SARS-CoV-2, a member of the Coronaviridae family, as Coronavirus Disease 2019 (COVID-19). It causes a highly contagious acute respiratory infection. At the end of 2019, the first cases of COVID-19 were detected in Wuhan, Hubei Province, People's Republic of China. The disease then spread rapidLy across the country and the world, eventually becoming a pandemic [1,2]. 

There is ample evidence of the acute symptoms of coronavirus disease 2019 (COVID-19) and severe COVID-19 can result in multiple organ failure and damage [3].

The primary functional receptor for SARS-CoV-2 infection is the angiotensin-converting enzyme 2. It is mostly located on the brush boundary of proximal tubular cells and podocytes in the kidneys [4]. As a result, kidneys may likewise be a significant target organ for SARS-CoV-2. According to new research, SARS-CoV-2 infection causes kidney injury both directly through virus cytotoxicity and indirectly through cytokine storm syndrome [5]. According to reports, people with COVID-19 who experience renal impairment have a 5.3-fold increased chance of dying in the hospital [6]. Thus, the need for dialysis and long-term Chronic Kidney Disease (CKD) may be reduced if AKI is identified and treated early [7].

The metabolism of nitrogen in humans produces Blood Urea Nitrogen (BUN) and Creatinine (Cr). They are readily eliminated from the nephrons due to their little size. Although creatinine is inadequately reabsorbed, renal tubules generally reabsorb approximately 30% to 40% of Blood Urea Nitrogen (BUN) [8]. Purine, which is derived from RNA and DNA, catabolically produces Uric Acid (UA). Other than medications and a high-purine diet, it is less influenced by other factors as a metabolic index. According to earlier research, UA is directly linked to immune system activation and oxygen free radical scavenging [9].

D-dimers are peptide fragments formed when plasmin degrades cross-linked fibrin. Any process involving the synthesis and degradation of fibrin, such as acute infections, surgical interventions and acute or chronic inflammatory conditions, would lead to an increase in its concentration [10]. The severity of COVID-19 was substantially correlated with elevated plasma D-dimer levels [11].

The liver produces C-reactive protein, an acute phase protein, in reaction to cytokines (such TNF-a and IL-6). In COVID-associated pneumonia, a Cytokine Response Storm (CRS) is triggered, which causes hepatocytes to generate CRP [12].

Study Design

From February to March 2022, 45 patients with confirmed COVID-19 were enrolled in this case control study at Tikrit Teaching Hospital. The present study concluded 25 males and 20 females from 30 to 75 years. Patients with a history of kidney disease were excluded from the study. In addition, control groups that included 15 individuals.

Sample Collection

All individuals, including patient and controls, had their venous blood samples taken. The blood was drawn into a tube using a standard technique called antecubital venipuncture. The 5 mL of remaining blood was transferred to an EDTA-free tube and left to coagulate in a water bath set at 37°C. Centrifugation was then used to separate the serum from the blood samples; after 10 minutes at 3000 rpm, the serum was separated into two tubes and kept at -20°C until analysis. Creatinine, Urea, Uric acid, D. dimer and CRP were assessed after the samples were allowed to thaw at room temperature.

Measurement of Biochemical Parameters

A spectrophotometer was used to assess the levels of urea, creatine and uric acid after obtaining the serum analysis kit from the French company Biolabo. ELISA was used to analyze CRP and D. dimer.

Statistical Analysis

The Minitab software was used to analyze the data using the ANOVA test. Using the Duncan multiple range test with a significance level of 0.05, the mean was found to be statistically significant.

Table 1 showed the impact of infection with Covid-19 on level of Creatinine, Urea, Uric acid, D. dimer and CRP. Level of Creatinine, Urea, Uric acid, D. dimer and CRP were significantly increased in Covid-19 patients that were (2.70±1.250mg/dL, 83.1±6.91mg/dL, 5.910±1.470mg/dL, 828±90.2, 65.30±14.22) compared to control (0.474±0.229, 31.50±3.65, 5.100±0.17, 322±78.1, 6.760±0.796) respectively. The difference was statistically significant (p<0.05).

Table 1: Level of Biochemical Test in COVID -19 Patients and Control

According to gender, the present study showed significant increase in the level of Creatinine, Urea and D. dimer in male according to sex, at p-value<0.05. As shown in Table 2. While no significant differences were showed in the level of uric acid and CRP at p-value>0.05.

Table 2: Level of Biochemical Test in in COVID -19 Patients According Sex

The participant divided into three age groups as G1 (Age groups 30-45), G2 (Age groups 46-60), G3 (Age groups 61-75). Non-significant differences (p-value>0.05) in the level of Creatinine, Uric acid and CRP between age groups (p-value>0.05). Urea level increased in group G3 and decrease in age group G1 and G2, at (p-value<0.05). While D. dimer increased in G2 and decreased in G1and G3, at (p-value<0.05). As shown in Table 3.

Table 3: Level of Biochemical Test in in COVID -19 Patients According Age

Renal failure from acute tubular necrosis brought on by hydration, sepsis, storm syndrome, rhabdomyolysis, cytokines and hypoxia are just a few of the effects that COVID-19 infection may have on the kidneys. Viruses may directly infiltrate the glomerulus or renal tubular cells now that the direct cytopathic action of viruses on some renal cells has been established. According to earlier research, the angiotensin-converting enzyme II receptors, which are found in large numbers in kidney cells, can mediate the entry of coronavirus into cells [13]. One prevalent finding in coronavirus patients has been recognized as renal dysfunction [14]. According to a study by Li et al. [15] on the renal function of 59 COVID-19 patients, 27% of the patients had high urea nitrogen levels, 19% of the patients had raised serum creatinine levels and 63% of the patients had proteinuria.

The present study demonstrated increase creatinine, blood urea and uric acid in covid patients, this result agree with [16], that showed increase urea and creatinine.

One indicator of renal function is creatinine. Patients with raised baseline serum creatinine levels had a significantly greater risk of acute renal injury and death during hospitalization compared to patients with normal baseline values, according to a prospective cohort study involving 701 COVID-19 patients [17]. Renal cell necrosis is thought to result from the virus's hematogenous propagation and accumulation in the kidney [17]. 
 

Hypouricemia in SARS-CoV-infected individuals is not uncommon, according to Wu et al. and it may indicate the severity of the illness and portend negative patient outcomes [9]. Serum indicators like D-dimer that are closely linked to the severity of COVID-19 patients have been the subject of several recent research [18–20]. D-dimer had the highest specificity and sensitivity for its early prediction when paired with IL-6 detection and it was found to be strongly correlated with the severity of COVID-19 patients [21].

Elevated CRP levels in patients with severe COVID-19 may be associated with an excess of inflammatory cytokines. Although cytokines combat microorganisms, an overactive immune system can harm lung tissue. CRP is therefore produced in COVID-19 individuals as a result of tissue damage and inflammatory cytokines [22].

The present study showed increase level of urea, creatinine and D-dimer in male as compared with female. This result agrees with [23] that showed increase urea and creatinine in male infected with covid as compared with female, while non-significant differences in level of CRP. A study done by [24] demonstrated no significant differences in level of these parameters according to sex.

The present study showed increase level of urea in older age, this elevation may be due to renal function strongly related to age. This result agrees with [25] that showed increase level of urea in older age in patients with covid-19.

This study showed increase level of D-dimer in group G3, this result may be d-dimer more related to severity and stage of infection rather than age. Infections correlated with higher D-dimer levels, reflecting a significant impact of the virus on coagulation pathways. Notably, age and gender demonstrated influential roles in infection rates and D-dimer elevation [26].

Elevated serum urea and creatinine levels are reliable indicators of renal involvement in COVID- 19. Early detection through routine testing can help prevent irreversible kidney damage and improve patient prognosis.

SARS-CoV-2, a member of the Coronaviridae family, as Coronavirus Disease 2019 (COVID-19). It causes a highly contagious acute respiratory infection. At the end of 2019, the first cases of COVID-19 were detected in Wuhan, Hubei Province, People's Republic of China. The disease then spread rapidLy across the country and the world, eventually becoming a pandemic [1,2]. 

There is ample evidence of the acute symptoms of coronavirus disease 2019 (COVID-19) and severe COVID-19 can result in multiple organ failure and damage [3].

The primary functional receptor for SARS-CoV-2 infection is the angiotensin-converting enzyme 2. It is mostly located on the brush boundary of proximal tubular cells and podocytes in the kidneys [4]. As a result, kidneys may likewise be a significant target organ for SARS-CoV-2. According to new research, SARS-CoV-2 infection causes kidney injury both directly through virus cytotoxicity and indirectly through cytokine storm syndrome [5]. According to reports, people with COVID-19 who experience renal impairment have a 5.3-fold increased chance of dying in the hospital [6]. Thus, the need for dialysis and long-term Chronic Kidney Disease (CKD) may be reduced if AKI is identified and treated early [7].

The metabolism of nitrogen in humans produces Blood Urea Nitrogen (BUN) and Creatinine (Cr). They are readily eliminated from the nephrons due to their little size. Although creatinine is inadequately reabsorbed, renal tubules generally reabsorb approximately 30% to 40% of Blood Urea Nitrogen (BUN) [8]. Purine, which is derived from RNA and DNA, catabolically produces Uric Acid (UA). Other than medications and a high-purine diet, it is less influenced by other factors as a metabolic index. According to earlier research, UA is directly linked to immune system activation and oxygen free radical scavenging [9].

D-dimers are peptide fragments formed when plasmin degrades cross-linked fibrin. Any process involving the synthesis and degradation of fibrin, such as acute infections, surgical interventions and acute or chronic inflammatory conditions, would lead to an increase in its concentration [10]. The severity of COVID-19 was substantially correlated with elevated plasma D-dimer levels [11].

The liver produces C-reactive protein, an acute phase protein, in reaction to cytokines (such TNF-a and IL-6). In COVID-associated pneumonia, a Cytokine Response Storm (CRS) is triggered, which causes hepatocytes to generate CRP [12].

Study Design

From February to March 2022, 45 patients with confirmed COVID-19 were enrolled in this case control study at Tikrit Teaching Hospital. The present study concluded 25 males and 20 females from 30 to 75 years. Patients with a history of kidney disease were excluded from the study. In addition, control groups that included 15 individuals.

Sample Collection

All individuals, including patient and controls, had their venous blood samples taken. The blood was drawn into a tube using a standard technique called antecubital venipuncture. The 5 mL of remaining blood was transferred to an EDTA-free tube and left to coagulate in a water bath set at 37°C. Centrifugation was then used to separate the serum from the blood samples; after 10 minutes at 3000 rpm, the serum was separated into two tubes and kept at -20°C until analysis. Creatinine, Urea, Uric acid, D. dimer and CRP were assessed after the samples were allowed to thaw at room temperature.

Measurement of Biochemical Parameters

A spectrophotometer was used to assess the levels of urea, creatine and uric acid after obtaining the serum analysis kit from the French company Biolabo. ELISA was used to analyze CRP and D. dimer.

Statistical Analysis

The Minitab software was used to analyze the data using the ANOVA test. Using the Duncan multiple range test with a significance level of 0.05, the mean was found to be statistically significant.

Table 1 showed the impact of infection with Covid-19 on level of Creatinine, Urea, Uric acid, D. dimer and CRP. Level of Creatinine, Urea, Uric acid, D. dimer and CRP were significantly increased in Covid-19 patients that were (2.70±1.250mg/dL, 83.1±6.91mg/dL, 5.910±1.470mg/dL, 828±90.2, 65.30±14.22) compared to control (0.474±0.229, 31.50±3.65, 5.100±0.17, 322±78.1, 6.760±0.796) respectively. The difference was statistically significant (p<0.05).

Table 1: Level of Biochemical Test in COVID -19 Patients and Control

According to gender, the present study showed significant increase in the level of Creatinine, Urea and D. dimer in male according to sex, at p-value<0.05. As shown in Table 2. While no significant differences were showed in the level of uric acid and CRP at p-value>0.05.

Table 2: Level of Biochemical Test in in COVID -19 Patients According Sex

The participant divided into three age groups as G1 (Age groups 30-45), G2 (Age groups 46-60), G3 (Age groups 61-75). Non-significant differences (p-value>0.05) in the level of Creatinine, Uric acid and CRP between age groups (p-value>0.05). Urea level increased in group G3 and decrease in age group G1 and G2, at (p-value<0.05). While D. dimer increased in G2 and decreased in G1and G3, at (p-value<0.05). As shown in Table 3.

Table 3: Level of Biochemical Test in in COVID -19 Patients According Age

Renal failure from acute tubular necrosis brought on by hydration, sepsis, storm syndrome, rhabdomyolysis, cytokines and hypoxia are just a few of the effects that COVID-19 infection may have on the kidneys. Viruses may directly infiltrate the glomerulus or renal tubular cells now that the direct cytopathic action of viruses on some renal cells has been established. According to earlier research, the angiotensin-converting enzyme II receptors, which are found in large numbers in kidney cells, can mediate the entry of coronavirus into cells [13]. One prevalent finding in coronavirus patients has been recognized as renal dysfunction [14]. According to a study by Li et al. [15] on the renal function of 59 COVID-19 patients, 27% of the patients had high urea nitrogen levels, 19% of the patients had raised serum creatinine levels and 63% of the patients had proteinuria.

The present study demonstrated increase creatinine, blood urea and uric acid in covid patients, this result agree with [16], that showed increase urea and creatinine.

One indicator of renal function is creatinine. Patients with raised baseline serum creatinine levels had a significantly greater risk of acute renal injury and death during hospitalization compared to patients with normal baseline values, according to a prospective cohort study involving 701 COVID-19 patients [17]. Renal cell necrosis is thought to result from the virus's hematogenous propagation and accumulation in the kidney [17]. 
 

Hypouricemia in SARS-CoV-infected individuals is not uncommon, according to Wu et al. and it may indicate the severity of the illness and portend negative patient outcomes [9]. Serum indicators like D-dimer that are closely linked to the severity of COVID-19 patients have been the subject of several recent research [18–20]. D-dimer had the highest specificity and sensitivity for its early prediction when paired with IL-6 detection and it was found to be strongly correlated with the severity of COVID-19 patients [21].

Elevated CRP levels in patients with severe COVID-19 may be associated with an excess of inflammatory cytokines. Although cytokines combat microorganisms, an overactive immune system can harm lung tissue. CRP is therefore produced in COVID-19 individuals as a result of tissue damage and inflammatory cytokines [22].

The present study showed increase level of urea, creatinine and D-dimer in male as compared with female. This result agrees with [23] that showed increase urea and creatinine in male infected with covid as compared with female, while non-significant differences in level of CRP. A study done by [24] demonstrated no significant differences in level of these parameters according to sex.

The present study showed increase level of urea in older age, this elevation may be due to renal function strongly related to age. This result agrees with [25] that showed increase level of urea in older age in patients with covid-19.

This study showed increase level of D-dimer in group G3, this result may be d-dimer more related to severity and stage of infection rather than age. Infections correlated with higher D-dimer levels, reflecting a significant impact of the virus on coagulation pathways. Notably, age and gender demonstrated influential roles in infection rates and D-dimer elevation [26].

Elevated serum urea and creatinine levels are reliable indicators of renal involvement in COVID- 19. Early detection through routine testing can help prevent irreversible kidney damage and improve patient prognosis.

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3. Panimathi, R. et al. “Impact of COVID-19 on renal function: A multivariate analysis of biochemical and immunological markers in patients.” Cureus, vol. 14, no. 2, 2022.

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5. Ok, F. et al. “Predictive values of blood urea nitrogen/creatinine ratio and other routine blood parameters on disease severity and survival of COVID-19 patients.” Journal of Medical Virology, vol. 93, no. 2, 2021, pp. 786–793.

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13. Valizadeh, R. et al. “Coronavirus-nephropathy; renal involvement in COVID-19.” Journal of Renal Injury Prevention, vol. 9, no. 2, 2020, article e18, https://doi.org/10.34172/jrip.2020.18.

14. Shalal, O.S. et al. “The value of some biochemical parameters in the prediction of kidney severity in COVID-19 Patients.” Al-Nisour Journal for Medical Sciences, vol. 4, no. 2, 2022, pp. 78–88.

15. Li, Z. et al. “Caution on kidney dysfunctions of 2019-nCoV Patients.” medRxiv, 2020, https://doi.org/10.1101/2020.02.08.20021212.

16. Malik, P. et al. “Biomarkers and outcomes of COVID-19 hospitalisations: Systematic review and meta-analysis.” BMJ Evidence-Based Medicine, vol. 26, no. 3, 2021, pp. 107–108.

17. Cheng, Y. et al. “Kidney disease is associated with in-hospital death of patients with covid-19.” Kidney International, vol. 97, 2020, pp. 829–838.

18. Chen, X. et al. “Detectable serum sars-cov-2 viral load (RNAaemia) Is closely associated with drastically elevated interleukin-6 (IL-6) level in critically ill covid-19 patients.” medRxiv, March 2020, https://doi.org/10.1101/2020.02.29.20029520.

19. Lippi, G. et al. “Thrombocytopenia Is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis.” Clinica Chimica Acta, vol. 506, 2020, pp. 145–148, https://doi.org/10.1016/j.cca.2020.03.022.

20. Liu, J. et al. “Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage.” medRxiv, February 2020, https://doi.org/10.1101/2020.02.10.20021584.

21. Gungor, B. et al. “Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in covid-19: A systematic review and meta-analysis.” The American Journal of Emergency Medicine, vol. 39, 2021, pp. 173–179.

22. Alobaidy, M.A.A. and S.A. Zbaar. “Evaluation the role of CRP, D-dimer and osteopontin as biomarkers in assessing the severity of covid-19 patients with pre-existing diabetes.” International Journal of Health Sciences, vol. 6, suppl. S4, 2022, pp. 9698–9707.

23. Smail, S.W. et al. “Deciphering gender disparities in laboratory biomarkers among deceased covid-19 patients in Erbil city–Iraq: A retrospective study.” Immunopathologia Persa, vol. 11, no. 1, 2024, pp. e40636–e40636.

24. Abbas, H.D. and A.H. Kudhair. “The effect of covid-19 infection on the incidence of renal abnormality for patients admitted to the communicable disease unit at al-hakeem hospital.” 2023, pp. 907.

25. Žulpaitė, G. et al. “The association between covid-19 infection and kidney damage in a regional university hospital.” Medicina, vol. 59, no. 5, 2023, pp. 898.

26. Omar, A.H. and A.O. Rasool. “D-dimer level variation in hospitalized covid-19 patients.” Qalaai Zanist Scientific Journal, vol. 10, no. 1, 2025, pp. 1154–1168.‏