ABSTRACT
Background: Life threatening thrombotic events involving both the arterial and venous systems are prominently present in SARS-CoV-2 infected individuals presenting with severe COVID-19. Abnormal clotting also occurs in asymptomatically or mildly infected individuals and in people experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). Clinical management of this clotting disorder has proven difficult in part because these fibrin clots are highly resistant to plasmin-mediated fibrinolysis. Methods: An array of different binding, biochemical, microscopic, and in vivo assays were performed in these studies. All experiments were performed at least three times in triplicate and reported differences were shown to be statistically significant. Results: We find that SARS-CoV-2 Spike directly binds to the terminal clotting factors, fibrinogen and fibrin (Kd of 5.3 μ M and 0.4 μ M respectively). Mixing Spike and plasma accelerates fibrin polymerization. Scanning electron microscopy reveals an abnormal clot structure with finer, denser, and roughened fibrin fibers. Scanning peptide competition assays indicate Spike binds fibrin at three sites: 1) the plasmin cleavage site needed for fibrinolysis;2) a site involved in innate immune signaling via fibrin binding to Complement Receptor 3 (CR3);and 3) a site with no known function. Examination of mice injected 24h earlier with Spike pseudotyped HIV-ΔEnv virions reveals extensive intra-and extravascular fibrin deposition in the lung accompanied by endothelial activation, loss of tight junctions, increased influx of macrophages, and the generation of high levels of reactive oxygen species. This thromboinflammatory response is not observed when Bald virions are injected or when Spike pseudotyped virions are injected into mice lacking fibrinogen. Intriguingly, these Spike-induced proinflammatory effects are blocked by an anti-fibrin monoclonal antibody, 5B8, which interferes with fibrin binding to CR3. Conclusion: Our findings reveal that the SARS-CoV-2 Spike protein binding to fibrinogen/fibrin results in the formation of structurally abnormal, fibrinolysis-resistant blood clots whose inflammatory effects are effectively neutralized by a specific fibrin-targeting monoclonal antibody. While COVID-19 clotting was thought to occur as a result of systemic inflammation, our findings suggest clotting during SARS-CoV-2 infection in fact is a driver of inflammation. Targeting fibrin could lead to novel therapeutic approaches for patients with acute COVID-19 and PASC.
ABSTRACT
Currently, due to the changes in social conditions caused by the spread of Covid19 infection, the increase and decrease in the stream of people in major downtown areas and tourist spots such as holiday resorts are attracting attention. These data have been analyzed from the accumulation of smartphone location data and sensor information, but their availability is limited. To solve this problem, we use the images from fixed-point cameras installed in each city, which are available on YouTube as open data, and analyze the flow of people using OpenCV to reflect and visualize the real-time congestion status in a 3D city model. © 2022 IEEE.
ABSTRACT
Objective: To find what freshman medical and nursing students in Japan, think about kissing behavior as practiced in Japan. Methods: Freshman students who entered the medical and nursing curriculum (N = 37, with 12 men and 25 women) at a national university in 2015 were asked the question: 'Write your impressions and criticism to a published editorial 'Kissing behavior among Japanese' (Internat Med J., 2014;21: 374-375) Results: Obtained results are summarized in two tables. Majority of the students expressed that kissing practices in Europe or America differs from the kissing behavior in Japan. Whereas kissing in public places are more common in Europe or America as a form of greeting, this is hardly seen in Japan because kissing is mainly considered as a gesture/signal of erotic love in Japan. Two female students raised a question and a concern related to kissing as a mode of transmission of AIDS disease. Another male student had humorously asked, "Aren't fellatio or cunnilingus, a kind of kissing?" Conclusion: Among the 37 responses on kissing behavior of Japanese, we highlight two;(1) More researchers should research about kissing, not independently but collaboratively;(2) The risk of infections caused by kissing behavior has to be investigated. These suggestions have high relevance now due to the coronavirus disease---2019 (COVID-19) lockdown experi-enced in Japan in 2020 and 2021.