Is low level of serum phosphorus within normal range a predictive parameter for disease severity in hospitalized COVID-19 patients?

Background: Patients with COVID-19 may develop several electrolyte imbalances that can cause multiple clinical complications. Muscle ATP synthesis decrease due to low serum phosphorous levels may also cause respiratory muscle weakness. We investigated the predictive power of serum phosphorus levels in patients with hospitalized COVID-19. Material and Methods: Our retrospective and observational study was carried out for 957 patients who suffered from SARS-CoV-2 diagnosed by real-time PCR testing and hospitalized due to moderate or severe pneumonia due to COVID-19. Results: Among 957 patients with COVID-19 pneumonia, 387 (40,4%) were moderate and 570 (59,6%) were severe. Although they were within the reference range, the phosphorus levels were significantly lower in severe patients. Our final analysis showed that age, respiratory rate, d-dimer, and phosphorus level were independent risk factors for disease severity. Phosphorus level was found to have a negative correlation with respiratory rate (r: 0,091, p=0,005) and positive with SPO2 (r: 0,069, p=0,03). Conclusion: Our results suggest that phosphorus level has a prognostic significance due to its correlation with the respiratory rate and must be considered to be an independent risk factor for the patient status, especially in severe cases. It is concluded that phosphorus monitoring, at least in severe patients, may prevent serious clinical consequences such as respiratory insufficiency.

Anahtar Kelimeler:

COVID-19 pneumonia, phosphorus, respiratory muscle, disease status

Is low level of serum phosphorus within normal range a predictive parameter for disease severity in hospitalized COVID-19 patients?

Background: Patients with COVID-19 may develop several electrolyte imbalances that can cause multiple clinical complications. Low serum phosphorous level usually leads to a decreased muscle ATP synthesis which may cause diaphragmatic or other kinds of respiratory muscle weakness. We investigated the predictive power of serum phosphorus levels in patients with hospitalized COVID-19. Material and Methods: This is a retrospective and observational study of 957 patients with SARS-CoV-2, who were diagnosed with COVID-19 by real-time PCR testing and hospitalized due to moderate and severe COVID-19 pneumonia. Results: Among 957 patients with COVID-19 pneumonia, 387 (40,4%) were moderate and 570 (59,6%) were severe. Phosphorus was significantly lower in severe patients, within the reference range. Our final analysis showed that age, respiratory rate, d-dimer, and phosphorus level were independent risk factors for disease severity. Phosphorus was found to be negative correlated with respiratory rate (r: 0,091, p=0,005) and was positive correlated with SPO2 (r: 0,069, p=0,03). Conclusion: Our results suggest prognostic significance of phosphorus level, which has correlation with the respiratory rate and has considered to be independent risk factor for disease status, especially in severe patients. It is concluded that phosphorus monitoring, at least in severe patients, may prevent serious clinical consequences such as respiratory insufficiency. Keyword; COVID-19, pneumonia, phosphorus, respiratory muscle, disease status, predictive value

Keywords:

COVID-19, pneumonia phosphorus, respiratory muscle, disease status, predictive value,

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1. Campos-Obando N, Lahousse L, Brusselle G, Stricker BH, Hofman A, Franco OH et al. Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men. Eur J Epidemiol. 2018;33(9):859–71.
2. Rajeev Goyal, Ishwarlal Jialal. Hyperphosphatemia.: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. 2020 Nov 21. Bookshelf ID: NBK551586
3. Berger G, Guetta J, Klorin G, Badarneh R, Braun E, Brod V et al. Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2011;301(1):L23–30.
4. Zhao Y, Li Z, Shi Y, Cao G, Meng F, Zhu W et al. Effect of hypophosphatemia on the withdrawal of mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease. Biomedical Reports. 2016;4(4):413–6.
5. Pesta DH, Tsirigotis DN, Befroy DE, Caballero D, Jurczak MJ, Rahimi Y et al. Hypophosphatemia promotes lower rates of muscle ATP synthesis. FASEB j. 2016;30(10):3378–87.
6. Aubier M, Murciano D, Lecocguic Y, Viires N, Jacquens Y, Squara P et al. Effect of Hypophosphatemia on Diaphragmatic Contractility in Patients with Acute Respiratory Failure. N Engl J Med. 1985;313(7):420–4.
7. Padelli M, Leven C, Sakka M, Plée-Gautier E, Carré J-L. Causes, conséquences et traitement de l’hypophosphorémie : une revue systématique de la littérature. La Presse Médicale. 2017;46(11):987–99.
8. Gravelyn TR, Brophy N, Siegert C, Peters-Golden M. Hypophosphatemia-associated respiratory muscle weakness in a general inpatient population. The American Journal of Medicine. 1988;84(5):870–6.
9. Agusti AGN, Torres A, Estopa R, Agustividal A. Hypophosphatemia as a cause of failed weaning: The importance of metabolic factors. Critical Care Medicine. 1984;12(2):142–3.
10. Lichtman MA. Reduced Red Cell Glycolysis, 2,3-Diphosphoglycerate and Adenosine Triphosphate Concentration, and Increased Hemoglobin-Oxygen Affinity Caused by Hypophosphatemia. Ann Intern Med. 1971;74(4):562.
11. Larsen VH, Waldau T, Gravesen H, Siggaard-Andersen O. Erythrocyte 2,3-diphosphoglycerate depletion associated with hypophosphatemia detected by routine arterial blood gas analysis. Scandinavian Journal of Clinical and Laboratory Investigation. 1996;56(sup224):83–7.
12. Sankaran RT, Mattana J, Pollack S, Bhat P, Ahuja T, Patel A et al. Laboratory abnormalities in patients with bacterial pneumonia. Chest. 1997;111(3):595–600.
13. Fisher J, Magid N, Kallman C, Fanucchi M, Klein L, McCarthy D et al. Respiratory Illness and Hypophosphatemia. Chest. 1983;83(3):504–8.
14. Newman JH, Neff TA, Ziporin P. Acute respiratory failure associated with hypophosphatemia. N Engl J Med. 1977;296(19):1101–3.
15. Saldías Peñafiel F, O’Brien Solar A, Gederlini Gollerino A, Farías Gontupil G, Díaz Fuenzalida A. [Community-acquired pneumonia requiring hospitalization in immunocompetent elderly patients: clinical features, prognostic factors and treatment]. Arch Bronconeumol. 2003;39(8):333–40.
16. Pei-Fang Wei. Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). Chin Med J (Engl). 2020;133(9):1087-1095.
17. Yang R, Li X, Liu H, Zhen Y, Zhang X, Xiong Q et al. Chest CT Severity Score: An Imaging Tool for Assessing Severe COVID-19. Radiol Cardiothorac Imaging. 2020;2(2):e200047.
18. Republic of Turkey Ministry of Health. Covid-19 (SARS-CoV-2 Infection) Guide. Available @:covid-19rehberieriskinhastatedavisipdf.pdf (saglik.gov.tr), (Accessed 20/07/2020.)
19. Betro MG, Pain RW. Hypophosphataemia and hyperphosphataemia in a hospital population. Br Med J. 1972;1(5795):273–6.
20. Hodkinson HM. Serum inorganic phosphate in a geriatric in-patient population. Gerontol Clin (Basel). 1973;15(1):45–9.
21. Ryback RS, Eckardt MJ, Pautler CP. Clinical relationships between serum phosphorus and other blood chemistry values in alcoholics. Arch Intern Med. 1980;140(5):673–7.
22. Wang L, Xiao C, Chen L, Zhang X, Kou Q. Impact of hypophosphatemia on outcome of patients in intensive care unit: a retrospective cohort study. BMC Anesthesiol. 2019;19(1):86.
23. Craddock PR, Yawata Y, VanSanten L, Gilberstadt S, Silvis S, Jacob HS. Acquired phagocyte dysfunction. A complication of the hypophosphatemia of parenteral hyperalimentation. N Engl J Med. 1974;290(25):1403–7.
24. Camp MA, Allon M. Severe hypophosphatemia in hospitalized patients. Miner Electrolyte Metab. 1990;16(6):365–8.
25. Patel U, Sriram K. Acute respiratory failure due to refeeding syndrome and hypophosphatemia induced by hypocaloric enteral nutrition. Nutrition. 2009;25(3):364–7.
26. Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore). 2000;79(1):1–8.
27. Heames RM, Cope RA. Hypophosphataemia causing profound cardiac failure after cardiac surgery. Anaesthesia. 2006;61(12):1211–3.
28. Osuka A, Matsuoka T, Idoguchi K. Is this the worst outcome of metabolic syndrome? Hypophosphatemia and resulting cardiac arrest during the treatment of diabetic ketoacidosis with hypertriglyceridemia. Intern Med. 2009;48(16):1391–5.
29. Lin K-K, Lee J-J, Chen H-C. Severe refeeding hypophosphatemia in a CAPD patient: a case report. Ren Fail. 2006;28(6):515–7.
30. Cariem AK, Lemmer ER, Adams MG, Winter TA, O’Keefe SJ. Severe hypophosphataemia in anorexia nervosa. Postgraduate Medical Journal. 1994;70(829):825–7.
31. Zazzo JF, Troché G, Ruel P, Maintenant J. High incidence of hypophosphatemia in surgical intensive care patients: efficacy of phosphorus therapy on myocardial function. Intensive Care Med. 1995;21(10):826–31.
32. O’Connor LR, Wheeler WS, Bethune JE. Effect of Hypophosphatemia on Myocardial Performance in Man. N Engl J Med. 1977;297(17):901–3.
33. Schwartz A, Brotfain E, Koyfman L, Kutz R, Gruenbaum SE, Klein M et al. Association between Hypophosphatemia and Cardiac Arrhythmias in the Early Stage of Sepsis: Could Phosphorus Replacement Treatment Reduce the Incidence of Arrhythmias? Electrolyte Blood Press. 2014;12(1):19.
34. Vaidyanathan D, Venkatesan S, Ramadesikan VK. Serum phosphate in acute myocardial infarction. Indian J Physiol Pharmacol. 2000;44(2):225–8.
35. Cohen J, Kogan A, Sahar G, Lev S, Vidne B, Singer P. Hypophosphatemia following open heart surgery: incidence and consequences. Eur J Cardiothorac Surg. 2004;26(2):306–10.
36. Ambühl PM, Meier D, Wolf B, Dydak U, Boesiger P, Binswanger U. Metabolic aspects of phosphate replacement therapy for hypophosphatemia after renal transplantation: Impact on muscular phosphate content, mineral metabolism, and acid/base homeostasis. American Journal of Kidney Diseases. 1999;34(5):875–83.
37. Shor R, Halabe A, Rishver S, Tilis Y, Matas Z, Fux A et al. Severe hypophosphatemia in sepsis as a mortality predictor. Ann Clin Lab Sci. 2006;36(1):67–72.
38. Chung P. Serum phosphorus levels predict clinical outcome in fulminant hepatic failure. Liver Transplantation. 2003;9(3):248–53.
39. Hoffmann M, Zemlin AE, Meyer WP, Erasmus RT. Hypophosphataemia at a large academic hospital in South Africa. J Clin Pathol. 2008;61(10):1104–7.
40. Zhong C, You S, Chen J, Zhai G, Du H, Luo Y et al. Serum Alkaline Phosphatase, Phosphate, and In-Hospital Mortality in Acute Ischemic Stroke Patients. J Stroke Cerebrovasc Dis. 2018;27(1):257–66.
41. Barash Y, Klang E, Soffer S, Zimlichman E, Leibowitz A, Grossman E et al. Normal-range emergency department serum phosphorus levels and all-cause mortality. Postgrad Med J. 2021;97(1144):83–8.
42. Cheungpasitporn W, Thongprayoon C, Mao MA, Kittanamongkolchai W, Sakhuja A, Erickson SB. Admission serum phosphate levels predict hospital mortality. Hosp Pract (1995). 2018;46(3):121–7.
43. Yılmaz K, Şen V. Is vitamin D deficiency a risk factor for COVID‐19 in children? Pediatr Pulmonol. 2020;55(12):3595–601.
44. Juan D, Elrazak MA. Hypophosphatemia in hospitalized patients. JAMA. 1979 Jul 13;242(2):163–4.
45. Shoenfeld Y, Hager S, Berliner S, Gallant LA, Pinkhas J. Hypophosphatemia as diagnostic aid in sepsis. N Y State J Med. 1982;82(2):163–5.