Spanish researchers claim that Valproic Acid is a potential weapon against COVID-19

Medical News: As the COVID-19 pandemic continues to challenge healthcare systems globally, researchers are exploring various drugs that could potentially be repurposed to fight the virus. One such drug is valproic acid (VPA), which is commonly used to treat epilepsy and other neurological conditions. A recent study conducted by a group of researchers from the Alicante General University Hospital and the Alicante Institute of Health and Biomedical Research (ISABIAL) in Spain suggests that VPA could have a significant impact on reducing the incidence and severity of COVID-19. This Medical News report delves into their findings, exploring the potential role of VPA in the battle against the virus.


Spanish researchers claim that Valproic Acid is a potential weapon against COVID-19

What Is Valproic Acid?
Valproic acid is a short-chain fatty acid that has been widely used as an antiepileptic drug to treat neurological disorders such as epilepsy. It works by inhibiting histone deacetylase, which influences the expression of various genes involved in neurological processes. While its primary use is in the treatment of epilepsy, VPA has also shown promise as a broad-spectrum antiviral agent in laboratory studies.
 
Previous studies have demonstrated that VPA can inhibit the replication of several enveloped viruses, including herpesviruses, cytomegalovirus, and the West Nile virus. Its antiviral potential has drawn the attention of researchers who are now investigating whether it could also be effective against the SARS-CoV-2 virus, which causes COVID-19.
 
The Study: Valproic Acid and COVID-19
The study, conducted between March and December 2020, involved a case-control study nested within a cohort of patients in the Alicante health department. The study aimed to investigate whether patients who were taking valproic acid had a lower incidence of SARS-CoV-2 infection and a reduced risk of hospitalization due to COVID-19. The researchers analyzed data from 281,035 residents in the Alicante area, identifying 6,183 PCR-confirmed COVID-19 cases during the study period. Of these, 746 were hospitalized.
 
The researchers focused on 691 patients who were on VPA treatment, with 628 of them taking the medication consistently throughout the study period. The primary indication for VPA use in this group was epilepsy. The study aimed to compare the incidence of COVID-19 infection and hospital admission among VPA users with that of the general population who were not on VPA treatment.
 
Key Findings
The study yielded some interesting results. Among the patients taking VPA for at least 20% of the study period, the incidence of PCR-confirmed COVID-19 was 1.736%, while in the general population, the incidence was 2.201%. This suggests that individuals taking VPA may have a lower risk of contracting the virus. Additionally, the study found that the incidence of COVID-19 in patients who were on VPA throughout the entire study period was 1.910%, also lower than the general population.
 
Moreover, when the researchers focused on patients whose VPA levels were within the therapeutic range (50–100 mcg/mL), they found an even more pronounced reduction in the risk of COVID-19. The study reported that the odds of infection were reduced by more than 75% for patients whose VPA levels were maintained within this therapeutic range. This article provides a glimpse into how VPA could potentially help in reducing the severity of COVID-19.
 
Hospital Admissions and Severity of COVID-19
The study also examined the impact of VPA on the severity of COVID-19, as indicated by the need for hospital admission. Among VPA users, the incidence of hospitalization was significantly lower than in the general population. Only one patient in the VPA group required hospitalization, resulting in an incidence rate of 0.144%, compared to 0.265% in the general population. While these results did not reach statistical significance, they suggest that VPA may have a protective effect against severe COVID-19 outcomes.
 
The only patient on VPA who was hospitalized was a middle-aged male with infantile cerebral palsy. His case was mild, and he recovered without complications, further supporting the notion that VPA could play a role in mitigating the severity of COVID-19 symptoms.
 
How Does Valproic Acid Work Against SARS-CoV-2?
The exact mechanisms by which VPA might reduce the risk and severity of COVID-19 are not yet fully understood. However, several hypotheses have been proposed based on previous studies of VPA's antiviral properties. One possibility is that VPA interferes with the early stages of viral infection, particularly the entry of the virus into host cells. VPA has been shown to reduce the expression of angiotensin-converting enzyme 2 (ACE-2), which is the main receptor that SARS-CoV-2 uses to enter human cells.
 
In addition to its effect on viral entry, VPA may also reduce inflammation and prevent some of the complications associated with severe COVID-19. Studies have shown that VPA can reduce the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6), which play a key role in the cytokine storms that can lead to severe respiratory complications in COVID-19 patients.
 
Furthermore, VPA has antithrombotic properties, meaning it may help prevent blood clots, a common and dangerous complication of severe COVID-19. By reducing both inflammation and the risk of blood clots, VPA could potentially help prevent the progression of mild COVID-19 cases to more severe forms that require hospitalization.
 
The Need for Further Research
While the findings of this study are promising, they also highlight the need for further research. The protective effects of VPA observed in this study warrant additional investigation through larger clinical trials. Future studies should aim to confirm the observed reduction in COVID-19 incidence and severity among VPA users and explore the mechanisms underlying these effects in greater detail.

It is important to note that this study was conducted retrospectively, meaning that the researchers analyzed existing data rather than conducting a prospective clinical trial. As a result, the findings are not conclusive, and more rigorous research is needed before VPA can be recommended as a treatment or preventive measure for COVID-19.
 
Conclusion
The study findings provide early evidence that valproic acid could play a role in reducing the risk and severity of COVID-19. While the results are encouraging, more research is needed to fully understand the potential of VPA in the fight against the virus. For now, VPA remains a promising candidate for repurposing as an antiviral agent, and its potential benefits in COVID-19 prevention and treatment will likely be explored in future studies.
 
The study findings were published in the peer-reviewed journal Neurología.
https://www.sciencedirect.com/science/article/pii/S2173580823000779
 
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