In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. While human immunity against COVID-19 is not fully understood, it is, so far, well documented, that both adaptive and innate cells have a critical role in protection against SARS-CoV-2. Here, we aimed to summarize the clinical and laboratory data on primary immunodeficiency (PID) patients in Israel, who were tested positive for SARS-CoV-2, in order to estimate the impact of COVID-19 on such patients. Data was collected from mid-February to end-September. During this time Israel experienced two “waves” of COVID-19 diseases; the first, from mid-February to mid-May and the second from mid-June and still ongoing at the end of data collection. A total of 20 PID patients, aged 4 months to 60 years, were tested positive for SARS-CoV-2, all but one, were detected during the second wave. Fourteen of the patients were on routine monthly IVIG replacement therapy at the time of virus detection. None of the patients displayed severe illness and none required hospitalization; moreover, 7/20 patients were completely asymptomatic. Possible explanations for the minimal clinical impact of COVID-19 pandemic observed in our PID patients include high level of awareness, extra-precautions, and even self-isolation. It is also possible that only specific immune pathways (e.g. type I interferon signaling), may increase the risk for a more severe course of disease and these are not affected in many of the PID patients. In some cases, lack of an immune response actually may be a protective measure against the development of COVID-19 sequelae.

A series of 198 consecutive patients with acute myocardial infarction were prospectively studied before hospital discharge and during 24.0 +/- 8.6 months of follow-up. A predischarge thrombus was found in 38 (31%) of 124 patients with anterior infarction but in none of 74 patients with inferior infarction (p less than 0.001). Early thrombolytic therapy in 34 patients did not decrease the rate of thrombus occurrence. Acute anterior infarction, ejection fraction less than or equal to 35% and apical dyskinesia or aneurysm (but not akinesia) were significantly related to the appearance of thrombus during hospitalization by stepwise logistic regression analysis. Echocardiographic follow-up of 159 patients for at least 6 months (mean 26.6 +/- 8.4) revealed that thrombus disappeared in 14 (48%) of 29. Disappearance of thrombus was related to predischarge apical akinesia (but not dyskinesia) and to warfarin therapy during the follow-up period. A new thrombus first appeared after hospital discharge in 13 of 130 patients, and in 7 of the 13 it resolved during further follow-up. Thus, 30% (13 of 42) of thrombi in these patients appeared after discharge from the hospital. Three factors were related to occurrence of new thrombi during the follow-up period: deterioration in left ventricular ejection fraction, predischarge ejection fraction less than or equal to 35% and ventricular aneurysm or dyskinesia. Systemic embolism occurred in six patients, all with a predischarge thrombus (p less than 0.001). Mobility of the thrombus was the only variable significantly related to subsequent embolic events (p = 0.001) by logistic regression analysis. Thus, the predischarge echocardiogram identifies patients with thrombus and those at highest risk of embolic events. It can indicate patients who are likely to have thrombus resolution and those at risk of developing a new thrombus after hospital discharge. Follow-up echocardiograms may help in guiding the length of long-term anticoagulant therapy. Four additional patients with a predischarge apical mobile thrombus (not part of the consecutive series) received thrombolytic therapy. In two of the four, lysis of thrombus was achieved without complications, but systemic embolism occurred in the other two, and proved fatal in one.

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PolyADP-ribosylation is a post-translational modification of nuclear proteins, catalyzed by polyADP-ribose polymerases (PARPs). In the nucleus, polyADP-ribosylation catalyzed by PARP-1 alters protein-protein and protein-DNA interactions, and is implicated in chromatin remodeling, DNA transcription, and repair. Previous results linked the activation of PARP-1 with long-term memory formation during learning in the marine mollusk Aplysia ( Science 2004, 304:1820-1822). Furthermore, PARP-1 was highly activated in mammalian cerebral neurons treated with neurotrophins and neurotrophic peptides promoting neurite outgrowth and synaptic plasticity. Here, we examine the possibility that PARP-1 activation is required for memory formation during learning in mammals. Mice were tested in two learning paradigms, object recognition and fear conditioning. PolyADP-ribosylation of PARP-1 and histone H1 were detected in their cerebral cortex and hippocampus immediately after their training session. Moreover, in both behavioral paradigms, suppression of PARP activity in the CNS during learning impaired their long-term memory formation, without damaging their short-term memory. These findings implicate PARP-1 activation in molecular processes underlying long-term memory formation during learning.