SARS-CoV-2 renal tropism associates with acute kidney injury

Braun, Fabian; Lütgehetmann, Marc; Pfefferle, Susanne; Wong, Milagros; Carsten, Alexander; Lindenmeyer, Maja T.; Nörz, Dominik; Heinrich, Fabian; Meißner, K.; Wichmann, Dominic; Kluge, Stefan; Groß, Oliver; Pueschel, Klaus; Schröder, Ann Sophie; Edler, Carolin; Aepfelbacher, Martin; Puelles, Victor G.; Huber, Tobias B.

doi:10.1016/s0140-6736(20)31759-1

Cited by 283 publications

(313 citation statements)

References 5 publications

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“…In turn, acute kidney injury can lead to CKD, and when superimposed on CKD, it increases the risk for mortality conveyed by CKD even further [ 26 , 27 ]. These data also indicate that SARS-CoV-2 has multiorgan tropism that includes glomerular and, as was later shown, tubular cells [ 28 , 29 ].…”

Section: Ckd Is the Disease Condition Conveying The Highest Risk For supporting

confidence: 54%

Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA

Ortíz

Cozzolino

Duivenvoorden

et al. 2020

Nephrology Dialysis Transplantation

298

163

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Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.

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Section: Ckd Is the Disease Condition Conveying The Highest Risk For supporting

confidence: 54%

Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA

Ortíz

Cozzolino

Duivenvoorden

et al. 2020

Nephrology Dialysis Transplantation

298

163

View full text Add to dashboard Cite

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“…Clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes were also detected. Post-mortem examination of the viral nucleocapsid protein in situ in the kidney also showed that SARS-CoV-2 antigens is accumulated in kidney tubules, suggesting that SARS-CoV-2 may infects kidney directly, leading to acute renal injury and potentially contributing to viral spread (183)(184)(185). This direct route of SARS-CoV-2 may be due to an ACE2-dependent pathway.…”

Section: Kidney and Bladdermentioning

confidence: 95%

Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2

et al. 2020

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The explosion of the new coronavirus (SARS-CoV-2) pandemic has brought the role of the angiotensin converting enzyme 2 (ACE2) back into the scientific limelight. Since SARS-CoV-2 must bind the ACE2 for entering the host cells in humans, its expression and body localization are critical to track the potential target organ of this infection and to outline disease progression and clinical outcomes. Here, we mapped the physiological body distribution, expression, and activities of ACE2 and discussed its potential correlations and mutal interactions with the disparate symptoms present in SARS-CoV-2 patients at the level of different organs. We highlighted that despite during SARS-CoV-2 infection ACE2-expressing organs may become direct targets, leading to severe pathological manifestations, and subsequent multiple organ failures, the exact mechanism and the potential interactions through which ACE2 acts in these organs is still heavily debated. Further scientific efforts, also considering a personalized approach aimed to consider specific patient differences in the mutual interactions ACE2-SARS-CoV-2 and the long-term health effects associated with COVID-19 are currently mandatory.

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“…Patients develop acute respiratory infection symptoms, and even acute respiratory distress syndrome (ARDS), acute respiratory failure, and other severe symptoms [ 4 , 5 , 8 , 9 ]. On the other side, complications that occurred outside the lungs, including acute kidney injury, liver function damage, and multiple organ failure, were commonly described in COVID-19 cases and even led to death, suggesting that the virus invades other organs at the same time [ 4 , 5 , 10 , 11 , 12 , 13 ]. SARS-CoV-2 enters the cell via the binding of spike (S) protein and angiotensin-converting enzyme II (ACE2) [ 14 , 15 , 16 , 17 ], the receptor protein of SARS-CoV, and NL63 [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

The scRNA-seq Expression Profiling of the Receptor ACE2 and the Cellular Protease TMPRSS2 Reveals Human Organs Susceptible to SARS-CoV-2 Infection

Zhou

Hua

et al. 2021

IJERPH

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COVID-19 patients always develop multiple organ dysfunction syndromes other than lungs, suggesting the novel virus SARS-CoV-2 also invades other organs. Therefore, studying the viral susceptibility of other organs is important for a deeper understanding of viral pathogenesis. Angiotensin-converting enzyme II (ACE2) is the receptor protein of SARS-CoV-2, and TMPRSS2 promotes virus proliferation and transmission. We investigated the ACE2 and TMPRSS2 expression levels of cell types from 31 organs to evaluate the risk of viral infection using single-cell RNA sequencing (scRNA-seq) data. For the first time, we found that the gall bladder and fallopian tube are vulnerable to SARS-CoV-2 infection. Besides, the nose, heart, small intestine, large intestine, esophagus, brain, testis, and kidney are also identified to be high-risk organs with high expression levels of ACE2 and TMPRSS2. Moreover, the susceptible organs are grouped into three risk levels based on the ACE2 and TMPRSS2 expression. As a result, the respiratory system, digestive system, and urinary system are at the top-risk level for SARS-CoV-2 infection. This study provides evidence for SARS-CoV-2 infection in the human nervous system, digestive system, reproductive system, respiratory system, circulatory system, and urinary system using scRNA-seq data, which helps in the clinical diagnosis and treatment of patients.

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SARS-CoV-2 renal tropism associates with acute kidney injury

Cited by 283 publications

References 5 publications

Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA

Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA

Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2

The scRNA-seq Expression Profiling of the Receptor ACE2 and the Cellular Protease TMPRSS2 Reveals Human Organs Susceptible to SARS-CoV-2 Infection

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