ABSTRACT
Background and Aims: SARS-CoV-2 mRNA vaccines have been approved to prevent COVID-19. We assessed immunogenicity, effectiveness and safety of vaccines in patients with compensated and decompesated cirrhosis. Method: This is a prospective single center study assessing humoral and cellular responses in cirrhotics compared to healthy controls, incidence post-vaccination SARS-CoV-2 infections and adverse events (AEs). Antibodies against the spike- and nucleocapside-protein (anti-S and anti-N) were tested at baseline, 21 days after the first and second doses and during follow-up. Spike-specific T-cells quantity assessment was longitudinally conducted by the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by IFN-γ and IL-2 measurement. Results: 182 cirrhotics (61 years, 75% males, 45% viral-related, 74% Child-Pugh A, 31% HCC, 85% COVID-19 naïve) and 38 healthy subjects were enrolled. Previous SARS-CoV-2 infection predicted higher anti-S titres at all time points after vaccination, in both groups. COVID-19 naïve cirrhotics showed significantly lower anti-S titres compared to controls [998.5 (0.4-12,500) vs 1,520 (259-12,500) U/mL, p=0.048], anti-S titres significantly decreased after a median of 133 (70-182) days [536 (0.4-8,777) U/mL, p<0.0001] and were lower in decompensated vs compensated cirrhosis [632 (0.4-12,500) vs 1,377 (0.4-12,500) U/mL, p=0.028]. By multivariable analysis in COVID-19 naïve cirrhotics, independent predictors of lower anti-S were active HCC, immunocompromised conditions, BNT162b2 and lower anti-S after first dose. The spike-specific T-cell response was evaluated in 14 cirrhotics, showing a heterogeneous magnitude of response, but on average the quantity and kinetics of decline of the spike-specific cellular responses diverged in cirrhotics compared to controls, with lower concentrations of both IFN-γ and IL-2. During follow-up, 4/133 (3%) COVID-19 naïve cirrhotics tested positive for anti-N, all asymptomatic. Neither unexpected nor severe AEs emerged. Conclusion: Humoral and cellular responses to SARS-CoV-2 mRNA vaccines appeared suboptimal in patients with cirrhosis, however the rate of post-vaccination infection seems low.
ABSTRACT
Background and aims: Although COVID-19 infection predominantly manifests with respiratory symptoms, recent studies have also reported the occurrence of neurological involvement in the acute phase as well as in the follow-up of recovered subjects Methods: Our study focuses on assessing the prevalence of neurological sequelae in COVID-19 patients hospitalized at Ospedale Maggiore Policlinico in Milan. Seventy-five COVID-19 recovered subjects followed a general follow-up protocol including pneumological, infectious and cardiovascular assessment 5-10 months after the onset of SARS-CoV2 infection;among them, a subset of 53 patients was evaluated through a self-administered 18-item questionnaire developed ad-hoc addressing sensory, motor and cognitive neurological symptoms. Results: Collected data has shown that 77.4% patients developed at least one neurological sequela, and 46.3% presented with more than three symptoms. Among symptomatic patients, the most prevalent manifestations were insomnia (65.9%) and daytime sleepiness (46.3%), followed by walking difficulties (31.7%). Other less frequent symptoms were headache (15.1%), hyposmia and hypogeusia (15.1%), and tremor (9.4%). Prevalence of symptoms 18-item questionnare showing the distribution of neurological manifestations Conclusion: Post-COVID-19 manifestations are reported in about 90% of recovered patients. This preliminary study suggests that neurological findings represent a significant part of such manifestations. We are currently expanding the questionnaire to a larger cohort of patients and correlating our findings with patients' demographical and clinical features, as well as with the severity of the previous SARSCoV2 infection. Currently, the same questionnaire is also being validated and administered to age-and sex-matched healthy controls who have not developed symptoms suggestive of Covid-19, and a cohort of non-COVID-19 hospitalized patients.