Bilirubin Levels as Potential Indicators of Disease Severity in Coronavirus Disease Patients: A Retrospective Cohort Study

Liu, Zeming; Li, Jinpeng; Long, Wei; Zeng, Wen; Gao, Rongfen; Zeng, Guang; Chen, Danyang; Wang, Shipei; Li, Qianqian; Hu, Di; Guo, Liang; Li, Zhengwei; Wu, Xiaohui

doi:10.3389/fmed.2020.598870

Cited by 35 publications

(28 citation statements)

References 22 publications

(19 reference statements)

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“…Additionally, we also found that increased serum total bilirubin level was a high-risk factor for mortality in severe COVID-19 patients with diabetes with 6.359 times higher odds for mortality. This finding was in accordance with other studies [ 44 , 45 ]. Further, low PO 2 was an effective predictor of mortality in our study.…”

Section: Discussionsupporting

confidence: 94%

The sex-related discrepancy in laboratory parameters of severe COVID-19 patients with diabetes: A retrospective cohort study

Hammad

Alseoudy

2021

Primary Care Diabetes

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Aim This study aimed at providing evidence to consider sex differences in interpretations of laboratory parameters of severe COVID-19 patients with diabetes. Methods For 118 diabetic patients, laboratory measurements and clinical outcomes were compared between males and females. This study also compared inflammatory ratios obtained from combinations of six inflammatory markers between the two groups. The risk factors for mortality were identified through logistic regression. Results Males were 54 (45.8%) and females were 64 (54.2%). Males showed a significant increase in ALT (P = 0.003), CRP (P = 0.03), mean platelet volume (MPV)-to-lymphocyte ratio (P = 0.001), and C-reactive protein-to-albumin ratio (P = 0.044), whereas females had a significant increase in lymphocytes (P < 0.005) and MPV (P = 0.01). In all participants, multivariate analysis illustrated that older age, male sex, increased serum total bilirubin, and decreased PO 2 were significant independent predictors of mortality (P < 0.05). Conclusion In severe COVID-19 patients with diabetes, there were significant sex differences in many laboratory characteristics with a higher risk of mortality among males.

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Section: Discussionsupporting

confidence: 94%

The sex-related discrepancy in laboratory parameters of severe COVID-19 patients with diabetes: A retrospective cohort study

Hammad

Alseoudy

2021

Primary Care Diabetes

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“…Chai et al [20] showed that the expression of ACE-2 receptors on cholangiocytes was equivalent to that of the type II alveolar cells; however, the number is 20 times less in the hepatocytes. A study done in China by Liu et al also showed that total bilirubin (HR: 9.45, 95% confidence interval (CI): 2.21-40.47, p = 0.002), direct bilirubin levels (HR: 4.38, 95% CI: 1.78-16.29, p = 0.03), and conjugated bilirubin/unconjugated bilirubin (CB/UCB) (HR: 2.49, 95% CI: 1.32-4.71, p = 0.01) were higher in the nonsurviving group [21] signifying toward an important mechanism of acute liver injury. COVID-19 being an infection triggers the inflammatory cascade and cytokines such as IL-6, IL-17, and TH-17, leading to SIRS, ARDS, and multiorgan failure.…”

Section: Discussionmentioning

confidence: 99%

Severe COVID-19 Associated With Liver Injury in Patients Without Preexisting Liver Disease

Altaf¹,

Abbas²,

Mandviwalla³

et al. 2021

Cureus

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“…S3), this final product of haem catabolism accumulates at higher levels in vivo (22). Moreover, elevated bilirubin levels correlate with the symptoms and mortality among COVID-19 patients (23)(24)(25)(26). Therefore, the tetrapyrroles likely share a role in SARS-CoV-2 immune evasion.…”

mentioning

confidence: 99%

SARS-CoV-2 recruits a haem metabolite to evade antibody immunity

Rosa

Pye

Graham

et al. 2021

Preprint

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The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of haem metabolism, with nanomolar affinity. Using cryo-electron microscopy and X-ray crystallography we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that the virus co-opts the haem metabolite for the evasion of humoral immunity via allosteric shielding of a sensitive epitope and demonstrate the remarkable structural plasticity of the NTD.

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Bilirubin Levels as Potential Indicators of Disease Severity in Coronavirus Disease Patients: A Retrospective Cohort Study

Cited by 35 publications

References 22 publications

The sex-related discrepancy in laboratory parameters of severe COVID-19 patients with diabetes: A retrospective cohort study

The sex-related discrepancy in laboratory parameters of severe COVID-19 patients with diabetes: A retrospective cohort study

Severe COVID-19 Associated With Liver Injury in Patients Without Preexisting Liver Disease

SARS-CoV-2 recruits a haem metabolite to evade antibody immunity

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