Impact of BNT162b2 mRNA anti-SARS-CoV-2 vaccine on interferon-alpha production by plasmacytoid dendritic cells and autoreactive T cells in patients with systemic lupus erythematosus: The COVALUS project.

OBJECTIVE: To evaluate the specific response of SLE patients to BNT162b2 vaccination and its impact on autoimmunity defined as in vivo production of interferon-alpha (IFNα) by plasmacytoid dendritic cells (pDCs) and autoreactive immune responses. METHODS: Our prospective study included SLE patients and healthy volunteers (HV) who received 2 doses of BNT162b2 vaccine 4 weeks apart. Subjects under immunosuppressive drugs or with evidence of prior COVID-19 were excluded. IgG anti-Spike SARS-CoV-2 (anti-S) antibodies, anti-S specific-B cells, anti-S specific T cells, in vivo INF-α production by pDCs, activation marker expression by pDCs and autoreactive anti-nuclear T cells were quantified before first injection, before second injection, and 3 and 6 months after first injection. RESULTS: Vaccinated SLE patients produced significantly lower IgG antibodies and specific B cells against SARS-CoV-2 as compared to HV. In contrast, anti-S T cell response did not significantly differ between SLE patients and HV. Following vaccination, the surface expression of HLA-DR and CD86 and the in vivo production of IFNα by pDCs significantly increased in SLE patients. The boosted expression of HLA-DR on pDCs induced by BNT162b2 vaccine correlated with the overall immune responses against SARS-CoV-2 (anti-S antibodies: r = 0.27 [0.05-0.46], p = 0.02; anti-S B cells: r = 0.19 [-0.03-0.39], p = 0.09); anti-S T cells: r = 0.28 [0.05-0.47], p = 0.016). Eventually, anti-SARS-CoV-2 vaccination was associated with an overall decrease of autoreactive T cells (slope = - 0.00067, p = 0.015). CONCLUSION: BNT162b2 vaccine induces a transient in vivo activation of pDCs in SLE that contributes to the immune responses against SARS-CoV-2. Unexpectedly BNT162b2 vaccine also dampens the pool of circulating autoreactive T cells, suggesting that vaccination may have a beneficial impact on SLE disease.

Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: a nationwide study.

OBJECTIVE: We analysed the incidence of, the specific outcomes and factors associated with COVID-19-associated organ failure (AOF) in patients with systemic lupus erythematosus (SLE) in France. METHODS: We performed a cohort study using the French national medical/administrative hospital database for the January 2011-November 2020 period. Each patient with SLE diagnosed in a French hospital with a COVID-19-AOF until November 2020 was randomly matched with five non-SLE patients with COVID-19-AOF. We performed an exact matching procedure taking age ±2 years, gender and comorbidities as matching variables. COVID-19-AOF was defined as the combination of at least one code of COVID-19 diagnosis with one code referring to an organ failure diagnosis. RESULTS: From March to November 2020, 127 380 hospital stays in France matched the definition of COVID-19-AOF, out of which 196 corresponded with patients diagnosed with SLE. Based on the presence of comorbidities, we matched 908 non-SLE patients with COVID-19-AOF with 190 SLE patients with COVID-19-AOF. On day 30, 43 in-hospital deaths (22.6%) occurred in SLE patients with COVID-19-AOF vs 198 (21.8%) in matched non-SLE patients with COVID-19-AOF: HR 0.98 (0.71-1.34). Seventy-five patients in the SLE COVID-19-AOF group and 299 in the matched control group were followed up from day 30 to day 90. During this period, 19 in-hospital deaths occurred in the SLE group (25.3%) vs 46 (15.4%) in the matched control group; the HR associated with death occurring after COVID-19-AOF among patients with SLE was 1.83 (1.05-3.20). CONCLUSIONS: COVID-19-AOF is associated with a poor late-onset prognosis among patients with SLE.

Arterial Thrombotic Events in Adult Inpatients With COVID-19.

OBJECTIVE: To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19). METHODS: All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form. RESULTS: Overall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001). CONCLUSION: A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.