Remdesivir Renal Failure

Attack on the kidney

“Relatively many patients experience kidney failure, and 20 to 25 percent need dialysis,” Zacharowski said. ACE2 receptors are also present in the endothelium of the kidney, so SARS-CoV-2 can infect the cells. According to a study in the journal Kidney International, of 701 Covid-19 patients in Wuhan, nearly half showed signs of kidney damage upon admission to the hospital: 44 percent had proteinuria and 27 percent had hematuria (DOI: 10.1016/j.kint.2020.03.005). These patients and those whose renal function was still massively deteriorating in the clinic were significantly more likely to die than patients with intact kidneys. Again, the question arises as to whether the damage to the organ is direct or indirect. This is because artificial ventilation can also cause or aggravate acute kidney failure. In addition, some drugs used to treat patients can damage the kidney. For example, the not-yet-approved antiviral remdesivir, which is currently being tested in clinical trials in Covid 19 patients, has nephrotoxic potential. And a cytokine storm, which seems to be starting in at least some patients, also drastically worsens renal perfusion, usually fatally.

Through the nose into the brain

The path of SARS-CoV-2 through the human body is not a one-way street, however. The coronavirus can also ascend rather than descend from the nose. In the upper nasal cavity, it enters the olfactory mucosa, where it can cause another symptom that many Covid-19 patients exhibit: Olfactory or taste disorders. Impairment of the ability to smell up to complete loss of the same, but also olfactory hallucinations are possible. According to the RKI, smell and taste disorders are by far the most common symptom of Covid-19 in Europe, with almost 70 percent of patients affected. However, the data come from studies in which the range of frequencies was large (34 to 86 percent). Photo: PZ/Stephan Spitzer When infected with the new coronavirus, SARS-CoV-2 first enters the nose and from there, in severe cases, the lungs. Other organs may be affected, including:

Brain and CNS: Some patients have central symptoms such as dizziness, headache and clouding of consciousness. However, seizures, meningitis, centrally triggered respiratory arrest and Guillain-Barré syndrome have also been described.
Eyes: Conjunctivitis occurs primarily in severely ill Covid 19 patients.
Nose: Disorders of the sense of smell and taste appear to be common in covid-19.
Lung: Gas exchange is impaired in Covid-19 patients with lung involvement. Blood oxygen saturation decreases. In addition to classic pneumonia, disruption of microcirculation in the lungs appears to be responsible.
Heart and blood vessels: SARS-CoV-2 can infect cells of the vascular endothelium and cause inflammation of the same. Increased thrombi are formed, which can cause heart attacks and strokes, among other things.
Liver: Elevated liver values have been described in Covid 19 patients. Experts currently interpret this as a general consequence of the disease and its therapy rather than an expression of direct damage to liver cells by the virus.
Kidneys: Kidney damage, including the need for dialysis, is common in severely ill Covid 19 patients. Possible causes include direct damage to the kidney by SARS-CoV-2, blood clots, and a drastic drop in blood pressure.
Gastrointestinal tract: SARS-CoV-2 can infect intestinal cells and replicate there. Gastrointestinal symptoms such as nausea, vomiting, and diarrhea occur. The virus is detectable in stool but is probably not infectious there.
Skin: spots, blisters, and itchy rashes are possible manifestations of covid-19 on the skin. Whether they are caused directly by the virus or are an indirect consequence of microthrombosis, for example, is still unclear.

The sensory cells on the epithelium of the olfactory mucosa have direct access to the olfactory bulb (bulbus olfactorius), which lies within the central nervous system (CNS), via a long thin nerve process. According to the German Professional Association of Otolaryngologists, the cells of the olfactory epithelium and bulbus olfactorius can be directly affected and damaged by SARS-CoV-2. This damage is mainly responsible for the olfactory disorder, according to a recent press release. Apparently, the coronavirus does not stop in the olfactory bulb in every case, but can penetrate from there further into central parts of the brain. This explains the occurrence of neurological symptoms affecting the CNS, which, according to a publication in “JAMA Neurology,” usually occur before patients develop respiratory symptoms (DOI: 10.1001/jamaneurol.2020.1127). In the study of 214 Covid 19 patients from Wuhan, one in four had central nervous symptoms, most commonly dizziness, headache and clouding of consciousness. Seizures, meningitis or centrally induced respiratory arrest are also possible consequences of CNS involvement of covid-19, according to the German Society of Neurology (DGN). In addition, SARS-CoV-2 could trigger Guillain-Barré syndrome (GBS), an autoimmune reaction that can occur as a result of infections and in which the myelin layer of peripheral nerves is attacked. With Covid-19, this severe neurological complication occurs after only five to ten days, whereas it usually takes two to four weeks for infection-associated GBS to occur, according to the DGN. You might also be interested in

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SARS-CoV-2 is considered a “multi-organ virus” and is not a pure respiratory virus. After the lungs, it primarily affects the heart and kidneys. As early as August 2020, Hamburg pathologists published a study showing that coronaviruses were detectable in the kidney of 60 percent of people who died from Covid-19. In February 2022, a study showed that “SARS-CoV-2 can directly infect kidney cells and cause cell injury with subsequent fibrosis.”

Post-Covid – When Covid-19 Hits the Kidneys.

Patients with prior kidney disease are more likely to have a severe course. Those infected show altered kidney values during urine checks. And furthermore, those who become severely ill with Covid-19 experience acute kidney failure in half of the cases. That’s true for Covid patients who need to be ventilated. “In 30 percent of these patients, the kidneys are so severely compromised that they require dialysis,” says Christoph Galle, president of the German Society of Nephrology.

Long covid – scar tissue impairs kidney function

Kidney problems are also common in other similarly severe diseases. It is not yet clear in detail exactly how the coronavirus affects the kidney. As researchers at RWTH Uniklinik Aachen, Germany, and Radboud University Medical Center, the Netherlands, showed, the coronavirus infects the kidneys directly and contributes to scarring of the tissue. And this scar tissue could have a long-term negative impact on kidney function. This is the context of a large study from the U.S. in November 2021 that involved more than 90,000 Covid gene recipients. The results show, among other things, that Covid survivors have an increased risk of severe kidney disease compared with non-infected individuals – even after the acute phase of the disease.

Covid-19 late effects – blood clots can harm kidneys

In addition, Covid-19 patients are given many drugs – such as antibiotics or even dehydrating medications – that can affect the kidneys. Doctors also observe that blood clots more quickly in people with severe Covid-19. This can lead to the formation of blood clots that block blood vessels. This can also happen in the kidneys, resulting in small infarcts in the kidney tissue. Post-Covid – As a late effect of Covid-19, the kidneys can become diseased.

“We see major problems in blood clotting with Covid-19, which shows up in things called microthrombi, small clumps, blockages in the lungs in the kidney. That could be one reason why the kidney is also damaged.”

Oliver Keppler, Munich virologist and director of the Max Pettenkofer Institute at LMU Munich, Germany

Long-Covid: Children can suffer vascular and kidney damage

A study of 112 young patients between the ages of five and 17, published in the journal Blood advances in December 2020, found that even when the disease progresses without symptoms, damage can remain in the blood vessels and kidneys. A biomarker in the blood, a specific biological feature in the blood, is elevated in these children and adolescents, indicating microthomboses.

“The results suggest that thrombotic microangiopathies [sometimes life-threatening conditions that cause dysfunction by damaging capillaries] are common in children infected with SARS-CoV-2 – even when symptoms are minimal.”

Caroline Diorio, pediatrician at Children’s Hospital of Philadelphia, USA

Severe disease progression: kidney problems a warning sign

From the perspective of a Covid sufferer, possible kidney damage sounds frightening, but from a scientific point of view, this connection offers advantages for disease prognosis: because worsened kidney values already serve as an early warning signal for severe courses and for a possibly increased risk of death. The physicians treating the patient can then react to these signs and initiate special measures.

Symptoms that may indicate kidney problems:

High blood pressure
Sharp headaches
Shortness of breath
Water retention (edema)
Foam on the urine

Post-Covid: Even those who have recovered from Covid-19 should go for follow-up care!

Not only therapy during the acute phase of the disease is important, but also post-covid care. For example, Freiburg University Hospital is one of the many hospitals that have set up a corona aftercare outpatient clinic. There, recovered patients suffering from after-effects such as altered kidney values can be examined and advised. Infectiologist Winfried Kern: “There are also patients in our aftercare outpatient clinic who still do not have normalized kidney functions, but still have conspicuous values. These are not critical, but still measurably indicate impaired kidney function.”

Tips for managing long-covid and kidney problems:

Keep an early eye on the kidneys in addition to the lungs, heart and nervous system during Covid 19 follow-up
Have kidney values checked regularly by primary care physician
Keep a symptom diary
Make Covid recovered patients aware of the possibility of long-term effects on the kidneys
Contact support groups and share any problems you may be experiencing

Long-Covid: kidneys can recover

Severe covid 19 disease can lead to acute kidney failure. This is problematic, but unlike chronic kidney failure, the organ usually recovers once the covid-19 disease is over. This is also indicated by research from January 2021. The researchers show that the organ can be restored to health, even if kidney function has to be temporarily taken over by machines. This is because new, effective therapies for treating kidney function loss have come on the market in just the last few years.

Related links to post covid and kidney problems:

Kidney Self-Help Group – Bavaria Regional Group
Treacherous disease – recognizing and treating kidney weakness in time (NDR)
Chronic kidney damage – causes, symptoms, treatment
Long-term Covid, German-language self-help group.

Broadcasts:

Long Covid – Living with Exhaustion. 17.11.2022, 10:55 a.m., ARD-alpha.
Health. Recovered – not healthy: Corona and the long-term consequences. 04.01.2022, 19:00, BR Television.
Klinik St. Hedwig – Help for children with Long-Covid. 07.12.2021, 17:30, BR Fernsehen.
aktiv und gesund – Health Magazine. Restful sleep: food for the kidneys. 22.07.2021, 14:15, BR Television.

It was recognized early that renal values can predict severe COVID-19 progression [1]. Therefore, the S3 guidelines for inpatient therapy [2] advise determination of urine and kidney values already in the emergency room. A new concern is that molecular tissue changes caused by the virus could lead to renal damage in the long term, not only in COVID-19 patients who have experienced acute renal failure, but also in those who experienced renal value abnormalities during the acute illness. Because these were not always detected, renal experts emphasize the importance of nephrologic follow-up after COVID-19. The kidneys are a target organ of COVID-19 and are affected very early in the course of the disease. However, this is precisely where a high prognostic potential lies: COVID-19-associated nephritis was already recognized last spring as an early warning signal for severe courses of the infectious disease and published accordingly [1]. To this end, the research group led by Professor Oliver Gross, Department of Nephrology and Rheumatology, University Medical Center Göttingen (UMG), screened 223 patients in a study and included 145 of them as a predictive cohort. Study endpoints were admission to the intensive care unit or death. As a result, early urinary changes easily detected by test strips indicated more severe COVID-19 progression. Combined as a predictive system (urine and serum markers), outcome could be predicted. “Kidney values are thus a seismograph for the course of COVID-19 disease,” explained study leader Prof. Gross at the kick-off press conference of the ERA-EDTA Congress 2021. In the general recommendation for action (S3 guideline [2]), recommendations were made for inpatient therapy of patients with COVID-19, where it is stated, among other things, that “in case of proven covid-19 infection and the need for hospitalization, a urine examination (repeated if necessary) with determination of albuminuria, hematuria, and leukocyturia should be performed.” But renal involvement is even more than a prognostic marker for disease progression. It is a very significant risk factor for mortality: several studies [3, 4] showed that renal involvement, i.e., albuminuria (and/or hematuria), often occurs early in the course of patients who develop COVID-19. A Chinese study [5] concluded that renal involvement in COVID-19 patients dramatically worsens the outcome of the novel viral disease and increases mortality by a factor of 10 (1.25% of patients without renal involvement died vs. 11.2% of patients with renal involvement). Until now, only the occurrence of acute kidney injury (AKI) was known to be an independent predictor of mortality [2], but it appears that even early signs of renal involvement, such as protein loss in the urine, protein reduction in the blood, and loss of antithrombin III, are prognostically significant [1]. This suggests the question of whether and what specific long-term effects can be expected after COVID-19 on the kidneys. The data on acute kidney injury (AKI) are relatively clear: In AKI (“acute kidney injury”), kidney function recovers after seven days, to be distinguished from AKD (“acute kidney disease”), in which recovery of kidney function takes longer, up to 90 days. However, there are also many patients in whom renal function does not recover at all but deteriorates successively as the disease progresses, i.e. they become chronically kidney disease. Kellum et al [6] showed that a total of 41.2% of patients in AKI stages 2 and 3 ultimately did not recover renal function. Relapses and long-term renal function impairment occurred even in 14.7% of those who initially recovered. The same study group also showed that these patients had a significantly worse outcome (death, need for dialysis) one year after suffering AKI. Similar warning signals now reach us about chronic kidney injury after COVID-19 from China [7]: “So we can say that a good half of patients who suffer an AKI go on to develop chronic kidney disease. This rate is also to be expected after a COVID-19-associated AKI. It is important to bring those affected into nephrological follow-up care so that adequate therapy can slow down or, if possible, halt the loss of kidney function,” explains Prof. Gross. But what about patients who have not experienced acute kidney failure, but “only” an initial derailment of kidney values? Here, too, the expert advises caution and follow-up: “Studies are currently underway, the results of which are still pending, but molecular SARS-CoV-2-associated tissue changes have already been detected in various organs in which virus replication has been detected.” In this respect, long-term damage to the affected organs and post-COVID entities are to be expected, he said. The most important conclusion of the Göttingen expert: “The kidney must be the focus of COVID-19 follow-up, along with the lungs, heart and nervous system. This is all the more important because early treatment can halt the loss of kidney function. New, effective therapies have come onto the market for this purpose in recent years in particular, such as the SGLT-2 inhibitors. Nowadays, the need for dialysis can often be postponed for years or even decades if the patient is treated consistently right from the start. Since kidney disease leads to symptoms at a very late stage, we would like to make people who have undergone COVID-19 disease aware of the possibility of long-term effects on the kidneys. It is important that the family doctor checks their kidney values (GFR, albumin in urine) at regular intervals, similar to other risk groups for kidney disease such as patients with diabetes mellitus and hypertension.” [1] Gross O, Moerer O, Weber M et al. COVID-19-associated nephritis: early warning for disease severity and complications? Lancet 2020; 395 (10236): e87-e88 [2] Kluge S, Janssens U, Welte T et al. S3 guideline-recommendations for inpatient therapy of patients with COVID-19. update: 05/17/2021. https://www.awmf.org/leitlinien/detail/ll/113-001LG.html [3] Li Z, Wu M, Guo J et al. Caution on Kidney Dysfunctions of 2019-nCoV Patients. medRxiv preprint doi: https://doi.org/10.1101/2020.02.08.20021212 [4] Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in-hospital death of COVID-19 patients. doi: https://doi.org/10.1101/2020.02.18.20023242 [5] Pei G, Zhang Z, Peng J et al. Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia. JASN May 2020, ASN.2020030276; DOI: https://doi.org/10.1681/ASN.2020030276 [6] Kellum JA, Sileanu FE, Bihorac A et al. Recovery after Acute Kidney Injury. Am J Respir Crit Care Med 2017; 195 (6): 784-791 [7] Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021 Jan 16;397(10270):220-232. doi: 10.1016/S0140-6736(20)32656-8. DGfN Press Office Dr. Bettina Albers Phone +49 3643 7764-23/mobile +49 174 2165629 [email protected] Features of this press release: Journalists Medicine National Research / Knowledge Transfer, Scientific Conferences German Remdesivir Renal Failure.