ABSTRACT
Background: Adapted anti-SARS- CoV- 2 vaccination schedules have been recommended for patients with IMID due to a higher risk of reduced vaccine response. Nonetheless, there is little data on how different vaccine schedules influence immune responses and on the long-term persistence of vaccination responses in this subset. Purpose(s): The aim of this study is to assess the long-term course of humoral responses to SARS-CoV- 2 vaccines in a large prospective cohort of IMID patients and non-IMID controls with up to 10 months of follow-up following the first vaccine dose. Method(s): In February 2020, we started a prospective cohort of IMID patients and healthy controls (HC) to evaluate immune responses to SARS-CoV- 2 vaccines and infection (1). Individuals who provided data starting 4 weeks before their first vaccination and forward were included. Serum anti-SARS- CoV- 2 spike protein IgG were measured by ELISA (EUROIMMUN, Lubeck, Germany) in units of Optical density (OD) at 450 nm. An OD <1.1 was considered as poor response. We used time splines to fit linear mixed-effect models for log-transformed antibody levels and logistic mixed-effects models, adjusting for age and sex to estimate marginal mean antibody levels and adjusted risk of poor response with 95 percent confidence intervals. Antibody levels of twice-vaccinated patients were also compared to those who received 3 vaccinations. Result(s): Between December 2020 and December 2021, 3733 IMID patients and HC contributed 5564 samples, with a median (IQR) follow-up of 23.3 (13.9-0.9) weeks following first immunization (Table 1). By the date of their most recent sampling, 3280 (88%) participants had received two vaccines and 241 (6%) received three. Age and sex-adjusted estimated marginal mean IgG in IMID patients declined after week 10 and were significantly lower at all timepoints compared to controls (Figure 1A, Table 1). Adjusted risk of poor response at week 40 was 2.9% (1.4%-6.1%) in HC whereas 26.1% (15.8-40.0) in IMID (Figure 1B). After a median 20 (10-26). weeks from the second dose, 147 (6%) IMID patients had received a third dose. Adjusted mean antibody levels at 40 weeks in IMID patients who received three vaccine doses were higher than in HC who received two doses (Figure 1C). Conclusion(s): IMID patients had a weaker humoral response to SARS-CoV- 2 vaccination than controls at all time points following the first dose with a high risk of poor response at 40 weeks. Nonetheless, a third dose in IMID patients could provide higher antibody levels compared to unboosted healthy individuals.
ABSTRACT
Background: The frst vaccine against SARS-CoV-2 was approved in December 2020. Immunogenicity of SARS-CoV2 vaccines in patients with immune-mediated infammatory disease (IMID) have so far been evaluated in the 2-6 weeks following complete vaccination and risk groups for poor early vaccine response have been identifed leading to specifc vaccination recommendations. However, data on the long-term course and persistence of vaccine response in IMID patients, as well as the outcomes of the specifc recommendations are lacking. Objectives: To evaluate the long-term course of humoral response to SARS-CoV-2 vaccination in a large prospective cohort of IMID patients and non-IMID controls with a follow-up duration of up-to to 10 months after the frst vaccine dose. Methods: We have initiated a prospective dynamic cohort of IMID patients and healthy controls in February 2020 to monitor immune response to SARS-CoV-2 and respiratory infections including COVID-19 (1). Participants who contributed data starting from the 4 weeks before their frst vaccination onwards were included in this analysis. Antibodies against SARS-CoV-2 spike protein were quantifed with an ELISA from Euroimmun (Lübeck, Germany) with an optical density cutoff of 0.8. We ftted linear mixed-effect models for log-transformed antibody levels using time splines with adjustment for age and sex. Marginal mean antibody levels with 95% confdence intervals (CI) were estimated at selected time points for IMID patients and controls with double vaccination. We descriptively analyzed the observed antibody levels over time in cohort participants receiving two vaccinations vs. three vaccinations. Results: Among 5076 cohort participants, 3147 IMID patients and healthy controls (mean (SD) age 49 (16)) provided 4756 samples for this analysis between December 2020 and 2021, with a median (IQR) 28 (14-31) weeks of follow-up after the frst vaccination (Table 1). 2965 (94%) participants had received at least 2 and 223 (7%) participants had received three vaccine doses by the date of their latest sampling. In IMID patients, age and sex-adjusted estimated marginal mean antibody levels waned after week 16 and were substantially reduced at all time points compared to the controls, fnally dropping to the borderline range (1.01, 95%CI 0.86 to 1.19) at week 40 (Figure 1A, Table 1). A third dose was given to 128 (7%) of IMID patients with a poor response to 2 vaccine doses after a median 20 weeks of the second dose (IQR 10 to 26 weeks). After the third dose, antibody levels in IMID patients were comparable to those of healthy controls at 40 weeks who had three vaccine doses. These were also higher than that of IMID patients and controls who did not receive a third dose (Figure 1B). Conclusion: Humoral response to vaccination against SARS-CoV-2 was weaker in IMID patients compared to controls at all time points after the frst vaccine dose and practically disappeared after 1 year. IMID patients can still achieve a good antibody response with a third dose even after a weak response with two doses.
ABSTRACT
Background: Patients with immune-mediated infammatory diseases (IMID), particularly if treated with B-cell depleting therapies, show reduced humoral responses to SARS-CoV-2 vaccines and increased risk of severe COVID-19 (1,2). Since pre-exposure prophylaxis (PrEP) with monoclonal antibodies against SARS-CoV-2 proved effective in preventing infection and COVID-19 (3) in the general population, PrEP could be used for passive immunization of vaccine-refractory patients with IMIDs. Objectives: To evaluate the persistence of serum and salivary anti-SARS-CoV-2 IgG antibodies in vaccine-refractory patients with IMID after PrEP with casiriv-imab/imdevimab. Secondary outcomes were safety, SARS-CoV-2 infection, and adverse COVID-19 outcomes. Methods: We performed a longitudinal analysis on anti-SARS-CoV-2 IgG titers in IMID patients who received a PrEP with 1200 mg of subcutaneous casirivimab/imdevimab due to high infection risk, as they had not developed an adequate humoral response at least 21 days after three COVID-19 vaccinations (Table 1). Serum and salivary anti-SARS-CoV-2 Spike IgG were quantifed by ELISA (EUROIMMUN, Lübeck, Germany) before PrEP and after 1, 14, and 30 days. IgG levels are given as antibody ratios by dividing the optical density of the sample by that of the calibrator. A cutoff of ≥1.1 was considered positive. Safety as well as polymerase chain reaction (PCR)-confrmed SARS-CoV-2 infection and adverse COVID-19 outcomes (hospitalization, mechanical ventilation, death) after PrEP were recorded. Results: We obtained 92 serum and 75 saliva samples from 26 participants at four consecutive timepoints (Figure 1). Anti-SARS-CoV-2 IgG titers were observed in serum and saliva samples of all participants from day 1 and throughout 30 days after PrEP independently of diagnosis, therapy, total IgG, and peripheral CD19+ B-cells. Serum IgG increased rapidly at day 1 and plateaued from day 14 to 30 (Figure 1A), reaching similar levels as seen in healthy subjects after full vaccination (1), while saliva IgG increased steadily from administration up to day 14 and plateaued at day 30 (Figure 1B). No side effects were reported. Five patients (19.2%) had a close contact with a SARS-CoV-2-infected person, after which all but one remained asymptomatic and with a negative PCR test. The patient who tested positive developed mild COVID-19 with fever and cough. Conclusion: SARS-CoV-2 PrEP induces stable serum and salivary antibody levels in IMID patients who did not respond to COVID-19 vaccination, regardless of pre-existing clinical and serological features. In IMID, PrEP with casiriv-imab/imdevimab is safe and has the potential to prevent infection and severe COVID-19.
ABSTRACT
Background: Studies on SARS-Cov-2 in Behet's syndrome (BS) patients are limited to two small case series from European centres.[1,2] Objectives: We aimed to assess the prevalence of SARS-CoV-2 infection among Italian BS patients referring to Careggi University Hospital (Florence, Italy) and to evaluate the possible association between BS disease activity and treatment and the risk of Sars-CoV-2 infection among patients with BS. Methods: A survey was conducted among 335 subjects diagnosed with BS and followed at Careggi University Hospital. Moreover, we conducted a case-control study. Cases were described in term of SARS-CoV-2 manifestation and prognosis, changes in disease activity, and in pharmacological therapies. Sars-CoV-2 negative controls matched 1:3 by sex, age and disease duration ± 5 years were randomly selected. Results: Out of 335 BS patients, 12 declared to have/have had SARS-CoV-2 infection (3.6%). Eight were females (median age of 40 years), with a median duration of BS disease of 6 years;five had active disease. Nine patients reported fever, 9 myalgia/arthralgia, 5 gastrointestinal symptoms, 5 anosmia/ageusia, 5 cough, 3 headache, 3 fatigue, 2 breathlessness, panic attacks and dizziness (one each). Before infection, patients were treated with corticosteroids, colchicine, hydroxychloroquine (HCQ), traditional DMARDs [azathioprine (n patients = 4), methotrexate (n=1)], and biologics DMARDs [adalimumab (n=6), infliximab (n=2), secukinumab (n=1), and canakinumab (n=1)]. Therapy was suspended for a median time of 33 days in 9patients and resumed after a median time of 5 days from negativation. Regarding SARS-CoV-2 treatment, most patients started or increased corticosteroids, whereas heparin and antipyretic drugs were used in 4 and 5 patients, respectively. Cases were comparable to controls in terms of disease manifestations, activity, and immunomodulating therapy, with the only exception of corticosteroids, whose daily dose was significantly higher in cases (Table 1). Conclusion: Prevalence of SARS-CoV-2 infection among Italian BS patients is 3.6%, similarly to the Italian general population (4.2%). Disease activity at time of infection was not associated with an increased risk of SARS-CoV-2 infection. Most patients interrupted biologic DMARDs. However, use of DMARDs, seemed not to be associated with an increased risk of SARS-CoV-2 infection, while higher doses of corticosteroids resulted to be more common among patients with SARS-CoV-2 infection as compared to controls. No patient required hospitalization or died. Our experience shows encouraging data about BS patients who do not appear be at greater risk of SARS-CoV-2 infection or complications than the general population.
ABSTRACT
OBJECTIVES: We aimed to assess the prevalence of SARS-CoV-2 infection among Behcet's syndrome (BS) patients, evaluating the possible association between demographic and clinical features and the risk of infection. Moreover, we aimed to evaluate the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. METHODS: A survey was conducted on BS patients followed at the Behcet's Centre of the Careggi University Hospital, Florence, Italy. We further evaluated the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. RESULTS: Out of 335 BS patients contacted, fourteen cases of SARS-CoV-2 were identified between April 1st, 2020 and February 9th, 2021, suggesting a prevalence of SARS-CoV-2 infection among BS patients of 4.2%, in line with the data of the general population in Italy (4.4%). When comparing clinical features between SARS-CoV-2 cases and matched SARS-CoV-2 negative BS patients, we found that the presence of different disease manifestations did not significantly differ between the two groups. SARS-CoV-2 cases and controls were also comparable in terms of immunosuppressive therapy, with the only exception of corticosteroids (71.4% vs. 35.7%, p=0.030), whose daily dose was significantly higher in cases than controls [5mg/day (IQR 0-10,) vs. 0 mg/day (IQR 0-5), p=0.005], suggesting that the right timing of usage and the more appropriate dosage of corticosteroid are a key question for the better management of these patients. CONCLUSIONS: Based on our results, patients with BS do not seem to be at a greater risk of SARS-CoV-2 infection or severe complications compared with the general population.