Preview

Bulletin Physiology and Pathology of Respiration

Advanced search

Impact of correction of homocisteinemia on clinical outcomes of lung damage associated with COVID-19 coronavirus infection

https://doi.org/10.36604/1998-5029-2023-87-8-17

Abstract

Aim. To assess the effect of serum homocysteine levels on treatment outcomes in patients with COVID19-associated lung damage, depending on the use of folic acid in complex treatment.

Materials and methods. An open, prospective comparative study included 71 hospitalized adult patients with COVID-19-associated lung disease who did not require mechanical ventilation. The main group included 51 patients who received folic acid 15 mg per day in a complex treatment in a fixed combination with pyridoxine hydrochloride and cyanocobalamin. The comparison group included 20 patients in whose therapy folic acid was not used.

Results. The use of folic acid was accompanied by a decrease in serum homocysteine concentration by 2.120 (-0.230; 3.680) µmol/L (p=0.004). When constructing a logistic regression model, the effect of a decrease in serum homocysteine (OR 1.289; 95% CI 1.026‒1.620; p=0.029), methylenetetrahydrofolate reductase MTHFR C677T genotype (OR 10.897; 95% CI 1.240‒95.772; p=0.031) on the achievement of 7th day of hospitalization, the cessation of isolation of SARS-CoV-2 virus RNA from the respiratory tract. Multiple linear regression analysis showed an association between the duration of hypoxemic respiratory failure, determined with SaO2≤93%, with the degree of change in serum homocysteine concentration after treatment, single nucleotide polymorphisms of methylenetetrahydrofolate reductase MTHFR C677T, methionine synthase MTR A2756G and methionine synthase reductase MTRR A66G, initial volume of lung damage ≥50% according to CT data, indicators of D-dimers, C-reactive protein, hemoglobin, platelets, concomitant hypertension, diabetes mellitus (R=0.699; R2=0.489; p=0.005).

Conclusion. The dynamics of the decrease in serum homocysteine after treatment is an important predictor of the cessation of isolation from the respiratory tract of the SARS-CoV-2 virus RNA on the 7th day of treatment, reducing the duration of hypoxemic respiratory failure in patients with lung damage associated with COVID-19 infection.

About the Authors

I. Ya. Tseimakh
Altai State Medical University; Barnaul City Hospital No.5
Russian Federation

Irina Ya. Tseymakh - MD, PhD, DSc (Med.), Associate Professor, Head of the Department of Pulmonology and Phthisiology.

40 Lenin Ave., Barnaul, 656038; 75 Zmeinogorsky tract, Barnaul, 656045



D. E. Bogachev
Altai State Medical University; Barnaul City Hospital No.5
Russian Federation

Dmitry E. Bogachev - MD, Assistant of the Department of Pulmonology and Phthisiology.

40 Lenin Ave., Barnaul, 656038; 75 Zmeinogorsky tract, Barnaul, 656045



G. I. Kostuchenko
Altai Regional Clinical Hospital
Russian Federation

Gennady I. Kostyuchenko - MD, PhD, DSc (Med.), Professor, Head of the Department.

1 Lyapidevsky Str., Barnaul, 656045



A. N. Mamaev
Barnaul City Hospital No.5
Russian Federation

Andrey N. Mamaev - MD, PhD, DSc (Med.), Head of the Laboratory of Hemostasis.

75 Zmeinogorsky tract, Barnaul, 656045



T. A. Kornilova
Barnaul City Hospital No.5
Russian Federation

Tatyana A. Kornilova - MD, Head of the Pulmonology Department.

75 Zmeinogorsky tract, Barnaul, 656045



I. S. Shemyakina
Altai State Medical University
Russian Federation

Irina S. Shemyakina - MD, Assistant of the Department of Pulmonology and Phthisiology.

40 Lenin Ave., Barnaul, 656038



A. E. Tseimakh
Altai State Medical University
Russian Federation

Alexander E. Tseimakh - MD, PhD (Med.), Associate Professor of the Department of Faculty Surgery named after Professor I.I.Neimark.

40 Lenin Ave., Barnaul, 656038



Ya. N. Shoikhet
Altai State Medical University
Russian Federation

Yakov N. Shoikhet - MD, PhD, DSc (Med.), Professor, Corresponding member of the Russian Academy of Sciences, Head of the Department of Faculty Surgery named after Professor I.I.Neimark.

40 Lenin Ave., Barnaul, 656038



References

1. Kolosov V.P., Manakov L.G., Polyanskaya E.V., Perelman J.M. [Impact of the COVID-19 pandemic on mortality dynamics in the Far Eastern Federal District]. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration 2021; (82):8–20 (in Russian). https://doi.org/10.36604/1998-5029-2021-82-8-20

2. Fjelltveit E.B., Blomberg B., Kuwelker K., Zhou F., Onyango T.B., Brokstad K.A., Elyanow R., Kaplan I.M., Tøndel C., Mohn K.G.I., Özgümüş T., Cox R.J., Langeland N.; Bergen COVID-19 Research Group. Symptom burden and immune dynamics 6 to 18 months following mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2): a case-control study. Clin. Infect. Dis. 2023; 76(3):e60‒e70. doi: 10.1093/cid/ciac655

3. Joffre J., Rodriguez L., Matthay Z.A., Lloyd E., Fields A.T., Bainton R.J., Kurien P., Sil A., Calfee C.S., Woodruff P.G., Erle D.J., Hendrickson C., Krummel M.F., Langelier C.R., Matthay M.A., Kornblith L.Z., Hellman J.; COVID-19 Multi-Phenotyping for Effective Therapies (COMET) Consortium; COVID-19 Associated Coagulopathy, Inflammation, and Thrombosis (Co-ACIT) Study Group. COVID-19-associated lung microvascular endotheliopathy: a «from the bench» perspective. Am. J. Respir. Crit. Care Med. 2022; 206(8):961‒972. https://doi.org/10.1164/rccm.202107-1774oc

4. Cacciola R., Gentilini Cacciola E., Vecchio V., Cacciola E. Cellular and molecular mechanisms in COVID-19 coagulopathy: Role of inflammation and endotheliopathy. J. Thromb. Thrombolysis 2021; 53(2):282‒290. https://doi.org/10.1007/s11239-021-02583-4

5. Perła-Kaján J., Jakubowski H. COVID-19 and one-carbon metabolism. Int. J. Mol. Sci. 2022; 23(8):4181. https://doi.org/10.3390/ijms23084181

6. Esse R., Barroso M., Tavares de Almeida I., Castro R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art. Int. J. Mol. Sci. 2019; 20(4): 867. https://doi.org/10.3390/ijms20040867

7. Ponti G., Pastorino L., Manfredini M., Ozben T., Oliva G., Kaleci S., Iannella R., Tomasi A. COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence. J. Clin. Lab. Anal. 2021; 35(7):e23798. https://doi.org/10.1002/jcla.23798

8. Amelina I.P., Solovieva E.Y. [Oxidative stress and inflammation as links in a chain in patients with chronic cerebrovascular diseases]. Zh. Nevrol. Psikhiatr. im S.S.Korsakova 2019; 119(4):106‒114 (in Russian). https://doi.org/10.17116/jnevro2019119041106. PMID: 31156231.

9. Li T., Yu B., Liu Z., Li J., Ma M., Wang Y., Zhu M., Yin H., Wang X., Fu Y., Yu F., Wang X., Fang X., Sun J., Kong W. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury. Nat. Commun. 2018; 9(1):11. https://doi.org/10.1038/s41467-017-02401-7

10. Kostakis I., Smith G.B., Prytherch D., Meredith P., Price C., Chauhan A.; Portsmouth Academic Consortium For Investigating COVID-19 (PACIFIC-19). The performance of the National Early Warning Score and National Early Warning Score 2 in hospitalised patients infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Resuscitation 2021; 159:150‒157. https://doi.org/10.1016/j.resuscitation.2020.10.039

11. Meisel E., Efros O., Bleier J., Beit Halevi T., Segal G., Rahav G., Leibowitz A., Grossman E. Folate levels in patients hospitalized with coronavirus disease 2019. Nutrients 2021; 13(3):812. https://doi.org/10.3390/nu13030812

12. Carpene G., Negrini D., Henry Brandon M., Montagnana M., Lippi G. Homocysteine in coronavirus disease (COVID-19): a systematic literature review. Diagnosis 2022; 9(3):306‒310. https://doi.org/10.1515/dx-2022-0042

13. Keskin A., Ustun G.U., Aci R., Duran U. Homocysteine as a marker for predicting disease severity in patients with COVID-19. Biomark. Med. 2022; 16(7):559‒568. https://doi.org/10.2217/bmm-2021-0688

14. Shmeleva V.M., Papayan L.P., Saltykova N.B., Kargin V.D., Kapustin S.I., Blinov M.N., Gurzhiy A.A., Smirnova O.A., Golovina O.G. [Clinical and laboratory diagnostics and treatment of thrombophilia caused by hyperhomocysteinemia: Medical technology]. St. Petersburg: RosNIIGT FMBA; 2015 (in Russian).

15. Lorini F.L., Di Matteo M., Gritti P., Grazioli L., Benigni A., Zacchetti L., Bianchi I., Fabretti F., Longhi L. Coagulopathy and COVID-19. Eur. Heart J. Suppl. 2021; 23(Suppl.E):E95‒E98. https://doi.org/10.1093/eurheartj/suab100

16. Hayden M.R., Tyagi S.C. Impaired folate-mediated one-carbon metabolism in type 2 diabetes, late-onset Alzheimer's disease and long COVID. Medicina (Kaunas) 2021; 58(1):16. https://doi.org/10.3390/medicina58010016


Review

For citations:


Tseimakh I.Ya., Bogachev D.E., Kostuchenko G.I., Mamaev A.N., Kornilova T.A., Shemyakina I.S., Tseimakh A.E., Shoikhet Ya.N. Impact of correction of homocisteinemia on clinical outcomes of lung damage associated with COVID-19 coronavirus infection. Bulletin Physiology and Pathology of Respiration. 2023;(87):8-17. (In Russ.) https://doi.org/10.36604/1998-5029-2023-87-8-17

Views: 298


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1998-5029 (Print)