ABSTRACT
Background: A considerable proportion of patients do not fully recover from COVID-19 infection and report symptoms that persist beyond the initial phase of infection: This condition is defined long-COVID-19 syndrome (LCS). LCS can involve lungs as well as several extrapulmonary organs, including the cardiovascular system. The risk and 1-year burden of cardiovascular diseases (CVD) is increased in COVID-19 survivors, even in subjects at low risk of CVD. Recently, we documented that acute COVID- 19 infection induces altered platelet activation state characterized by a prothrombotic phenotype and by the formation of platelet-leukocyte aggregates (PLA), that may be involved in the pulmonary microthrombi found in autoptic specimens. No data are yet available on the contribution of platelet activation to residual pulmonary impairment and procoagulant potential in LCS patients. Purpose(s): To study platelet activation status, microvesicle (MV) profile, platelet thrombin generation capacity (pTGC) in LCS patients enrolled at 6 months after resolution of the acute phase (6mo-FU), compared to acute COVID-19 infection patients. Method(s): 6mo-FU COVID-19 patients (n=24) with established LCS were enrolled at Centro Cardiologico Monzino. Residual pulmonary impairment was assessed by Cardiopulmonary Exercise Testing (CPET) and 64-rows- CT scan evaluation. Platelet activation (P-selectin, Tissue Factor [TF] and PLA) and MV profile were assessed by flow cytometry;pTGC by calibrated automated thrombogram. 46 patients enrolled during acute COVID-19 infection and 46 healthy subjects (HS) were used for comparison. Result(s): Dispnea in LCS patients was confirmed by CPET showing compromised alveolus-capillary membrane diffusion and residual pulmonary impairment. TF+-platelet and -MV levels were 3-fold (1.5% [1.2-2.9] vs 2.4% [1.6-5.7]) and 2-fold (217/mul [137-275] vs 435/mul [275-633]) lower at 6mo-FU compared to acute phase, being comparable to HS. pTGC behaved similarly. At 6mo-FU, the MV profile, in terms of total number and cell origin, returned to physiological levels. Conversely, although lower than that measured in acute phase, a 2.5-fold higher platelet P-selectin expression (6.9% [3-13.5] vs 11.7% [5.2-18.9]) and PLA formation (35.5% [27.4- 46.8] vs 67.7% [45.7-85.3]) was observed at 6mo-FU compared to HS. Interestingly, a significant correlation between PLA formation and residual pulmonary impairment was observed (r=-0.423;p=0.02). Conclusion(s): These data strengthen the hypothesis that the presence of PLA in the bloodstream, and thus also in the pulmonary microcirculation, may contribute to support pulmonary dysfunction still observed in LCS patients.
ABSTRACT
Background: It is known that a lot of global consequences after COVID 19 infection were seen. In symptomatic cases, after discharge from hospital, global psychological and physical status was changed in approximately 75% of patients, as was reported in recent literature. We follow up recovery of chest x-ray changes and disappearance of lung function sequels six months after discharge. Aim and objectives: To analyze what was the time frame for recovery of function of alveolo-capillary membrane, assessed by measurement of transfer factor for carbon monoxid (DLco) across the alveolo-capillary membrane. Method(s): Patients treated for COVID 19 in General hospital Tesanj were analyzed. Measurement of DLco was performed three months after discharge from hospital. Patients with severe disease, according to classification adopted for assessment of COVID 19 infection, were included in the study. Result(s): We analyzed 60 patients, 30 of them with therapy by metil prednisolone and 30 without. Therapy with metil prednisolone was 8 mg BID (two times a day) 10 days after discharge, then 4 mg BID in next 10 days. Average DLco was 68.45% of predicted value in patients with no steroid treatment, and 76.49 % in treated group. Chest X-ray resolution of sequels of COVID 19 was better in patients with steroid treatment than in those without. Symptoms of cough and fatigation disappeared more effectively in treated group. Conclusion(s): In patients after COVID 19 infection inappropriate DLco was seen, but recovery of function of diffusion of gases across alveolo-capillary membrane, measured by DLco, was better in patients treated with tablets of metal prednisolone than in those without.
ABSTRACT
Background: Many patients recovered from COVID-19 infection present a variety of symptoms which limits overall quality of life, as reduced exercise performance, dysfunctional breathing, cough, dyspnea, weakness and anxiety. This condition has been named long COVID. The origin of this symptomatology is still unclear. This study has the aim to analyse the relation between symptoms and respiratory function, focusing on the alveolar capillary membrane. Method(s): Consecutive patients with long COVID 19 symptoms after 6 months were included. Patients underwent full clinical evaluation, laboratory tests, echocardiography, thoracic CTscan, spirometry including alveolar capillary membrane diffusion by means of combined carbon dioxide and nitric oxide lung diffusion (DLCO/ DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar capillary function. A questionnaire allowed to evaluate symptoms. Result(s): We evaluated 204 post COVID-19 patients (age 56.5+/-14.5 y, 89 females (44%), BMI 25.7+/-4.0, 6% active smokers) referring to our hospital 171+/-85 days after the end of acute COVID-19 infection (Fig. 1). None of spirometry data was associated with long COVID 19 referred symptoms. SPB was not associated to differences in any of the referred symptoms. Subjects with lower capillary volume (VCap) have more frequently dyspnea, tiredness, fatigability and hair loss (Fig.2). CT scan lung damage correlated with SPB and membrane diffusion but not with VCap, exercise performance or VE/VCO2 slope. The strongest correlation of SPB were with lung parenchyma damage and Vcap. Conclusion(s): Our data suggest that a relevant reduction of alveolar capillary membrane function plays a central role in the long COVID cardiorespiratory symptoms. (Figure Presented).
ABSTRACT
Beside lowering the surface tension at air-liquid interface in the alveoli, the pulmonary surfactant has a pivotal role in triggering the elimination of pathogens or any hazardous materials introduced with breathing. Among the components of the pulmonary surfactant, surfactant protein-D (SP-D) is a low abundant (0.6%) hydrophilic protein that is able to promote pathogens clearance binding highly conserved glycosidic residues on their surface. SP-D also cooperates in the maintenance of lung homeostasis by directly modulating immune system activity. Previous investigations on acute respiratory distress syndrome (ARDS) patients demonstrated a significant increment of SP-D serum level compared with healthy donors. Since in physiological condition SP-D is not permeable to alveoli-capillary membrane and poorly express by other tissues, this enhancement is likely due to an impairment of the pulmonary barrier caused by prolonged inflammation. In view of the above, the present work aims to investigate SP-D as diagnostic and/or prognostic marker for COVID-19. In particular, a retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio (i.e., 79 mild cases plus 123 severe cases) was conducted to assess differences of the hematic levels of this biomarker among COVID-19 patients and healthy donors and if SP-D serum levels resulted a risk factor for disease severity and mortality. The performed analyses, using an Anova-Mixed model, showed a significant difference in the mean of log SP-D between COVID-19 patients and healthy donors: 150 ng/mL was identified as threshold value to best discriminate the mentioned groups. Significant differences were also found between dead vs survived patients, as well among severe vs non-severe cases. In all cases, SP-D serum levels presented significantly higher values for COVID-19 patients, dead and severe cases.Moreover, further analysis conducted with Logistic Mixed models, highlighted that SP-D, in a model with Age, C-reactive protein and cancer status, resulted the strongest significant risk factor of mortality (model predictive accuracy, AUC=0.826), and in a lesser extent for risk of severity.The overall data suggest that SP-D can be a predictive marker of COVID-19 disease and its outcome.
ABSTRACT
Background: Long-COVID- 19 syndrome (LCS) is defined as symptoms persisting beyond initial phase of infection. Among them, pulmonary fibrotic damage remains in 25-30% of COVID-19 patients at 3-6 month-follow- up. We documented that acute COVID-19 patients have massive platelet activation characterized by the formation of platelet-leukocyte aggregates (PLA), that may be involved in the pulmonary microthrombi found in autoptic specimens, and by a prothrombotic phenotype. No data are currently available on contribution of platelet activation to residual pulmonary impairment and procoagulant potential in LCS patients. Aim(s): To characterize platelet activation, microvesicle (MV) profile, platelet thrombin generation capacity (pTGC) in LCS patients at 6-month- follow- up (6mo-FU) compared to acute COVID-19 infection patients. Method(s): Twentyfour 6mo-FU COVID-19 patients with established LCS defined according to their residual pulmonary impairment assessed by Cardiopulmonary Exercise Testing (CPET) and 64-rows- CT scan evaluation were enrolled. Platelet activation (P-selectin, Tissue Factor [TF] and PLA) and MV profile were evaluated by flow cytometry;pTGC by calibrated automated thrombogram. Fortysix patients enrolled during acute COVID-19 infection and 46 healthy subjects (HS) were used for comparison. Result(s): Dispnea in LCS patients was confirmed by CPET showing compromised alveolus-capillary membrane diffusion and residual pulmonary impairment. TF+-platelet and -MV levels were 3-and 2-fold lower at 6mo-FU compared to acute phase, being comparable to HS, as well as pTGC. At 6mo-FU, the MV profile (total number and derived from different cells) returned to physiological levels. Conversely, although lower than that measured in acute phase, a 2.5-fold higher platelet P-selectin expression and PLA formation was observed at 6mo-FU compared to HS. Interestingly, a significant correlation between PLA formation and residual pulmonary impairment was observed. Conclusion(s): These data strengthen the hypothesis that the presence of PLA in the bloodstream, and thus also in the pulmonary microcirculation, may contribute to support pulmonary dysfunction still observed in LCS patients.
ABSTRACT
Introduction: Despites reports of glomerulonephritis associated with COVID-19 mRNA vaccines, no study has reported about the dense deposit disease (DDD). Here we present a case of pseudolung cancer lymphadenopathy following COVID-19 mRNA vaccine, following which the patient developed idiopathic tubulointerstitial nephritis (TIN) and DDD. Case Description: A 74-year-old man received his second dose of the mRNA vaccine, and he developed fever, urticaria, and dyspnea. On further examination, he had pleural effusion and right hilar lymphadenopathies, which were improved with conservative therapy. On 48 days after the second vaccination, he developed renal dysfunction and new-onset hematuria. Light microscopy findings by a renal biopsy demonstrated apparent mesangial cell proliferation and diffuse inflammatory cell infiltration in the interstitium. Immunofluorescence analysis revealed 1+ positive results for IgG and IgM, negative results for IgA, and 2+ positive results for C3 with a garland pattern on the capillary walls. Electron microscopy detected that continuous and thickened highly dark-stained spotty dense deposits in the glomerular basement membrane. Based on the decrease in C3 and pathological findings, idiopathic TIN accompanied with DDD was diagnosed. Discussion(s): After vaccination acute allergic reaction, pseudolung cancer lymphadenopathy, hematuria, and hypocomplementemia were observed. Thus, both coincidental onset with DDD and TIN following acute allergic response that occurred about 7 weeks before made us think that each event or disease might be associated with COVID-19 mRNA vaccination as part of immunological reactions. In complement activation related pseudoallergy syndrome, it is recently recognized that several modernday therapeutic molecules may activate complements via the nonIgE mediated mechanism with the C3a and C5a anaphylatoxins binding to mast cells, triggering that the release of a number of several vasoactive mediators that cause the clinical features associated with hypersensitivity reactions. mRNA vaccine might have contributed to the development of lymphadenopathies, TIN and DDD in this case. Moreover, TIN and DDD might be associated with the activated alternative pathway induced by the mRNA vaccine.
ABSTRACT
Objective: To assess clinical and pathomorphological features of kidney damage in patients with arterial hypertension (AH) who died of the new coronavirus infection COVID-19. Design and method: A complex analysis of 268 kidney autopsies was carried out, including the study of macro- and microscopic changes reflected in the protocols of pathological and anatomical autopsies and identified during the histological examination. In 224 patients (83.6%) with AH, the diagnosis was confirmed by isolating the SARS-CoV-2 RNA using the polymerase chain reaction;in 44 (16.4%) - through computed tomography of the lungs. The causes of deaths were the following: in 31 patients (11.6%) acute myocardial infarction;in 40 (14.9%) cerebrovascular accident;in 11 (4.1%) pulmonary embolism;222 patients (83%) had acute respiratory distress syndrome. The analysis included 130 men aged 36 to 92 (72.6 years old on average) and 138 women aged 40 to 106 (77.1 years old on average). Results: In the kidneys we detected ischemic changes caused by disturbances in the microvasculature. These are stases, sludges, erythrocyte and fibrin thrombi predominantly in the medulla. In the glomeruli diapedesis hemorrhages, mesangial cells proliferation, basement membrane thickening and fibrinoid necrosis of the capillary wall were observed. In the epithelium of the convoluted tubules, a granular, hyaline-drop dystrophy and a necrosis as the extreme degree of the damage were noted. In the kidneys, a pronounced lymphoid and leukocyte infiltration was detected. These changes were accompanied by inflammation and renal failure symptoms. In particular, the level of C-reactive protein was 140.6 ± 7.42 mg/l;blood ferritin 1258.0 ± 110.1 mcg/l;blood leukocytes 15.0 ± 0.67 10