ABSTRACT
Lung transplant recipients (LuTxR) are at greater risk of COVID-19 and have attenuated response to vaccinations. In Italy, immunocompromised patients received the indication to be administered mRNA vaccines only. We aimed to evaluate the safety and immunogenicity of these vaccines in our cohort of LuTxR;we are now presenting the preliminary data of their serologic responses. We conducted a single-center observational prospective study including all consecutive LuTxR who were administered two doses of mRNA antiCOVID19 vaccine at our institution in March 2021;NCT05116748. We investigated the incidence of systemic and local adverse events and, in order evaluate immunogenicity, we used ImmunoAssay in ECLIA for the quantitative detection of anti-protein S1 (spike) antibodies (including IgG) on venous blood samples at 60 and 80 (+/- 10) days from the vaccine administration. 116 patients were enrolled, 52 females. Table 1 summarizes the basic characteristics of our population. Figure 1 focalizes on different serologic responses based on immunosuppressive regimens. No serious adverse events were reported. The most common solicited adverse events were fever (52% of our patients), headache, fatigue, myalgia, chills, and injection-site pain. Our initial findings are reassuring. Humoral SARS-CoV-2 specific immunity in our cohort of patients tended to be stronger than expected. mRNA vaccines appeared to be safe in the transplant population, and have not raised serious concern about the possible onset of graft dysfunction or other serious adverse events in the first period after their administration. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Background: From January 2022 the Omicron SARS-CoV-2 variant became the dominant circulating variant worldwide, showing increased transmissibility and the ability to evade immunity. Booster vaccinations improved the protective effects of neutralizing antibodies and might have lowered the risk of hospitalization and mortality, as recently observed. Aim: to evaluate the prevalence and outcome of Omicron-related infection in a cohort of liver transplant (LT) recipients. Material and Methods: From January to September 2022, we enrolled in a longitudinal study all LT recipients who became SARS-CoV-2 infected (95% vaccinated;88% receiving a 1st booster dose and 25% a 2nd booster). All patients were included in a protocol of testing anti-spike (a-S) and anti-nucleocapsid (a-N) antibodies titres before/after each dose (Elecsys Anti-SARS-CoV-2, Roche Diagnostic). Diagnostic criteria for SARS-CoV-2 infection were 1) presence of a positive nasopharyngeal swab (NFS) by PCR or antigenic assays or 2) presence of a-N seroconversion (if previously a-N negative). Reinfection was defined by a new NFS positivity or an increased value of a-N titre. Results: Overall, 201 LT-recipients have been infected by SARS-CoV-2 (62% males, median age=61yr, 50% viral-etiology, 35% with HCC, all received a CNI-based regimen, plus MMF=63%). Most of infections were diagnosed by NFS (72%);mild flu-like symptoms were observed in 59% of our LT recipients;72% of them remained untreated, while 28% received antivirals (11%) or monoclonal antibodies (17%). Fifteen LT recipients were hospitalized, 6 of them for interstitial pneumonia and 2 (both with previous lung diseases) died for COVID-19. Conclusions: A mild or asymptomatic infection occurred frequently in our LT recipients with a less severe outcome than the past waves. A possible explanation could be the high prevalence of vaccinated patients in our cohort. Interestingly, the overall prevalence of SARS Cov2 infection might be underestimated without a careful monitoring of SARS-CoV-2 serology against nucleocapsid.
ABSTRACT
Background and aim. The SAVE-MORE study showed that the early start of treatment with the IL-1alpha/beta inhibitor anakinra, guided by suPAR (Soluble Urokinase-Type Plasminogen Activator Receptor) >=6ng/mL, in patients with moderate or severe COVID-19, significantly reduced the risk of worse clinical outcome at day 28. With press release 665 of 28/09/2021, AIFA has approved the inclusion of anakinra in the 648/96 list for the treatment of hospitalized adults with COVID-19 and suPAR >=6ng/mL. However, suPAR methods are not widely available, which hinders the prescription and clinical use of anakinra. Aim of this study was to identify a panel of biochemical tests as a surrogate marker of suPAR positivity (>=6ng/mL). Methods. The study included 456 (median (IQR) age: 75 ys (60-83);M: F 54:46%) hospitalized patients in the Infectious Disease Unit (n=124) and Medical ICU (n=332) of the Maggiore Policlinico Hospital of Milan with molecular diagnosis of COVID-19. suPAR was measured at admission by suPARnostic TurbiLatex kit (Vendor: ViroGates A/S, Denmark;Italian distributor: B.S.N. Srl) on Roche Cobas c702. Results. Median suPAR was 7.6ng/mL (4.8-10.8), with 63% of patients displaying suPAR >=6ng/mL. At the univariate logistic regression analysis, suPAR was found to be associated with age (p<0.001), WBC (p=0.002), #NE (p<0.001), Hb (p<0.001), CREA (p<0.001), LDH (p=0.005), FERR (p=0.006), CRP (p<0.001), Fib (p=0.005), DD (p<0.001), but not with sex (p=0.943), #LY (p=0.444), #MO (p=0.233), PLT (p=0.064), ALT (p=0.238), TBIL (p=0.534), TnT (p=0.153) and TSH (p=0.970). However, at the multivariate analysis, only age (p<0.001), Hb (p=0.043), CREA (p<0.001), LDH (p=0.021), CRP (p=0.005) and DD (p=0.004) were found as independent predictors of suPAR positivity. Percentage of correct classification (< vs >= 6ng/mL) and AUC of the multivariate model were 75.1% and 0.83 (95%CI 0.80-0.87). Conclusions. suPAR is independently associated with age, Hb, CREA, LDH, CRP and DD. Due to the moderate % of correct classification of the multivariate model (75%), we conclude that this combination of blood markers cannot be used as a surrogate of suPAR for anakinra prescription. Further clinical validation is needed to assess a possible role of the model in predicting COVID-19 severity and mortality.
ABSTRACT
Background: Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), has resulted in an ongoing world-wide pandemic. Vaccination is the key countermeasure of the COVID-19 pandemic. Data on the efficacy, safety and immunogenicity of COVID-19 vaccination in patients with hemophilia -and in particular in those with HIV -are still scarce. Aim(s): The aim of our study was to characterize the immunogenicity and biomarkers of coagulation and endothelial perturbation after mRNA-COVID- 19 vaccination in HIV-positive hemophilic patients. Method(s): We collected blood from 24 adult HIV-positive hemophilic patients followed at our centre (19 with hemophilia A, 5 with hemophilia B) before and two weeks after the administration of the complete vaccination schedule with mRNA-1273 (Moderna Biotech). Most patients had severe hemophilia (n = 21). We measured antibodies to SARS-CoV- 2 spike protein by Elecsys (Roche) to assess immunogenicity and we evaluated protein C, VWF, D-dimer plasma levels as biomarkers of coagulation and endothelial perturbation. Anti-Platelet Factor 4 (PF4) antibodies were also measured. Result(s): Before vaccination, three patients out of 24 showed anti-Spike IgG levels >0.8 U/ml (cut-off value). Two weeks after completing the vaccination schedule, all patients had high values of anti-Spike IgG (min-max 2,387-12,500 U/ml). Mean (standard deviation) basal values of protein C, VWF and D-dimer (106 +/- 21%, 171 +/- 45%, 593 +/- 692 ng/ml respectively) were not significantly different from values measured two weeks after the second dose of vaccine (103 +/- 20%, 162 +/- 43%, 583 +/- 531 ng/ml). Anti-PF4 antibodies were detected in three patients with no associated clinical manifestations. None of the patients reported bleeding in the site of inoculation nor serious adverse events after the vaccination. Conclusion(s): Since immune abnormalities can occur in HIV-positive patients, it is important to collect data on COVID-19 vaccination immunogenicity. We demonstrated that hemophilic HIV-positive patients have a normal antibody response against SARS-CoV- 2 spike protein. In addition, mRNA-1273 had no effect on coagulation and endothelial perturbation.
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: Recent studies have shown that patients diagnosed with coronarivus disease 2019 (COVID-19) and also with previous cardiovascular diseases have a higher mortality due to worsening heart disease. At the same time, patients without previous cardiovascular disease may also have cardiac complications. The aim of this multicenter study was to assess high sensitivity cardiac troponin T (hs-cTnT) in patients with COVID-19 and to evaluate the incidence of myocardial injury. Methods: In this multicenter study we enrolled 543 patients, 57.8% males, median age 63 years (range 18-99) from three selected hospitals: University Hospital Tor Vergata in Rome, Fondazione IRCCS Ca 'Granda Ospedale Maggiore Policlinico, in Milan, S Chiara Hospital in Trento. We measured hs-cTnT in all patients to assess myocardial injury and correlations with patient's age, symptoms and disease course. Results: The data showed that, among the 543 patients studied, 257 patients (47.3%) had hs-cTnT values higher than the upper reference limit (URL) of 14 ng/L. Patients with high hscTnT had more frequently fever (p < 0.01) and respiratory symptoms (p < 0.01), compared to the group with hscTnT values below URL. The results showed also that patients with hs-cTnT above URL had a higher frequency of previous cardiovascular disease (p < 0.01) as well as of hypertension (p < 0.01). Instead, among 231 patients with no previous cardiovascular disease, 81 (31.5%) had hs-cTnT values above the URL. Finally. the majority of the patients with high hs-cTnT were admitted to the intensive care unit (p < 0.01). Conclusion: Our data suggest the assessment of high sensitivity cardiac troponin in patients with COVID-19 for early diagnosis of cardiac involvement.
ABSTRACT
Introduction: Registration studies have shown high efficacy of BNT162b2 mRNA COVID-19 vaccine. We evaluated vaccine effectiveness (VE) of BNT162b2 mRNA COVID-19 vaccine in a cohort of healthcare workers (HCWs) of a large hospital in Milan, Lombardy, Italy. Material and Methods: Follow-up started on 27 December 2020 (beginning of the vaccination campaign). HCWs without history of SARS-CoV-2 infection before the start date and with at least a nasopharyngeal test afterwards were included. Vaccination was treated as a time-dependent variable. For selected periods after vaccination we calculated incidence rate ratios (IRR) and 95% confidence intervals (CI) of infection with a Poisson regression model adjusted for gender, age, occupation, and 30-day periods, and then VE as (1 – IRR)x100 using unvaccinated person-time as reference. Databases were closed on 27 September 2021. The study was approved by the hospital’s ethics committee (Milano Area 2, Prot. No. 828_2021bis). Results and Conclusions: We included 3,809 HCWs, 131 still unvaccinated and 3,678 vaccinated (3,576 with two doses). We identified 134 infections (62% symptomatic). Adjusted VE was 77% (CI: 43-91) from day 14 after the first vaccine dose and 87% (CI: 79-92) at least 7 days after the second dose. After full vaccination schedule VE was 89% (CI: 82-94) for symptomatic and 77% (CI: 45-90) for asymptomatic infections. In conclusion, we found high effectiveness of BNT162b2 vaccine in reducing incidence of both symptomatic and asymptomatic infections. The follow-up is continuing to assess long-term effectiveness, also considering emerging SARS-CoV-2 variants.
ABSTRACT
Introduction Randomized controlled trials showed efficacy of vaccines against coronavirus disease 19 (COVID-19). There is the need to quantify vaccine effectiveness in real-word contexts, including people at high risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as health care workers (HCWs). Objectives To evaluate vaccine effectiveness among hospital HCWs. Methods We performed a cohort study among HCWs of a large University hospital in Milan, Lombardy, Italy by merging routinely collected data on demographics, COVID-19 vaccination, and polymerase chain-reaction (PCR) tests performed on nasopharyngeal swabs. Follow-up started on December 27, 2020 (start of vaccination campaign). We included HCWs never PCR-positive before the start date and with at least a PCR test afterwards. Vaccination was treated as a time-dependent variable by calculating person-years (PY) at risk before and after vaccine doses. Subjects contributed PY until first positive PCR test (cases) or last test for never positive HCWs (to avoid immortal time bias). We calculated infection rates (cases per 1000 PY), rate ratios (RR, with a Poisson regression model adjusted for gender, age, occupation and 30-day periods), vaccine effectiveness (VE = (1-RR)x100) and 95% confidence intervals (CI) taking never vaccinated HCWs as reference. Results As of May 10, there were 3,152 vaccinated (97% with BNT162b2, 140 with one dose, 2,679 with two doses) and 333 non-vaccinated. We counted 29 infected cases (rate 385) among non-vaccinated, 6 (rate 65) from day 14 after the first dose (VE 79%, CI 49-92%), and 24 (rate 65) from day 7 after the second dose (VE 89%, CI 80-94%). Most cases after vaccination were asymptomatic or mildly symptomatic. Conclusion In these preliminary analysis we found high effectiveness of COVID-19 vaccine in HCWs in our hospital. Further work is needed to assess long-term effectiveness and to better plan future preventive strategies among this high-risk occupational group.
ABSTRACT
Introduction: In the fight against the COVID-19 pandemic, the determination of the serum antibodies against SARS-CoV-2 is highly relevant, although the reliability of the results delivered is sometimes questionable. The aim of this paper is to evaluate the performances of a rapid immunochromatography test for IgG and IgM antibodies, comparing them with an immunochemiluminescence method. Methods: we analyzed 357 sera for the presence of IgG anti-SARS-CoV-2 spike proteins S1/S2 with an automated immunochemiluminescent test (DiaSorin®) and the presence of IgG and IgM anti-SARS-CoV-2 nucleocapside protein with an immunochromatography method (LEPU®) based on lateral flow technology. Results: with Diasorin® method, 248 subjects resulted to be negative and 109 positives, whereas LEPU® test was positive (IgM+ and/or IgG+) in 98 subjects. The overall concordance between LEPU® and DiaSorin®, was 94.1% (95% CI 91.0-96.2). Cohen's kappa was 0.86 (95% CI 0.80-0.92), indicating good agreement. 21 out of 357 (5.9%) samples had a discordant result and were re-analyzed with a third method (Roche Diagnostics Electrochemiluminescence®): 4 out of 5 DiaSorin® negative/LEPU® positive samples were confirmed as negative by Roche®;conversely, among the 16 DiaSorin® positive/LEPU® negative samples, 5 were confirmed as positive by Roche®, 6 as negative and 5 were not retested due to insufficient sample volume. Conclusions: Despite the methods were designed to detect different antibodies an overall high agreement between techniques was found. Discrepant results were found and were likely due to different antigen targets recognized by methods. The observation that only 6 out of 11 DiaSorin® positive samples were not confirmed by ROCHE®, supports the antigen-dependent hypothesis.
ABSTRACT
OBJECTIVES: The management of healthcare workers (HCWs) exposed to confirmed cases of coronavirus disease 2019 (COVID-19) is still a matter of debate. We aimed to assess in this group the attack rate of asymptomatic carriers and the symptoms most frequently associated with infection. METHODS: Occupational and clinical characteristics of HCWs who underwent nasopharyngeal swab testing for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a university hospital from 24 February 2020 to 31 March 2020 were collected. For those who tested positive and for those who tested positive but who were asymptomatic, we checked the laboratory and clinical data as of 22 May to calculate the time necessary for HCWs to then test negative and to verify whether symptoms developed thereafter. Frequencies of positive tests were compared according to selected variables using multivariable logistic regression models. RESULTS: There were 139 positive tests (8.8%) among 1573 HCWs (95% confidence interval, 7.5-10.3), with a marked difference between symptomatic (122/503, 24.2%) and asymptomatic (17/1070, 1.6%) workers (p < 0.001). Physicians were the group with the highest frequency of positive tests (61/582, 10.5%), whereas clerical workers and technicians had the lowest frequency (5/137, 3.6%). The likelihood of testing positive for COVID-19 increased with the number of reported symptoms; the strongest predictors of test positivity were taste and smell alterations (odds ratio = 76.9) and fever (odds ratio = 9.12). The median time from first positive test to a negative test was 27 days (95% confidence interval, 24-30). CONCLUSIONS: HCWs can be infected with SARS-CoV-2 without displaying any symptoms. Among symptomatic HCWs, the key symptoms to guide diagnosis are taste and smell alterations and fever. A median of almost 4 weeks is necessary before nasopharyngeal swab test results are negative.