In a recent study posted to the medRxiv* preprint server, researchers explored the association between coronavirus disease 2019 (COVID-19) risk and blood N-3 fatty acid levels.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the associated pandemic have been investigated with respect to several aspects, including physiologic and demographic characteristics and nutritional considerations. Studies have proposed that long-chain n-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against COVID-19. EPA and DHA are the primary precursors, such as resolvins, maresins, and protectins, that serve as mediators to resolve inflammation.  

About the study

In the present study, researchers compared the risk associated with COVID-19 outcomes of testing positive for SARS-CoV-2, hospitalization, and death with respect to baseline plasma DHA levels.

The study involved a population-based, prospective cohort of 500,000 individuals enrolled in the UK Biobank between 2007 and 2010 across England, Scotland, and Wales. Baseline data were obtained from biological samples, questionnaires, and physical evaluations reported by all participating individuals, while longitudinal monitoring was performed via a mix of electronic medical records and in-person data. The participants answered a touchscreen questionnaire, obtaining data on diet, socio-demographic characteristics, and lifestyle factors.

The team obtained blood fatty acid data related to 117,946 participants from the UK Biobank cohort, which decreased to 111,240 after excluding mortalities. The primary exposure of the study was plasma DHA, estimated from blood samples obtained at the time of study enrollment using nuclear magnetic resonance (NMR). The red blood cell levels of EPA + DHA (the Omega-3 Index, O3I) correlated to these DHA levels were estimated using an equation that calculated the association between observed and estimated O31 as 0.83. Moreover, the primary outcomes included (1) death due to COVID-19, (2) hospitalization after a confirmed SARS-CoV-2 infection, and (3) testing COVID-19-positive.       

Results

The study results showed that the average of the 110,688 individuals enrolled in the study was 68 years in the initial phase of the pandemic, with a majority of the participants being White and over half being men. The average value of plasma DHA was 2%, while the evaluated O3! Was 5.6%. The team noted that less than 1% of the study cohort were COVID-19-hospitalized, and 20% succumbed to the infection.

Among the 26,620 individuals tested for SARS-CoV-2 infection, approximately 15% tested positive between 1 January 2020 and 23 March 2021, with a similar DHA value noted among all the tested individuals. When categorized into quintiles, the team observed that the plasma DHA% was between less than 1.48% in quintile 1 to more than 2.49% in quintile 5. Moreover, the median O3I values estimated ranged from 3.54% in quintile 1 to 7.96% in quintile 5.

A robust, dose-related, and inverse association was detected between the risk of testing COVID-19-positive and levels of plasma DHA%. This association displayed partial attenuation with every level of multivariable adjustment. Also, in the fully adjusted model, participants from quintile 5 had a 21% lesser chance of testing positive for COVID-19 compared to those in quintile 1, while the risk for testing positive was 8% lower for each standard deviation increase in the level of plasma DHA%.

With respect to hospitalization due to COVID-19, there was a significant and inverse association with plasma DHA% which also displayed partial attenuation with higher levels of adjustment. The fully adjusted model revealed that individuals from quintile 5 had a 27% lower risk of requiring hospitalization than those in quintile 1.

For mortality caused by COVID-19, the association with DHA% was complicated. For all the models, the risk for mortality was lower in quintile 4 compared to quintile 1. In contrast, in quintile 5, the reduction of risk was partially attenuated and not noteworthy in three of the models. In the unadjusted model as well as model 2, the risk for mortality was 17% and 22%, respectively.

Furthermore, for all three primary outcomes, some level of attenuation was observed due to covariable adjustment in the association of risk with DHA%. The highest attenuation of risk was noted for hospitalization and mortality due to COVID-19, as observed in model 3 with the adjustment of covariates of age, gender, waist circumference, and race. Moreover, the team observed that race and gender had an insignificant impact on the concordance of DHA% and any primary outcome, while waist circumference and age were the most crucial covariates.

Conclusion

Overall, the study findings showed that a low n-3 status was related to an increased risk of COVID-19-related hospitalization. The researchers suggested that increasing the consumption of n-3 should be encouraged to improve O3I to potentially reduce the risk for COVID-19.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.