Background: Acting as a viral entry for coronavirus to invade human cells, TMPRSS2 has become a target for the prevention and treatment of COVID-19 infection. Cutaneous manifestations of COVID-19: report of three cases and a review of literature, IL-6 pathway in the liver: from physiopathology to therapy. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HHX, Luo M, Chen L, Zhao Y. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19, Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Previous data from the SARS epidemic suggests 35% of heart specimens showed presence of viral RNA in the myocardium. Contrary to earlier studies, a recent study by Wang et al. Bertram S, Glowacka I, Mller MA, Lavender H, Gnirss K, Nehlmeier I, Niemeyer D, He Y, Simmons G, Drosten C, Soilleux EJ, Jahn O, Steffen I, Phlmann S. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. Oudit GY, Kassiri Z, Jiang C, Liu PP, Poutanen SM, Penninger JM, Butany J. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS, COVID-19 and the endocrine system: exploring the unexplored, Nephrotoxicity of cancer immunotherapies: past, present and future. Chen IY, Moriyama M, Chang MF, Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Drugdrug interaction between Nitazoxanide and Azithromycin is Furthermore, treatment approaches may be further tailored to the disease course of the patient by bolstering immune response earlier during disease progression to enhance an efficient antiviral response and blocking inflammation once severe disease develops. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Kidney involvement in COVID-19 and rationale for extracorporeal therapies, Management of acute kidney injury in patients with COVID-19, Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Several studies have demonstrated significantly elevated levels of classical markers of cardiac injury and failure [i.e., cardiac troponin and brain natriuretic peptides (BNP)] in patients with greater disease severity (53a, 78). Recent autopsy data from Italy also observed fibrin thrombi in pulmonary small arterial vessels in 87% of fatal cases examined, suggesting the contribution of coagulation in diffuse alveolar and endothelial damage (15). 1: SARS-CoV-2 enters alveolar epithelial cells by binding to angiotensin converting enzyme 2 (ACE2) through surface spike (S) protein mediated by transmembrane serine protease 2 (TMPRSS2). WebImmunophenotyping of neutrophils, lymphocytes, and monocytes has demonstrated that the neutrophil-to-lymphocyte ratio, especially with a reduction in CD8 + T cells, is a marker of Interestingly, a recent study characterizing a small cohort of previously healthy children and adolescents who developed an inflammatory profile related to COVID-19 in New York City described a unique cytokine pattern characterized by elevated IL-6 and IL-10 production, as well as increased interferon signaling components. Conclusion Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. The mechanisms behind progressive lymphopenia in severe COVID-19 remain unclear, although T-cell redistribution via pulmonary recruitment, exhaustion, as well as depletion through TNF--mediated apoptosis or even direct cytopathic injury have been suggested (35, 147). Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin. Gould TJ, Vu TT, Swystun LL, Dwivedi DJ, Mai SHC, Weitz JI, Liaw PC. Qin L, Li X, Shi J, Yu M, Wang K, Tao Y, Zhou Y, Zhou M, Xu S, Wu B, Yang Z, Zhang C, Yue J, Cheng C, Liu X, Xie M. Gendered effects on inflammation reaction and outcome of COVID19 patients in Wuhan. Advanced polymer hydrogels that promote diabetic ulcer healing Although more data is urgently needed to elucidate the global epidemiology of COVID-19 (80), a wide spectrum of clinical severity is evident, with most patients able to mount a sufficient and appropriate immune response, ultimately leading to viral clearance and case resolution. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, Daler-Plenker J, Guerci P, Huynh C, Knight JS, Loda M, Looney MR, McAllister F, Rayes R, Renaud S, Rousseau S, Salvatore S, Schwartz RE, Spicer JD, Yost CC, Weber A, Zuo Y, Egeblad M. Targeting potential drivers of COVID-19: neutrophil extracellular traps, Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. In terms of exocrine-related damage, a study by Wang et al. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. coronavirus Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): A pooled analysis and review. WebThe coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Finally, recent data also suggest SARS-CoV-2-specific antibody titers are elevated in patients with severe disease (98). Although hepatocytes have not been shown to exhibit high ACE2 expression, previous studies have demonstrated a high level of ACE2 expression in cholangiocytes, suggesting direct bile duct infection/damage as a potential cause of abnormal liver enzymes (17). However, the validity of these mechanisms have been debated, since abnormal liver enzymes have been reported at hospital admission before any drug treatment as well as in patients without the need for mechanical ventilation (7). Jin JM, Bai P, He W, Wu F, Liu XF, Han DM, Liu S, Yang JK. Premkumar L, Segovia-Chumbez B, Jadi R, Martinez DR, Raut R, Markmann A, Cornaby C, Bartelt L, Weiss S, Park Y, Edwards CE, Weimer E, Scherer EM, Rouphael N, Edupuganti S, Weiskopf D, Tse LV, Hou YJ, Margolis D, Sette A, Collins MH, Schmitz J, Baric RS, de Silva AM. Molecular mechanism of interaction between SARS-CoV-2 and Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J, Diorio C, Fitzgerald JC, Topjian A, John ARO. biological mechanisms RA,, Plebani SARS-CoV-2 is mostly transmissible through large respiratory droplets, directly infecting cells of the upper and lower respiratory tract, especially nasal ciliated and alveolar epithelial cells (161). Both these mechanisms combine to enhance inhibition of RNA synthesis for SARS-CoV-2 more than for HCV. A recent meta-analysis suggested serum IL-6 cut-offs of >55 pg/ml and >80 pg/ml to identify patients at high risk for severe COVID-19 and mortality, respectively (5). HHS Vulnerability Disclosure, Help The mechanisms of the increase in the incidence of diabetes have been unclear, and there has been discussion on whether the increase results from a direct effect of SARS-CoV-2 infection or other simultaneously altered environmental factors, says Professor Mikael Knip, who headed the study. biochemistry, study of the chemical substances and processes that occur in plants, animals, and microorganisms and of the changes they undergo during Guillain-Barr Genetic predispositions have also been proposed, including polymorphisms in ACE2 and genetic variability in histocompatibility complex (MHC) class I genes (96). Kathryn Tewson on Twitter An official website of the United States government. Bloom PP, Meyerowitz EA, Reinus Z, Daidone M, Gustafson J, Kim AY, Schaefer E, Chung RT. In addition to age, emerging clinical and epidemiological data suggest sex-specific differences in the clinical characteristics and case-to-fatality ratio of COVID-19, with worse prognosis observed in males (66, 92). Laboratory/clinical profile and key potential mechanisms underlying extrapulmonary manifestations observed in severe COVID-19 patients. Since its emergence in December 2019 in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) created a worldwide pandemic of coronavirus disease (COVID-19) with nearly 136 million cases and approximately 3 million deaths. Additional pathophysiological mechanisms underlying liver injury include drug-induced liver injury as well as hypoxic hepatitis. Preliminary reports from the Chinese Center for Disease Control and Prevention have estimated that the large majority of confirmed SARS-CoV-2 cases are mild (81%), with ~14% progressing to severe pneumonia and 5% developing acute respiratory distress syndrome (ARDS), sepsis, and/or multisystem organ failure (MOF) (144). Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Zambrano LD, Nahabedian J, Anderson K, Gilboa SM. COVID-19 and myocarditis: What do we know so far? Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JC, Fogerty AE, Waheed A, Goodarzi K, Bendapudi P, Bornikova L, Gupta S, Leaf D, Kuter DJ, Rosovsky RP. The mechanisms of the increase in the incidence of diabetes have been unclear, and there has been discussion on whether the increase results from a direct effect of SARS-CoV-2 infection or other simultaneously altered environmental factors, says Professor Mikael Knip, who headed the study. Potential mechanisms include 1) viral entry via ACE2 receptors into the endothelia that line the blood capillaries and subsequent neuro-invasion, 2) neurological edema and brain stem compression as a result of breached blood-brain barrier, 3) neurological edema and hypercoagulability as a result of cytokine storm syndrome, and 4) propagation via mechanoreceptors and chemoreceptors in the lung and lower respiratory airways (65). However, there is a paucity of studies In Viral-mediated cell death causes release of various damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), which are believed to be recognized by pattern-recognition receptors on alveolar macrophages and endothelial cells. JCM | Free Full-Text | Long-Term Effects of SARS-CoV-2 in the Considering this, it is still unclear what factors influence the transition from normal physiological to pathogenic hyperinflammatory response. Risks associated with surgical pathology and some cytology procedures occur when manipulating fresh tissue and body fluids from patients who may have an unknown or known infectious disease, such as COVID-19. The pathophysiological mechanisms behind this novel disease are unknown. Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, Satlin MJ, Campion TR Jr, Nahid M, Ringel JB, Hoffman KL, Alshak MN, Li HA, Wehmeyer GT, Rajan M, Reshetnyak E, Hupert N, Horn EM, Martinez FJ, Gulick RM, Safford MM. Spike protein mRNA are injected into the body. drafted manuscript; M.K.B., A.H., L.S., B.J., S.S., and K.A. The pathophysiological mechanisms behind key events in the progression from mild to severe disease remain unclear, warranting further investigation to inform therapeutic decisions. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP; the Northwell COVID-19 Research Consortium . It is also important to note that immune-cell infiltration can lead to the excessive secretion of proteases and reactive oxygen species, fostering further damage and hyperinflammation (130). mechanisms of COVID Due to the low specificity of lipase elevations, exocrine pancreatic injury and inflammation is challenging to confirm without abdominal imaging (32). Although these reports indicate a milder COVID-19 profile in pediatric patients compared with adults (159), reports from China and the CDC indicate that the documented hospitalization and mortality rates in pediatric cases are concerning and emphasize the importance of comprehensive studies to examine the clinical picture of pediatric disease (15a, 36). This not only suggests the importance of defining the timing of antibody response through serological testing in multiple age groups but also points toward the increasing complexity of COVID-19. In a case study series of 214 patients diagnosed with COVID-19, neurological symptoms were observed in 36.4% of patients, and this percentage increased to 45.5% when examining patients with severe infection (86). This molecular mimicry has been identified as an efficient evolutionary adaptation that some viruses have acquired for exploiting the host cellular machinery. Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, Franciotta D, Baldanti F, Daturi R, Postorino P, Cavallini A, Micieli G. Guillain-Barr Syndrome associated with SARS-CoV-2. They describe settings where transmission of the COVID-19 virus spreads more easily: Crowded places; Close-contact settings, especially where people have However, a recent case report showed evidence of SARS-CoV-2 in the syncytiotrophoblast cells of a pregnant COVID-19 patient in the second trimester of gestation with preeclampsia (59). Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Anatomic pathology includes surgical pathology, histotechnology, cytology, and autopsy. Can COVID-19 in pregnancy cause preeclampsia? Liver biochemistries in hospitalized patients with COVID-19. Cytokine and anti-cytokine interventions. Hasnain M, Pasha MF, Ghani I, Budiarto R. Protection challenges of pregnant women against vertical transmission during COVID-19 epidemic: a narrative review. Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, Thompson RF. Cell entry mechanisms of SARS-CoV-2 | PNAS Naunyn-Schmiedeberg's Arch Pharmacol 393, 1) Potential mechanisms of COVID-pain (SARS-CoV-2/COVID-19-induced pain) (A) ACE2/RAS pathway and the direct virus-induced damage. Inclusion in an NLM database does not imply endorsement of, or agreement with, COVID-19 Given the homology between these viruses, such direct viral invasion should not be discounted (100, 106). Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. This paper proposes a model algorithm based on convolutional neural network combined with attention mechanism to realize fast and accurate identification of biological image. Naunyn-Schmiedeberg's Arch Pharmacol 393, 11531156 (2020). A recent, large, multi-center U.S. study of 186 patients who met the broad CDC criteria for MIS-C reported 92% of patients had at least four laboratory results indicating inflammation, including but not limited to elevated CRP and ferritin, lymphocytopenia, neutrophilia, hypoalbuminemia, thrombocytopenia, anemia, as well as elevated D-dimer and fibrinogen (44). Wong SF, Chow KM, Leung TN, Ng WF, Ng TK, Shek CC, Ng PC, Lam PWY, Ho LC, To WWK, Lai ST, Yan WW, Tan PYH. Individuals with Alzheimers disease (AD) and related dementia, as well as persons with Down syndrome (DS), are especially vulnerable to COVID-19, but the Wang Y, Liu S, Liu H, Li W, Lin F, Jiang L, Li X, Xu P, Zhang L, Zhao L, Cao Y, Kang J, Yang J, Li L, Liu X, Li Y, Nie R, Mu J, Lu F, Zhao S, Lu J, Zhao J. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. Martnez-Rojas MA, Vega-Vega O, Bobadilla NA. Before this, TMPRSS2 has presented biological functions in cancer, but the roles remain controversial and the mechanism remains unelucidated. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Gtzinger F, Santiago-Garca B, Noguera-Julin A, Lanaspa M, Lancella L, Cal Carducci FI, Gabrovska N, Velizarova S, Prunk P, Osterman V, Krivec U, Lo Vecchio A, Shingadia D, Soriano-Arandes A, Melendo S, Lanari M, Pierantoni L, Wagner N, LHuillier AG, Heininger U, Ritz N, Bandi S, Krajcar N, Rogli S, Santos M, Christiaens C, Creuven M, Buonsenso D, Welch SB, Bogyi M, Brinkmann F, Tebruegge M, Pfefferle J, Zacharasiewicz A, Berger A, Berger R, Strenger V, Kohlfrst DS, Zschocke A, Bernar B, Simma B, Haberlandt E, Thir C, Biebl A, Vanden Driessche K, Boiy T, Van Brusselen D, Bael A, Debulpaep S, Schelstraete P, Pavic I, Nygaard U, Glenthoej JP, Heilmann Jensen L, Lind I, Tistsenko M, Uustalu , Buchtala L, Thee S, Kobbe R, Rau C, Schwerk N, Barker M, Tsolia M, Eleftheriou I, Gavin P, Kozdoba O, Zsigmond B, Valentini P, Ivakeviciene I, Ivakevicius R, Vilc V, Schlvinck E, Rojahn A, Smyrnaios A, Klingenberg C, Carvalho I, Ribeiro A, Starshinova A, Solovic I, Falcn L, Neth O, Minguell L, Bustillo M, Gutirrez-Snchez AM, Guarch Ibez B, Ripoll F, Soto B, Ktz K, Zimmermann P, Schmid H, Zucol F, Niederer A, Buettcher M, Cetin BS, Bilogortseva O, Chechenyeva V, Demirjian A, Shackley F, McFetridge L, Speirs L, Doherty C, Jones L, McMaster P, Murray C, Child F, Beuvink Y, Makwana N, Whittaker E, Williams A, Fidler K, Bernatoniene J, Song R, Oliver Z, Riordan A; ptbnet COVID-19 Study Group .
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