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      COVID-19 and multiorgan failure: A narrative review on potential mechanisms

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          Abstract

          The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in December 2019 form Wuhan, China leads to coronavirus disease 2019 (COVID-19) pandemic. While the common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients. The involvement of different organs in severe patients results in lengthening the hospitalization duration and increasing the mortality rate. In this review, we aimed to investigate the involvement of different organs in COVID-19 patients, particularly in severe cases. Also, we tried to define the potential underlying mechanisms of SARS-CoV2 induced multiorgan failure. The multi-organ dysfunction is characterized by acute lung failure, acute liver failure, acute kidney injury, cardiovascular disease, and as well as a wide spectrum of hematological abnormalities and neurological disorders. The most important mechanisms are related to the direct and indirect pathogenic features of SARS-CoV2. Although the presence of angiotensin-converting enzyme 2, a receptor of SARS-CoV2 in the lung, heart, kidney, testis, liver, lymphocytes, and nervous system was confirmed, there are controversial findings to about the observation of SARS-CoV2 RNA in these organs. Moreover, the organ failure may be induced by the cytokine storm, a result of increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs. Therefore, further investigations are needed to detect the exact mechanisms of pathogenesis. Since the involvement of several organs in COVID-19 patients is important for clinicians, increasing their knowledge may help to improve the outcomes and decrease the rate of mortality and morbidity.

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          Most cited references204

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

              In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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                Author and article information

                Contributors
                mokhtari.tmn@mails.ucas.ac.cn
                Fatima1737@yahoo.com
                n.ghafari73@gmail.com
                ebrahimib@razi.tums.ac.ir
                atousayarahmadi1373@yahoo.com
                hassanzadeh@tums.ac.ir
                Journal
                J Mol Histol
                J Mol Histol
                Journal of Molecular Histology
                Springer Netherlands (Dordrecht )
                1567-2379
                1567-2387
                4 October 2020
                : 1-16
                Affiliations
                [1 ]GRID grid.454868.3, ISNI 0000 0004 1797 8574, CAS Key Laboratory of Mental Health, , Institute of Psychology, ; Beijing, China
                [2 ]GRID grid.410726.6, ISNI 0000 0004 1797 8419, Department of Psychology, , University of Chinese Academy of Sciences, ; Beijing, China
                [3 ]GRID grid.417689.5, Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, , ACECR, ; Tehran, Iran
                [4 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Anatomy, School of Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
                [5 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
                [6 ]Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
                Article
                9915
                10.1007/s10735-020-09915-3
                7533045
                33011887
                f5d1f604-32ee-4efe-826a-5657c7b3cf71
                © Springer Nature B.V. 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                Categories
                Review Paper

                Pathology
                covid-19,sars-cov2,multi-organ failure,angiotensin-converting enzyme-2,cytokine storm,coagulation

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