Sicilian semi- and supercentenarians: identification of age-related T-cell immunophenotype to define longevity trait.

The immunophenotype of oldest centenarians, i.e. semi- and supercentenarians, could provide important information about their ability to adapt to factors associated with immune changes, including ageing per se and chronic Cytomegalovirus infection. We investigated, by flow cytometry, variations in percentages and absolute numbers of immune cell subsets, focusing on T cells, and pro-inflammatory parameters in a cohort of 28 women and 26 men (age range 19-110 years). We observed variability in hallmarks of immunosenescence related to age and Cytomegalovirus serological status. The eight oldest centenarians showed the lowest percentages of naïve T cells, due to their age, and the highest percentages of T-effector memory cells re-expressing CD45RA (TEMRA), according to their cytomegalovirus status, and high levels of serum pro-inflammatory parameters, although their means were lower than that of remaining 90+ donors. Some of them showed CD8 naïve and TEMRA percentages, and exhaustion/pro-inflammatory markers comparable to the younger ones. Our study supports the suggestion that immune ageing, especially of oldest centenarians, exhibits great variability that is not only attributable to a single contributor but should also be the full result of a combination of several factors. Everyone ages differently because he/she is unique in genetics and experience of life and this applies even more to the immune system; everybody has had a different immunological history. Furthermore, our findings on inflammatory markers, TEMRA and CMV seropositivity in centenarians, discussed in the light of the most recent literature, suggest that these changes might be not unfavourable for centenarians, and in particular for the oldest ones.

A severe case of Israeli spotted fever with pleural effusion in Italy.

BACKGROUND: The most common Italian rickettsiosis is Mediterranean Spotted Fever (MSF). MSF is commonly associated with a symptom triad consisting of fever, cutaneous rash, and inoculation eschar. The rash is usually maculopapular but, especially in severe presentations, may be petechial. Other typical findings are arthromyalgia and headache. Herein, we describe for the first time an unusual case of Israeli spotted fever (ISF) associated with interstitial pneumonia and pleural effusion in which R. conorii subsp. israelensis was identified by molecular methods in the blood, as well as in the pleural fluid. CASE PRESENTATION: A 72-year-old male presented with a 10-day history of remittent fever. On admission, the patient's general condition appeared poor with confusion and drowsiness; the first assessment revealed a temperature of 38.7°, blood pressure of 110/70 mmHg, a blood oxygen saturation level of 80% with rapid, frequent, and superficial breathing using accessory muscles (28 breaths per minute), and an arrhythmia with a heart rate of 90 beats per minute. qSOFA score was 3/3. Chest CT revealed ground-glass pneumonia with massive pleural effusion. Petechial exanthema was present diffusely, including on the palms and soles, and a very little eschar surrounded by a violaceous halo was noted on the dorsum of the right foot. Awaiting the results of blood cultures, broad-spectrum antibiotic therapy with meropenem 1 g q8h, ciprofloxacin 400 mg q12h, and doxycycline 100 mg q12h was initiated. Doxycycline was included in the therapy because of the presence of petechial rash and fever, making us consider a diagnosis of rickettsiosis. This suspicion was confirmed by the positivity of polymerase chain reaction on whole blood for R. conorii subsp. israelensis. Thoracentesis was performed to improve alveolar ventilation. R. conorii subsp. israelensis was again identified in the pleural fluid by PCR technique. On day 4 the clinical condition worsened. Blood exams showed values suggestive of secondary hemophagocytic lymphohistiocytosis; 4 out of 8 diagnostic criteria were present and empirical treatment with prednisone was started resulting in a gradual improvement in general condition. CONCLUSIONS: Israeli spotted fever may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis.

Norovirus GII.17 as Major Epidemic Strain in Italy, 2015-16.

In winter 2015-16, norovirus GII.17 Kawasaki 2014 emerged as a cause of sporadic gastroenteritis in children in Italy. Median patient age was higher for those with GII.17 than GII.4 infection (55 vs. 24 months), suggesting limited cross-protection for older children.

Epidemiological dynamics of norovirus GII.4 variant New Orleans 2009.

Norovirus (NoV) is one of the major causes of diarrhoeal disease with epidemic, outbreak and sporadic patterns in humans of all ages worldwide. NoVs of genotype GII.4 cause nearly 80-90 % of all NoV infections in humans. Periodically, some GII.4 strains become predominant, generating major pandemic variants. Retrospective analysis of the GII.4 NoV strains detected in Italy between 2007 and 2013 indicated that the pandemic variant New Orleans 2009 emerged in Italy in the late 2009, became predominant in 2010-2011 and continued to circulate in a sporadic fashion until April 2013. Upon phylogenetic analysis based on the small diagnostic regions A and C, the late New Orleans 2009 NoVs circulating during 2011-2013 appeared to be genetically different from the early New Orleans 2009 strains that circulated in 2010. For a selection of strains, a 3.2 kb genome portion at the 3' end was sequenced. In the partial ORF1 and in the full-length ORF2 and ORF3, the 2011-2013 New Orleans NoVs comprised at least three distinct genetic subclusters. By comparison with sequences retrieved from the databases, these subclusters were also found to circulate globally, suggesting that the local circulation reflected repeated introductions of different strains, rather than local selection of novel viruses. Phylogenetic subclustering did not correlate with changes in residues located in predicted putative capsid epitopes, although several changes affected the P2 domain in epitopes A, C, D and E.

Identification of the novel Kawasaki 2014 GII.17 human norovirus strain in Italy, 2015.

Surveillance of noroviruses in Italy identified the novel GII.17 human norovirus strain, Kawasaki 2014, in February 2015. This novel strain emerged as a major cause of gastroenteritis in Asia during 2014/15, replacing the pandemic GII.4 norovirus strain Sydney 2012, but being reported only sporadically elsewhere. This novel strain is undergoing fast diversification and continuous monitoring is important to understand the evolution of noroviruses and to implement the future strategies on norovirus vaccines.

A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia.

Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.

Evaluation of T2 Magnetic Resonance (T2MR®) Technology for the Early Detection of ESKAPEc Pathogens in Septic Patients.

Bloodstream infections (BSIs) and sepsis are a major cause of morbidity and mortality. Appropriate early antibiotic therapy is crucial for improving the survival of patients with sepsis and septic shock. T2 magnetic resonance (T2MR®) technology may enable fast and sensitive detection of ESKAPEc pathogens directly from whole-blood samples. We aimed to evaluate concordance between the T2Bacteria® Panel and standard blood culture and its impact on antibiotic therapy decisions. We conducted a single-centre retrospective study on patients with sepsis-induced hypotension or septic shock admitted to general, post-operative/neurosurgical, and cardiothoracic Intensive Care Units who were tested with the T2Bacteria® Panel from January 2021 to December 2022. Eighty-five consecutively admitted patients were included, for a total of 85 paired tests. A total of 48 ESKAPEc pathogens were identified by the T2Bacteria® Panel. The concordance rate between the T2Bacteria® Panel and blood cultures was 81% (69/85), with 20 concordant-positive and 49 concordant-negative cases. For the 25 microorganisms grown from accompanying blood cultures, blood pathogen coverage by the T2Bacteria® Panel was 88%. In this cohort of severely ill septic patients, the T2Bacteria® Panel was highly concordant and was able to detect more ESKAPEc pathogens, with a significantly shorter turn-around time compared to conventional blood cultures. The T2Bacteria® Panel also significantly impacted decisions on antibiotic therapy.

Increase of multidrug-resistant bacteria after the COVID-19 pandemic in a major teaching Hospital in Sicily (2018-2021).

INTRODUCTION: The COVID-19 pandemic has further highlighted the continuing threat of antimicrobial resistance (AMR) to global health and economic development. In the last two decades, AMR has raised increasing concern, with an estimated 4.95 million deaths globally due to bacterial AMR in 2019 alone. The aim of this study was to analyse the impact of the pandemic on the spread of multidrug-resistant organisms (MDROs) using data from the Hospital "P. Giaccone" in Palermo, comparing pre-pandemic and pandemic periods. METHODS: This observational study involved adult patients who were discharged from the hospital between 01 January 2018 and 31 December 2021. Hospital Discharge Cards were linked with microbiological laboratory reports to assess MDRO isolations. SARS-CoV-2 positivity during hospitalisation was evaluated using the National Institute of Health surveillance system. RESULTS: A total of 58 427 hospitalisations were evaluated in this study. Half the patients were aged over 65 years (N=26 984) and most admissions were in the medical area (N=31 716). During the hospitalisation period, there were 2681 patients (5%) with MDROs isolations, and 946 patients (2%) were positive for SARS-CoV-2. Multivariable analyses showed that during 2020 and 2021, there was a significantly increased risk of isolation of Staphylococcus aureus, Acinetobacter baumannii, and Klebsiella pneumoniae. Age, weight of the Diagnosis-Related Group (DRG), wards with higher intensity of care, and length-of-stay were associated with a higher risk of MDRO isolation. CONCLUSION: This study provides new insights into the impact of the COVID-19 pandemic on MDRO isolation and has important implications for infection control and prevention efforts in healthcare facilities. Age, DRG-weight, and longer hospital stays further increased the risk of MDRO isolation. Thus, it is imperative to improve and follow hospital protocols to prevent healthcare-associated infections.

Comparison of Different HIV-1 Resistance Interpretation Tools for Next-Generation Sequencing in Italy.

BACKGROUND: Next-generation sequencing (NGS) is gradually replacing Sanger sequencing for HIV genotypic drug resistance testing (GRT). This work evaluated the concordance among different NGS-GRT interpretation tools in a real-life setting. METHODS: Routine NGS-GRT data were generated from viral RNA at 11 Italian laboratories with the AD4SEQ HIV-1 Solution v2 commercial kit. NGS results were interpreted by the SmartVir system provided by the kit and by two online tools (HyDRA Web and Stanford HIVdb). NGS-GRT was considered valid when the coverage was >100 reads (100×) at each PR/RT/IN resistance-associated position listed in the HIVdb 9.5.1 algorithm. RESULTS: Among 629 NGS-GRT, 75.2%, 74.2%, and 70.9% were valid according to SmartVir, HyDRA Web, and HIVdb. Considering at least two interpretation tools, 463 (73.6%) NGS-GRT had a valid coverage for resistance analyses. The proportion of valid samples was affected by viremia <10,000-1000 copies/mL and non-B subtypes. Mutations at an NGS frequency >10% showed fair concordance among different interpretation tools. CONCLUSION: This Italian survey on NGS resistance testing suggests that viremia levels and HIV subtype affect NGS-GRT coverage. Within the current routine method for NGS-GRT, only mutations with frequency >10% seem reliably detected across different interpretation tools.

Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination.

The introduction of anti-SARS-CoV-2 vaccines in late 2020 substantially changed the pandemic picture, inducing effective protection in the population. However, individual variability was observed with different levels of cellular response and neutralizing antibodies. We report data on the impact of age, gender, and 16 single nucleotide polymorphisms (SNPs) of cytokine genes on the anti-SARS-CoV-2 IgG titers measured 31 and 105 days after administration of the second dose of BNT162b2 vaccine to 122 healthy subjects from the health care staff of the Palermo University Hospital, Italy. The higher titers at 31 days were measured in the younger subjects and in subjects bearing T-positive genotypes of IL-1R1 rs2234650 or the GG homozygous genotype of IL-6 rs1800795 SNP. T-positive genotypes are also significantly more common in subjects with higher titers at day 105. In addition, in this group of subjects, the frequency of the CT genotype of IL-4 rs2243250 is higher among those vaccinated with higher titers. Moreover, these SNPs and TNFA rs1800629 are differently distributed in a group of subjects that were found infected by SARS-CoV-2 at day 105 of evaluation. Finally, subjects that were found to be infected by SARS-CoV-2 at day 105 were significantly older than the uninfected subjects. Taken together, these data seem to suggest that age and polymorphisms of key cytokines, which regulate inflammation and humoral immune response, might influence the magnitude of the antibody response to vaccination with BNT162B2, prompting speculation about the possible benefit of a genetic background-based assessment of a personalized approach to the anti-COVID vaccination schedule.

Cefiderocol Efficacy in a Real-Life Setting: Single-Centre Retrospective Study.

The current carbapenem-resistant gram-negative bacteria (CR-GN) treatment guidelines lack strong evidence about cefiderocol (CFD) efficacy against CR-GN, especially CRAB. The study's purpose is to evaluate the effectiveness of CFD in a real-life setting. We made a single-center retrospective study of 41 patients who received CFD in our hospital for several CR-GN infections. Bloodstream infections (BSI) affected 43.9% (18/41) of patients, while CRAB affected 75.6% (31/41) of isolated CR-GN patients. Thirty-days (30-D) all-causes mortality affected 36.6% (15/41) of patients, while end-of-treatment (EOT) clinical cure affected 56.1% (23/41). Finally, microbiological eradication at EOT affected 56.1% (23/41) of patients. Univariate and multivariate analysis showed that septic shock is an independent factor associated with mortality. Subgroup analyses showed no difference in CFD effectiveness between monotherapy and combination therapy.

The Use of Intravenous Fosfomycin in Clinical Practice: A 5-Year Retrospective Study in a Tertiary Hospital in Italy.

Fosfomycin in intravenous (IV) formulation has re-emerged as a valuable tool in the treatment of multi-drug resistant (MDR) and extensively drug-resistant (XDR) infections because of its broad spectrum of antibacterial action and pharmacokinetic characteristics. This retrospective study aimed to evaluate how fosfomycin was used in patients admitted to the Polyclinic of Palermo between January 2017 and July 2022. Clinical indications, therapeutic associations, clinical outcomes, and any side effects were analyzed. Intravenous fosfomycin was used in 343 patients, 63% male, with a mean age of 68 years (range 15-95). Urinary tract infections (UTIs) and hospital-acquired pneumonia (HAP) were the main indications for treatment (19% and 18% of the total cases, respectively), followed by skin and soft tissue infections and sepsis. IV fosfomycin was administered in combination with other antibacterial agents, the most common of which were ceftazidime/avibactam (35%), meropenem (17%), and colistin (14%). Nineteen patients received it as monotherapy for UTIs. About 66% had resolution of the infectious process with clinical remission (cure or discharge). Electrolyte disturbances occurred in 2.6% and gastrointestinal symptoms occurred in 2.9%. The data showed that IV fosfomycin is a safe and effective therapeutic option in the treatment of infections with multidrug-resistant microorganisms.

Wastewater-Based Epidemiology as a Tool to Detect SARS-CoV-2 Circulation at the Community Level: Findings from a One-Year Wastewater Investigation Conducted in Sicily, Italy.

Wastewater-based epidemiology is a well-established tool for detecting and monitoring the spread of enteric pathogens and the use of illegal drugs in communities in real time. Since only a few studies in Italy have investigated the correlation between SARS-CoV-2 in wastewater and the prevalence of COVID-19 cases from clinical testing, we conducted a one-year wastewater surveillance study in Sicily to correlate the load of SARS-CoV-2 RNA in wastewater and the reported cumulative prevalence of COVID-19 in 14 cities from October 2021 to September 2022. Furthermore, we investigated the role of SARS-CoV-2 variants and subvariants in the increase in the number of SARS-CoV-2 infections. Our findings showed a significant correlation between SARS-CoV-2 RNA load in wastewater and the number of active cases reported by syndromic surveillance in the population. Moreover, the correlation between SARS-CoV-2 in wastewater and the active cases remained high when a lag of 7 or 14 days was considered. Finally, we attributed the epidemic waves observed to the rapid emergence of the Omicron variant and the BA.4 and BA.5 subvariants. We confirmed the effectiveness of wastewater monitoring as a powerful epidemiological proxy for viral variant spread and an efficient complementary method for surveillance.

An Analysis of the Neutralizing Antibodies against the Main SARS-CoV-2 Variants in Healthcare Workers (HCWs) Vaccinated against or Infected by SARS-CoV-2.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "breakthrough infections" have been documented in patients with complete primary vaccination courses. Most of the SARS-CoV-2 neutralizing antibodies produced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and the infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of a host. The aim of this study was to compare the titers of neutralizing antibodies (NtAbs) against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). A total of 293 HCWs were enrolled and divided into three cohorts as follows: 91 who had recovered from SARS-CoV-2 infection (nVP); 102 that were vaccinated and became positive after the primary cycle (VP); and 100 that were vaccinated with complete primary cycles and concluded the follow-up period without becoming positive (VN). Higher neutralization titers were observed in the vaccinated subjects' arms compared to the nVP subjects' arms. Differences in neutralization titers between arms for single variants were statistically highly significant (p < 0.001), except for the differences between titers against the Alpha variant in the nVP and in VP groups, which were also statistically significant (p < 0.05). Within the nVP group, the number of subjects with an absence of neutralizing antibodies was high. The presence of higher titers in patients with a complete primary cycle compared to patients who had recovered from infection suggested the better efficacy of artificial immunization compared to natural immunization, and this further encourages the promotion of vaccination even in subjects with previous infections.

IL-1 Superfamily Member (IL-1A, IL-1B and IL-18) Genetic Variants Influence Susceptibility and Clinical Course of Mediterranean Spotter Fever.

Mediterranean Spotted Fever (MSF) is one of the most common spotted fever Rickettsioses. Most cases of MSF follow a benign course, with a minority of cases being fatal. The severity of the infection depends on bacterial virulence, dose and host factors such as effective immune response and genetic background. Herein, we reported data on typing by competitive allele-specific PCR of functionally relevant polymorphisms of genes coding for MyD88 adapter-like (Mal/TIRAP) protein (rs8177374), interleukin(IL)-1 cluster (IL-1A rs1800587, IL-1B rs16944 and rs1143634) and IL-18 (rs187238), which might be crucial for an efficient immune response. The results enlighten the role that IL-1 gene cluster variants might play in susceptibility against Rickettsia conorii infection. In particular, the IL-1A rs1800587TT genotype was significantly increased in patients alone and combined in a haplotype composed by minor alleles rs1800587T, rs16944A and rs1143634A. This result was confirmed using the decision tree heuristic approach. Using this methodology, IL-1A rs1800587TT genotype was the better discrimination key among MSF patients and controls. In addition, the IL-1 gene cluster SNP genotypes containing minor alleles and IL-18 rs187238G positive genotypes were found as associated with risk of severe complications such as sepsis, septic shock, acute respiratory distress syndrome and coma. In conclusion, these data suggest that the evaluation of IL-1A, IL-1B and IL-18 gene SNPs can add useful information on the clinical course of patients affected by Mediterranean Spotted Fever, even if further confirmatory studies will be necessary.

Neutralizing Antibodies Response against SARS-CoV-2 Variants of Concern Elicited by Prior Infection or mRNA BNT162b2 Vaccination.

In order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35-52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic.

Multidimensional Frailty and Vaccinations in Older People: A Cross-Sectional Study.

It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association are still missing. Therefore, we aimed to investigate the prevalence of four recommended vaccinations (influenza, herpes zoster, pneumococcal and diphtheria-tetanus-pertussis) and the association with multidimensional frailty assessed using a self-reported comprehensive geriatric assessment tool, i.e., the multidimensional prognostic index (SELFY-MPI). Older participants visiting the outpatient clinic of Azienda Ospedaliera Universitaria, Palermo, Italy were included. The SELFY-MPI questionnaire score was calculated based on eight different domains, while the vaccination status was determined using self-reported information. We included 319 participants from the 500 initially considered (63.8%). Vaccination against influenza was observed in 70.5% of the cases, whilst only 1.3% received the vaccination against diphtheria-tetanus-pertussis. Participants with higher SELFY-MPI scores were more likely to report vaccination against pneumococcus (45.6 vs. 28.3%, p = 0.01), whilst no significant differences were observed for the other vaccinations. In conclusion, the coverage of recommended vaccinations is low. Higher SELFY-MPI scores and vaccination status, particularly anti-pneumococcus, appear to be associated, but future studies are urgently needed for confirming that frailty is associated with vaccination status in older people.

Clinical Onset and Multiple Sclerosis Relapse after SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with several neurological disorders including headache, facial palsy, encephalitis, stroke, demyelinating disorders. The present report will discuss cases of multiple sclerosis (MS) onset and relapse both beginning early after SARS-CoV-2 infection. In both cases, magnetic resonance imaging (MRI) showed widespread bilateral subcortical and periventricular active lesions. Serum IgG against SARS-CoV-2 Spike antigens confirmed seroconversion with titers that are considered not definitely protective against possible reinfection. We hypothesize that SARS-CoV-2 infection, as previously reported for other viruses, could drive an active inflammatory response that can contribute either to the onset of MS or its relapse. The presented data further support the importance of vaccination in individuals with MS.

Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients.

COVID-19 is a current global threat, and the characterization of antibody response is vitally important to update vaccine development and strategies. In this study we assessed SARS-CoV-2 antibody concentrations in SARS-CoV-2 positive patients (N = 272) and subjects vaccinated with the BNT162b2 m-RNA COVID-19 vaccine (N = 1256). For each participant, socio-demographic data, COVID-19 vaccination records, serological analyses, and SARS-CoV-2 infection status were collected. IgG antibodies against S1/S2 antigens of SARS-CoV-2 were detected. Almost all vaccinated subjects (99.8%) showed a seropositivity to anti-SARS-COV-2 IgG and more than 80% of vaccinated subjects had IgG concentrations > 200 AU/mL. In a Tobit multivariable regression analysis, SARS-CoV-2 vaccination was statistically significantly associated with increased IgG concentrations (ß coef = 266.4; p < 0.001). A statistically significant reduction in SARS-CoV-2 IgG concentrations was found with older age (ß coef = -1.96 per year increase; p < 0.001), male sex (ß coef = -22.3; p < 0.001), and days after immunization (ß coef = -1.67 per day increase; p < 0.001). Our findings could support the vaccination campaigns confirming the high immunogenicity of the SARS-CoV-2 vaccine under investigation with respect to the natural infection. Further studies will be required for evaluating the role of age and days after immunization in the persistence of vaccine antibodies and protection from the disease.

COVID-19 Vaccine and Death: Causality Algorithm According to the WHO Eligibility Diagnosis.

The current challenge worldwide is the administration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Even if rarely, severe vascular adverse reactions temporally related to vaccine administration have induced diffidence in the population at large. In particular, researchers worldwide are focusing on the so-called "thrombosis and thrombocytopenia after COVID-19 vaccination". This study aims to establish a practical workflow to define the relationship between adverse events following immunization (AEFI) and COVID-19 vaccination, following the basic framework of the World Health Organization (WHO). Post-mortem investigation plays a pivotal role to support this causality relationship when death occurs. To demonstrate the usefulness and feasibility of the proposed workflow, we applied it to two exemplificative cases of suspected AEFI following COVID-19 vaccination. Based on the proposed model, we took into consideration any possible causality relationship between COVID-19 vaccine administration and AEFI. This led us to conclude that vaccination with ChAdOx1 nCov-19 may cause the rare development of immune thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4), which clinically mimics heparin-induced autoimmune thrombocytopenia. We suggest the adoption of the proposed methodology in order to confirm or rule out a causal relationship between vaccination and the occurrence of AEFI.