Efficacy of combined folic acid, cyanocobalamin, and pyridoxine hydrochloride therapy in the comprehensive management of pneumonia associated with COVID-19

Aim. To evaluate the clinical efficacy and the effect on serum homocysteine levels of combined folic acid, cyanocobalamin, and pyridoxine hydrochloride therapy in the comprehensive treatment of pneumonia in hospitalized patients with COVID-19.

Materials and methods. An open-label, prospective, comparative study included 75 hospitalized patients with moderate to severe pneumonia associated with COVID-19 confirmed by detection of SARS-CoV-2 RNA in the respiratory tract. The main group consisted of 28 patients who received micronutrient therapy with 30 mg/day of folic acid plus cyanocobalamin and pyridoxine in addition to standard treatment. The comparison group comprised 47 patients who did not receive additional micronutrient therapy. The Charlson Comorbidity Index was 1.14 ± 0.93 in the main group and 0.47 ± 0.69 in the comparison group (p ≤ 0.001). Disease severity before and after treatment was assessed using the NEWS, qSOFA, 4C Mortality, and WHO Ordinal scales. Chest computed tomography (CT) was performed. Laboratory parameters included complete blood count, serum levels of C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), homocysteine, triglycerides, and low- and high-density lipoprotein cholesterol (LDL, HDL).

Results. In the main group, elimination period of SARS-CoV-2 RNA was achieved in 7.2 ± 3.4 days versus 15.6 ± 6.3 days in the comparison group (p < 0.001). After micronutrient therapy, disease severity decreased according to qSOFA and 4C Mortality scales. The main group showed a reduction in the total pneumonia volume from 32.0 (19.8–73.0)% to 26.5 (11.8–50.8)% (p = 0.035) and a reduction in the volume of parenchymal consolidation from 9.0 (0.0–37.3)% to 2.0 (0.0–17.0)% (p = 0.027). In the comparison group, there was no decrease in the total volume of lung involvement, and the area of parenchymal consolidation increased. These clinical and CT findings were associated with reductions in CRP, serum homocysteine, and LDL levels. Multiple linear regression models demonstrated that administration of the folic acid, cyanocobalamin, and pyridoxine hydrochloride combination shortened the elimination period of SARS-CoV-2 RNA from the respiratory tract (regression coefficient β = –8.648 ± 1.781; p < 0.001) and contributed to a decrease in parenchymal consolidation volume after treatment (β = –13.492 ± 4.834; p = 0.011), with the effect also linked to baseline LDH levels (β = 0.0235 ± 0.00857; p = 0.008) and patient age (β = 0.167 ± 0.0608; p = 0.008).

Conclusion. The use of folic acid, cyanocobalamin, and pyridoxine hydrochloride in the comprehensive management of patients with COVID-19-associated pneumonia is associated with a shorter SARS-CoV-2 RNA elimination period from the upper respiratory tract, a more pronounced reduction in disease severity, and a decreased extent of lung parenchymal consolidation. These effects coincide with lower serum homocysteine levels.  

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