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. 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. These data clearly suggest a state of hypercoagulability in severe COVID-19. M,, Lippi Kathryn Tewson on Twitter Many groups have suggested extrapulmonary involvement in COVID-19 is a direct result of unrestrained inflammation. Multiple organ infection and the pathogenesis of SARS. Importantly, it is possible that the neurological manifestations of COVID-19 could be a result of hypoxia, respiratory, and/or metabolic acidosis at end-stage disease (6). NT-proBNP, NH2-terminal-proB-type natriuretic peptide; ALT, alanine aminotransferase; AST, aspartate aminotransferase; aPTT, activated partial thromboplastin time; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; ESR, erythrocyte sedimentation rate. Immunol. Single-cell RNA sequencing suggests that ACE2 is expressed in both the exocrine and islet cells of the pancreas (81). 2: pulmonary recruitment of macrophages and dendritic cells in response to chemokine and cytokine release (early phase). Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. Uncovering the molecular mechanism that underlies the entry of SARS-CoV-2 is one of the most important puzzles in understanding how to block its infection. Bioactive compounds from Huashi Baidu decoction possess both In a case study series of >2,000 children with suspected or confirmed COVID-19 in China, 5% of symptomatic children had dyspnea or hypoxemia, and only 0.6% progressed to ARDS or MOF (36). Researchers Discover Mechanisms Behind Emergence of COVID Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. The main drivers of this response have been postulated and thoroughly reviewed elsewhere (125, 130, 151). Recruitment of neutrophils by activated endothelial cells can also synthesize and release multiple cytokines into the circulation, further accelerating this process (93). Physiological host immune response to SARS-CoV-2 infection. Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, Yi F, Yang HC, Fogo AB, Nie X, Zhang C. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. A team of Russian researchers has uncovered the mechanisms behind the emergence of new and dangerous coronavirus variants, such as Alpha, Delta, Omicron, and others. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Human leukocyte antigen susceptibility map for severe acute respiratory syndrome Coronavirus 2, The neurological manifestations of COVID-19: a review article. A timely, localized, and well-coordinated immune response presents the first line of physiological defense against SARS-CoV-2 infection (FIGURE 2). Online ahead of print. This molecular mimicry has been identified as an efficient evolutionary adaptation that some viruses have acquired for exploiting the host cellular machinery. G,. mechanisms of COVID Zhou Z, Zhao N, Shu Y, Han S, Chen B, Shu X. Some authors have proposed this is due to direct exocrine damage, whereas others suggest it is likely resultant from the gastrointestinal symptoms observed in many COVID-19 patients (32). However, antibody kinetics of different immunoglobulins have not been well characterized, and reported findings are conflicting (12). Contrary to earlier studies, a recent study by Wang et al. Molecular mechanism of interaction between SARS-CoV-2 and Current literature suggests seroconversion in COVID-19 patients occurs ~714 days post symptom onset (12). JCM | Free Full-Text | Long-Term Effects of SARS-CoV-2 in the Okba NMA, Mller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, Lamers MM, Sikkema RS, de Bruin E, Chandler FD, Yazdanpanah Y, Le Hingrat Q, Descamps D, Houhou-Fidouh N, Reusken CBEM, Bosch BJ, Drosten C, Koopmans MPG, Haagmans BL. Cytokine and anti-cytokine interventions. SARS and MERS: recent insights into emerging coronaviruses. Zhang H, Zhou P, Wei Y, Yue H, Wang Y, Hu M, Zhang S, Cao T, Yang C, Li M, Guo G, Chen X, Chen Y, Lei M, Liu H, Zhao J, Peng P, Wang CY, Du R. Histopathologic changes and SARS-COV-2 immunostaining in the lung of a patient with COVID-19. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. In Previous data from the SARS epidemic suggests 35% of heart specimens showed presence of viral RNA in the myocardium. Notably, increased levels of IL-6, IL-2, IL-7, IL-10, granulocyte colony-stimulating factor (G-CSF), IP-10, MCP1, IFN, macrophage inflammatory protein 1 (MIP1), and tumor necrosis factor (TNF) have all been implicated in COVID-19 severity, suggesting a combined T-helper type 1 (Th1) and Th2 cell response (61, 130). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases From the Chinese Center for Disease Control and Prevention. 13, 938837. The first step in COVID-19 pathogenesis is viral invasion via its target host cell receptors. Prospective validation of these proposed cut-offs across different assay methodologies and patient populations are urgently awaited to establish clinical utility. Here, we review the current literature and summarize key proposed mechanisms of COVID-19 pathophysiological progression (FIGURE 1). observed abundant SARS-CoV-2 viral particles in hepatocytes of postmortem specimens, prompting further research on hepatic viral infection/clearance (141). Autopsy findings in SARS-CoV infections have shown strong evidence of neuro-invasion, with demonstrated viral presence in the cerebrospinal fluid (6, 95). Soy M, Keser G, Atagndz P, Tabak F, Atagndz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown Similar to SARS-CoV, several researchers have identified human angiotensin converting enzyme 2 (ACE2) as an entry receptor for SARS-CoV-2 (75, 99, 148, 156). Early reports from Wuhan, China demonstrated prolonged activated partial thromboplastin time (aPTT) and prothrombin time, and elevated D-dimer as well as thrombocytopenia (20, 139, 155). Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z, Mu Z, Chen X, Chen J, Hu K, Jin Q, Wang J, Qian Z. Coronavirus Bloom PP, Meyerowitz EA, Reinus Z, Daidone M, Gustafson J, Kim AY, Schaefer E, Chung RT. Like, check this out -- Rizzo, E. Ivermectin, antiviral properties and COVID-19: a possible new mechanism of action. Interestingly, SARS-CoV-2 has developed a unique S1/S2 cleavage site in its S protein, characterized by a four-amino acid insertion, which seems to be absent in all other coronaviruses (4). Before Biological Mechanisms of COVID-19 Acute Respiratory Distress Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Spike protein mRNA are injected into the body. In addition to prolonged prothrombin time, studies in other cohorts have reported high prevalence of lupus anticoagulant in the circulation (13). In addition to direct infection, uncontrolled cytokine release, thrombosis, and ischemia can also result in further kidney dysfunction, characterized by intrarenal inflammation, increased vascular permeability, and volume depletion (88). The covid-19 pandemic during the time of the diabetes pandemic: Likely fraternal twins? 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). However, whether furin-like protease-mediated cleavage is required for SARS-CoV-2 host entry has yet to be determined. Given the correlation of IL-6 levels with increased fibrinogen and D-dimer in severe COVID-19 patients, it is likely that cytokine-mediated procoagulant changes are partially responsible for the specific thrombosis profile observed in critically ill patients (41, 110). Gadiparthi C, Bassi M, Yegneswaran B, Ho S, Pitchumoni CS. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutirrez-Ocampo E, Villamizar-Pea R, Holguin-Rivera Y, Escalera-Antezana JP, Alvarado-Arnez LE, Bonilla-Aldana DK, Franco-Paredes C, Henao-Martinez AF, Paniz-Mondolfi A, Lagos-Grisales GJ, Ramrez-Vallejo E, Surez JA, Zambrano LI, Villamil-Gmez WE, Balbin-Ramon GJ, Rabaan AA, Harapan H, Dhama K, Nishiura H, Kataoka H, Ahmad T, Sah R; Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19). Bohn MK, Lippi G, Horvath A, Sethi S, Koch D, Ferrari M, Wang C-B, Mancini N, Steele S, Adeli K. Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence. Multisystem inflammatory syndrome in children during the Coronavirus 2019 pandemic: a case series. M.K.B. Liver biochemistries in hospitalized patients with COVID-19. Henry BM, Benoit. and transmitted securely. Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. Based on the current evidence, it is clear that, although direct SARS-CoV-2 infection of multiple organs as well as hypoxia and stress-related injury may contribute to COVID-19 pathophysiological progression, systemic inflammation and aberrant cytokine regulation is a hallmark of disease severity. This disproportionate clinical epidemiology may be explained by sex-specific regulation of ACE2, increased incidence of preexisting comorbidities in males (i.e., hypertension, diabetes, cardiovascular disease), as well as sex-specific differences in viral immune response, as described elsewhere (47, 109). Direct viral infection of macrophages and/or dendritic cells is estimated to propagate further cytokine and chemokine release, subsequently activating late-phase immune-cell recruitment of antigen-specific T cells to destroy virally infected alveolar cells (61, 130, 132, 149). This condition appears to be associated with prevalent cutaneous manifestations as well as significant GI symptoms. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, Li T, Chen Q. The immune system mobilizes and records the shape of the SARS-CoV-2 protein. Although prominent changes in blood coagulation may be a contributing mechanism to COVID-19 mortality, its pathogenesis is estimated to be tightly linked to inflammation and cytokine release. The M, E, and N proteins are critical for viral particle assembly and release, whereas the S protein is responsible for viral binding and entry into host cells (33, 76, 89, 143, 148). Naunyn-Schmiedeberg's Arch Pharmacol 393, 11531156 (2020). Finally, several comorbidities have been associated with poor outcomes, likely due to the fact that organ and immune function may already be compromised and in a state of subclinical inflammation (53, 158). sharing sensitive information, make sure youre on a federal Mechanisms Severe Coronavirus infections in pregnancy: a systematic review. Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. 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. 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). 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. A multicenter European study of children with PCR-confirmed SARS-CoV-2 infection also reported that 8% of pediatric patients required ICU admission, 4% required mechanical ventilation, 3% required inotropic support, and <1% required extracorporeal membrane oxygenation (49). the contents by NLM or the National Institutes of Health. Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J, Diorio C, Fitzgerald JC, Topjian A, John ARO. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. The global epidemiology of coronavirus disease 2019 (COVID-19) suggests a wide spectrum of clinical severity, ranging from asymptomatic to fatal. 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 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). 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 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). RA,, Plebani 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. Interestingly, although the S proteins of SARS-CoV-2 and SARS-CoV share 72% homology in amino acid sequences, SARS-CoV-2 has been reported to have a higher affinity for the ACE2 receptor (18, 21, 143). Characterization of key events in COVID-19 disease pathophysiological progression. In most COVID-19 patients, the combined immune response of initial cytokine release and activation of antiviral interferon response followed by immune-cell recruitment should result in successful SARS-CoV-2 clearance from the lungs (FIGURE 2). COVID and Coagulation: Bleeding and Thrombotic Manifestations of SARS-CoV2 Infection. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements.
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