ABSTRACT
The cellular responses to the BNT162b2 vaccine and their correlation with antibody titer and gender determinants are critical to assess. We aimed to evaluate the cellular response kinetics, correlating it with gender and antibody titer.Peripheral Blood Mononuclear Cells (PBMC) were stimulated with SARS-CoV-2 Spike protein, and the IFN-gamma was evaluated by Elispot assay at 5 different timepoints, for up to 9 months after the BNT162b2 vaccine. 107 healthcare workers were divided into 4 age groups: <40 and >40 years for men, based on the gradual decline of testosterone with aging;<48 and >48 years for women based on the decrease of estrogen with menopause. Furthermore, seropositive individuals were analyzed at baseline to avoid confounding factors caused by the previous infection with SARS-CoV-2. We also analyzed pre-pandemic samples as controls to consider the cross-reactivity toward other coronaviruses. Among seronegative at baseline, the T-cell response against Sprotein changed from a median of 2 spot forming cells (SFC)/400.000 PBMC (Interquartile range, IQR, 0-17) before vaccination to a median of 42 (17.5-78.0) after the second dose. Then, it progressively decreased to 13 (0-34) at 6 months after vaccination and 11 (0-31) after 9 months. At all timepoints, the differences were statistically significant compared to baseline values. Moreover, the results obtained after the second dose were significantly higher than those observed at any other time point. Indeed, a significant correlation was observed between T-cell response and anti-S antibody titer (p<0.001), previously analyzed, even if it was weak in magnitude (r=0.314). Natural seropositive showed higher T cell response at baseline than seronegative ones (median: 2 vs. 29, p=0.003), even if there were no significant differences in response at later time points. Our data suggest that T-cell reactiveness is poorly impacted by sex and age, whereas age was significantly associated with anti-S antibody titer. T-cell response declines 9 months later administration, indicating a waning of immune response over time. So, the positive correlation with the antibody titer confirms a linkage between different arms of adaptive responses and potentially converts future vaccinations into a tailored process.
ABSTRACT
A recent study called FRASNET enrolled on a voluntary basis a cohort on 1240 elderly people. They were either patients of the Nephrology and Dialysis unit at San Raffaele hospital in Milan, guests of care homes, or members of cultural, social and recreational centers for the elderly in the wider Milan area. Demographic, anthropometric and biochemical data were collected, together with information on comorbidities and pharmacological therapies, psychophysical test results and biological samples. After the first wave of the SARS-Cov-2 pandemic, we have interviewed the members of this same cohort to gather information on possible coronavirus infections and evaluate the impact of the pandemic on frail patients. It emerged that the prevalence of SARS-Cov-2 infections was 0.7% within this cohort. This encouraging result seems to confirm the effectiveness of the measures taken at the start of the pandemic, especially social distancing and personal protective equipment.
ABSTRACT
Background: It is well known that SARS-CoV-2 infection is associated with the development of acute kidney disease;however, not much is known about the long-term kidney effects of this pathology. Methods: We analyzed kidney function data during hospitalization and subsequent follow-up (6 months) of 150 (of which 51 with CKD) patients hospitalized for COVID-19. Results: 28% of subjects developed AKI during hospitalization;proteinuria and microhematuria were present in 53% and 40% of subjects respectively. At discharge, 61% of patients had already fully recovered their basal kidney function;the presence of proteinuria and microhematuria was reduced to 4% and 6% at subsequent follow-up. However, looking at the trend of the eGFR during the follow-up, an accelerated reduction in the glomerular filtration rate at 3 and 6 months was observed in subjects with AKI being admitted (73.30±17.08 ml/min vs 62.43±17.13 ml/min at six months;p=0.004). This result was confirmed even after exclusion from the analysis of those patients already known for CKD (eGFR < 60 ml/min) at the time of admission for COVID (eGFR 79.05±14.28 vs 66.17±16.99;p=0.004;figure 1). Conclusions: Starting from these data, we can assume that COVID-19 patients, with intra-hospital AKI development, have an accelerated loss of renal function during followup. Further studies are needed to identify pathogenic mechanisms and the long-term evolution of kidney damage after Sars-Cov-2 infection.
ABSTRACT
Background: Several risk factors for Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) infection are well established, including advanced age, male gender, strong inflammatory response, neutropenia and lymphopenia, and more recently hypoferremia. Hepcidin, the liver peptide hormone whose role is to regulate plasma iron concentration, is at the crossroad between iron metabolism and inflammation, being positively regulated by iron itself and proinflammatory cytokines. However, its role as potential biomarker of COVID-19 severity has not been explored in depth. Aims: Aim of the study is to investigate whether plasma hepcidin, measured at admission, can be considered a marker of COVID-19 severity and mortality. Methods: Plasma hepcidin and iron levels were analyzed in a well-characterized cohort of 111 Italian COVID-19 patients hospitalized between March 18th and May 5th, 2020 at San Raffaele University Hospital (UH), in Milan, Italy, one regional COVID-19 reference hospital. Diagnosis of COVID-19 was based on a positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR) from a nasal and/or throat swab together with signs, symptoms, and/or radiological findings suggestive of COVID-19. The cohort had a median age of 57.6 (48.5-66.3) years, and included prevalently males (64%). Blood samples were obtained at admission, plasma immediately retrieved and frozen until analyzed for the concentration of iron, hepcidin (ELISA kit from Intrinsic LifeSciences), proinflammatory markers as C-reactive protein (CRP) and ferritin, and cytokines with a role in hepcidin modulation, as interleukin IL6, IL1b, TNFa and Interferon gamma (IFNg). Results: In this cohort of COVID-19 patients, iron concentration was below normal range in 93.7% of patients, whereas hepcidin levels were significantly increased in 61.3% of patients. However, considering that hypoferremia suppresses hepcidin expression, even normal hepcidin is inappropriately high in most cases. Patients with higher hepcidin levels were significantly older and had higher concentrations of markers of inflammation (CRP and ferritin) and cell damage (AST and LDH). Negative correlations were observed with the severity of respiratory failure, as reflected by the PaO2/FiO2 ratio. The role of hepcidin is strengthened by the Kaplan-Meier survival curve (Figure 1A) and confirmed by the Regression Tree analysis, which identified hepcidin as the most important predictor of death among the others recognized predictors. On the other hand, iron levels do not affect survival, likely because of the uniformly low levels in all patients (Figure 1B). Interestingly, limiting the analysis to critical patients in ICU, high hepcidin predicts mortality (Figure 1C), independently of age lung function, inflammation and tissue damage. Summary/Conclusion: Overall our data suggest that hepcidin can be considered a marker of morbidity and outcome of COVID-19, of special value for severely compromised patients in ICU (Nai et al., AJH 2021). Further studies are needed to verify whether targeting the hepcidin axis may influence the disease outcome.
ABSTRACT
The clinical picture of coronavirus disease 2019 (COVID-19) in various target organs has been extensively studied and described. However, relatively little is known about the characteristics of oral cavity involvement. This is surprising, considering that oral mucosal and salivary gland cells are known targets for the direct replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that the presence of the virus in saliva is a source of transmission of the infection. The aim of our study was to investigate the presence and prevalence of oral manifestations in COVID-19 survivors. We profiled the oral involvement in 122 COVID-19 survivors that were hospitalized and followed up at a single-referral university hospital in Milan, Italy, between July 23, 2020 and September 7, 2020, after a median (interquartile range) time from hospital discharge of 104 (95 to 132) d. We found that oral manifestations, specifically salivary gland ectasia, were unexpectedly common, with oral manifestations being detected in 83.9% while salivary gland ectasia in 43% of COVID-19 survivors. Salivary gland ectasia reflected the hyperinflammatory response to SARS-CoV-2, as demonstrated by the significant relationship with C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at hospital admission, and with the use of antibiotics during acute disease. Both LDH levels and antibiotic administration survived as independent predictors of salivary gland ectasia at multivariable analysis. Temporomandibular joint abnormalities, facial pain, and masticatory muscle weakness were also common. Overall, this retrospective and prospective cohort study of COVID-19 survivors revealed that residual damage of the oral cavity persists in the vast majority of patients far beyond clinical recovery, and suggests that the oral cavity represents a preferential target for SARS-CoV-2 infection. Further studies are needed to clarify the connection between SARS-CoV-2 infection and oral disorders.