The third dose of BNT162b2 COVID-19 vaccine is efficacious and safe for systemic lupus erythematosus patients receiving belimumab.

INTRODUCTION: Over 95% of healthy subjects develop anti-COVID IgG antibodies after receiving two doses of BNT162b2 COVID-19 vaccine. In comparison, 20%-30% of SLE patients do not seroconvert following 1-2 doses of COVID vaccines, potentially due to immunosuppression. The aim of this study was to assess immunogenicity and safety of BNT vaccine in SLE patients treated with Belimumab and especially the yield of a booster third dose in this population. METHODS: SLE patients treated with Belimumab in the Sheba Medical Center, Israel, were included in this study. All were recommended to receive the BNT vaccine according to national guidelines; and were advised to perform serologic tests after receiving second and third doses. Clinical data included demographics, SLE treatments, adverse effects to vaccines and SLEDAI scores performed 2 weeks before vaccinations and 6-12 weeks after receiving the second or third dose of the vaccine. RESULTS: Our cohort included 17 patients, 14 (82.35%) females, median age 50 ± 14.2 years, and disease duration 12 ± 10.57 years. Belimumab therapy was given for a mean of 6 ± 2.5 years. Of them, 15/17 patients received 3-doses of BNT vaccine. Serologic assessment was performed for 10 patients, 7/10(70%) became seropositive following the second dose, while 2/3 patients seroconverted only after the third dose. Vaccinations were well tolerated with minimal adverse events and no disease flares. SLEDAI scores before and after vaccinations were 4 ± 3.8 and 4 ± 2.7 (p = 0.69), respectively. CONCLUSIONS: Immunization with the BNT vaccine is efficacious and safe for SLE patients treated with Belimumab. Following the third dose of vaccine, immunogenicity among SLE patients mounted to 90%, thereby approximating the general healthy population. No SLE disease flares and/or significant adverse events were noted in our cohort. Assessment of seroconversion and consideration of subsequent boosters of COVID-vaccine should be considered in this group of patients.

[A RARE COMBINATION OF DELAYED TYPE HYPERSENSITIVITY REACTIONS TO BETA-LACTAMS IN A PATIENT WITH MSSA BACTEREMIA].

INTRODUCTION: A male patient aged 81, with a history of atrial fibrillation, pacemaker implantation and hip replacement was admitted due to pneumonia. Subsequent Methicillin Sensitive Staphylococcus Aureus (MSSA) bacteremia and septic arthritis of his prosthetic joint was diagnosed, and treated with Oxacillin. Two weeks later, an exanthematous rash appeared, involving most of his body surface, evolving to blisters that dried up and led to extensive exfoliation of the skin, consistent with a delayed type hypersensitivity drug reaction. Other possible etiologies for this rash were ruled out. Antibiotic treatment was changed to Cefalexin, assuming that there is no cross reactivity between penicillins and cephalosporins, regarding late drug reactions. Thereafter, the rash subsided, but his renal function deteriorated and interstitial nephritis due to a hypersensitivity reaction to cephalosporin was diagnosed. Hypersensitivity to penicillins and other beta-lactam antibiotics is reported by 10% of the population, only 1/10 of them are verified using standardized allergic testing (1-3). Delayed type hypersensitivity to beta-lactams is more common than immediate type allergy. It evolves days and weeks following exposure to the offending drug. Late responses are classified as type II- IV hypersensitivities, type IV being the most prevalent (4-7). We present a patient who developed two distinct delayed type phenomena to two different beta lactam antibiotics during the same hospitalization. The possibility of a hypersensitivity reaction should rise in the differential diagnosis of the deteriorating patient most notably as such might be life threatening on the one hand, and reversible, after drug withdrawal, on the other hand.

Assessment of Immediate Allergic Reactions After Immunization With the Pfizer BNT162b2 Vaccine Using Intradermal Skin Testing With the COVID-19 Vaccines.

BACKGROUND: Allergic reactions to the coronavirus disease 2019 (COVID-19) vaccines have raised concerns, particularly as repeated doses are required. Skin tests with the vaccines excipient were found to be of low value, whereas the utility of skin tests with the whole vaccine is yet to be determined. OBJECTIVE: To evaluate a panel of skin tests and the outcomes of subsequent doses of immunization among subjects who suffered an immediate allergic reaction to the BioNTech (BNT162b2) COVID-19 vaccine. METHODS: Between March and December 2021, patients who experienced symptoms consistent with immediate allergic reactions to the BNT162b2 vaccine and were referred to the Sheba Medical Center underwent skin testing with polyethylene glyol (PEG)-containing medicines, Pfizer-BNT162b2, and Oxford-AstraZeneca vaccine (AZD1222). Further immunization was performed accordingly and under medical observation. RESULTS: A total of 51 patients underwent skin testing for suspected allergy to the COVID vaccines, of which 38 of 51 (74.5%) were nonreactive, 7 of 51(13.7%) had no skin sensitization but suffered a clinical reaction during skin testing (mainly cough), and 6 of 51 (11.7%) exhibited immediate skin sensitization. Both skin sensitization and cough during testing were related to a higher use of adrenaline following immunization (P = .08 and P = .024, respectively). Further immunization with the BNT162b2 vaccine was recommended unless sensitization or severe reaction to previous immunization was evident. The latter were referred to be tested/receive the alternative AZD1222 vaccine. Ten patients underwent skin testing with AZD1222: 2 of 10 (20%) demonstrated skin sensitization to both vaccines; thus, 8 of 10 were immunized with the AZD1222, of which 2 of 8 (25%) had allergic reactions. CONCLUSIONS: Immediate allergic reactions to COVID-19 vaccines are rare but can be severe and reoccur. Intradermal testing with the whole vaccine may discriminate sensitized subjects, detect cross-sensitization between vaccines, and enable estimation of patients at higher risk.

The innate immune perspective of autoimmune and autoinflammatory conditions.

Innate immunity is one of two immune defence system arms. It is present at birth and does not require 'learning' through exposure to foreign organisms. It activates various mechanisms collectively to eliminate pathogens and hold an infection until the adaptive response are mounted. The innate immune system consists of four elements: the epithelial barrier, cells (e.g. macrophages, NK cells), plasma proteins (e.g. complement) and cytokines. These components act in concert to induce complex processes, as well as recruitment, activation and differentiation of adaptive responses. The innate response is more than just the 'first line of defence', as it essentially withholds the vast majority of any intruder, has a complex interplay with the adaptive arm and is crucial for survival of the host. Finally, yet importantly, a myriad of diseases has been linked with innate immune dysregulation. In this mini-review we will shed some light on these conditions, particularly regarding autoinflammatory ones.

A Stroke in the Young with Surprising Recovery.

INTRODUCTION: The differential diagnosis of stroke in a comparatively young adult should always include cardiovascular aetiologies as well as central nervous system infection. CASE PRESENTATION: A 56-year-old man, with no significant medical history, presented with headache, nausea and vomiting, and right hemiparesis. Routine stroke investigation was initiated, while CNS infection was also sought. Diagnoses of HIV infection, neurosyphilis, HCV and HBV were established. Targeted therapy resulted in prompt clinical improvement. CONCLUSION: This case highlights the importance of considering CNS infection as a cause of neurological deficits in parallel with other investigations in cases of stroke in a comparatively young adult. LEARNING POINTS: The differential diagnosis should be wide for all patients presenting with stroke.Neurosyphilis should be included in the differential diagnosis of stroke in the young and middle-aged.Newly diagnosed HIV patients should be screened for other, sexually transmitted coinfection.