ABSTRACT
OBJECTIVES: To assess the prevalence of autoantibodies (AAbs) in mechanically ventilated COVID-19 patients and to investigate whether AAbs influence the clinical outcome. METHODS: Serum samples were drawn within the first 48 hours upon admission to the intensive care unit (ICU) from 217 consecutive patients, from January 1st, 2021, to May 10th, 2021, and investigated for the presence of AAbs using conventional techniques. Serum samples (n=117) of age- and sex-matched healthy individuals collected before COVID-19 pandemic were used as controls. RESULTS: COVID-19 patients in the ICU had more commonly AAbs compared to age- and sex-matched controls (174/217, 80.2% vs. 73/117, 62.4%, p<0.001). Patients expressed more frequently ANAs (48.4% vs. 21.4%, p<0.001), anti-dsDNA (5.1% vs. 0%, p=0.01), anti-CCP (8.3% vs. 1.7%, p=0.014) and anti-CL IgM AAbs (21.7% vs. 9.4%, p=0.005) than controls, respectively. Simultaneous reactivity against at least three autoantigens, occurred in 144 out of 174 (82.8%) patients. The two groups did not differ in terms of clinicoepidemiologic characteristics or the mortality ratio within the ICU. Patients who died compared to convalescents were older, had higher ferritin, D-dimers levels, APACHE II score, lower oxygen saturation, higher prevalence of comorbidities and cognitive dysfunction. However, AAbs were not found to correlate with the clinical outcome. CONCLUSIONS: Patients with severe COVID-19 express AAbs more commonly compared to controls. No correlation was found between AAbs and disease outcome.
ABSTRACT
The novel mRNA-based vaccines against SARS-CoV-2 display encouraging safety and efficacy profiles. However, there is a paucity of data regarding their immunogenicity and safety in patients with liver diseases (PWLD), especially in those with cirrhosis. We prospectively assessed anti-SARS-CoV-2 S-spike IgG antibodies and neutralizing activity in fully vaccinated PWLD (n = 87) and controls (n = 40). Seroconversion rates were 97.4% (37/38) in cirrhotic PWLD, 87.8% (43/49) in non-cirrhotic PWLD and 100% (40/40) in controls. Adequate neutralizing activity was detected in 92.1% (35/38), 87.8% (43/49) and 100% (40/40) of cirrhotics, non-cirrhotics and controls, respectively. On multivariable analysis, immunosuppressive treatment was negatively correlated with anti-SARS-CoV-2 antibody titers (coefficient (SE): -2.716 (0.634), p < 0.001) and neutralizing activity (coefficient (SE): -24.379 (4.582), p < 0.001), while age was negatively correlated only with neutralizing activity (coefficient (SE): -0.31(0.14), p = 0.028). A total of 52 responder PWLD were reassessed approximately 3 months post-vaccination and no differences were detected in humoral responses between cirrhotic and non-cirrhotic PWLD. No significant side effects were noted post vaccination, while no symptomatic breakthrough infections were reported during a 6-month follow up. Overall, our study shows that m-RNA-based SARS-CoV-2 vaccines are safe and efficacious in PWLD. However, PWLD under immunosuppressive treatment and those of advanced age should probably be more closely monitored after vaccination.
Subject(s)
2019-nCoV Vaccine mRNA-1273/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , BNT162 Vaccine/immunology , COVID-19/prevention & control , Immunoglobulin G/blood , Liver Diseases/complications , 2019-nCoV Vaccine mRNA-1273/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , BNT162 Vaccine/administration & dosage , COVID-19/immunology , Female , Humans , Immunoglobulin G/immunology , Immunosuppression Therapy/adverse effects , Liver Diseases/drug therapy , Liver Diseases/virology , Male , Middle Aged , Seroconversion , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.