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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 20  |  Issue : 4  |  Page : 191-203

Coronavirus 2019 pandemic and renal diseases: a review of the literature


1 Hamed Al-Essa Organ Transplant Center; Urology and Nephrology Center, Mansoura University, Mansoura, Egypt, Kuwait
2 Hamed Al-Essa Organ Transplant Center; Chest Department, Zagazig University, Zagazig, Egypt, Kuwait
3 Hamed Al-Essa Organ Transplant Center, Kuwait
4 Dasman Diabetes Institute; Faculty of Nursing, Mansoura University, Mansoura, Egypt, Kuwait

Date of Submission30-May-2020
Date of Acceptance21-Jun-2020
Date of Web Publication16-Oct-2020

Correspondence Address:
Dr. Osama Gheith
Gomhoria Street, Urology and Nephrology Center, Mansoura, PO Box: 35516
Kuwait
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jesnt.jesnt_19_20

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  Abstract 


Objectives Most people with coronavirus 2019 (COVID-19) develop mild illness, but a minority may require active medical care because of the acute respiratory distress syndrome, sepsis and septic shock, and multiorgan failure, including acute kidney injury (AKI) and cardiac injury. The effect of this infection in those with chronic kidney disease (CKD) including kidney transplant recipients has not been evaluated properly. We aimed to highlight the effect of COVID-19 on patients with CKD and the preventive measures to be taken in addition to possible therapeutic modalities till the end of May 2020.
Patients and methods We have reviewed most of the literature concerning COVID-19 and focused on the renal implications.
Results Patients with CKD (especially dialysis patients and kidney transplant recipients) are at high risk of death because comorbidities increase the risk of dying owing to COVID-19; moreover, COVID-19 infection exaggerates comorbidities and causes possible drug interactions. Patients with COVID-19-induced AKI should be seen regularly by nephrologists, because the risk of these patients to develop CKD is high. In this review, we evaluated the different studies dealing with such topic.
Conclusion Kidney involvement seems to be frequent in patients with COVID-19 infection, and AKI is an independent predictor of mortality. Management of patients on dialysis will need special precautions with strict protocols to minimize the risk to other patients and health care personnel taking care of these patients. Immunocompromised patients, such as transplant recipients and those who are maintained on immunosuppressive medications, will need special care.

Keywords: acute kidney injury, prevention, COVID-19, dialysis, immunosuppression, kidney diseases, prevention, transplant


How to cite this article:
Gheith O, Maher A, Abbas A, Emam M, Halim MA, Zain Eldein SM, Mahmoud T, Othman N, Nair P, Abd Elazim A, Al-Otaibi T. Coronavirus 2019 pandemic and renal diseases: a review of the literature. J Egypt Soc Nephrol Transplant 2020;20:191-203

How to cite this URL:
Gheith O, Maher A, Abbas A, Emam M, Halim MA, Zain Eldein SM, Mahmoud T, Othman N, Nair P, Abd Elazim A, Al-Otaibi T. Coronavirus 2019 pandemic and renal diseases: a review of the literature. J Egypt Soc Nephrol Transplant [serial online] 2020 [cited 2020 Oct 23];20:191-203. Available from: http://www.jesnt.eg.net/text.asp?2020/20/4/191/298251




  Introduction Top


Coronavirus 2019 (COVID-19) disease initially was a zoonotic disease, which then got transmitted to humans and evolved into human-to-human transmission. It is a respiratory tract infection caused by a newly emergent beta coronavirus that was first recognized in Wuhan, China, in December 2019. Most people with COVID-19 infection develop mild or uncomplicated illness; however, 14% develop severe disease that requires hospitalization and oxygen support, and 5% required active medical care [1] because of the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure, including acute kidney injury (AKI) and cardiac injury [2].

The virus − initially named as 2019-nCOV, then severe acute respiratory syndrome coronavirus (SARS-COV2) and then COVID-19–binds to angiotensin-converting enzyme 2 (ACE2) receptor like SARS-COV1 located on type II alveolar cells and intestinal epithelial cells [3].

The incubation period is usually between 2 and 14 days in the general population; however, recent reports suggest incubation can be as long as 24 days [4].

The effect of COVID-19 on chronic kidney disease (CKD) has not been reported, but it presents an exceptional threat to dialysis patients. A total of seven of 37 patients on hemodialysis (HD) in a single center, in Wuhan University of China, died, of whom six had COVID-19 infection. However, HD patients with COVID-19 had less lymphopenia, lower serum levels of inflammatory cytokines, and milder clinical disease than nondialysis patients [5].

Akalin et al. [6] reported a very high early mortality among kidney transplant recipients with COVID-19–28% at 3 weeks as compared with the reported 1–5% mortality among patients with COVID-19 in the general population who have undergone testing in the United States and the reported 8–15% mortality among patients with COVID-19 who are older than 70 years of age.

Epidemiology

Since the first reports from Wuhan, nearly nine million confirmed cases in more than 213 countries have been reported (till June 20, 2020). Initially cases outside China occurred mainly among travelers from China and those who have had contact with travelers from China. However, COVID-19 is now considered as pandemic by the WHO [7].

Pathophysiology

The exact mechanism of kidney involvement is unclear: hypothesized mechanisms include sepsis leading to cytokine storm syndrome or viral-induced direct cellular injury. ACE ([Figure 1]) and dipeptidyl peptidase 4 receptors, both conveyed on renal tubular cells, were identified as binding partners for SARS-COV and Middle East respiratory syndrome coronavirus (MERS-COV), respectively [8],[9]. Viral RNA has been identified in kidney tissue and urine in both infections [10],[11]. Zhong’s laboratory in Guangzhou has successfully isolated COVID-19 from the urine sample of an infected patient, suggesting the kidney as the target of this novel virus [12].
Figure 1 Shows the mechanism of action of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in relation to COVID-19 virus target site.

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The kidney involvement in COVID-19 is likely to be multifactorial ([Figure 2]), with cardiovascular comorbidity and predisposing factors (e.g. sepsis, hypovolemia, and nephrotoxins) as important contributors [13]. Cardiorenal syndrome, particularly right ventricular failure secondary to COVID-19 pneumonia, might lead to kidney congestion and subsequent AKI. Similarly, left ventricular dysfunction might lead to low cardiac output and kidney hypoperfusion. Autopsy data [14] indicate that the endothelium is affected in the lung and in the kidney, where it is probably responsible for proteinuria. Furthermore, virus particles were reported to be present in renal endothelial cells, suggesting viremia-induced endothelial damage in the kidney and a probable contributor to AKI.
Figure 2 Shows the possible mechanisms of COVID-19- induced acute kidney injury.

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Additionally, SARS-COV2 can directly infect the renal tubular epithelium and podocytes through an ACE2-dependent pathway through mitochondrial dysfunction, acute tubular necrosis, the formation of protein reabsorption vacuoles, collapsing glomerulopathy, and protein leakage in Bowman’s capsule [15],[16]. Moreover, another potential mechanism of AKI involves SARS-COV2-related immune response dysregulation, as indicated by observed lymphopenia and cytokine release syndrome (cytokine storm) [17]. Other contributors to AKI might include rhabdomyolysis, macrophage activation syndrome, and the development of microemboli and microthrombi in the context of hypercoagulability and endotheliitis [14],[18].

There are several reports of hospitalized patients with thrombotic complications, most frequently deep venous thrombosis and pulmonary embolism [19],[20]. Other reported manifestations include microvascular thrombosis of the toes, clotting of catheters, myocardial injury with ST-segment elevation, and large vessel strokes [21],[22].

The pathogenesis for COVID-19-associated hypercoagulability remains unknown. However, hypoxia and systemic inflammation secondary to COVID-19 may lead to high levels of inflammatory cytokines that cross-talk coagulation system pathway [23].

In the lung tissue, it induces ARDS characterized by diffuse alveolar damage [24]. Moreover, some cases may respond by cytokine storm reaction with bacterial sepsis or hemophagocytosis, which is characterized by elevated C-reactive protein and ferritin [25].

Mode of transmission

Epidemiologic investigation at the beginning of the disease identified an initial association with a sea food market that sold live animals, where most patients had worked or visited. However, person-to-person spread became the mean mode of transmission later on [26].

Large droplet infection

The virus is transmitted in a classic way as infleunza for a distance up to 6 feets. This method might be preventable by using the usual surgical mask.

Airborne transmission

The spread of COVID-19 by airborne transmission is controversial and will need N95 mask − rather than the usual mask during procedures that induce aerosols such as intubation, CPR, and BAL [27] and to consider airborne protection when managing infected cases [28].

Contact transmission

When the virus is shed during cough or sneezing, and droplets settle on surfaces, making thin film and persist for 1 week, and are easily transmitted by hands to mucous membranes of others. Regular cleaning of surfaces by 70% alcohol or 0.5% sodium hypochlorite and proper hand hygiene are quiet effective preventive measures. Moreover, the virus is sensitive to ultraviolet rays and heat at 56°C for 30 min but not sensitive to chlorhexidine [29].

Risk factors

COVID-19 can be complicated by older age and comorbid diseases, such as cardiovascular disease, chronic respiratory diseases, and diabetes mellitus, which have been reported as risk factors for death, and recent multivariable analysis confirmed older age and added higher Sequential Organ Failure Assessment score and D-dimer more than 1 μg/l on admission to the risk factors of higher mortality [30],[31].

In children with COVID-19, the symptoms are usually less severe than adults and present mainly with cough and fever, and coinfection has been observed [32],[33]. Relatively few cases have been reported of infants confirmed with COVID-19; those experienced mild illness [34]. There is currently no known difference between the clinical manifestations of COVID-19 pregnant and nonpregnant women or adults of reproductive age.

Ma et al. [5] − in another study − mentioned that pregnant women, extremes of age, and patients with comorbidities like diabetes mellitus, hypertension, and cardiovascular disease are likely to have more severe illness and often require ICU care.

Clinical course and risk factors

COVID-19 is suspected in patients with fever and/or respiratory symptoms (cough, dyspnea) with history of recent travel to infected countries (during the last 14 days), or being in close contact with confirmed or suspected case (6 feet, for prolonged time) and absence of other diagnoses. The possibility of COVID-19 should also be considered in patients with severe lower respiratory tract illness when an alternative etiology cannot be identified, even if there has been no clear exposure [35].

Classically it presents with fever (in most cases) and constitutional features, upper respiratory symptoms, lower respiratory symptoms (sometimes present with silent hypoxia without dyspnea especially in elderly), and less commonly gastrointestinal features (up to 10%) [31],[36],[37].

Pneumonia appears to be the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging [30],[36],[38],[39]. There are no specific clinical features that can yet reliably distinguish COVID-19 from other viral respiratory infections. In a study describing 138 patients with COVID-19 pneumonia in Wuhan, the most common clinical features at the onset of illness were [36] fever in 99%, fatigue in 70%, dry cough in 59%, anorexia in 40%, myalgias in 35%, dyspnea in 31%, and sputum production in 27%.

The incubation period can be as long as 24 days [4]. The median duration of viral shedding was 20.0 days (interquartile range, 17.0–24.0) in survivors, but SARS-COV2 was detectable until death in nonsurvivors. The longest observed duration of viral shedding in survivors was 37 days.

Asymptomatic infections have also been described, but their frequency is unknown.

In children with COVID-19, the symptoms are usually less severe than adults and present mainly with cough and fever, and coinfection has been observed [32],[33]. Relatively few cases have been reported of infants confirmed with COVID-19; those experienced mild illness [34]. This observation could be explained by the fact that most children have healthier lungs and more potent immune system. There is currently no known difference between the clinical manifestations of COVID-19 pregnant and nonpregnant women or adults of reproductive age.

Coronavirus 2019-induced cytokine storm syndromes and immunosuppression

Severe COVID-19 might have a cytokine storm syndrome which could be due to hyperinflammation which will need to be diagnosed earlier and treated appropriately to reduce the rising mortality [25].

Current management of COVID-19 is supportive, and respiratory failure from ARDS is the leading cause of mortality [25]. Secondary hemophagocytic lymphohistiocytosis (3.7–4.3% of sepsis cases, triggered by viruses) is characterized by a fulminant and fatal hypercytokinemia with multiorgan failure. This syndrome is characterized by unremitting fever, cytopenias, and hyperferritinemia; pulmonary involvement (including ARDS) occurs in ∼50% of patients [40]. A cytokine profile showed increased interleukin (IL)-2, IL-7, granulocyte colony-stimulating factor, interferon-γ-inducible protein 10, monocyte chemo-attractant protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α [30].

Similarly, in a recent retrospective, multicenter study of 150 confirmed COVID-19 cases in Wuhan, China, showed elevated ferritin (mean, 1297.6 ng/ml in nonsurvivors vs. 614.0 ng/ml in survivors, P<0.001) and IL-6 (P<0 · 0001) suggesting that mortality might be owing to virally induced hyperinflammation.

Are kidneys targeted by coronavirus 2019?

Two studies [41],[42] showed a high rate of kidney affection among COVID-19-positive patients who were admitted to hospital. They reported 34% of the 59 patients [41] developed heavy proteinuria, and 63% of the study patients developed proteinuria while in hospital, and many of them also had hematuria. Impaired kidney function was reported in nearly one-third (27%) of the study population and in two-thirds (66%) of the patients who died owing to the coronavirus infection. These findings were also supported by another study that included 710 hospitalized patients [42]. They reported combined hematuria and proteinuria in 44%, isolated hematuria in 26.7%, whereas kidney dysfunction was reported in only 15%.

Implementation of the Kidney Disease: Improving Global Outcomes supportive care guideline (e.g. avoidance of nephrotoxins, regular monitoring of serum creatinine and urine output, and consideration of hemodynamic monitoring) in such critically ill patients with kidney affection is likely to reduce the occurrence and even the severity of AKI in COVID-19, but this requires validation [43]. The application of lung-protective ventilation parameters lowers the risk of new or worsening AKI by limiting ventilation-induced hemodynamic effects and the cytokine burden on the kidney [44]. Another important issue is to adjust fluid balance to restore normal volume status to avoid volume overload and reduce the risk of pulmonary edema, right ventricular overload, congestion, and subsequent AKI. Volume depletion at admission might be expected in COVID-19-infected patients, as they typically present with fever, and prehospital fluid resuscitation is rarely performed [45].

Initial studies have concluded that AKI is an independent risk factor for mortality in hospitalized patients with confirmed infection. These patients should be treated in accordance with the best-practice guidelines in nephrology, which include supportive management as well as dialysis.

If conservative management fails, renal replacement therapy (RRT) and extracorporeal support should be considered in patients with volume overload, especially those with refractory hypoxemia. In patients with COVID-19 and AKI, early initiation of RRT and sequential extracorporeal organ support seem to provide adequate organ support and prevent progression of disease severity [46]. Continuous renal replacement therapy (CRRT) is the preferred modality in hemodynamically unstable patients with COVID-19. With prone position (the best caring position of such cases), the dialysis catheter needs to be secured and monitored to avoid dislocation or kinking. The right jugular vein is the preferred insertion site during such positioning. In an Italian study involving 1591 ICU patients with COVID-19, 27% required prone positioning. Extracorporeal membrane oxygenation was performed in 1% of these patients. When RRT is carried out, it will be through venous access independent of the extracorporeal membrane oxygenation circuit [47].

On the contrary, patients with CKD (especially those on dialysis) are at high risk of death because comorbidities increase the risk of dying owing to COVID-19. Another aspect of view is that recovered patients with AKI should be seen regularly by nephrologists, because the risk of these patients to develop CKD is high. Otherwise, there is a risk that the corona epidemic will be followed by an epidemic of CKD and end-stage kidney disease [48].

In renal transplants, the symptoms are predominantly respiratory and associated with fever. Most patients − either in case reports or case series − had their immunosuppression reduced and were treated with supportive therapy [49].

Diagnosis and laboratory workup

Complete blood count is usually normal, but lymphopenia and mild thrombocytopenia are common. COVID-19 can increase C-reactive protein, erythrocyte sedimentation rate, and D-dimer but not procalcitonin; increased procalcitonin suggests pure bacterial infection. Isolation of other respiratory viruses lowers the index of suspicious toward COVID-19; however, coinfection is still there. The importance of testing for other pathogens was highlighted in a report of 210 symptomatic patients with suspected COVID-19; 30 tested positive for another respiratory viral pathogen, and 11 tested positive for SARS-COV2 [50].

In the United States, the Center for Disease Control and Prevention (CDC) recommends collection of a nasopharyngeal swab specimen to test for SARS-COV2 [51]. An oropharyngeal swab can be collected but is not essential; if collected, it should be placed in the same container as the nasopharyngeal specimen. Sputum should only be collected from patients with productive cough; induction of sputum is not indicated.

SARS-COV2 RNA is detected by reverse-transcription (RT). A positive test result for SARS-COV2 confirms the diagnosis of COVID-19. If initial testing is negative but the suspicion for COVID-19 remains, the WHO recommends resampling and testing from multiple respiratory tract sites [52]. For safety reasons, specimens from a patient with suspected or documented COVID-19 should not be submitted for viral culture.

Positive virus-specific IgM antibody within 3–5 days can be detected especially in immunocompetent patients with rising IgG titer (four folds) within convalescence period. Such immunoglobulin tests are considered good screening method but not to be used alone for disease confirmation, especially among immunosuppressed patients.

Computed tomography (CT) chest showed ground glass opacities with or without consolidation, denoting viral pneumonia that tends to be bilateral, basal, and peripherally predominant with absence of pleural effusion [25],[53].

In a study of 1014 patients in Wuhan who underwent both RT-PCR testing and chest CT for evaluation of COVID-19, a positive chest CT result for COVID-19 (as determined by a consensus of two radiologists) had a sensitivity of 97%, using the PCR tests as a reference; however, specificity was only 25% [54]. The low specificity may be related to other etiologies causing similar CT findings.

Chest CT abnormalities have also been identified in patients before the development of symptoms and even before the detection of viral RNA from upper respiratory specimens [37],[55].

Management

Prevention is better than cure

Given the potential for greater infectivity, strict isolation precautions should be followed for anyone with suspected COVID-19. Although the virus is not airborne, CDC has recommended use of airborne precautions, and N95 masks when it is available. Surgical masks are acceptable alternatives when supplies are limited. The N95 masks or their equivalents should be reserved for procedures that are more likely to generate respiratory aerosolization as tracheal intubation and bronchoscopy [56].

Preventive measures among kidney transplant patients and other immunocompromised patients

Complete data on transplant recipients with COVID-19 are scarce. However, based on the data from influenza and SARS, if infection occurs, progression to pneumonia may be more common in the immunocompromized population, including transplant recipients. It is anticipated that transplant recipients may have a larger viral burden and shedding, resulting in greater infectivity and probable spread to others. For health care centers with active cases of COVID-19, consideration should be given for postponing nonessential transplant clinic visits [56].

Health care professionals are advised to follow local/regional/national guidelines. Moreover, the most recent information can be found on the websites of WHO and the CDC [51],[57].

The CDC has recommended to suspend all nonessential travel by air, as well as cruise travel for all people at increased risk for getting very sick from COVID-19 including transplant recipients. Moreover, transplant patients should avoid overcrowded situations. The benefit of wearing masks in public is controversial even for transplant patients. However, universal masking is already standard practice in many places worldwide especially in hospitals.

Therefore, the recommended cloth face coverings are not surgical masks or N95 respirators. As recommended by current CDC guidance, N95 masks are critical supplies that must continue to be reserved for health care workers and other medical first responders. Social distancing together with frequent hand washing or hand sanitizer use helps prevent infection.

Temporary suspension of elective living donor transplantation or nonurgent deceased donor transplants may need to be considered. In stable patients, virtual/telemedicine communication may be appropriate, and laboratory testing may be performed locally.

All donors should be screened for concern for COVID-19 infection. Screening should be done at three levels: (a) epidemiologic level of screening for travel and potential exposures; (b) clinical level of screening for symptoms suggestive of COVID-19, and (c) laboratory level of screening using nucleic acid testing.

Preventive measures for dialysis patients

COVID-19 represents specific challenges for dialysis patients, especially for in-center HD patients. Uremic patients are susceptible to infection with much variation in clinical presentations and infectivity. The risk of transmission of infection increases significantly among in-center HD patients involving medical and para-medical staff in addition to family members.

According to Chinese Society of Nephrology [58] and Taiwan Society of Nephrology [59] guidelines for dialysis units during the COVID-19 outbreak, the following steps should be applied:
  1. Dialysis team should receive training in updated clinical knowledge of epidemic COVID-19, notification of infection at risk, epidemic prevention tools, and guidelines from the government, academic society, and hospital authority. The list of staff should be recorded and be retained by dialysis hospitals.
  2. Regular collection and update of significant information concerning travel, occupation, contacts, and clusters history of each medical staff, dialysis patient, their family members, residents of the same institution, and colleagues at work.
  3. Latest care recommendations and training can be done online.
  4. Minimization of all group activities, including group rounds, group studies, and case discussions.
  5. Staff members should take their meals at different time to avoid dining together. Goggles, masks, and hats should be removed before meals, and hands washed with flowing water. Talking during meals must be reduced to decrease the spread of droplets.
  6. Staff should self-monitor their symptoms and should inform the team leader in case they or their family members develop any of the symptom(s) suggestive of COVID-19 infection.
  7. Entrance control, identification and shunting of people at risk of infection, hand washing, body temperature measurement, wearing proper (surgical or N95) masks throughout the process, machine disinfection, environmental cleanliness, and good air conditioning and ventilation conditions should be instituted.
  8. Patients and accompanying persons should be given hands-free hand sanitizer while entering the dialysis room. Patients should wear medical masks and avoid meals during dialysis. They can bring convenience food such as candy to prevent hypoglycemia.
  9. Patients with suspected or confirmed COVID-19 infection should be admitted to negative pressure isolation ward of specified hospitals. If the capacity of the isolation facility is overloaded, the strict isolated dialysis is recommended for dialysis patients under the 14-day period of quarantine for possible contact with COVID-19.
  10. Patients should continue HD at the same original HD center without change.
  11. Do not change dialysis shifts and caregiver staff to avoid cross-contamination and infection.
  12. Patients who need vascular access surgery should be screened for COVID-19 before the surgery. Operations on patients with confirmed or suspected COVID-19 infection should be carried out in a designated room with necessary protection for medical staff.
  13. Public transport should not be used and patients should arrange personal transportation with fixed transportation routes. Transport personnel and escorts should wear surgical grade or N95 masks throughout.
  14. All patients who have fever should be screened for COVID-19 infection and should be given dialysis in the last shift of the day until infection is excluded.
  15. Pass route for entering hospital and dialysis unit: the pick-up and drop-off should not be shared with other dialysis patients. The route, mode, and time of transport of dialysis personnel should be fixed.
  16. Precautions in dialysis unit: patients should not be in close proximity; treatment and waiting areas should have good air conditioning and ventilation to remove droplet particles from the air.
  17. All personnel involved in direct patient care should undertake full protection, including long-sleeved waterproof isolation clothing, hair caps, goggles, gloves, and medical masks (surgical mask grade or above). Hand hygiene should be strictly implemented regularly.
  18. Dialysis machine: equipment that may come into contact with patients or potentially contaminated material should be disinfected according to standard protocols.
  19. If a new confirmed or highly suspected case of COVID-19 infection in dialysis centers is identified, disinfection should be carried out immediately. Areas in close contact with these patients should not be used for other patients until cleared.
  20. The medical waste from confirmed or suspected patients with COVID-19 infection should be considered as infectious medical wastes and disposed accordingly.


Therapeutic management of patients with coronavirus 2019

No consensus on a certain antiviral drug therapy for COVID-19 infection has been reached. Many drugs are under trial or empirically included in treatment protocols for COVID-19. [Table 1] summarizes the WHO interim guidance of clinical management of COVID-19 [60], and [Figure 3] shows COVID-19 pathway as recommended by the WHO [60].
Table 1 Summarizes WHO interim guidance of clinical management of coronavirus 2019 [60]

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Figure 3 Shows COVI-19 pathway in the management of screened patients.

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Prevention of complications

  1. Prophylactic or therapeutic anticoagulation.
  2. Care should be given to drug–drug interaction and medications adverse effects used in the context of COVID-19.
  3. Reduction of mechanical ventilation and ventilation-associated pneumonia:
    1. Daily assessment, early mobilization, and minimization of sedation.
    2. Oral intubation, closed suction, regular change of moisture exchanger and semi-recumbent position.
  4. Reduction of pressure ulcers by frequent change of position.
  5. Reduction of gastric stress ulcers by use of histamine 2 receptor blockers or proton pump inhibitors.
  6. Avoidance of antibacterial resistance by its optimal use (when indicated) and de-escalation protocol especially in stable patients.
  7. Mental and psycho-social support for all cases especially with sleep disorders and anxiety.
  8. Rehabilitation programs especially for critically ill, old patients, and those with organ dysfunction.


Empiric treatment

Empiric treatment for community-acquired pneumonia is considered when the COVID-19 diagnosis is uncertain, because the clinical features of both cannot be distinguished, especially if there is clinical suspicion for superimposed bacterial infection (e.g. new fever after defervescence with new consolidation on chest imaging). Re-evaluation of the need to continue antibiotic therapy should be done daily by bacterial staining, cultures, and urinary antigen testing [61]. Nebulized medications should be restrained to avoid the risk of aerosolization of SARS-COV2 through nebulization [62].

Pharmacologic prophylaxis of venous thromboembolism for all hospitalized patients with COVID-19 is favored, consistent with recommendations from several expert societies [63],[64].

WHO and CDC recommended against systemic glucocorticoids use in patients with COVID-19, unless there are other indications (e.g. exacerbation of chronic obstructive pulmonary disease), because of the increased risk for mortality in patients with influenza and the delayed viral clearance in patients with MERS-COV infection [65],[66],[67].

Antiviral preparations under trials

Remdesivir

Remdesivir, a novel nucleotide analog, has activity against severe SARS-COV2 infection in vitro. Preliminary results from one large trial indicated that remdesivir reduced time to recovery; in a smaller second trial that was stopped early for poor enrollment, there was also a trend toward reduced time to recovery with remdesivir, but it was not statistically significant. Whether remdesivir reduces mortality remains uncertain. The pharmacokinetics of remdesivir in the setting of renal impairment are uncertain, and it is prepared in a cyclodextrin vehicle that accumulates in renal impairment and may be toxic; thus, remdesivir is not recommended in patients with an estimated glomerular filtration rate less than 30 ml/min/1.73 m2 [68],[69],[70].

Convalescent plasma

Use of convalescent plasma has been described in some case series. One case series described administration of plasma from donors who had completely recovered from COVID-19 to five patients with severe COVID-19 on mechanical ventilation and persistently high viral titers despite investigational antiviral treatment. The patients had decreased nasopharyngeal viral load, decreased disease severity score, and improved oxygenation by 12 days after transfusion. However, these findings do not establish a causal effect, and the efficacy of convalescent plasma remains unknown [71].

Favipiravir

It is an RNA polymerase inhibitor that is available in some Asian countries for treatment of influenza, and it is being evaluated in clinical trials for treatment of COVID-19 in the United States. In a nonrandomized, open-label study of patients with nonsevere disease; its use was associated with faster rates of viral clearance and more frequent radiographic improvement compared with lopinavir–ritonavir [72].

Lopinavir–ritonavir, combined protease inhibitor, which has primarily been used for HIV, has in-vitro activity against the SARS-COV. In a randomized trial, it did not decrease the time to clinical improvement compared with standard care alone, and regarding mortality, the difference was statistically insignificant [73],[74].

Other supportive medications

Tocilizumab

It is an IL-6 receptor inhibitor used for rheumatic diseases and is being evaluated in randomized trials. Case reports and observational studies have described its use in patients with severe COVID-19 who had laboratory results suggesting a pro-inflammatory and pro-thrombotic state. No major adverse events were thought to be directly related to tocilizumab (given intravenously or subcutaneously), as it was associated with a decrease in C-reactive protein, D-dimer, and ferritin levels. However, there was a 14-day mortality rate of 11% [75],[76],[77],[78],[79],[80].

Hydroxychloroquine or chloroquine

The FDA has issued an emergency use authorization to allow the use of hydroxychloroquine or chloroquine in adults hospitalized for COVID-19 when participation in clinical trials is not feasible [81]. When a clinical trial is not available, it is not suggested for routine use given the lack of clear benefit from limited data and potential for toxicity (prolongation of the QT interval and retinopathy or cardiomyopathy with longer term use and higher cumulative doses). In a multinational registry study, 15 000 patients had received hydroxychloroquine or chloroquine (with or without a macrolide) within the first 48 h of diagnosis; neither drug was associated with a reduction in in-hospital mortality. One trial comparing two doses of chloroquine for COVID-19 was stopped early because of a higher mortality rate in the high-dose group. In the large registry study mentioned before, hydroxychloroquine or chloroquine use was independently associated with an increased risk of new-onset ventricular arrhythmias, recorded in 6% with hydroxychloroquine and 4% with chloroquine [82],[83].

Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers

ACE inhibitors or angiotensin receptor blockers should be continued if there is no other reason for discontinuation (e.g. hypotension and AKI). There has been speculation that patients with COVID-19 who are receiving these agents may be at increased risk for adverse outcomes, but this has not been supported by findings from observational studies. Conversely, angiotensin receptor blockers have also been proposed to have potential protective effects based on their mechanism of action [84] ([Figure 1]).

Immunosuppressant agents

Use of immunosuppressant agents has been associated with increased risk for severe disease with other respiratory viruses, and the decision to discontinue immunosuppressive

drugs in the setting of COVID-19 must be determined on a case-by-case basis. For individuals with underlying conditions who require treatment with these agents and do not have suspected or documented COVID-19, there is no evidence that routinely discontinuing treatment is of any benefit [85],[86].

Extracorporeal treatments

CRRT has been successfully applied in the treatment of SARS, MERS, and sepsis [87],[88]. High-volume hemofiltration in a dose of 6 l/h removed inflammatory cytokines (IL-6) and improved the Sequential Organ Failure Assessment scores at day 7 in patients with sepsis [89]. Therefore, CRRT may play a role in patients with COVID-19 and sepsis syndrome. The potential role of extracorporeal therapy techniques needs to be evaluated.

Critically ill patients

In spite of the fact that corticosteroids are not routinely recommended as it might exacerbate COVID-19-associated lung injury [30],[67], in a retrospective study of patients with SARS-COV and sepsis, steroids, in a mean daily dose of 105.3±86.1 mg in 147 (59.0%) of 249 noncritical patients reduced mortality and shortened duration of hospitalization, whereas 121 (79.6%) of 152 critical patients received corticosteroids at a mean daily dose of 133.5±102.3 mg, and 25 died [67,90]. However, in hyperinflammation, immunosuppression is likely to be beneficial. A phase 3 randomized controlled trial of IL-1 blockade (anakinra) in sepsis showed significant survival benefit in patients with hyperinflammation, without increased adverse events [30],[90]. Another multicenter, randomized controlled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19 pneumonia and elevated IL-6 in China (ChiCTR2000029765) [91],[92]. Janus kinase inhibition could affect both inflammation and cellular viral entry in COVID-19 [92],[93],[94].

Therefore, all patients with severe COVID-19 should be screened for hyperinflammation using laboratory trends (e.g. increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) to identify the subgroup of patients for whom immunosuppression could improve mortality. Therapeutic options include steroids, intravenous immune globulin, selective cytokine blockade (e.g. anakinra or tocilizumab), and Janus kinase inhibition.


  Conclusion Top


COVID-19 is a global pandemic human threat. Kidney involvement seems to be frequent, and AKI is an independent predictor of mortality. The effect of this infection in those with CKD has not been studied. Management of patients on dialysis will needed special precautions with strict protocols to minimize the risk to other patients and health care personnel taking care of these patients. Immunocompromised patients, such as transplant recipients and those who are on immunosuppressive medications, will need special care.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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