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Introduction: Favipiravir and remdesivir are antiviral drugs being used in the present pandemic and were also used previously for other viral infections in the past. Monoclonal antibody (Mab) Casirivimab-Imdevimab is a Coronavirus Disease 2019 neutralising antibody approved in the last one year. Therefore, a clinical comparison with the existing treatment modalities is imperative. Aim: To compare Mab with remdesivir and favipiravir for mild to moderate COVID-19 disease. Materials and Methods: A retrospective, observational and single-centre study was conducted at a COVID-19 infection facility and private tertiary care hospital, Mumbai, Maharashtra, India. Data of patients admitted during the period of 1st June 2021 to 31st August 2021 was collected and analysed in the months of September 2021 and October 2021. Adults participants diagnosed to have COVID-19 infection, not requiring critical care or oxygen therapy were included in the study. Time to recovery from treatment onset and the need for treatment escalation were the primary outcome measures. Data was entered into Microsoft Excel spreadsheet version 16 and analysed. Statistical analysis was carried out using Chi-square test for the significance of association between tabulated values of data for qualitative and categorical data. Two-tailed unpaired t-test and Analysis of Variance (ANOVA) was used for quantitative tabulated data. Results: This study included 158 participants, grouped into remdesivir(n=63),favipiravir(n=30)andMab(n=65)treatmentgroups. Gender distribution was comparable in all groups (p-value=0.08). The three groups were compared for need of treatment escalation and time of recovery. The Mab treatment group (on comparing with other treatment arms) had earlier symptom recovery when given to patients with mild COVID-19 disease (p-value=0.006 for major symptoms) or when treatment was started within five days of symptom onset (p-value <0.001). Patients in Mab treatment group with mild illness required no treatment escalation compared to other groups (p-value=0.011). However, time to recovery patients in all treatment groups was comparable in case of patients with moderate COVID-19 illness (p-value=0.7381). In patients with moderate COVID-19 illness Mab treatment group required more frequent treatment escalation compared to remdesivir treatment group (p-value=0.044), when treatment was started within 5 days of symptom onset remdesivir and mab were comparable for treatment escalation (p=0.144). Vaccination status of the three groups differed significantly (p-value=0.033) hence a further subanalysis was done. On further analysis, non-vaccinated patients receiving Mab recovered from minor symptoms (p-value=0.0006) earlier than those receiving Remdesivir. Amongst the participants of the Mab treatment-group, vaccinated and non-vaccinated patients had comparable recovery time and need for treatment escalation (p-value=0.57 and p-value=0.76, respectively). Participants who received Mab-treatment within five days of symptom onset;recovered earlier compared to those who received Mab treatment after five days (p-value=0.019). Conclusion: Monoclonal antibody treatment group compared to the other treatment groups had earlier recovery in non vaccinated patients, mild COVID-19 disease, and when treatment was started before or on the 5th day of symptom onset.
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Introduction. It is important for SARS-CoV2 vaccine providers, vaccine recipients, and those not yet vaccinated to be well informed about vaccine side effects. We sought to estimate the risk of post-vaccination VTE to meet this need. Methods. We conducted a retrospective cohort study to quantify excess VTE risk associated with SARS-CoV2 vaccination in US veterans age 45 and older using data from the Department of Veterans Affairs (VA) National Surveillance Tool. The vaccinated cohort received at least one dose of a SARS-CoV-2 vaccine at least 60 days prior to 3/06/22 (N=855,686). The control group were those not vaccinated (N=321,676). All patients were COVID-19 tested at least once before vaccination with a negative test. The main outcome was VTE documented by ICD10-CM codes. Results. Vaccinated persons had a VTE rate of 1.3755 (CI: 1.3752-1.3758) per thousand, which was 0.1 percent over the baseline rate of 1.3741 (CI: 1.3738-1.3744) per thousand in the unvaccinated patients, or 1.4 excess cases per 1,000,000. All vaccine types showed a minimal increased rate of VTE (rate of VTE per 1000 was 1.3761 (CI: 1.3754-1.3768) for Janssen;1.3757 (CI: 1.3754-1.3761) for Pfizer and for Moderna the rate was 1.3757 (CI: 1.3748-1.3877)). The tiny differences in rates comparing either Janssen or Pfizer vaccine to Moderna were statistically significant (p<0.001). Adjusting for age, sex, BMI, 2-year Elixhauser score, and race, the vaccinated group had a minimally higher relative risk of VTE as compared to controls (1.0009927 CI: 1.007673-1.0012181;p<0.001) Conclusion. The results provide reassurance that there is only a trivial increased risk of VTE with the current U.S. SARS-COV2 vaccines used in veterans older than age 45. This risk is significantly less than VTE risk amongst hospitalized COVID-19 patients. The risk-benefit ratio favors vaccination, given the VTE rate, mortality and morbidity associated with COVID-19 infection.
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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.
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Purpose: To evaluate the SARS-CoV- 2 infection rate among vaccinated RMD patients in a tertiary hospital and its associations. Methodology: This cross-sectional study was performed among adult rheumatology patients who attended follow up at our centre from 1st April 2022 to 30th April 2022. Demographics and clinical data were compared between the vaccinated patients with SARS-CoV- 2 infection, Group 1 (G1) and without SARS-CoV- 2 infection, Group 2 (G2). Descriptive and inferential statistics were conducted using SPSS version 26. Result(s): We enrolled a total of 212 patients with underlying diagnosis of rheumatoid arthritis (94 patients, 44.3%), systemic lupus erythematosus (59 patients, 27.8%), spondyloarthropathies (30 patients, 14.2%) and others (29 patients, 13.7%). Of all these patients, 57 (26.9%) had SARS-CoV- 2 infection (G1) with mean (SD) age of 45.2 (+/-14.65) years compared to 53.4 (+/-15.22) years in G2 (P = 0.001). In G1, 50 (87.7%) were female, 32 (56.1%) were Malay and 26 (45.6%) with >= 1 comorbidity. Most patients in G1 received 3 doses of vaccine (n = 36, 63.2%) while 21 (36.8%) completed 2 doses of vaccine. Majority in G1 (n = 46, 80.7%) had clinical stage 2 SARS-CoV- 2 infection. Seven required admission to health care facilities with median stay of 6 +/- 2 days. Twenty-three patients (32.9%) in G1 received more than one immunosuppressive drug. Twenty-one out of 63 patients (33.3%) who had 2 doses of SARS-CoV- 2 vaccine had SARS-CoV- 2 infection compared to 36 out of 149 patients (24.2%) who received 3 doses of vaccine, albeit not significant. Conclusion(s): Despite a quarter of the cohort acquired SARS-CoV- 2 infection, the disease was notably less severe, attributed to younger age, less comorbidity and vaccine effectiveness. Type of immunosuppression and use of more than one immunosuppressive drugs were not associated with SARS-CoV- 2 infection.
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Aim/Introduction: Austria started its COVID-19-vaccination program in December 2020 with three different vaccines. As the vaccination program continues, we encountered increased F-18- FDG-activity not only in axillary lymph nodes ipsilateral to the injection site but also in other organs. The aim of this retrospective study is to present results of the metabolic activity of ipsilateral axillary lymph nodes, liver, blood pool, spleen, and bone marrow after three different vaccines. Material(s) and Method(s): The data of 220 eligible vaccinated patients (127 with BioNTech/Pfizer, 61 with Moderna, and 32 with AstraZeneca) examined with F18-FDG-PET/ CT were enrolled. The PET/CT examinations were evaluated from day 1 to day 120 (SD: 23.2, Median: 26) after different vaccinations. Seventy out of these 220 patients were at least once examined with F18-FDG-PET/CT before vacciantion. SUVmax of axillary node(s), and blood pool, liver, spleen, and bone marrow as reference organs were calculated. Relation of SUVmax activity of axillary lymph node to reference organs was also compared in all patients. Result(s): Ten days after BioNTech/Pfizer and AstraZeneca vaccination the axillary FDG uptake was at its highest activity. This was with Moderna vaccination after 30 days. There was no significant statistical difference of SUVmax of lymph nodes or its ratios to other reference organs between three groups of vaccines. SUVmax in lymph nodes in relation to SUVmax in the liver, spleen, and bone marrow was statistically significant with p-values of <.001, 0.044, and 0.001, respectively. In the group of 70 patients with a pre-vaccination PET/CT examination, the SUVmax of lymph nodes (median: 0.820, standard deviation 1.233) changed significantly after vaccination (p <.001). A significant change of tracer activity in the liver was also observed (p = 0.032). There was no significant change of tracer activity after vaccination in other reference regions or between different types of vaccines. Conclusion(s): Local site and ipsilateral axillary lymph node activity in F18-FDG PET/CT after COVID19-vaccination is suggested in many studies. The main challenge is recognizing the changes in lymph nodes after vaccination to minimize false interpretation, foremost in patients with oncological diagnoses. Moreover, different vaccines cause different system metabolic changes. The knowledge of vaccine type, the time interval between vaccination and PET/CT scan is essential, especially in therapy evaluation.
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Objectives: To assess humoral and cellular immune responses and safety profiles after two doses of different mRNA vaccine against SARS-CoV- 2;BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in patients with rheumatic musculoskeletal disease (RMD). Method(s): We enrolled consecutive, previously uninfected RMD patients with inflammatory rheumatic diseases receiving mRNA vaccine including BNT162b2 and mRNA-1273. Healthy participants all receiving BNT162b2 were recruited as control. Blood samples were obtained 3weeks after second dose of vaccines. We measured titres of neutralizing antibodies against SARS-CoV- 2 with chemiluminescent enzyme immunoassay to evaluate humoral responses and assessed T-cell immunity responses with interferon releasing assay against SARS-CoV- 2 in a part of the patients. Adverse reaction symptoms were obtained from participants through questionnaire. Result(s): A total of 1040 RMD patients and healthy 621 control participants were enrolled. Among RMD patients with immunosuppressants, 704 were received BNT162b2 and 156 were received mRNA-1273. Neutralizing antibody titres 3 weeks after vaccination and positive seroconversion rates were significantly higher in healthy participants with BNT162b2 and RMD patients with mRNA-1273 compared with RMD patients with BNT162b2;neutralizing antibody titre, 23.9 +/- 14.2 IU/mL vs 29.4 +/- 33.9 IU/mL vs 10.8 +/- 16.5 IU/mL, p < 0.001;seroconversion rates, 99.5% vs 99.4% vs 80.2%, p < 0.001, respectively, We identified that age, glucocorticoid (prednisolone dose > 7.5mg/day), and use of immunosuppressants including methotrexate, mycophenolate and rituximab, are associated with attenuation of humoral responses in patients with BNT162b2. T cell reaction against SARS-CoV- 2 were also higher in patients with RMD vaccinated with mRNA-1273 than those with BNT162b2 (Interferon gamma levels for antigen 1, 3.2 +/- 6.5 IU/mL vs 0.6 +/- 1.3 IU/mL, p = 0.002;for antigen 2, 3.2 +/- 6.3 IU/mL vs 1.0 +/- 2.1 IU/mL, p = 0.021, respectively). Regarding adverse reaction of mRNA vaccine, the proportion of systemic adverse reactions including fever and general fatigue are significantly higher in healthy controls and RMD patients with mRNA-1273 than those with BNT162b2;fever, 46.2% vs 56.7% vs 14.3%, p < 0.001;general fatigue, 62.6% vs 73.0% vs 38.5%, p < 0.001, respectively, while the frequency of background RMD flare after vaccination were not significantly different between mRNA-1273 and BNT162b2 (5.2% [n = 8] vs. 3.7% [n = 26], p = 0.41) Conclusion(s): We demonstrated higher humoral, cellular immunogenicity of the SARS-CoV- 2 mRNA-1273 (Moderna) compared with the BNT162b2 (Pfizer-BioNTech) in RMD patients. Although reactogenicity including systemic adverse reaction including fever and fatigue were observed mRNA1273 vaccinated patients, proportion of RMD relapse were similar between the patients with mRNA-1273 and BNT162b2.
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Background: We assessed the risk factors and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRD) who contracted infection while on background treatment with tofacitinib. Method(s): This is a non-interventional, cross-sectional, questionnaire based telephonic study which included consecutive AIRD patients on tofacitinib co-treatment. Data related to the AIRD subset, disease modifying anti rheumatic drugs (DMARDs) including glucocorticoids and comorbidities, was collected from 7 rheumatology centers across Karnataka during the second wave of COVID-19 pandemic. The information about COVID-19 occurrence and COVID-19 vaccination was recorded. Result(s): During the study period (June-July 2021), 335 AIRD patients (80.6% female) on treatment with tofacitinib were included. The mean duration of tofacitinib use was 3.4 +/- 3.1 months. Thirty-six (10.75%) patients developed COVID-19. Diabetes mellitus P = 0.04 (OR 2.60 [1.13-5.99]) was identified as a risk factors for COVID-19 in our cohort. Almost half of our cohort was COVID-19 vaccinated with at least one dose, with resultant decline in incidence of COVID-19 (OR 0.15 [0.06-0.39]) among the vaccinated. Recovery among COVID-19 infection group was 91.2%. Conclusion(s): The AIRD patients on co-treatment with tofacitinib had a higher incidence of COVID-19 than the general population during the same time period. Diabetes mellitus was identified as an independent risk factor in our cohort. COVID-19 vaccinated patients contracted COVID-19 at a significantly lesser rate than the non-vaccinated patients.
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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.