type 2 diabetes, and obesity presented with progressively worsening shortness of breath and cough. She was found to be hypoxic to 80% on arrival and tested positive for COVID-19. She was subsequently intubated and admitted to the ICU. Her D-dimer was noted to be 9.04mcg/mLFEU (0-0.55mcg/mLFEU), ferritin 256ng/mL(10-291ng/mL), LDH 707 U/L(130-270U/L), CRP 138mg/L (< 10mg/L). She was treated with a ten-day course of dexamethasone and a five-day course of Remdesivir. On Day 7, purple discoloration was noted in the second to fifth digits of the left hand, concerning acute ischemia. Left upper extremity ultrasound revealed intraluminal heterogeneous echogenicity likely occlusive ulnar arterial thrombus with no flow to mid or distal segment and normal flow in the radial artery into a complete palmar arch. This was seen to be classical for micro-embolic phenomenon attributable to the hypercoagulable state associated with Covid-19 infection. Treatment with Heparin drip was initiated along with the local application of nitro paste. The patient was subsequently discharged home but re-presented a month later for gastrointestinal bleeding. At this admission, her left second digit was noted to express purulent drainage. Imaging confirmed osteomyelitis in the second through fifth digits and was referred to a tertiary center for definitive treatment. DISCUSSION: Covid-19 has been shown to provoke catastrophic inflammatory responses by triggering a dysfunctional cascade of thrombosis in the pulmonary vasculature leading to both micro and macroangiopathic manifestations. The quick progression of ischemia to digital gangrene, despite collateral circulation and early intervention, indicates severe microangiopathy. CONCLUSIONS: Thus physicians must always have a high index of suspicion for thromboembolic complications in patients with Covid-19. The development of severe complications despite prompt anticoagulation highlights the need for alternative or newer therapies like targeted immunotherapy that would effectively manage these complications of SARS-CoV-2. Reference #1: Digital Gangrene as a Sign of Catastrophic Coronavirus Disease 2019-related Microangiopathy Jessica S. Wang, MD,* Helena B. Pasieka, MD, MS,† Vesna Petronic-Rosic, MD, MSc, MBA,† Banafsheh Sharif-Askary, MD,* and Karen Kim Evans, MDcorresponding author Reference #2: Galván Casas C, Català A, Carretero Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez-Villa Lario A, Navarro Fernández I, Ruiz-Villaverde R, Falkenhain-López D, Llamas Velasco M, García-Gavín J, Baniandrés O, González-Cruz C, Morillas-Lahuerta V, Cubiró X, Figueras Nart I, Selda-Enriquez G, Romaní J, Fustà-Novell X, Melian-Olivera A, Roncero Riesco M, Burgos-Blasco P, Sola Ortigosa J, Feito Rodriguez M, García-Doval. Classifications of the cutaneous manifestations of Covid-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020 Jul;183(1):71-77. doi: 10.1111/bjd.19163. Epub 2020 Jun 10. Reference #3: Mouhamed Yazan Abou-Ismail 1, Akiva Diamond 2, Sargam Kapoor 3, Yasmin Arafah 2, Lalitha Nayak 4.The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management Thromb Res. 2020 Oct;194:101-115. doi: 10.1016/j.thromres.2020.06.029. Epub 2020 Jun 20. DISCLOSURES: No relevant relationships by Navyamani Kagita No relevant relationships by ABHIGNA KULKARNI No relevant relationships by Rajesh Thirumaran
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Disorders in pulmonary vascular integrity are a prominent feature in many lung diseases, including acute respiratory distress syndrome (ARDS), capillary leak syndrome, and COVID19. Paracrine signals are enriched in the lung and are critically important in regulating the homeostasis of the functional pulmonary microvasculature. Here, we employed single-cell RNA-sequencing (scRNAseq) to study ligand and receptor interactions in the native human lung microvascular niche, and identified soluble factors that are critical in endothelial integrity. The scRNAseq data reveals a total of 47 cell populations consisting of five vascular endothelial subtypes in human lungs, including general capillary EC, aerocyte capillary EC (EC aCap), arterial EC, pulmonary venous EC, and systemic venous EC. Using EC aCap as a signal receiving core (Receptors) and the putative adjacent cell types (alveolar fibroblast, ATI, ATII, pericyte, plasma cell, etc.) in the EC aCap niche as senders (Ligands), we identified that SLIT2-ROBO4, ANGPT1-TIE1, ADM-RAMP2, VEGFD-KDR, and BMP5-BMPR2 are the top specific and abundant pairs in the niche. Immunostaining and ELISA assays confirmed their spatial information and secretion level. Furthermore, upon treatment with these ligands, real-time resistance recorded using an electric cell-substrate impedance sensing (ECIS) system revealed that VEGFD, ANGPT1 (angiopoietin 1), and ADM (adrenomedullin) could markedly increase the electrical resistance of human lung microvascular, arterial, and venous endothelial cells, suggesting their strong impact on the endothelial barrier function. Deciphering the cell-cell soluble signals that improve endothelial integrity in human lungs lays the foundation for uncovering the pathogenesis of pulmonary vascular disorders and the development of ex vivo functional lung vasculature.
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Introduction: Older age is an important risk factor for severe COVID-19 disease. Understanding the biological mechanisms that link aging to the pathogenesis of COVID-19 is essential for developing of therapeutic strategies. We hypothesized that cell senescence, a basic aging process that plays a pivotal role in lung diseases, is involved in the pathogenesis of COVID-19 including the development of long-lasting lung alterations. Methods: To evaluate the impact of SARS-CoV-2 infection on cell senescence, we 1) analyzed publicly available datasets of scRNA-seq performed in BALF cells from patients with moderate or severe/critical COVID-19;2) investigated lung samples from cynomolgus macaques infected with 106 pfu of a SARS-CoV-2 clinical isolate. Two macaques were sacrificed at 4 days post-infection (dpi.) and two others at 30 dpi. Results: In BALF obtained within 10 days after symptom onset, the expression of several senescence markers, i.e., CDKN2A, CDKN1A (encoding p21), uPAR, CXCL8, IGFBP3, and GDF15 was significantly increased in epithelial cells in BALF from patients with severe COVID-19, suggesting that lung-cell senescence induction was contemporary of viral detection. Next, we investigated macaques at 4 and 30 dpi, corresponding respectively to the viral load peak and to the absence of detectable viral RNA in BALF (1). Immunohistochemical analysis revealed numerous SARS-CoV-2 antigen-stained cells, also co-stained for senescence markers p16- and p21. The lungs at 30 dpi no longer contained the consolidated parenchymal areas seen at 4 dpi but showed extensive lung parenchyma remodelling, with thickening of the alveoli and pulmonary vessel walls and abundant extracellular matrix deposits as assessed by collagen staining. These lesions were accompanied with massive accumulation of p16- and p21-positive cells, mostly pneumocytes II and ECs. Of note, p16 staining of most ECs was seen in pulmonary vessels, notably those occluded by thrombosis and showing intraluminal vWF staining. Cells stained for p16 were also stained for the DNA damage markers γ-H2AX protein and p53-binding protein 1. Conclusions: Our data constitute the first evidence of temporal and topographic relations between senescent-cell accumulation and pulmonary lesions induced by SARS-CoV-2 infection.