ABSTRACT
Background: Patients with autoimmune systemic diseases have an increased risk to contract infections and develop severe complications;infections in turn can reactivated and worsen the disease itself in a vicious circle. Thus, vaccination is the main weapon to prevent infectious diseases and represents an important and safe instrument of care for rheumatic patients that needs to be further promoted. However, the immunosuppressive drugs used to treat rheumatic diseases may impair response to vaccines, in particular those targeting B or T cells directly (1). Objectives: The aim of this study is to evaluate the B and T-cell mediated immune response to mRNA vaccination in patients with systemic autoimmune diseases, such as vasculitis or systemic connective tissue diseases, early or continuously treated with B-cell targeting therapies, rituximab (RTX) or beli-mumab (BEL), by comparing with controls and each other. Secondary we evaluated the in vitro effective neutralizing capacity in belimumab-exposed patients. Methods: Twenty-eight consecutive patients under treatment with rituximab (RTX, n=11) or belimumab (BEL, n=17) and 13 age/sex matched controls (non-rheumatic healthcare personnel) were enrolled in the study. Nobody presented anti-SARS-CoV2 antibodies related to previous viral contact and all were always negative at the molecular swab monthly control. All patients and controls received mRNA vaccines and were tested three to four weeks after complete vaccination. All RTX patients started vaccination within 5 months from the last infusion, and all but one of them were B-cell depleted. Anti-SARS-CoV-2 RBD total antibodies were analysed by a diagnostic assay (Elecsys, Roche) while T-cell response was evaluated using the IGRA test (Euroimmun). A subgroup of BEL-patients was tested with pseudovirus neutralization assay. Results: Detectable anti-SARS-CoV2 RBD antibodies were documented in 1/11 RTX patients versus 16/17 BEL patients (p<0.0001). The median concentration was signifcantly lower than that observed in controls (39.6 AU/ml vs 1133 AU/ml, p<0.0001). A very low titer of anti-RBD antibodies were documented only in 1 out of 11 patients in the RTX subgroup (0.93 U/ml, positive if >0,79 U/ml) and the patient was the only one who showed an initial B-cell recovery (CD19+ B-cell 5 cells/microL). Anti-RBD antibodies were documented in 16 out 17 of patients in the BEL subgroup. The median anti-RBD antibody titer in patients receiving BEL was 243 [77.55-744.0] U/ml, and it was signifcantly lower compared to the controls (p=0.002). The IGRA test was positive in 8/11 (72.7%) RTX patients vs 16/17 (94.1%) BEL patients (p=0.7), with interferon release comparable to control subjects (p=0.2). Six patients with BEL were also stratifed according to total antibodies (IgG+I-gA+IgM) against-RBD into high responders (>800 AU/mL, n=3) and low responders (≤45 AU/mL, n=3) and tested with pseudovirus neutralization assay. Two thirds of low titer group of patients neutralized the Wuhan-Hu1 strain at medium-low titer (IC50 ≈102) but were almost ineffective in inhibiting the B.1.1.7 entry into target cells (IC50 =10). Regarding high responders, while two patients were able to inhibit both the strains at medium-high titer (approximately IC50 ≈103 for Wuhan-Hu1 and B.1.1.7), one patient neutralized only the WT strain. Conclusion: B-cell targeting therapies do not preclude SARS-CoV-2 vaccination since a cellular immunity can raise even in the absence of circulating B cells. Most importantly, the immunogenicity of COVID-19 vaccination in SLE patients treated with belimumab is supported. However, patients showing the lowest humoral response to vaccine could remain at higher risk of infections, due to low neutralizing capacity.
ABSTRACT
The objective of this paper is to explore the policies that have been implemented and planned in relation to the impacts that the COVID-19 health crisis has had on the Italian food system. This is an evaluation exercise useful to understand what the directions imprinted on the food system will be in relation to some frameworks of particular importance at the international level, such as the 2030 Agenda, the Farm to Fork Strategy, the Biodiversity Strategy, the UN Food Summit, and the agroecological perspective. The article is divided into multiple sections. In paragraph 1.1 and 1.2, the shocks generated by COVID-19 in the global context and in the Italian national context are examined. In both, attention is drawn to changes in GDP, employment, poverty, and the food system. In paragraph 3, the methodological approach, based on the DPSIR model, is explained, as well as the materials used for the drafting of the work. In paragraph 4, all of the components (Driving Forces, Pressures, States, Impacts) of the DPSIR model are analyzed. In paragraph 5, attention is focused on all policy responses implemented during COVID-19, both on the Italian and European side. In paragraph 6, a detailed analysis of the Italian responses is made in order to fully understand the degree of influence on the Italian economy and food system. The analysis carried out, therefore, highlights the socioeconomic threats faced by the Italian government and the main measures adopted to counter them. Through a critical analysis of policies, it was possible to identify their criticalities and propose possible integrations, starting from the concept of “syndemia”. This concept was introduced in the 1990s by Merril Singer, and in this paper, it plays an important role because it takes into account the negative effects of the pandemic at the economic, health, and social levels and the importance of the sustainability of the food chain. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
ABSTRACT
Background: Data on the dynamics and duration of immune response to SARS-CoV-2 infection in hematologic patients are still lacking. Preliminary studies, in non immunocompromised subjects with COVID- 19, reported that seroconversion was observed 7 to 14 days following symptom onset with an increase of the IgM and IgG titers during the first month. IgM levels, after peaking by day 30, gradually decreased and can be undetectable by day 180 post-onset. The long-lasting persistence of IgG is not clearly confirmed. Aims: We evaluate the seroconversion and the kinetics of IgM and IgG against SARS-CoV-2 in hematologic patients who were followed after reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmation of SARS-CoV-2 infection. Methods: Here we report the preliminary data regarding the first 25 COVID-19 positive hematologic patients that were tested for humoral response. The median age was 59 years (range 21-85). The underling hematologic diseases were: lymphoma (10/25), myeloma (7/25), chronic lymphoproliferative diseases (5/25) and acute leukemia (3/25). SARSCoV- 2 infection was mild symptomatic in 5/25 cases and symptomatic in 20/25. Four of these 20 patients had pneumonia that required hospitalization. The median value of IgG, IgM and IgA, at onset of the SARS-CoV-2 infection, was 832 mg/dl (167-2210), 54,5 mg/dl (6-2510) and 54 mg/dl (8-605), respectively. The median value of lymphocytes was 1100/mmc (250-3300). The IgM and IgG antibodies against SARSCoV- 2 spike protein (subunity S1 and S2) were tested by chemiluminescence immunoassay (CLIA) with a positive cut-off value of 15 UA/ ml for both IgG and IgM. To assess the kinetics of antibody titers, in our convalescent COVID-19 patients, serum IgM and IgG levels were longitudinally measured at established time points: one month (T1) two months (T2), three months (T3) and four months (T4) after their first positive nasopharyngeal swab test. Results: Among these first 25 COVID-19 cases, 21/25 (84%) developed specific anti SARS-CoV-2 antibodies with a titer > 15 UA/ml in almost one of the specific time points. However, as reported in Figure A and B, after a peak of the IgG and an overall mild increase of IgM, the antibody titer declined from 4 months after the disease onset under the positive cut-off value, although variation between patients was detected. In detail the mean and median titers were: 1) at T1: 56 UA/ml and 75,5 UA/ml for IgG, 15 UA/ml and 6 UI/ml for IgM;2) at T2: 68 UA/ml and 73 UA/ ml for IgG, 7 UA/ml and 2,6 UA/ml for IgM;3) at T3: 54 UA/ml and 55 UA/ml for IgG and 5 UA/ml and 1,35 UA/ml for IgM;4) at T4: 7 UA/ml and 5,3 UA/ml for IgG and 0,2 UA/ml and 0,2 UA/ml for IgM. Summary/Conclusion: Although the number of patients is still limited, our preliminary results show a short lifespan of antibody response in hematologic patients, suggesting a short duration of antibody-mediated protection against re-infection with SARS-CoV-2. If confirmed in a larger number of cases, these results would suggest to maintain infection prevention and control measures even for hematologic patients who have recovered from COVID-19. In addition, this population should get vaccinated periodically. Additional studies, exploring both humoral and cellular immunity (T cells and memory B cells), will be require to better understand the overall immunologic response against SARS-CoV-2 (and its duration) in hematologic patients.