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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311563

ABSTRACT

Background: Identifying preventive strategies in Covid-19 patients will help to improve resource-allocation and reduce mortality. In this Journal, we recently demonstrated in a post-mortem cohort that SARS-CoV-2 renal tropism was associated with kidney injury, disease severity and mortality. We also proposed an algorithm to predict the risk of adverse outcomes in Covid-19 patients harnessing urinalysis and protein/coagulation parameters on admission for signs of kidney injury. Here, we aimed to validate this hypothesis in a multicenter cohort.Methods: Patients hospitalized for Covid-19 at four tertiary centers were screened for an available urinalysis, serum albumin (SA) and antithrombin-III activity (AT-III) obtained prospectively within 48h upon admission. The respective presumed risk for an unfavorable course was categorized as “low”, “intermediate” or “high”, depending on a normal urinalysis, an abnormal urinalysis with SA ≥2 g/dl and AT-III ≥70%, or an abnormal urinalysis with at least one SA or AT-III abnormality. Time to ICU or death within ten days served as primary, in-hospital mortality and required organ support served as secondary endpoints.Findings: Among a total of N=223 screened patients, N=145 were eligible for enrollment, falling into the low (N=43), intermediate (N=84), and high risk (N=18) categories. The risk for ICU transfer or death was 100% in the high risk group and significantly elevated in the composite of high and intermediate risk as compared to the low risk group (63·7% vs. 27·9%;HR 2·6;95%-CI 1·4 to 4·9;P=0·0020). Having an abnormal urinalysis was associated with mortality, need for mechanical ventilation, extra-corporeal membrane oxygenation (ECMO) or renal replacement therapy (RRT).Interpretation: Our data confirm that Covid-19-associated urine abnormalities on admission predict disease aggravation. This supports the conceptual relevance of Covid-19-associated kidney injury. By engaging a simple urine dipstick our algorithm allows for early preventive measures and appropriate patient stratification. Trial Registration: (ClinicalTrials.gov number NCT04347824)Funding Statement: This work was supported by the DFG (GR 1852/6-1 to OG;CRC1192 to JET, EH and TBH), (HU 1016/8-2, HU 1016/11-1, HU 1016/ 12-1 to TBH) and (GR 1852/6-1 to OG);by the BMBF (STOP-FSGS-01GM1518C and NephrESA-031L0191E to TBH), by the Else-Kröner Fresenius Foundation (Else Kröner-Promotionskolleg –iPRIME to TBH), and by the H2020-IMI2 consortium BEAt-DKD (115974 to TBH). In addition, the UMG Göttingen applied for Government funding (Covid-19 program) by The German Federal Ministry of Education and Research and the application currently is under consideration.Declaration of Interests: All authors report no conflict of interest in relation to this observational cohort-study. Ethics Approval Statement: According to the German Medicines Act, the study was approved by the leading institutional review board (IRB) of the UMG Göttingen (41/4/20), and all others.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311562

ABSTRACT

Purpose: Identifying preventive strategies in Covid-19 patients helps to improve ICU-resource-allocation and reduce mortality. We recently demonstrated in a post-mortem cohort that SARS-CoV-2 renal tropism was associated with kidney injury, disease severity and mortality. We also proposed an algorithm to predict the need for ICU-resources and the risk of adverse outcomes in Covid-19 patients harnessing urinalysis and protein/coagulation parameters on admission for signs of kidney injury. Here, we aimed to validate this hypothesis in a multicenter cohort. Methods: : Patients hospitalized for Covid-19 at four tertiary centers were screened for an available urinalysis, serum albumin (SA) and antithrombin-III activity (AT-III) obtained prospectively within 48h upon admission. The respective presumed risk for an unfavorable course was categorized as “low”, “intermediate” or “high”, depending on a normal urinalysis, an abnormal urinalysis with SA ≥2 g/dl and AT-III ≥70%, or an abnormal urinalysis with at least one SA or AT-III abnormality. Time to ICU or death within ten days served as primary, in-hospital mortality and required organ support served as secondary endpoints. Results: : Among a total of N=223 screened patients, N=145 were eligible for enrollment, falling into the low (N=43), intermediate (N=84), and high risk (N=18) categories. The risk for ICU transfer or death was 100% in the high risk group and significantly elevated in the composite of high and intermediate risk as compared to the low risk group (63.7% vs. 27.9%;HR 2.6;95%-CI 1.4 to 4.9;P=0.0020). Having an abnormal urinalysis was associated with mortality, need for mechanical ventilation, extra-corporeal membrane oxygenation (ECMO) or renal replacement therapy (RRT). Conclusion: Our data confirm that Covid-19-associated urine abnormalities on admission predict disease aggravation and need for ICU. By engaging a simple urine dipstick on hospital admission our algorithm allows for early preventive measures and appropriate patient stratification. (ClinicalTrials.gov number NCT04347824)

3.
Mol Med ; 27(1): 120, 2021 09 26.
Article in English | MEDLINE | ID: covidwho-1440900

ABSTRACT

BACKGROUND: Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called 'long COVID' and 'neuroCOVID', becomes increasingly evident. Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term 'hypoxia paradox'. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this 'hypoxia paradox' caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues. SHORT CONCLUSION: Substitution of EPO may-among other beneficial EPO effects in severe COVID-19-circumvent downstream consequences of the 'hypoxia paradox'. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted.


Subject(s)
COVID-19/complications , COVID-19/drug therapy , Erythropoietin/genetics , Hypoxia/drug therapy , Lung/drug effects , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Erythropoietin/analogs & derivatives , Erythropoietin/therapeutic use , Humans , Hypoxia/genetics , Hypoxia/pathology , Hypoxia/virology , Lung/pathology , Lung/virology , Pandemics , Recombinant Proteins/genetics , Recombinant Proteins/therapeutic use , SARS-CoV-2/drug effects
6.
J Clin Med ; 10(14)2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1308366

ABSTRACT

In COVID-19, guidelines recommend a urinalysis on hospital admission as SARS-CoV-2 renal tropism, post-mortem, was associated with disease severity and mortality. Following the hypothesis from our pilot study, we now validate an algorithm harnessing urinalysis to predict the outcome and the need for ICU resources on admission to hospital. Patients were screened for urinalysis, serum albumin (SA) and antithrombin III activity (AT-III) obtained prospectively on admission. The risk for an unfavorable course was categorized as (1) "low", (2) "intermediate" or (3) "high", depending on (1) normal urinalysis, (2) abnormal urinalysis with SA ≥ 2 g/dL and AT-III ≥ 70%, or (3) abnormal urinalysis with SA or AT-III abnormality. Time to ICU admission or death served as the primary endpoint. Among 223 screened patients, 145 were eligible for enrollment, 43 falling into the low, 84 intermediate, and 18 into high-risk categories. An abnormal urinalysis significantly elevated the risk for ICU admission or death (63.7% vs. 27.9%; HR 2.6; 95%-CI 1.4 to 4.9; p = 0.0020) and was 100% in the high-risk group. Having an abnormal urinalysis was associated with mortality, a need for mechanical ventilation, extra-corporeal membrane oxygenation or renal replacement therapy. In conclusion, our data confirm that COVID-19-associated urine abnormalities on admission predict disease aggravation and the need for ICU (ClinicalTrials.gov number NCT04347824).

7.
Nephrologe ; 16(1): 26-32, 2021.
Article in German | MEDLINE | ID: covidwho-986660

ABSTRACT

The aim of this article is to explain the clinical benefits of the growing knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to the lungs, SARS-CoV­2 can invade multiple cell types in other organs, such as the kidneys and replicate there. Important damaging pathways of the virus, such as vascular endotheliitis, thrombotic events and systemic cytokine release are still incompletely understood. Coronavirus disease 2019 (COVID-19) is a systemic disease that necessitates intensive medical care and in particular, internal medicine involvement and represents a major challenge for all disciplines of internal medicine. Among these, nephrology in particular is involved in the fight against COVID-19 in a variety of ways: urine investigations can provide indications of multiple organ involvement, endotheliitis, microthrombi and microcirculation damage, etc. Experience with low serum albumin levels and antithrombin III activity in nephrotic patients helps to point out the decreasing effects of loop diuretics and heparin to other specialist disciplines. Nephrological knowledge of the complications of hypoalbuminemia and "resistance" to diuretics must lead to an early implementation of renal replacement procedures in order to be able to prevent mechanical ventilation in COVID-19 intensive care patients with increased extracellular lung fluid. The kidneys can be used as a seismograph for severe courses of COVID-19 and nephrological knowledge can be brought to use to optimize the intensive medical care for critically ill patients. Both together have the potential to considerably reduce morbidity and mortality further.

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