Comment on an article: “Coagulopathy in COVID‐19”

Dear Editors‐in‐Chief Lillicrap and Morrissey,

We have read with great attention the article “Coagulopathy in COVID‐19” written by Toshiaki Iba et al, published in the September issue of the journal.¹ The authors performed an effective and informative review. Nevertheless, we welcome the opportunity to make a short comment as well.

This very interesting article evaluates current literature regarding the harmful hypercoagulable milieu of COVID‐19. Surprisingly, we cannot see that the authors recommended other diagnostic considerations such as checking for hyperhomocysteinemia in patients with COVID‐19. Undoubtedly, hyperhomocysteinemia has neurotoxic, neuroinflammatory, neurodegenerative, prooxidative, as well as proatherogenic/prothrombotic effects.² Also, recent evidence introduces the role of hyperhomocysteinemia as a strong risk factor for thromboembolism, given its influence in platelet reactivity.3., 4. In our opinion, it is very important to have this finding, because the simultaneous occurrence of hyperhomocysteinemia and pulmonary embolism in patients with COVID‐19.

Herein, as a consequence of SARS‐CoV‐2 infection, a high number of pulmonary embolism has been noted in COVID‐19 pneumonia patients (20.6%‐‐28%), despite the fact that 90% of them were receiving prophylactic antithrombotic treatment according to the current guidelines.5., 6. Interestingly, according to studies of Yang et al⁷ as well as Ponti et al⁸ on 273 and 40 COVID‐19 patients, respectively, levels of homocysteine were significantly higher and showed predictive value for computed tomography imaging progressions in pulmonary embolism. In this setting, hyperhomocysteinemia may be also a predisposing but not well‐recognized risk factor for vascular accidents in the coagulopathic state of COVID‐19.

Hopefully, values of folic acid (B9 vitamin) and B12 vitamin are in negative correlation with levels of homocysteine.⁹ Furthermore, B vitamins are enhancers of the immune system.¹⁰ Our studies from Bosnia and Herzegovina showed that the intake of folic acid, sometimes with B12 vitamin as well, was efficient in creating normalized homocysteine levels in older patients with ischemic stroke and Parkinson's disease.11., 12.

Despite knowledge gaps and lack of randomized controlled trials, there is an urgent need for different opinions and recommendations, when proper data are absent due to the speed of the COVID‐19 disaster. Perhaps, it is necessary to add‐on other medications in an attempt to minimize evident cardiovascular risk and improve health condition of COVID‐19 patients with the possibility of pulmonary embolism. So, intake of B vitamins as a co‐prophylaxis and proper diet control should be established as early as possible, not only in the COVID‐19 population but also in other healthy individuals in the age of SARS‐CoV‐2, on the basis of Latin phrase primum non nocere.

Taken together—inadequate evidence, expert opinions, and previous experiences—we hypothesize about a potential connection between pulmonary embolism and hidden hyperhomocysteinemia in patients with COVID‐19. In light of this, we suggest that levels of homocysteine, folic acid, and B12 vitamin should be measured at clinical follow‐up in all patients with COVID‐19, immediately after hospitalization. If persistant, hyperhomocysteinemic hypercoagulability should be promptly decreased in the acute phase of COVID‐19 with folic acid, and in some cases with the addition of B12 vitamin. All in all, B vitamins can, ad hoc, become the medication of second echelon in the treatment of unhidden COVID‐19 hyperhomocysteinemia. In conclusion, we emphasize that further studies will show harmful potential of hyperhomocysteinemia on pulmonary embolism in COVID‐19 patients as well as beneficial therapeutic add‐on effects of various B vitamins.

CONFLICT OF INTEREST

All authors declare that there is no conflict of interest.