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Background: Hydroxychloroquine (HCQ) may be an effective, safe, and affordable treatment for Covid-19 that can be used in selected patients. However, more evidence on its association when it is used in different stages of the disease with clinical outcomes is required. This observational study investigates the association between treatment with HCQ and mortality in patients with Covid-19. Method(s): The data from 6217 patients who died or were discharged from 24 Spanish hospitals were analyzed. Propensity matching scores (PMS) were used. Result(s): 5094 patients received HCQ. Death was recorded for 17.5% of those who had HCQ and 34.1% of those who did not have it. Mortality was lower for those who had HCQ, OR=0.41 (95% CI=0.34-0.48). The PMS analysis also showed that mortality was lower for those receiving HCQ, OR=0.47 (95%CI=0.36-0.62). PMS analysis for categories revealed an association between HCQ and lowered mortality for patients over 65 years of age, with a past medical history of hypertension, for those who were diagnosed during admission with sepsis related organ failure or pneumonia, and for those with lymphocytopenia, raised troponin, LDH, ferritin and D-dimer. No increase in mortality associated with HCQ was observed in any category of any of the variables investigated. Conclusion(s): HCQ could be associated with lower mortality for older patients, those with more severe disease and raised inflammatory markers. Further RCTs, observational studies, and summaries of both types of evidence on this topic are necessary to select the precise profile of patients that may benefit from HCQ.Copyright © 2023 Bentham Science Publishers.
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Background: Acute myocarditis (AM) is a heart inflammatory disease that may also rarely occur as a complication of COVID-19 vaccines. Inflammation is involved in arrhythmogenic cardiomyopathy (ACM) pathogenesis. Little is known regarding the COVID-19 vaccines influence on ACM relapses. We present two cases of vaccine related AM revealing a pre-existent (silent) ACM. Cases presentation: Table shows a summary of the patients' main clinical characteristics. Discussion(s): We presented 2 cases of arrhythmic myocarditis-like clinical presentation in patients without previous cardiovascular history, whose timing was temporally related to a dose of vaccine against COVID-19. Subsequent diagnostic workup suggested the possible presence of an underlying silent ACM. In our case series, tissue characterization provided by CMR played a fundamental role as a diagnostic tool, showing in all cases a prominent left ventricle involvement and identifying both the underlying ACM disease and the superimposed myocardial inflammation. We hypothesize that a vaccine-induced AM could have revealed the presence of a pre-existent ACM, on which an inflammatory acute phase triggered the arrhythmic manifestation. Conclusion(s): Vaccine-induced AM could reveal the presence of a pre-existent ACM. Our report suggests that a high index of suspicion and a multidisciplinary approach is required, in order to continue the diagnostic process once the acute event has been resolved, as it may have fundamental implication in the patient management. Further studies are required to verify if some of the vaccine-triggered AM represent the ACM first manifestation..
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Background: Interaction between HIV and SARS-CoV-2 infection has not yet been fully characterized. To this purpose, an in-vitro HIV/SARS-CoV-2 coinfection assay was set up. Furthermore, the results obtained in the in-vitro model were verified in a cohort of HIV/SARS-CoV-2 coinfected young individuals. Methods: We designed an in-vitro SARS-CoV-2/HIV coinfection. We challenged PBMCs derived from 10 healthy volunteers with 1 ng/1×106 cells of HIV-1BaL and subsequently co-cultured them with a human lung epithelial cell line (CaLu3) infected with SARS-CoV-2 at 0.015 MOI. At 96 hours post HIV-1 infection, both PBMCs and CaLu3 cells were harvested for mRNA expression and proteomic analysis. Furthermore, we enrolled 85 ART-treated HIV-vertically transmitted patients (mean age 22.4 years) followed at the Unit of Pediatric Infectious Diseases, Sacco Hospital in Milan, Italy. Real-time PCR was performed to detect SARS-CoV-2 and plasma samples were tested for anti-SARS-CoV-2-specific IgG (Euroimmun Kit). The subjects who contracted SARS-CoV-2 infection (H+/S+) were compared to the HIV-positive, SARS-CoV-2 negative ones (H+/S-) and to a cohort of SARS-CoV-2 positive, HIV-negative age-matched patients (H-/S+, mean age 22.8 years). We evaluated mRNA expression of factors involved in the anti-viral immune response on PBMCs upon stimulation with SARS-CoV-2 antigens (Quantigene Plex assay) and secreted cytokines/chemokines on plasma (Multiplex Cytokine Array). Results: We observed a significant reduction of SARS-CoV-2 replication on CaLu3 cells when exposed to HIV-pre-infected PBMCs in-vitro. IL-10 expression and production were significantly higher in the coinfected condition, in both CaLu3 cells and PBMCs. The upregulation of IL-10 was associated to higher expression levels of STAT3. In the HIV-vertically transmitted cohort, 4 out of 85 subjects contracted SARS-CoV-2 infection (H+/S+). All H+/S+ patients were asymptomatic. Similarly to the data obtained in-vitro, a significant increase in both expression and production of IL-10 emerged in comparison to H+/S-and H-/S+. Conclusion: In-vitro, a dampening in SARS-CoV-2 replication, along with a higher IL-10 mRNA expression and production, have been observed in the HIV/SARS-CoV-2 coinfected condition. Presumably, IL-10 exerted its activity through the STAT3 pathway. These results were confirmed in HIV/SARS-CoV-2 coinfected subjects in which an upregulation of IL-10 was observed. Our data might be useful defining HIV/SARS-CoV-2 coinfected young individuals pathogenesis.
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Background: Recent studies highlight the dynamic nature of virus-host interaction during SARS-CoV-2 infection, raising intriguing questions about the role and timing of interferon (IFN) responses. In fact, SARS-CoV-2 delays/antagonizes Type-I, and to a definitely lesser extent, Type II-IFNs. While paving the way for potential antiviral therapies based on immune activation, the molecular mechanisms linking different IFN pathways to SARS-CoV-2 susceptibility remain to be elucidated. The present study investigates the role of Type-I &-II IFNs in SARS-CoV-2 replication in human lung cells, with a focus on molecular pathways related with innate and adaptive immunity. Methods: Human lung carcinoma cells (CaLu3) were pretreated with IFN-α,-β or-γ (from 1 to 1000 U/mL), O.N. Cells were infected with SARS-CoV-2 (MOI 0.05) for 3h, and IFNs were added during infection. In another set of experiments, IFNs were added only p.i. Supernatants were harvested at 24 and 48h p.i. to assess viral replication by RT-qPCR, and to quantify the levels of cytokines/chemokines through Multiplex assay. At 48h post-infection, cells were collected and RNA was retrotranscribed to investigate a variety of transcriptional targets. Cell viability was assessed by MTT. Results are presented as the average of the relative expression units to the GAPDH gene, calculated by the 2-ΔΔCt equation. Statistical analyses were performed through the Student t-test. Results: Pretreatment with both Type-I &-II IFNs dramatically reduces SARS-CoV-2 replication in the absence of cell toxicity. Such an effect is maintained, though at a lower magnitude, when IFNs are added only p.i. The antireplicative effects of Type-I &-II IFNs are associated with both convergent and divergent mechanisms. Both Types decrease the expression and/or protein levels of most pro-inflammatory mediators while augmenting anti-inflammatory and anti-apoptotic factors. Surprisingly, IFN-γ shows the strongest effect in potentiating antiviral effectors besides boosting adaptive immunity pathways. Remarkably, a convergent effect of both IFN Types is observed upon the expression of genes associated with DA activity, including DA receptors (D1-D5) and the DA transporter (DAT), which are dramatically altered by SARS-CoV-2. Conclusion: Both Type-I &-II IFNs halt SARS-CoV-2 replication by acting through complementary mechanisms. Their effects also disclose a potential role for DA activity, and neuromodulators in general, in host immunity during SARS-CoV-2 infection in pulmonary cells.
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Introduction: Preliminary reports from the early phase of COVID-19 epidemic in Italy reported a dramatic reduction in hospital admission rates for acute coronary syndromes (ACS) coupled with longer times from symptoms onset to hospital presentation. Purpose: To assess the impact of COVID-19 on hospital admission rates and ACS patterns, as well as time to presentation and clinical outcomes, following the acute pandemic phase in 2020 compared to previous year. Methods: We conducted a single institution retrospective analysis conducted in a cardiovascular hub serving a large metropolitan area in Italy. Number and monthly distribution of hospital admissions for ACS from January 1 to December 31, 2020 were compared to the respective figures in 2019. Baseline clinical features, time from symptoms onset to hospital admission and main clinical outcomes were collected. Results: A total of 599 ACS cases were recorded in 2020 vs. 386 cases in 2019, with a net 55% increase. ACS presentation rate in 2020 showed a bimodal pattern, paralleling the most contagious outbreak periods (Figure 1). SARS-CoB-2 nasopharyngeal swab or specific antibody tests were positive in 34 (5.7%) patients. Time from symptoms onset to hospital presentation tended to be longer in 2020 than in 2019, being two-fold longer during the peak epidemic phase (February 21-May 3, 2020;median time 2.0 vs. 5.0 hours, p=0.030). The proportion of late-presenting STEMI (>8 hrs from symptoms onset) was higher in 2020 compared to 2019 (30% vs. 18%, p=0.003),as well as higher was in-hospital mortality (15% in 2020 vs 6% in 2019, p=0.001), partly due to a three-fold increase in cardiogenic shock on ACS presentation. Conclusions: ACS admission rate significantly increased during the 2020 COVID-19 epidemic outbreak for several reasons only partially explained by a SARS-CoV-2 infection trigger effect on ACS. Longer presentation times and higher rates of cardiogenic shock and mortality were observed, urging the need health-care systems to keep a high priority on cardiovascular emergencies response networks. (Figure Presented).
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Background: The COVID-19 outbreak harmed acute coronary syndromes. During the national lockdown in Italy, the fear of post-admission contagion translated into significant delays in seeking medical help among STEMI (ST-elevation myocardial infarction) patients. Objective and methods: Our analysis aimed to assess the ACS (Acute Coronary Syndromes) admissions during the pandemic, together with time to presentation and clinical outcomes compared to 2019 in a cardiovascular hub in Milan. Data of ACS patients admitted during the pandemic year 2020 were extracted by the hospital & rsquo;s database and compared to a historical cohort of patients admitted for the same clinical indications in 2019. Results: A total of 599 ACS cases were recorded in 2020 vs. 386 cases in 2019, with a net 55% increase, associated with late clinical presentations, a threefold increase in cardiogenic shock, and a more than two-fold higher mortality rate. Conclusions: The ultimate goal of this analysis is to preserve the life-saving focus on universal and prompt STEMI diagnosis and treatment, even in a time of dynamic global crisis.
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BACKGROUND: Investigations demonstrated a decrease of admissions for myocardial infarction (MI) during the CoronaVirus Disease-19 (COVID-19) outbreak. No study has evaluated the time required to reverse this downward curve of MI admissions. METHODS: This is a retrospective analysis on patients (N = 2415) admitted to the Emergency Departments for acute MI in nine Italian centers. Primary endpoint was the incidence rates (IRs) of MI admissions in the post-lockdown COVID-19 period (case-period: from May 4 to July 12, 2020) vs. the following control periods: January 1-February 19, 2020 (pre-lockdown period);February 20-May 3, 2020 (intra-lockdown period);May 4-July 12, 2019 (inter-year non-COVID-19 period). RESULTS: IR of admissions for MI in the post-lockdown period was higher than the intra-lockdown period (IR ratio, IRR: 1.60, 95% CI 1.42-1.81;p = 0.0001), was lower than the pre-lockdown period (IRR: 0.86, 0.77-0.96;p = 0.009) and similar to the inter-year non-COVID-19 period (IRR: 0.96, 0.87-1.07;p = 0.47). Within the case period, the increase in MI admissions was more pronounced in earlier vs later weeks (IRR 1.19, 95% CI 1.02-1.38, p = 0.024) and, compared to the inter-year control period, was significant for non ST-segment elevation MI (IRR: 1.25, 95% CI 1.08-1.46, p = 0.004), but was not observed for ST-segment elevation MI (STEMI), where hospitalizations were reduced (IRR 0.76, 95% CI 0.65-0.88, p = 0.0001). CONCLUSIONS: Our study first indicates an increase in the number of admissions for MI after the removal of the national lockdown for COVID-19 in Italy. This increase was prevalent in the first weeks following the lockdown removal, but was under-represented in STEMI patients.
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INTRODUCTION: The impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined. METHODS: Consecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1-February 19, 2020) and previous-year control periods (February 20-May 3, 2019). ACS patients with Covid-19 were further compared with those without. RESULTS: Among 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively;p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%;p 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p < 0.001) compared to patients without. Moreover, higher rates of cardiovascular death, cardiogenic shock and sustained ventricular tachycardia were found in Covid-19 patients. CONCLUSION: ACS patients presenting during the Covid-19 pandemic experienced increased all-cause mortality, driven by Covid-19 positive status due to higher rates of cardiogenic shock and sustained ventricular tachycardia. No differences in cardiovascular mortality compared to non-pandemic scenarios were reported.
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Purpose Lung transplantation (LT) after severe SARS-CoV-2 infection is emerging as a life-saving medical procedure for selected patients who experience acute respiratory distress syndrome (ARDS). We present the first immunopathological evaluation of a lung allograft rejection in a patient who underwent LT because of irreversible ARDS related to COVID-19. Methods Two male patients with irreversible ARDS caused by COVID-19 underwent bilateral LT at our Institution. A surveillance transbronchial biopsy (TBB) was performed 2 months after LT in the first patient (Pt#1), while the second patient (Pt#2) died because of allograft rejection at day 62 post LT and explanted lungs were retrieved. CT imaging of the lungs was performed three days before death. Morphological examination was performed by H&E, whereas the immunophenotyping was performed by immunohistochemistry. Results Imaging and morphological examination of Pt#2 lungs indicated the presence of a graft dysfunction with features of a restrictive, widespread usual interstitial pneumonia-like syndrome (Fig. 1A, B). The immunophenotyping showed that B-lymphocytes (CD20-positive) were nearly absent, CD8-T-cells were not particularly expanded (mean positive cells within the lung stroma=13.8%;Fig. 1C), and the CD4/CD8 ratio was not decreased (Fig. 1D). The T-regs (Foxp3-positive) were 6% of the overall population (Fig. 1E). Analysis of the immune checkpoint molecules PD1, Tigit, CTLA4 and PDL1 showed that the expression of PD-L1 alone was highly increased in vases and in alveolar cells of rejected lungs, whereas it was nearly undetectable in the TBB from Pt#1 (Fig. 1F, G). Conclusion PDL1 expression in vases was previously documented as a sign of indirect ARDS. Together with our preliminary data, we can hypothesize that PDL1 may play a role in tissue effacement and graft failure, possibly indicating poor allograft prognosis.