In addition, direct viral infection of immune cells such as monocytes and macrophages have been proposed to contribute to dysregulated immune response, as has been observed in SARS (23, 52, 136). why and to what extent? However, other contributing mechanisms have been proposed and are explored below (FIGURE 3). Notably, the cytokine concentrations observed in hospitalized COVID-19 patients are rarely elevated to the same extent as in secondary hemophagocytic lymphohistiocytosis and cytokine release syndrome following CAR-T cell treatment (64). These data clearly suggest a state of hypercoagulability in severe COVID-19. biological mechanisms Altered sense of taste or smell can be present in up to 80% of patients with mild to moderate COVID-19 (73). Their study demonstrated frequent elevations in CRP, procalcitonin, and LDH in severe pediatric COVID-19, similar to adult findings (56). Virus-induced breath biomarkers: A new perspective to study the That variant, classified as XBB.1.16 by the World Health Organization, was designated as a variant under monitoring by the organization last month. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis. reported that 17% of COVID-19 patients in their cohort (n = 52) had serologic evidence of exocrine pancreatic injury, defined as elevated amylase or lipase (140). Single-cell analyses and host genetics highlight the role of innate Effect of gastrointestinal symptoms on patients infected with COVID-19. Now considered a valuable prognostic indicator for COVID-19 survival, AKI is estimated to affect 2040% of critically ill patients in intensive care, necessitating renal replacement therapy and extracorporeal support therapies such as blood purification (112, 155). Galang RR, Chang K, Strid P, Snead MC, Woodworth KR, House LD, Perez M, Barfield WD, Meaney-Delman D, Jamieson DJ, Shapiro-Mendoza CK, Ellington SR. Shapiro J, Sciaky N, Lee J, Bosshart H, Angeletti RH, Bonifacino JS. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Structure analysis of the receptor binding of 2019-nCoV. FOIA Modelling COVID-19 epidemic with confirmed cases-driven Circulating levels of IL-1 in COVID-19 patients suggests local inflammasome activation with no systemic manifestations (61). Like, check this out -- Rizzo, E. Ivermectin, antiviral properties and COVID-19: a possible new mechanism of action. COVID Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, Lei F, Wang H, Xie J, Wang W, Li H, Zhang P, Song X, Chen X, Xiang M, Zhang C, Bai L, Xiang D, Chen MM, Liu Y, Yan Y, Liu M, Mao W, Zou J, Liu L, Chen G, Luo P, Xiao B, Zhang C, Zhang Z, Lu Z, Wang J, Lu H, Xia X, Wang D, Liao X, Peng G, Ye P, Yang J, Yuan Y, Huang X, Guo J, Zhang BH, Li H. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes, Coronavirus infections in children including COVID-19: An overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children, Dissecting antibody-mediated protection against SARS-CoV-2. In addition to the lungs, ACE2 is also expressed in various other human tissues, such as the small intestine, kidneys, heart, thyroid, testis, and adipose tissue, indicating the virus may directly infect cells of other organ systems when viremia is present (77). Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, Thompson RF. Anand P, Puranik A, Aravamudan M, Venkatakrishnan AJ, Soundararajan V. SARS-CoV-2 strategically mimics proteolytic activation of human ENaC, Elevated interleukin-6 and severe COVID-19: A meta-analysis, Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms, COVID-19 and the liver: little cause for concern. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, Cani DS, Cerini M, Farina D, Gavazzi E, Maroldi R, Adamo M, Ammirati E, Sinagra G, Lombardi CM, Metra M. Cardiac involvement in a patient with Coronavirus disease 2019 (COVID-19). These factors need to be observed more thoroughly to complete our clinical understanding of COVID-19. 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). Authors Zhengnan Cen 1 , Bingqing Lu 1 , Yongyan Ji 1 , Jian Chen 1 , Yongqian Liu 1 , Jiakui Jiang 1 , Xue Li 2 , Xiang Li 3 Affiliations 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). An official website of the United States government. Anatomic pathology includes surgical pathology, histotechnology, cytology, and autopsy. In addition to the observed maladaptive cytokine release, elevations in more traditional biochemical markers of acute infection, including C-reactive protein (CRP) and ferritin (both positive acute phase reactants), as well as continual decreases in lymphocytes and significant elevations in neutrophils, are evident (43, 79). COVID-19 coronavirus The pathophysiological mechanisms behind the neurological manifestations of COVID-19 have not been well elucidated. 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. MHS,, Hsieh 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. A recently concluded study has revealed that during the initial 18 months of the COVID-19 pandemic, a higher number of minors in Finland than usual were diagnosed SARS-CoV-2 viral entry has been described in detail elsewhere (138). 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. A Deep Look into the Biology and Evolution of COVID-19 Biochemical Mechanisms - an overview | ScienceDirect Topics Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, MacDonald V, Green L, Sivapalaratnam S, Pasi KJ, MacCallum P. Lupus anticoagulant and abnormal coagulation tests in patients with COVID-19. The https:// ensures that you are connecting to the Amanat F, Stadlbauer D, Strohmeier S, Nguyen THO, Chromikova V, McMahon M, Jiang K, Arunkumar GA, Jurczyszak D, Polanco J, Bermudez-Gonzalez M, Kleiner G, Aydillo T, Miorin L, Fierer DS, Lugo LA, Kojic EM, Stoever J, Liu STH, Cunningham-Rundles C, Felgner PL, Moran T, Garca-Sastre A, Caplivski D, Cheng AC, Kedzierska K, Vapalahti O, Hepojoki JM, Simon V, Krammer F. A serological assay to detect SARS-CoV-2 seroconversion in humans. Accessibility In t Biological mechanisms for these neurological symptoms need to be investigated and may include both direct and indirect effects of the virus on the brain and In addition to exocrine damage, there is much debate regarding the impact of COVID-19 on the endocrine pancreas and its subsequent effect on glucose regulation. COVID The cell uses the mRNA from the vaccine as the blueprint to build the SARS-CoV-2 spike protein. Furthermore, limited available data in the pediatric population suggests a distinct and diverse spectrum of disease completely different from adults, further reinforcing the importance of age-related immune responses (84, 145). Lei F, Liu YM, Zhou F, Qin JJ, Zhang P, Zhu L, Zhang XJ, Cai J, Lin L, Ouyang S, Wang X, Yang C, Cheng X, Liu W, Li H, Xie J, Wu B, Luo H, Xiao F, Chen J, Tao L, Cheng G, She ZG, Zhou J, Wang H, Lin J, Luo P, Fu S, Zhou J, Ye P, Xiao B, Mao W, Liu L, Yan Y, Liu L, Chen G, Li H, Huang X, Zhang BH, Yuan Y. Longitudinal association between markers of liver injury and mortality in COVID-19 in China, Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses, Evidence for a common evolutionary origin of coronavirus spike protein receptor-binding subunits, Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues, Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis, Laboratory abnormalities in patients with COVID-2019 infection, Defining the epidemiology of Covid-19 - Studies needed. The dark blue shading indicates physiological viral host response over time, and the dark red shading indicates pathogenic hyperinflammatory host response over time. In addition to understanding relevant risk factors, there is increasing suspicion of delayed but severe COVID-19 presentation, particularly in children, even after viral clearance (113). For example, the activation of complement pathways can lead to initiation of the coagulation cascade (30, 127). Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, Zhong W, Hao P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Importantly, COVID-19 appears to enhance complications in patients with diabetes, likely due to viral-induced pancreatic dysfunction as well as associated immune dysregulation, vasculopathy, and coagulopathy (29, 37). However, despite evidence of mild COVID-19 in pregnant patients, a recent report by the CDC suggests pregnant women may be at higher risk for more severe outcomes, estimating a higher proportion of pregnant women with COVID-19 undergo hospitalization compared with nonpregnant women (38). Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, Liu XQ, Chen RC, Tang CL, Wang T, Ou CQ, Li L, Chen PY, Sang L, Wang W, Li JF, Li CC, Ou LM, Cheng B, Xiong S, Ni ZY, Xiang J, Hu Y, Liu L, Shan H, Lei CL, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Cheng LL, Ye F, Li SY, Zheng JP, Zhang NF, Zhong NS, He JX; China Medical Treatment Expert Group for COVID-19 . Direct renal infection and damage presents one potential contributing mechanism. The main drivers of this response have been postulated and thoroughly reviewed elsewhere (125, 130, 151). However, as described above, there is potential for SARS-CoV-2 to significantly affect the placenta and thus negatively impact fetal development. Currently, there is insufficient evidence to support direct viral infection of cardiomyocytes, although SARS-CoV-2 genomes have been effectively detected in endomyocardial biopsies, mostly involving immune cell infiltrates (40, 149). Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y, Liu Y, He Q, Chen J, Liu L, Xu L. Carsana L, Sonzogni A, Nasr A, Rossi RS, Pellegrinelli A, Zerbi P, Rech R, Colombo R, Antinori S, Corbellino M, Galli M, Catena E, Tosoni A, Gianatti A, Nebuloni M. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study, Centers for Disease Control and Prevention, Coronavirus disease 2019 in childrenUnited States, February 12April 2, 2020, Gastrointestinal and hepatic manifestations of COVID-19: A comprehensive review. 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). 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). Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Individuals with Alzheimers disease (AD) and related dementia, as well as persons with Down syndrome (DS), are especially vulnerable to COVID-19, but the A pneumonia outbreak associated with a new coronavirus of probable bat origin. Henry BM, Benoit. In an endeavor to understand the pathogenic mechanisms, extensive experimental studies have been conducted across the globe involving cell culture-based In Fan Z, Chen L, Li J, Cheng X, Yang J, Tian C, Zhang Y, Huang S, Liu Z, Cheng J.
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