Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.

Background/Objectives: ACE (angiotensin-converting enzyme) is considered a serological marker of sarcoidosis as elevated levels have been reported in 30–80% of patients. However, elevated ACE levels are also encountered in other medical conditions, and the clinical correlation between ACE levels and disease activity in sarcoidosis is disputable as well. To determine the significance of elevated ACE levels in the diagnosis and follow-up of sarcoidosis patients. Methods: All electronic patient records in which an ACE level was recorded in a large tertiary hospital were identified using a computerized algorithm. Medical diagnoses, ACE numerical values, and clinical data were also automatically extracted. Furthermore, all records with a diagnosis of sarcoidosis were manually reviewed for ascertainment of the diagnosis and searched for additional clinical manifestations and treatment responses. Results: A total of 1416 records with a documented ACE level were found in the database, and 146 of the records had a diagnosis of sarcoidosis in the medical record. However, the diagnosis was excluded in 27 of these cases after a manual review of the records. Elevated ACE levels were most commonly encountered among patients with sarcoidosis, non-Hodgkin’s lymphoma, cirrhosis, and interstitial lung disease. Elevated ACE levels had a positive predictive value of 12.76% and a negative predictive value of 94.6% for the diagnosis of sarcoidosis in our cohort, with a sensitivity of 63.5% and a specificity of 59.5%. Among patients with sarcoidosis, ACE levels around the time of diagnosis were higher than ACE levels in remission. However, a paired analysis did not find a statistically significant difference in ACE levels between the two timepoints. A positive correlation between lack of cardiac involvement and elevated ACE levels was found on multivariate analysis. Conclusions: ACE levels are a non-specific serological marker with low specificity and sensitivity for sarcoidosis and a poor positive predictive value, but with a negative predictive value of 94.6%. Furthermore, elevated ACE levels correlated poorly with disease activity in our cohort.

The common practice in the Israel defense Forces is that exertional heat related injury patients undergo a heat tolerance test 6–8 weeks post event as part of the “return to duty” process. In the case of a positive heat tolerance test the individual is classified as heat intolerant, in some cases however, the thermoregulatory recovery may be longer (several months), and therefore a second heat tolerance test is scheduled 6-8 weeks later. The presented case reports emphasize the possibility of different recovery periods of the thermoregulatory center and the distinction between congenital and acquired physiological heat intolerance. Two young healthy males (A and B) were diagnosed with exertional heat related injury during a pre-recruitment sorting process. Both underwent a heat tolerance test, and were found heat intolerant. During the next months they repeated the test several times. Patient A was finally diagnosed as heat tolerant and patient B was diagnosed as heat intolerant. Susceptibility to heat is a significant determinant for active young people such as athletes and soldiers. Both cases emphasize the importance of the heat tolerance test (and repeated test when needed) as a criteria for an exertional heat related injury patient to return to duty/play and to perform intense physical activities. These cases also emphasize the effectiveness and sensitivity of the test in identifying a temporary and a permanent state of heat intolerance.

Full Papers; Authors: A. Druyan, E. Giat, A. Livneh, C. Grossman, I. Ben-Zvi, M. Lidar