After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensinconverting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2-and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect M.P. and D.M. contributed equally to this work as corresponding authors. Edited by: H.-U. Simon, Bern.

The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.

Patients with the underlying valvular heart disease are at the high risk of developing sub-acute or chronic endocarditis secondary to Coxiella burnetii. Q fever endocarditis is the most common manifestation along with persistent the infection. There is some serologic and molecular evidence of C. burnetii infection in humans and livestock in Iran. As it is possible to observe chronic Q fever in Iran, it seems necessary to study the prevalence of Q fever endocarditis in this country. In the present study, Infective Endocarditis (IE) patients (possible or definite based on Duke Criteria) hospitalized in Rajaie Cardiovascular Medical and Research Center were enrolled from August 2016 to September 2018. Culture-negative endocarditis patients were evaluated by Raoult criteria for diagnosis Q fever endocarditis. The serological results for brucellosis were negative for all subjects. All blood and tissue samples including valve samples were tested for C. burnetii infection using serology and Polymerase Chain Reaction (PCR). In this study, 126 patients who were admitted to the hospital were enrolled; of which 52 subjects were culture-negative IE. Among the participants, 16 patients (30.77%) were diagnosed with Q fever IE and underwent medical treatment. The mean age of patients was 46.6 years ranging from 23 to 69 years and 75% of them were male. Considering the high prevalence of Q fever IE, evaluation of the patients with culture-negative IE for C. burnetii infections was highly recommended.