ABSTRACT
Background: COVID-19 infection can lead to a constellation of longlasting post-infectious sequelae, including myocardial dysfunction, whose outcome is strongly affected by a fine-tuned balance between pro-and anti-inflammatory systemic immune responses. Plasma cytokines are key mediators of this immunological balance. In this preliminary study we evaluated the cross-sectional association between the circulating levels of the main pro-and anti-inflammatory cytokines and cardiac magnetic resonance (CMR) abnormalities. Method(s): 71 subjects (59% female, mean age 52+/-14) with previous diagnosis of COVID-19 infection were enrolled at our institution for MULTICOVID protocol, comprehensive of CMR and biomarkers assessment performed >3 months and <1 year following the first negative swab test. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Plasma levels of cytokines TNF-alpha, IL-1beta, IL-1alpha, IFN-alpha2, IL-6, IL-8, IL-13, IL-10, IL-17A, IL-18, IP-10, MIG and MCP-1 were quantified by Multiplex Immunoassays on the Luminex technology platform. Soluble cardiologic and biochemical biomarkers were measured by routine laboratory analysis. Result(s): After a median of 9 (IQR 6-11) months following negative swab, CMR was normal in 48 subjects, while in 23 (32%) it revealed tissue characterization abnormalities (myocardial late enhancement and/or edema). By multivariate regression analysis (adjusted for age, sex, vaccination, severity degrees of the initial COVID disease, presence of comorbidities, smoke, time interval between COVID diagnosis and CMR assessment) the cytokine ratio TNF-alpha/(IL-10+IL-13) was independently associated (OR=2.89, 95% CI 1.19-7.04, p=0.02) with CMR abnormalities. Interestingly, the cumulative pro-/anti-inflammatory cytokine ratio (IL-1beta+TNF-alpha+IFN-alpha2+IL-6+IL-17A+IL-8)/(IL-10+IL-13) showed a positive (OR=1.70, 95% CI: 1.04-2.75) and significant (p=0.03) association with CMR imaging aspects. Also, the ratio IFN-alpha2/(IL-10+IL-13), although without achieving a complete statistical significance (p=0.09), was associated positively with CMR findings. Conclusion(s): The preliminary results of this cross-sectional study suggest that the systemic inflammatory environment, long-lasting unbalanced towards a prevalent cytokine-driven pro-inflammatory condition following COVID infection, could affect the development of CMR-detectable myocardial edema and fibrosis in long-term post-COVID subjects.
ABSTRACT
Introduction: On December 21st, 2020, the European Medicine Agency authorized the first SARS-CoV-2/COVID-19 vaccine. As far as the organizational, procedural and monitoring aspects of the vaccination campaign are concerned, it was necessary to follow the regional guidelines and activate the health authority paths. Target: Defining the training plan for preparation and administration based on bookings, availability of vaccine doses and proper storage. Planning the vaccination process. Materials and Methods: Applying a Work Breakdown Structure we have decomposed the project in sub-projects into sub-projects and their macro-activities, chosen the health care workers involved, scheduled the meetings, drafted the internal path coordinating with logistics and resources. We met daily to standardize information and establish the steps achieved and tackle the next ones. We organized the training sessions and recruited the dedicated staff. Results: The vaccination organization structurally required 5 nursing clinics and 6 medical clinics and a booking agenda. Sending an e-mail communication containing all the information and the forms for informed consent and medical history facilitated and speeded up the medical examination. The training involved 16 nurses and 6 doctors. The nurses followed a theoretical-practical course with simulation for dosage and drawing the right amount in order to guarantee the presence of the 6th dose. We identified a vaccine-like bottle filled with the expected total liquid amount. To guarantee everyone the test, we set up more testing stations, the people concerned repeated the sequences also verbally. The health care professionals prepared, using the standard aseptic technique, all the steps from dressing to handling, dilution and withdrawal, in order to obtain the 6th dose. The outcome of the training process was verified on the very day of the vaccinations when we counted the final results with the possibility of obtaining the 7th dose from the single bottle and/or the recovery of one dose for every two bottles used. Conclusions: This process requires special care in order to ensure a correct and safe practice with the goal of optimizing vaccine doses and vaccinate more people. The staff responded with excellent participation and enthusiasm, without taking anything for granted. Training, as it always happens, is at the basis of all consolidated and new processes.