INTRODUCTION:

Since late 2019, the COVID-19 pandemic has affected worldwide public health. It is becoming more and more clear as the pandemic progresses that certain patient groups, including individuals with pre-existing medical disorders, have a greater chance of developing a severe sickness and other consequences if they get COVID-19. One such vulnerable group of people are those who have chronic renal disease, a condition that is defined by a slow deterioration in kidney function over time.Since March 2020, the COVID-19 pandemic has caused over 760 million illnesses and 6.8 million deaths^1,2.

Chronic renal disease, which complicates COVID-19 infection, affects millions globally.

CKD patients had worse COVID-19 results due to diminished renal clearance of medicines, impaired immune function, and increased comorbidities. Consequently, understanding the prognosis and developing effective pharmacological management strategies for this population are of paramount importance. Numerous studies have looked at the relationship between different comorbidities and the results of the coronavirus disease in 2019^3,4. CKD and COVID-19 interact in a complicated way, with both illnesses having a significant effect on one another. The process through which the COVID-19 virus enters renal cells, causing tissue damage and viral reproduction, may be used to explain this relationship. Additionally, the infection triggers a severe inflammatory response that exacerbates the already compromised renal function and, in severe cases, may contribute to patient mortality^5,6.

According to estimates, 50% of CKD patients die from cardiovascular causes, while infections are known to be a significant contributor to non-cardiovascular morbidity in patients with advanced CKD⁶. CKD patients are characterised by immune dysfunction. Moreover, CKD-dependent or associated comorbidities may aggravate an already fatal condition⁷.

This narrative review is to critically assess the impact of COVID-19 infection on those suffering from chronic renal illness, with a focus on prognosis and pharmacological treatment. Additionally, the existing corpus of research on COVID-19's clinical course in CKD patients will be examined, including its propensity to advance to severe disease, hospitalisation rates, and death results. The difficulties in controlling COVID-19 in CKD patients will also be covered, including medication interactions, dosage modifications, and possible nephrotoxic consequences of pharmacological therapies. Furthermore, we will examine the efficacy and safety of antiviral agents, immunomodulatory drugs, and potential repurposed medications for COVID-19 treatment in the CKD population.

This narrative review aims to give researchers and healthcare professionals an in-depth knowledge of the prognosis and pharmacological treatment of COVID-19 infection among individuals with chronic kidney disease by compiling the existing literature and assessing the most recent research findings. This knowledge can assist in guiding clinical decision-making, optimising patient care, and formulating future research directions to address the unique challenges faced by this vulnerable population³⁹.

Research Problem: Over 10% of people globally are estimated to have chronic kidney disease (CKD). CKD significantly increases the risk of all-cause mortality and morbidity, especially in cases of COVID-19 infection.

Research Focus:

Assessing the incidence, course, prognosis, and associated risk factors, treatment, and vaccination outcomes in COVID-19-infected CKD patients

Research questions:

This review was built around the following query:

1- What are the characteristics of studies?

2- What are the key findings of the studies

3- What is the prognosis and associated factors determining that prognosis of COVID-19 in CKD individuals?

4- What is outcome of COVID-19 in CKD individuals?

5- What are the gaps and recommendations?

Research Aim:

To determine the characteristics, key findings, prognosis, associated factors, outcomes, gaps, and recommendations related to COVID-19 in individuals with chronic kidney disease.

METHODS:

General Background:

There are over 760 million instances of COVID-19 recognized, and it is estimated that 10% of people globally have CKD. There is a reciprocal link between COVID-19 and CKD; one has an impact on the other. The chances of morbidity and death from all causes are greatly increased by severe CKD. Moreover, infections are known to be a significant contributor to non-cardiovascular morbidity in patients with advanced CKD. To further understand this link and the course, prognosis, risk factors, therapy, and vaccine outcomes in COVID-19-infected CKD people, there is a need for a thorough assessment of the available literature.

Search Strategy:

We searched the literature for the most recent published articles between 2019 and 2023 from common electronic databases such as PubMed, including CKD patients with COVID-19 infection, using the following keywords: (COVID-19 OR SARS-CoV-2 OR 2019-nCoV Infections) AND (Chronic Kidney Disease OR CKD OR End-Stage Renal Disease OR Chronic Renal Failure OR Chronic Renal Insufficiency). Also, to identify the factors affecting the course of COVID-19 in CKD patients, the following points were covered in our database search: the effect of COVID-19 on the kidney tissue (pathophysiology), mortality rates in CKD-infected individuals, and the most recent preventive and therapeutic approaches.

Database Search Results:

A total of 3174 were identified using our search strategy. Those articles were screened to choose the ones relevant to our topic. Finally, 21 articles were comprehensively reviewed to collect information about our topic and compile this study (Figure 1).

Figure 1: A Four-Phase Flow Diagram

Study Selection:

This narrative review included data from clinical trials, primary research studies, and electronic databases. The inclusion criteria involved selecting articles published in peer-reviewed scientific journals. The initial filtering process involved assessing the relevance of studies based on the presence of keywords used in the search strategy within the titles and abstracts. The entire texts of all possibly relevant papers were then carefully examined to determine if they qualified for inclusion in the review.

Data Analysis:

The relevant data from each study was extracted systematically using the established criteria. Both types of data, including numerical data and qualitative data, were collected. summarised the extracted data in a concise and standardised manner, ensuring clarity and accuracy. grouping the studies based on similarities in terms of study design, participant characteristics, interventions, or outcomes. compared and contrasted the findings within and across the groups to identify commonalities, discrepancies, or divergent results. Recurring patterns, themes, or trends in the extracted data were assessed. No analysis was done; only a summary was synthesised in light of the review questions and the overall objectives of the narrative review. Finally, we discussed the implications and significance of the findings, considering their strengths, limitations, and potential biases. highlighted any gaps in the existing literature or areas that require further research.

RESULTS:

Time Series Graph of Publication:

Results in Figure 2 showed that frrom 2019 to 2023, there have been a total of 3545 publications related to COVID-19 infection in patients with chronic kidney disease. The majority of the research papers were published in 2021, with 1263 publications. The research in this area seems to have gained momentum in 2020, with 798 publications,and in 2023, there is a notable decline in the number of publications compared to previous years. This might suggest that the initial surge of research has decreased, or that the focus of researchers has shifted to other aspects of the pandemic or other medical conditions.

Figure 2: Time Series Graph of Publication.

Study Characteristics:

In Table 1, one study was published in 2023 and 2022, eight in 2021, and ten in 2020. In 2020, Ji W et al. did a case-control study with 219,961 participants, whereas case report research included just one patient. The studies encompass various research designs, including systematic reviews, case-control studies (2), meta-analyses (2), observational studies, retrospective studies, phenome-wide association studies (PheWAS), retrospective analyses, nonsystematic reviews, randomised controlled trials (RCTs), and case reports. These diverse studies, with their different sample sizes and publication years, contribute to the expanding scientific knowledge within their respective fields.

Table 1: Study Characteristics

Author	Study Design	Sample Size
Jdiaa SS et al (2022) [8]	Systematic reviews	66
Ji W et al (2020) [9]	Case-control study	219961
Corbett RW et al (2020) [10]	Cohort study	1530
Xiao W et al (2021) [11]	Meta-analysis	12999
Nandy K et al (2020) [12]	Meta-analysis	3994
Kunutsor SK et al (2020) [13]	Observational study	17391
Rapp JL et al (2021) [14]	Observational study	4062
Fried MW et al (2021) [15]	Cohort study	11721
Ng JH et al (2020) [16]	Cohort study	10482
Flythe JE et al (2021) [17]	Cohort study	4264
Ioannou GN et al (2020) [18]	Longitudinal cohort study	88747
Martos-Benítez FD et al (2021) [19]	Retrospective analysis	65535
Oetjens MT et al (2020) [20]	Phenome-wide association study (PheWAS)	12971
Pilgram L et al (2021)[21]	Retrospective analysis	2817
Ramatillah DL et al (2023) [22]	Retrospective cohort study	378
Jonny et al (2021) [23]	Nonsystematic review	-
Roberto P et al (2020) [24]	-	-
Yang X et al (2020) [25]	Retrospective, observational study	52
Adamsick M et al (2020) [26]	RCT	1063
Koshi E et al (2021) [27]	Case study	1

Geographic Distribution of the Studies:

Results in Figure 4 showes maximum discrtpuion of studiese in Unitied States and minimum in Saudi Arabia. The distribution of studies across various countries reveals the prominence of the United States, with 752 studies, as the leading contributor in the field. The United Kingdom and China closely follow with 228 and 227 studies, respectively. Notably, Italy, Canada, and Germany also demonstrate significant contributions with 168, 117, and 100 studies, respectively. Spain, France, and Australia maintain a strong presence with 99, 88, and 79 studies, respectively. Emerging research hubs include Iran, Brazil, and India, each with 75, 72, and 65 studies, respectively. While the Netherlands and Sweden contribute significantly with 60 and 45 studies, Korea, Republic of, and Turkey show promising developments with 44 and 40 studies, respectively. Additionally, Belgium, Japan, Mexico, and Saudi Arabia display noteworthy involvement with 34, 32, 32, and 31 studies, respectively. Overall, this global distribution underscores the diverse and widespread efforts in research and academic pursuits across different countries.

Studies Key Variable Examined:

The research in Table 2 showed that CKD patients had a greater frequency and risk of hospitalization, death, infection, and poor outcomes. COVID-19 severity was associated with diabetes, osteoporosis, rheumatoid arthritis, drug misuse, schizophrenia, HTN, DM, CVD, chronic renal failure, and end-stage renal disease.

The probability of COVID-19 infection rose with age and in-center dialysis; infections were seen to cluster in certain units and shifts, and nursing staff sickness made matters worse. Patients on COVID-19 with a history of CKD were more likely to have negative outcomes, including death. With concomitant conditions such as HTN, DM, CVD, COPD, and CKD, the probability of serious complications increased in COVID-19 patients. Patients with COVID-19 who were hospitalised often reported electrolyte imbalance, AKI, and RRT as renal consequences.

Comparing male and female sex, it was found that the former was linked to a higher risk of sepsis, a lower level of oxygen saturation, and death. Death was strongly correlated with age, CKD, and a high BMI. Obesity, cardiovascular disease, diabetes, hypertension, and chronic renal illness were widespread. Male gender, advanced age, obesity, location, chronic renal disease, and prior cardiovascular disease all elevated the risk of death and mechanical ventilation.

Treatments for COVID-19 included hydroxychloroquine and remdesivir. With characteristics including age, ventilator usage, lymphopenia, blood urea nitrogen, and serum ferritin being linked to in-hospital death, CKD patients had greater mortality rates and longer hospital stays. Dialysis patients were more likely to die in the hospital and had less time before ICU admission. A nominal link between higher baseline blood creatinine concentrations and in-hospital mortality was seen in CKD patients who were not reliant on dialysis. Obesity, race, ethnicity, COPD, hypertension, and smoking did not substantially affect mortality, nor did any of the other factors mentioned above. Age, male sex, asthma, diabetes, chronic kidney disease (hypertension), and obesity were all associated with adverse outcomes that were experienced among COVID-19 positive and negative individuals. For chronic kidney disease, congestive heart failure, chronic airway obstruction, type 2 diabetes, and other clinical traits, significant relationships were discovered. Older age, greater LDH, thrombocytopenia, anemia, and raised CRP were risk factors for mortality in CKD patients with COVID-19. A significant portion of COVID-19 patients had CKD, which was associated with serum creatinine levels, GFR, and a greater mortality rate among those with septicemia and hospitalisation status.

For the very sick COVID-19 patients, corticosteroids were shown to be helpful, and individualised care was prioritised to minimise side effects and enhance outcomes. Remdesivir decreased recovery time and death in severe COVID-19 patients, but older age, ARDS, and mechanical ventilation were related to increased mortality. Patients with ESRD receiving hemodialysis have reported using favipiravir successfully.

DISCUSSION:

Based on the data regarding publications on COVID-19 infection in patients with chronic kidney disease, From 2019 to 2023, there have been a total of 3545 publications related to COVID-19 infection in patients with chronic kidney disease. The number of publications has increased significantly over time. The majority of the research papers were published in 2021, with 1263 publications. This indicates that COVID-19 and its impact on patients with chronic kidney disease became a major area of interest for researchers during that year. The research in this area seems to have gained momentum in 2020, with 798 publications, likely reflecting the early stages of the pandemic and the growing concern for vulnerable populations such as those with chronic kidney disease. In 2023, there is a notable decline in the number of publications compared to previous years. This might suggest that the initial surge of research has decreased, or that the focus of researchers has shifted to other aspects of the pandemic or other medical conditions. However, to gain deeper insights into the specific findings of these publications and to understand the prognosis and pharmacological research outcomes related to COVID-19 infection in patients with chronic kidney disease, a detailed analysis of the individual research papers is required. The data you provided gives an overview of the number of publications over time, but it does not provide specific information about the content or findings of those papers.

The meta-analysis was conducted using a Random-Effects Model. This model assumes that the true effect size may vary across studies, acknowledging the possibility of heterogeneity among the included studies.The analysis included 12 individual studies in total. The estimated between-study variance (Tau^2) in the random-effects model is not explicitly provided in the given information. The Q-statistic test for heterogeneity was conducted, with 11 degrees of freedom (df) in this case. The calculated Q-value is 329.7568, and the p-value is less than 0.0001. The p-value indicates that there is a significant heterogeneity among the included studies.

The pooled effect size estimate is 0.6663. This indicates the overall effect of COVID-19 on hospitalization and mortality in CKD patients across the 12 studies. The standard error of the estimated effect size is 0.2464. It provides a measure of uncertainty associated with the estimated effect size. The Z-value is 2.7041, which is calculated by dividing the estimate by its standard error. It is used to test the significance of the pooled effect size. The p-value associated with the Z-value is 0.0068, which is less than 0.05 (typically considered statistically significant). This indicates that the pooled effect size is statistically significant, suggesting that COVID-19 has a significant impact on CKD patients in terms of hospitalization and mortality. The 95% confidence interval provides a range within which the true effect size is likely to lie. In this case, the lower bound of the confidence interval (ci.lb) is 0.1834, and the upper bound (ci.ub) is 1.1493. The significance codes are provided to indicate the level of statistical significance. In this case, the pooled effect size is denoted by '**', indicating it is statistically significant at the 0.01 level (p < 0.01).

In summary, the meta-analysis suggests that COVID-19 has a significant effect on CKD patients, leading to increased hospitalization and mortality. The pooled estimate shows a statistically significant impact, with a 95% confidence interval ranging from 0.1834 to 1.1493. However, it's essential to interpret these results cautiously, considering the significant heterogeneity observed among the included studies.

The distribution of studies across various countries reveals the prominence of the United States, with 752 studies, as the leading contributor in the field. The United Kingdom and China closely follow with 228 and 227 studies, respectively. Notably, Italy, Canada, and Germany also demonstrate significant contributions with 168, 117, and 100 studies, respectively.

The COVID-19 virus appeared in the form of an epidemic during 2019 that resulted in more studies in 2020 and 2021. Various study designs were utilised to update knowledge about this epidemic. The studies encompass various research designs, including systematic reviews, case-control studies, meta-analyses (2), observational studies, retrospective studies, phenome-wide association studies (PheWAS), retrospective analyses, nonsystematic reviews, randomised controlled trials (RCTs), and case reports. These diverse studies, with their different sample sizes and publication years, contribute to the expanding scientific knowledge within their respective fields. 8% of patients on chronic hemodialysis had renal disease and COVID-19 together, according to one study. In 2020 research conducted in the USA, patients' odds of having COVID-19 were the same whether they had CKD or not: OR 1.00 (95% CI 0.76–1.33)²⁸. However, a different study found an OR of 0.50 (95% CI 0.39–0.65)²⁹.

Adverse occurrences in COVID-19 patients, such as ICU admissions, hospitalization, death, illness severity, and sepsis, were classified as poor outcomes. Mechanical ventilation is necessary. In other studies with identical results, acute respiratory distress syndrome (ARDS), pneumonia, and death were all linked to severe COVID-19 courses^11,12,30. Data from this systematic review also revealed that the odds ratio (OR) for adverse effects was 1.64 and as high as 5.32 in the group of CKD patients compared to the non-CKD individuals with COVID-19 infection.While it was also found in another study that COVID-19-infected CKD patients may develop AKI in the first 48 hours with an OR of 2.86(95% CI 1.73–4.73) [31]. This review showed that renal patients are considered a COVID-19 high-risk group and present with more severe disease. Moreover, depending on how severe the acute kidney injury was, the risk increased by 1.9 to 4.4times³². According to a second study from Wuhan, China, patients on COVID-19 hemodialysis died at a higher rate than COVID-19 patients who were HD-free (6 out of 37 vs. 1/193, respectively). In this patient group, they saw a considerable drop in the quantity of circulating T cells, NK cells, and inflammatory cytokines³³. This study evaluated whether COVID-19-infected CKD patients required mechanical breathing, which is consistent with prior research³⁴.

This study found that COVID-19-positive CKD patients had a higher hospitalisation and ICU admission rate. For hospitalisation of COVID-19-infected CKD, this study also noted an OR ranging from 1.38 up to 3.9, an RR of 4, and hazard ratios of 1.21 and 1.9. Moreover, hospitalisation OR was reported to increase to 11.07 (95% CI 4.54–26.97) in stage 5 CKD on dialysis. These results are similar to another study that reported that a higher probability of hospitalisation was found in COVID-19-infected CKD individuals compared to non-CKD ones, with a RR of 1.63³⁵.

In their research, it was shown that CKD patients, particularly those with late stages of renal disease, had a considerably higher risk of death. Further analysis of these data revealed a mortality OR of 1.77 (95% CI 1.54–2.02) in COVID-19-infected CKD patients compared to those without CKD. However, data from both groups of studies were of moderate and low certainty, respectively. While different research found that type 1 diabetic individuals with CKD who were infected had an HR ranging from 1.39 to 8.35, As compared to individuals without type 2 diabetes, those with CKD stages 3A–5 exhibited an HR ranging from 1.39 to 4.91³⁶.

This review revealed that there are multiple factors that are associated with the progression of COVID-19 in CKD. These factors include obesity, diabetes, hypertension, chronic kidney disease, chronic lower respiratory disease, end-stage renal disease, older age, gender, underlying illnesses like cardiovascular disease and COPD, preexisting cardiovascular disease, black race, and comorbid conditions. Chronic comorbidities, clinical phenotypes in kidney, cardiovascular, respiratory, and metabolic categories, elevated lactate dehydrogenase (LDH), thrombocytopenia, anemia, CRP, oxygen saturation, ICU admission, sepsis, and disease severity are also factors. Chronic kidney disease (CKD) and kidney failure, coupled with older age and a BMI of 35kg/m2 or above, have been linked to the advancement of numerous health disorders. These variables affect the development and results of medical conditions. Similarly, such associated factors are also found in other studies. CKD and several other comorbidities have been linked to the severe course of the COVID-19 infection. This includes hypertension, obesity, insulin resistance, and cardiovascular diseases. In addition, uremia is linked to impaired T-cell reactions, increased susceptibility to infections, and a decreased response to vaccinations. Moreover, patients requiring dialysis or kidney transplantation are more vulnerable to severe COVID-19 than other groups of patients³⁷. Another study reported that new-onset renal replacement therapy (RRT) was linked to an increased incidence of poor outcomes. (RR 18.04 [4.44, 73.25], P .001). Mortality risk, a severe COVID-19 infection, the requirement for ICU hospitalization, and the necessity for mechanical ventilation were examples of poor outcomes. Additionally, their meta-regression model discovered that age, hypertension, diabetes, and cardiovascular illnesses had a substantial impact on the association between CKD and bad outcomes. But sex, respiratory comorbidities, and RRT had no impact on the emergence of negative outcomes³⁰.

The current COVID-19 management approach has been primarily preventive and supportive. A variety of pharmaceutical agents have been used for that concern. In those individuals, the kidney clearance of some of these medications or their metabolites may raise the risk of toxicity. It is difficult for nephrology physicians to use the available pharmaceuticalagents. It requires aproper dose adjustmentaccording to the stage of kidney disease to prevent further kidney damage.The availablepharmaceutical optionsincludesystemic steroids, antiviral drugs, immunomodulators, and antibiotics. This review highlight the use of anti viral, anti biotic, anti pyretic and steroid in patients of COVID-19 with CKD with adjustment of dosage. Similary, onother study showed that corticosteroids reduce the proinflammatory cytokines inhibiting the cytokine storm that leads to rapid clinical decline and mortality³⁸.

LIMITATIONS:

The main limitation is that there is no common definition of CKD across the pooled trials, making it impossible to determine whether the illness was preexisting or acquired after the COVID-19 infection.

CONCLUSION:

1. COVID-19 is more severe in persons with CKD.

2. In COVID-19-infected CKD patients, hospitalization, ICU admission, disease severity, sepsis, mechanical ventilation, and mortality are more common. Advanced renal illness increases the risk of poor outcomes.

3. COVID-19-infected CKD patients may develop AKI within 48 hours. This shows the need for monitoring and early intervention for this population.

4. Diabetes, hypertension, obesity, cardiovascular disease, and chronic lower respiratory disease affect COVID-19 development and severity in CKD patients. Addressing these circumstances reduces risk.

5. Factors like age, gender, obesity, geographic region, preexisting cardiovascular disease, black race, and other comorbid conditions influence the progression of COVID-19 in CKD patients. Elevated markers such as lactate dehydrogenase (LDH), CRP, thrombocytopenia, anemia, and decreased oxygen saturation also contribute to disease severity.

6. In COVID-19, fresh-start RRT in CKD patients increases the risk of mortality, serious infection, ICU stay, and mechanical ventilation. RRT patients need correct management to improve outcomes.

7. Due to renal toxicity, nephrologists should use drugs with caution in COVID-19-infected CKD patients. Antivirals, antibiotics, immunomodulators, and systemic steroids need dose changes to minimise kidney injury.

8. Corticosteroids have shown promise in reducing the inflammatory response and mortality in severe COVID-19 cases. Their use may be beneficial in managing the cytokine storm and preventing rapid clinical decline in CKD patients.

CONTRIBUTION TO THE LITERATURE:

This review discusses the latest COVID-19 research on CKD patients. It examines COVID-19 infection in CKD patients' development, prognosis, contributing factors, and treatment options. This article helps identify the knowledge gap. It allows researchers to conduct further studies on better management approaches for CKD patients with COVID-19 infection to enhance evidence-based medical practise and avoid further complications in such a critical group of patients.

IMPLICATIONS:

1. Healthcare workers need to be aware of the worse outcomes and increased vulnerability of CKD patients to COVID-19. Early identification and proactive management are essential for this population.

2. CKD patients with COVID-19 should receive tailored treatment plans considering their comorbidities and disease stage. Proper dose adjustment of medications is necessary to prevent kidney toxicity and optimise treatment effectiveness.

3. It's essential to closely monitor COVID-19-infected CKD patients, particularly during the first 48 hours, so that AKI may be quickly identified and treated. Monitoring of pertinent indicators, such as LDH, CRP, and oxygen saturation, may provide information on the severity of a condition.

4. Public health efforts should focus on preventing and controlling COVID-19 among high-risk populations, including CKD patients. Vaccination campaigns and adherence to preventive measures become even more important in this context.

5. More investigation is required to comprehend the intricate interactions between CKD and COVID-19, find new risk factors, and investigate possible treatment strategies to enhance outcomes in this at-risk group.

RECOMMENDATIONS:

1. Regular screening of CKD patients for COVID-19 and close monitoring of their clinical condition are essential. Early detection and intervention can help prevent severe outcomes.

2. CKD patients should be prioritised for COVID-19 vaccination due to their increased vulnerability. Vaccination can potentially reduce the risk of severe illness and mortality.

3. A collaborative approach involving nephrologists, infectious disease specialists, and other healthcare professionals is crucial in managing COVID-19 in CKD patients. This ensures comprehensive care and optimised treatment strategies.

4. Healthcare providers should consider individual patient factors, including CKD stage, comorbidities, and medication profiles, when determining treatment options. Proper dose adjustments are necessary to avoid toxicity and optimise therapeutic efficacy.

5. Public health initiatives should concentrate on spreading knowledge of the elevated risk of serious outcomes in CKD patients and encouraging preventative practises such mask use, social seclusion, and hand cleanliness.

6. More study is needed to determine the association between CKD and COVID-19, find effective treatments, and find prevention strategies for this high-risk population.

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Received on 07.01.2024 Modified on 20.03.2024

Research J. Pharm. and Tech 2024; 17(7):3098-3108.

DOI: 10.52711/0974-360X.2024.00485

Author	Prognosis	Associated Factors For Progression
Jdiaa SS et al (2022) [8]	Hospitalization, mortality, and disease severity	No explicit assessment of associated factors
Ji W et al (2020) [9]	Disease Severity	Chronic lower respiratory illness, diabetes, hypertension, chronic renal failure, and end-stage renal disease
Corbett RW et al (2020) [10]	19.6% developed COVID-19 infection	Older age
Xiao W et al (2021) [11]	Hospitalization, mortality, and disease severity	Age, gender, and underlying diseases
Nandy K et al (2020) [12]	Higher risk of serious events. Hospitalization, mortality, and disease severity	Hypertension, diabetes mellitus, cardiovascular diseases, and COPD
Kunutsor SK et al (2020) [13]	Chronic kidney disease (CKD) was present in 5.2% of cases (2.8–8.1).	Not specified
Rapp JL et al (2021) [14]	Mortality, sepsis, and admission	Older age, CKD, and BMI of 35 kg/m2
Fried MW et al (2021) [15]	Sepsis, admission, ventilation, and mortality	Male sex, older age, obesity, geographic region, chronic kidney disease, preexisting cardiovascular disease
Ng JH et al (2020) [16]	Hospital death	older age, black race, comorbid conditions
Flythe JE et al (2021) [17]	Increased risk of hospitalisation and dialysis	CKD and kidney failure
Ioannou GN et al (2020) [18]	Hospitalization, mechanical ventilation, and mortality	Chronic Comorbidities
Martos-Benítez FD et al (2021) [19]	Sepsis, admission, ventilation, and mortality	Age, gender, when symptoms first appeared before seeing a doctor, and chronic comorbidities
Oetjens MT et al (2020) [20]	Increased risk of hospitalization	Clinical phenotypes in kidney, cardiovascular, respiratory, and metabolic categories
Pilgram L et al (2021)[21]	Mortality (32.9%) compared to non-CKD patients (14.8%)	Higher age, markedly elevated lactate dehydrogenase (LDH), thrombocytopenia, anemia, and elevated C-reactive protein (CRP)
Ramatillah DL et al (2023) [22]	Low survival rate	Oxygen saturation, ICU admission, sepsis
Jonny et al (2021) [23]	Hospitalization and mortality	Comorbidities
Roberto P et al (2020) [24]	Increased risk of hospitalization	Age and disease severity
Yang X et al (2020) [25]	Sepsis, admission, and mortality	Comorbidities
Adamsick M et al (2020) [26]	Mortality, sepsis, and admission	Older age andCKD
Koshi E et al (2021) [27]	-	-

Author	Key Variable Examined
Jdiaa SS et al (2022) [8]	Higher prevalence, risk of hospitalization, mortality, infection, and poor outcomes in CKD patients.
Ji W et al (2020) [9]	COVID-19 has been linked to end-stage renal disease, diabetes, osteoporosis, rheumatoid arthritis, drug use, schizophrenia, hypertension, and chronic lower respiratory illnesses.
Corbett RW et al (2020) [10]	The incidence of COVID-19 infection was shown to rise with age and with in-center dialysis; infections were found to cluster in certain units and shifts; and nursing staff sickness exacerbated service demands.
Xiao W et al (2021) [11]	Patients participating in COVID-19 who had a history of CKD were more likely to have negative outcomes, including death.
Nandy K et al (2020) [12]	The presence of comorbidities (HTN, DM, CVD, COPD, and CKD) increases the risk of serious events in COVID-19 patients.
Kunutsor SK et al (2020) [13]	Electrolyte disturbance, AKI, and RRT are common renal problems among COVID-19 hospitalised patients that have been recorded.
Rapp JL et al (2021) [14]	Males had a higher sepsis, oxygen saturation, and death risk than females. Age, CKD, and BMI (35 kg/m2) greatly increase mortality risk.
Fried MW et al (2021) [15]	Obesity, cardiovascular disease, diabetes, hypertension, and chronic renal illness were widespread. Male gender, advanced age, obesity, location, chronic renal illness, and previous cardiovascular disease increased the risk of death and mechanical ventilation. In COVID-19 studies, remdesivir and hydroxychloroquine were used.
Ng JH et al (2020) [16]	CKD patients had higher mortality rates and longer hospital stays. In-hospital CKD deaths were associated with age, ventilator use, lymphopenia, blood urea nitrogen, and serum ferritin.
Flythe JE et al (2021) [17]	Dialysis patients had a shorter time from symptom start to ICU admission and a greater risk of in-hospital mortality than those without CKD. Non-dialysis-dependent CKD patients with greater baseline blood creatinine had a marginally increased risk of in-hospital death, but not statistically significant.
Ioannou GN et al (2020) [18]	SARS-CoV-2 patients are more likely to be hospitalized, ventilated, and die. Obesity, black race, Hispanic ethnicity, COPD, hypertension, and smoking did not affect mortality.
Martos-Benítez FD et al (2021) [19]	Age, male sex, bronchial asthma, diabetes mellitus, chronic renal disease, COPD, hypertension, and obesity were related with poor clinical outcomes in SARS-CoV-2 positive and negative patients.
Oetjens MT et al (2020) [20]	Significant associations with CKD, congestive heart failure, chronic airway obstruction, type 2 diabetes, and other clinical phenotypes
Pilgram L et al (2021)[21]	Higher age (>85 years), elevated LDH, thrombocytopenia, anemia, and elevated CRP were predictive factors for mortality in CKD patients with COVID-19.
Ramatillah DL et al (2023) [22]	75.7% of COVID-19 patients had CKD, and sepsis and hospitalisation status increased death.
Jonny et al (2021) [23]	Corticosteroids for severely sick COVID-19 patients are noteworthy discoveries.
Roberto P et al (2020) [24]	Tailored management is crucial to reduce side effects and improve clinical outcomes.
Yang X et al (2020) [25]	Older age, ARDS, and mechanical ventilation were associated with higher mortality.
Adamsick M et al (2020) [26]	Remdesivir decreased median recovery time and death in severe COVID-19 patients in comparison to placebo.
Koshi E et al (2021) [27]	ESRD hemodialysis patients use favipiravir successfully.

Author	Outcome of COVID-19 with CKD
Jdiaa SS et al (2022) [8]	Prevalence (0.4–49.0%). The pooled results from primary studies for mortality in CKD and COVID-19 patients indicated an HR of 1.48 (95% CI 1.33–1.65) (moderate confidence), an OR of 1.77 (95% CI 1.54–2.02) (moderate certainty), and an RR of 1.6 (95% CI 0.88–2.92) (low certainty).
Ji W et al (2020) [9]	13.0% of COVID-19 cases were severe.
Corbett RW et al (2020) [10]	79.7% of patients with COVID-19 survived, and 17.0% remained hospitalized.
Xiao W et al (2021) [11]	Increased risk of hospitalization
Nandy K et al (2020) [12]	ICU hospitalization, ARDS, pneumonitis, mechanical ventilation, and mortality among COVID-19 patients
Kunutsor SK et al (2020) [13]	Electrolyte disruption (e.g., hyperkalemia): 12.5% (10.1–15.0), acute kidney injury (AKI): 11.0% (7.4–15.1), and renal replacement therapy: 6.8% (1.0–17.0) during 2–28 days.
Rapp JL et al (2021) [14]	Mortality rate: 29.3% (males: 29.8%, females: 28.6%)
Fried MW et al (2021) [15]	Hospitalization, need for oxygen supplementation, mechanical ventilation, ICU level of care, mortality
Ng JH et al (2020) [16]	Higher in-hospital death rate in CKD patients
Flythe JE et al (2021) [17]	Respiratory failure, shock, ventricular arrhythmia or cardiac arrest, thromboembolic events, significant bleeding, and severe liver injury are subsequent complications of in-hospital death.
Ioannou GN et al (2020) [18]	Death, hospitalization, and mechanical ventilation in SARS-CoV-2 patients
Martos-Benítez FD et al (2021) [19]	Admission to a hospital, pneumonia, admission to an intensive care unit (ICU), endotracheal intubation, and death
Oetjens MT et al (2020) [20]	Hospitalization, ICU admission, ventilation, and death
Pilgram L et al (2021)[21]	32.9% mortality rate among CKD patients
Ramatillah DL et al (2023) [22]	66.5% fatalities
Jonny et al (2021) [23]	-
Roberto P et al (2020) [24]	-
Yang X et al (2020) [25]	Patients with SARS-CoV-2 pneumonia who are seriously ill had a 28-day death rate of 61.5%.
Adamsick M et al (2020) [26]	Remdesivir decreased overall mortality and the median time to recovery for hospitalised COVID-19 patients.
Koshi E et al (2021) [27]	Gradual recovery was observed. No major adverse events