Immunogenicity and safety of the mRNA-based BNT162b2 vaccine in systemic autoimmune rheumatic diseases patients.

BACKGROUND: The COVID-19 outbreak has led to the rapid development and administration of the COVID-19 vaccines worldwide. Data about the immunogenicity and adverse effects of the vaccine on patients with systemic autoimmune rheumatic diseases (SARDs) is emerging. AIM: To evaluate Pfizer/BioNTech (BNT162b2) mRNA-based vaccine second-dose immunogenicity and safety, and the relation between them, in patients with SARDs. METHODS: A total of one hundred forty tow adults who received two doses of the BNT162b2 vaccine were included in the study. The SARDs group included Ninety-nine patients and the control group (forty-three participants) comprised a mixture of healthy participants and patients who were seen at the rheumatology clinic for non-SARDs. Anti-SARS-CoV-2 IgG antibodies against the Spike protein were evaluated using a SARS-CoV-2 IgG immunoassay. A level of > 150 AU/mL was considered positive. An adverse effects questionnaire was given to the participants upon their first visit to the clinic after their BNT162b2 vaccination. RESULTS: Of the 142 participants, 116 were seropositive (81.7%) and 26 (18.3%) were seronegative. Of the seronegative participants, 96.2% were SARDs patients. The proportion of seropositivity in the SARDs patients treated with any immunosuppressant was significantly lower (69.9%) compared to the control group and SARDs patients not receiving immunosuppressants (96.8%). A significant negative correlation between seronegativity and treatment with rituximab, mycophenolate mofetil (MMF), and prednisone was found in the SARDs group (p = 0.004, 0.044, 0.007 respectively). No fever was observed following the BNT162b2 vaccine in seronegative patients, and the frequency of musculoskeletal adverse effects upon the second dose of the BNT162b2 vaccine was significantly higher in seropositive compared to seronegative patients and in the control group compared to the SARDs patients (p = 0.045, p = 0.02 respectively). CONCLUSION: A decline in the immunogenicity to the second dose of BNT162b2 mRNA is seen in patients with SARDs, especially in patients treated with rituximab, MMF, and prednisone. Adverse effects of the vaccine including fever and musculoskeletal symptoms might be a signal for the acquisition of immunity in those patients. KEY POINTS: • BNT162b2 mRNA vaccine is less immunogenic in SARDs patients compared to the control group. • Rituximab, prednisone, and mycophenolate mofetil significantly reduced immunogenicity to the vaccine. • There is a correlation between immunogenicity and adverse effects of the vaccine.

Mortality prediction using a modified R2CHA2DS2-VASc score among hospitalized COVID-19 patients.

The CHA2DS2-VASc score incorporates several comorbidities which have prognostic implications in COVID-19. We assessed whether a modified score (M-R2CHA2DS2-VASc), which includes pre-admission kidney function and male sex, could be used to classify mortality risk among people hospitalized with COVID-19. This retrospective study included adults admitted for COVID-19 between March and December 2020. Pre-admission glomerular filtration rate (GFR) was calculated based on serum creatinine and used for scoring M-R2CHA2DS2-VASc. Participants were categorized according to the M-R2CHA2DS2-VASc categories as 0-1 (low), 2-3 (intermediate), or ≥ 4 (high), and according to initial COVID-19 severity score. The primary outcome was 30-day mortality rates. Secondary outcomes were mortality rates over time, and rates of mechanical ventilation, hemodynamic support, and renal replacement therapy. Eight hundred hospitalizations met the study criteria. Participants were 55% males, average age was 65.2 ± 17 years. There were similar proportions of subjects across the M-R2CHA2DS2-VASc categories. 30-day mortality was higher in those in higher M-R2CHA2DS2-VASc category and with severe or critical COVID-19 at admission. Subjects in the low, intermediate, and high M-R2CHA2DS2-VASc categories had 30-day mortality rates of 4.7%, 17% and 31%, respectively (p < 0.001). Higher category was also associated with increased need for mechanical ventilation and renal replacement therapy. All-cause 90-day mortality remained significantly associated with M-R2CHA2DS2-VASc. The M-R2CHA2DS2-VASc score is associated with 30-day mortality rates among patients hospitalized with COVID-19, and adds predictive value when combined with initial COVID-19 severity.

Disease severity and renal outcomes of patients with chronic kidney disease infected with COVID-19.

INTRODUCTION: While there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking. METHODS: This retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization ("baseline serum creatinine") and at admission, as well as minimum and maximum serum creatinine levels during hospitalization. RESULTS: Among 658 patients, 152 had eGFR < 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8-8.7; p < 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1-10.8) for renal replacement therapy (p < 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p < 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p < 0.001). CONCLUSION: Despite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased.