key: cord-1010006-osdo2kcm authors: Soliman, Neveen A. title: COVID-19 Infection and the Kidneys: Learning the Lesson date: 2021-05-26 journal: J Infect Public Health DOI: 10.1016/j.jiph.2021.05.010 sha: ed033a610968a3132fa3e41aecabe74f4dce3bd3 doc_id: 1010006 cord_uid: osdo2kcm The novel coronavirus 2019 pandemic has become a global health crisis. In an attempt to decipher how kidneys are affected by COVID-19 infection, this review focuses on pathogenic and clinical links between COVID-19 infection and the kidneys. SARS-CoV-2 infected patients are target for kidney affection, renal tropism, among other multiorgan complications. COVID-19 related kidney affection is reported not only in infected chronic kidney disease patients but also in those with no prior history of kidney disease. As nephrologists try to keep up with the rapidly evolving, sometimes hasty, reports on renal affection in COVID-19, kidneys continue to be deleteriously affected particularly in critical care settings. This review aims to briefly portray renal involvement in COVID-19 amid this unprecedented deluge of scientific data. Based on gained knowledge and expertise, it is prudent to develop and regularly update preventive, diagnostic and therapeutic strategies to improve clinical outcome and reduce mortality. COVID-19 is a newly emerging human infectious disease that marked the beginning of the third decade of the 21 st century. The novel coronavirus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first reported in the city of Wuhan, china and rapidly spread across the country causing an epidemic. COVID-19 affected most countries around the globe and has been reported in all ages, including children 1. On 11 th of March 2020, the WHO declared COVID-19 a pandemic that was later described by WHO on 23 rd of March as "accelerating pandemic" when cases eclipsed 350,000. To date worldwide cases climb above 116 million and deaths over 2.5 million 2. COVID-19 pandemic has profoundly affected everyone, yet its impact on patients continues to unfold. To date the understanding of its epidemiology, pathogenesis and clinical manifestations is still evolving. Scientists and researchers across the globe are extensively studying the disease to expand the currently limited scientific knowledge on this novel virus. Although COVID-19 primarily involves the lungs manifesting as acute respiratory disease, other organ involvement has been reported including kidney, gastrointestinal tract, liver, heart, and central nervous system. Therefore, the novel coronavirus 2019 pandemic has led to an unprecedented high alert among almost all health care disciplines including nephrology 6 7 8 J o u r n a l P r e -p r o o f Pathogenesis SARS-CoV-2 has an identical confining structure to that of SARSCoV-1, hence COVID-19 pathogenesis largely resembles that of SARS-CoV-1. SARS-CoV-2 spike glycoprotein expressed on the viral envelope binds angiotensin-converting enzyme 2 (ACE2) with around 10 fold higher affinity than SARS-CoV1. ACE2 is known to be abundantly expressed on multi-ciliated cells of the airway epithelium that SARS-CoV-2 preferentially infect. After binding, SARS-CoV-2 enters host cells where it encounters the innate immune response. It infects the new host by inhibiting or eluding its innate immune signaling. Nevertheless, how SARS-CoV-2 manages to elude immune response and drive pathogenesis is still largely unclear 9. Kidney involvement is a major complication of COVID-19 infection and a significant risk factor of death. COVID-19 impact on healthy and diseased kidneys continues to unfold. Data on AKI in COVID-19 is increasing with variable incidence of this severe complication. This seems understandable given the accelerated pace of the pandemic particularly with the overwhelming impact of lower respiratory involvement and respiratory failure. AKI is a commonly reported complication of COVID-19 that has been linked to increased morbidity and mortality. Recently, SARS-CoV-2 RNA was detected in the kidneys of 23 (72%) of 32 patients with AKI, compared to lower frequency of SARS-CoV-2 renal tropism in patients without AKI with viral RNA only found in three (43%) of seven patients 28. In a large cohort of 1,099 patients with COVID-19, 93.6% were hospitalized, 91.1% had pneumonia, 5.3% were admitted to the ICU, 3.4% had acute respiratory distress syndrome (ARDS) yet only 0.5% had AKI 29. In another single-center case series of 138 hospitalized patients with confirmed COVID-19 pneumonia in Wuhan, China, AKI was reported in 3.6% of all patients. Unsurprisingly when calculated among the subset of study ICU admitted patients ICU, AKI increased to 8.3% 7. Moreover researchers reported an association between kidney disease and mortality in hospitalized patients. More than 40% had evidence of abnormal kidney function and 5.1% had AKI during their hospital stay. The incidence of AKI was significantly higher in patients with elevated baseline serum creatinine (11.9%) compared to patients with normal baseline values (4.0%), Also, proteinuria, hematuria, and AKI over stage 2 were associated with increased risk of mortality. Excess risk of mortality by at least 4 times had been reported among those with stage 3 AKI with seemingly critical role of lungkidney crosstalk 30 . Electrolyte disturbances not only have clinical implications on patient management, but also aid in exploring the underlying pathogenetic mechanisms in COVID-19. Increased release of antidiuretic hormone in response to a volume depletion presumably contributes to hyponatremia in COVID-19 patients. As SARS-CoV-2 binds to its ACE2 host receptor, it reduces ACE2 expression, resulting in increased urinary potassium in response to high angiotensin II. Hypokalaemia further exacerbates ARDS and acute cardiac injury, particularly in patients with lung or heart comorbidities. 31 32 In this context, close monitoring of kidney function and electrolytes in hospitalized COVID-19 patients, particularly those in critical setting, and use of sensitive AKI biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and/or kidney injury molecule 1 (KIM-1) are warranted to risk-stratify patients and direct resources towards prevention or early detection of AKI and timely intervention to reduce AKI progression and mortality risk. Medical care of dialysis patients during COVID-19 pandemic is quite challenging as patients have depressed immune system let alone associated comorbidities as diabetes and cardiovascular disease. Many strategies for managing dialysis and providing dialysis support for patients during this COVID-19 outbreak had been developed. In a recent report, authors shared the key considerations in planning dialysis services to ensure adequate resources for the provision of uninterrupted dialysis to end stage During this pandemic the main concern, is therefore, immunosuppression rendering kidney allograft recipients more prone to infections including COVID-19. This pandemic not only affected how we care for kidney transplanted patients, but also had its impact A novel coronavirus from patients with pneumonia in China Coronaviruses post-SARS: Update on replication and pathogenesis Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical Characteristics of 138 Hospitalized Patients with Novel Coronavirus-Infected Pneumonia in Wuhan, China Clinical features of patients infected with 2019 novel coronavirus in Wuhan An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients Coronavirusesdrug discovery and therapeutic options Should COVID-19 Concern Nephrologists? Why and to What Extent? the Emerging Impasse of Angiotensin Blockade Coagulation abnormalities and thrombosis in patients with COVID-19 Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study A catabolic state in a kidney transplant recipient with COVID-19 Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: A prospective study Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Multiorgan and Renal Tropism of SARS-CoV-2 Lung-kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup Acute kidney injury in COVID-19: Emerging evidence of a distinct pathophysiology Endothelial cell infection and endotheliitis in COVID-19 Kidney involvement in COVID-19 and rationale for extracorporeal therapies Lung-kidney cross-talk in the critically ill patient SARS-CoV-2 renal tropism associates with acute kidney injury Clinical characteristics of coronavirus disease 2019 in China Kidney disease is associated with in-hospital death of patients with COVID-19 Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19) Electrolyte imbalance in COVID-19 patients admitted to the Emergency Department: a case-control study Coronavirus Disease 2019 (COVID-19) and Dialysis: The Experience in Singapore Recommendations for prevention and management of COVID-19 in peritoneal dialysis patients. Chronic Dis The Novel Coronavirus 2019 epidemic and kidneys Are kidney transplant patients at higher risk? The European experience COVID-19: implications for immunosuppression in kidney disease and transplantation COVID-19 and Kidney Failure in the Acute Care Setting: Our Experience From Seattle