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: 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: High non-adherence rates to CPAP remain a major obstacle to good outcomes in OSA. In trials, 29%-83% of patients do not adhere to CPAP. CPAP adherence in clinical practice, and the effect of clinical pathways and interventions, remain unknown because of incomplete datasets and use of non-clinically relevant criteria for adherence in previous studies. Patients are reported to become adherent or non-adherent to CPAP from treatment onset, forming the basis of current clinical practice, but the studies have been small. We addressed these evidence gaps using a large, UK multicentre clinical dataset, using changes to sleep centres' treatment pathways during the COVID-19 pandemic as a natural experiment. Method(s): Five sleep centres that telemonitored patient data in 2019 and 2020 were recruited. Using a 18% difference in CPAP adherence between years (Philips Respironics data), 80% power, alpha < 0.05, n = 92 was required. Objective CPAP-usage data over the first three months of treatment was collected from 100 patients who started CPAP prepandemic (April 2019) and 100 patients post-start of pandemic (September 2020), per centre. CPAP adherence criteria: Mean CPAP use >=4 h/night for >=70% of nights (for Night 1-3 period, median CPAP use used, as data non-normally distributed). Growth mixture modelling (GMM) and logistic regression were performed using all centres' data (1000 patients). Result(s): Three months after treatment started, only 34% of patients were treatment-adherent in 2019 and 42% in 2020 (p = 0.24). GMM identified six distinct, CPAP-usage behaviours over the first month, each with a different likelihood of CPAP non-adherence at three months. Four behaviours consisted of changing (increasing or decreasing) CPAP use (54% of patients), two behaviours consisted of consistent good or no use (remaining 46%). Treatment pathway determined prevalence of behaviours and CPAP adherence at three months;OSA severity was a weaker determinant of CPAP adherence at three months. Conclusion(s): CPAP use at treatment onset does not predict long-term adherence in most patients. This can explain why current practice is ineffective, and may even be detrimental, as the changing users are inappropriately managed as consistent users . Our data supports precision medicine tailored to specific behaviour from Week 2 of treatment.
ABSTRACT
Objective: Background: Hypertension is associated with increased risk of severe COVID-19 and increased mortality. The knowledge about the impact of blood pressure lowering medications on outcomes is still incomplete: whilst studies about renin-angiotensin-aldosterone system inhibitors did not show association with increased mortality, less is known about the impact of other antihypertensive classes. Diuretics, in particular, are frequently used in patients with hypertension thus we aimed to investigate the association between diuretics and mortality in a cohort of COVID-19 patients hospitalized in two referral centers in the Lombardy region (Istituto Auxologico Italiano and Humanitas Research Hospital) Methods: Data of con firmed COVID-19 patients, with information available about drug treatment and outcomes, were pooled together. Socio-demographic clinical features, and medications pre and during hospitalization were retrieved patients were classi fied according to the use of diuretics before and/or during hospitalization. The effect of diuretic use before and during hospitalization on death was estimated by means of a multiple Poisson regression model with robust variance and reported as Relative Risk (RR) and 95% con fidence interval (95% CI) Design and method: From the pooled sample of 637 patients, a final sample of 502 patients with complete data was analyzed (mean age 67 years, 67% males, 54% patients with hypertension). Among hypertensive patients, 64% were not treated with diuretics either pre-or during hospitalization (Reference group), 15% had diuretic treatment only during hospitalization (Group A), 9% only pre-hospitalization (Group B) and 12% both pre-and during hospitalization (Group C) After adjusting for confounders (age, sex, respiratory rate at admission, number of comorbidities, number of other drugs taken during hospitalization, orotracheal intubation), use of diuretics only during hospitalization was signi ficantly associated with mortality (Figure 1) Conclusion: Our data show an association between diuretic use only during hospitalization and worse outcome in patients with COVID-19. Such association needs to be further investigated in order to possibly improve outcomes in patients admitted for COVID-19 Figure 1: Relative Risks and 95% con fidence intervals of patients treated with diuretics only during hospitalization (Group A), only during pre-hospitalization (Group B) and during both pre-and hospitalization (Group C). The subgroup of patients not treated with diuretics neither pre-nor during hospitalization was taken as the reference group.