Evaluation of Thiamine as Adjunctive Therapy in COVID-19 Critically Ill Patients

A Two-Center Propensity Score Matched Study

Khalid Al Sulaiman; Ohoud Aljuhani; Maram Al Dossari; Asma Alshahrani; Aisha Alharbi; Rahmah Algarni; Majed Al Jeraisy; Shmeylan Al Harbi; Abdulmalik Al Katheri; Fahad Al Eidan; Abdulkareem M. Al Bekairy; Nouf Al Qahtani; Mashael Al Muqrin; Ramesh Vishwakarma; Ghassan Al Ghamdi

Disclosures

Crit Care. 2021;25(223) 

In This Article

Abstract and Introduction

Abstract

Background: Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies; however, it's role in COVID-19 patients is still unclear. The aim of this study was to evaluate the use of thiamine as an adjunctive therapy on mortality in COVID-19 critically ill patients.

Methods: This is a two-center, non-interventional, retrospective cohort study for critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older admitted to ICUs between March 1, 2020, and December 31, 2020, with positive PCR COVID-19 were eligible for inclusion. We investigated thiamine use as an adjunctive therapy on the clinical outcomes in critically ill COVID-19 patients after propensity score matching.

Results: A total of 738 critically ill patients with COVID-19 who had been admitted to ICUs were included in the study. Among 166 patients matched using the propensity score method, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR = 0.39; 95% CI 0.19–0.78; P value = 0.008) as well as the 30-day mortality (OR = 0.37; 95% CI 0.18–0.78; P value = 0.009). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay [OR (95% CI) 0.19 (0.04–0.88), P value = 0.03].

Conclusion: Thiamine use as adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19. Additionally, it was associated with a lower incidence of thrombosis. Further interventional studies are required to confirm these findings.

Introduction

With the rapid spread of the disease, as well as the high mortality rates among critically ill patients, there are many studies with different methodology approaches conducted among COVID-19 patients to investigate the effectiveness of many medications (e.g., steroids, antivirals, immunomodulators) and respiratory support strategies (e.g., prone position, volume protected strategy).[1–3] Several proposed vitamins and trace elements therapies are currently under investigation, such as ascorbic acid and zinc.[4–7] However, the role of other vitamins, especially thiamine in COVID-19 critically ill patients, is still unclear.

Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate (TPP) required for glucose metabolism; it improves the immune system function and has been shown to reduce the risk of several diseases.[8] Besides that, thiamine diphosphate (TDP)-dependent enzymes are a vast group of proteins that contribute to many catabolism reactions of enzymes, along with neurotransmitters biosynthesis and antioxidant activity.[9] Thiamine deficiency is a serious medical condition that may lead to many complications requiring medical interventions such as Wernicke's encephalopathy, delirium, and beriberi.[10–12]

The role of thiamine in COVID-19 patients is still unclear; however, its role in critically ill patients has been addressed in multiple studies.[13–15] A randomized controlled trial by Moskowitz et al. shows that thiamine was associated with significantly lower lactate levels, serum creatinine and a possible decrease in 30-day mortality.[13] In addition, another observational study shows that thiamine administration within 24 hours was associated with an improved possibility of lactic acid clearance and reduced 28-day mortality in critically ill patients with septic shock.[14]

The question remains about the thiamine role in COVID-19 critically ill patients. Antibodies and, importantly, T-cells are required to eliminate the SARS-CoV-2 virus; thiamine deficiency can potentially result in inadequate antibody responses and more severe symptoms.[8] Thiamine also works as a carbonic anhydrase isoenzyme inhibitor; thus, high doses of thiamine given to patients at the early stages of COVID-19 could limit hypoxia and decrease hospitalization.[16] Additionally, an in-vitro study found that high-dose thiamine lowers the T-helper cells (Th-17) cell pro-inflammatory response believed to be associated with the COVID-19 cytokine storm.[17]

As of July 15, 2020, over 300 COVID-19 patients were treated with a protocol named MATH+ protocol which combines a range of substances: methylprednisolone, ascorbic acid, thiamine, heparin and several additional components, including melatonin, zinc, vitamin D, atorvastatin and famotidine.[4] Unfortunately, no current studies specifically investigate thiamine's effect in COVID-19 patients to the best of our knowledge. Therefore, our study aims to determine the association between thiamine use as an adjunctive therapy and the clinical outcomes in COVID-19 critically ill patients.

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