Table 1.
First Author; (year) | Place (Country) | Sample size | Type of study | Age | Review period or Comparison date | Quality Assessment | Examined indicators |
---|---|---|---|---|---|---|---|
Zapata B et al. (2021) [32] | Chile | 74: Male: 39 Female: 35 (74 patients (39 m and 35 f) with severe COVID-19 and 10 healthy quality-control) |
Cross sectional | Patients: 21–82 (59.68 ± 13.6) | November 2020 and April 2021 | Good | - Omega-3 Index in patients with severe COVID-19: 4.15% ± 0.69% - Risk of mechanical ventilation for the lowest O3I quartile (<3.57%) compared to higher quartiles: OR = 1.348, 95%CI: 0.925–1.964; P = 0.183 - Risk of death for the lowest O3I quartile (<3.57%) compared to higher quartiles: OR = 3.111, 95%CI:1.261–7.676; P = 0.032 - Reduction in the risk of mechanical ventilation for the highest O3I quartile (>4.51%) compared to the lo west quartile: OR = 0.257, 95%CI: 0.083–0.791; P = 0.026 - Reduction in the risk of death for the highest O3I quartile of (>4.51%) compared to the lowest quartile: OR = 0.195 95%CI: 0.024–1.605; P = 0.165 |
Archambault et al. (2021) [35] | Canada | 25 healthy subjects and 33 COVID-19 patients | – | healthy subjects:26 ± 1 COVID-19 patients: 58 ± 3 |
between May and June 2020, before COVID-19 |
Poor | - Higher in bronchoalveolar lavage of COVID-19 patients compared with healthy subjects Mean ± SD of: - arachidonic acid, 89.3 ± 6.4 vs. 16 ± 9 nmol/ml - docosahexaenoic acid, 290 ± 35 vs. 35 ± 20 nmol/ml - eicosapentaenoic acid, 8.9 ± 0.9 vs. 8.6 ± 0 nmol/ml |
Asher et al. (2021) [3] | USA | 100: 59 male, 41 female (86 alive, 14 dead) |
pilot study | 72.5 (16.5; 25,100) | from March 1, 2020 onwards | Good | - patients with an O3 index at 5.7% or greater: 75% lower risk for death compared with those below that value (p = 0.071) - Q4: O3I ≥ 5.7% omega-3 index with death adjusted for age and sex: 32.0% (8/25); OR = 0.25, 95% CI: 0.03–1.11; p = 0.071 - Omega-3 Index and death: Q3 (4.7 < O3I < 5.7%) vs other quartiles: OR = 3.13, 95% CI: 0.82–14.30; p = 0.1 |
Doaei et al. (2021) [38] | Iran | 101 patients infected with COVID-19: 28 fortified formula with n3-PUFA and 73 controls; 60 male, 41 female. Interventions: 15 m, 13 f; controls: 45 m, 28 f |
A double-blind, randomized clinical trial | between 35 and 85 years (Interventions: 66 (14.58); Controls:64 (14.25)) |
from May to July 2020 | Good | Effects of omega-3 supplementation(one capsule of 1000 mg omega-3 daily (Vita Pharmed, Switzerland) containing 400 mg EPAs and 200 mg DHAs for 14 days) in intervention group vs. control group: - On 1-month survival rate: significantly higher, 21% (n = 6) vs. 3% (n = 2); P = 0.003 - On kidney function: levels of BUN (35.17 vs 43.19, F = 4.76, P = 0.03) and Cr (1.29 vs 1.68, F = 5.90, P = 0.02), significantly lower and the amount of urine excreted (2101 vs 1877.02, F = 12.26, p = 0.01), significantly higher. - On arterial blood gas (ABG) parameters: levels of arterial pH (7.30 vs 7.26, F = 19.11, P = 0.01), HCO3 (22.00 vs 18.17, F = 10.83, P = 0.01), and Be (−4.97 vs −3.59, F = 23.01, P = 0.01), significantly higher. - On the mean of Glasgow coma scale (GCS): at admission time8.37 vs. 7.90, P > 0.05, significantly lower; after 14 days 7.90 vs 7.49, F = 6.07, P = 0.05. No significant difference in APACHE II score (15.54 ± 1.73 vs 15.42 ± 1.92, P = 0.78). - On serum electrolytes: The level of K, significantly reduced (4.00 vs 4.14, F = 10.15, P = 0.01) after 14 days. No significant differences between the levels of serum electrolytes including Na, Ca, and P. - On blood clotting function and cell blood count (CBC): The lymphocyte count increased, marginally significant (11.59 vs 11.80, F = 4.08, P = 0.05). no significant differences in levels of PTT, hematocrit, neutrophil, monocyte, hemoglobin, and Plt - On the other blood factors: No significant differences in blood glucose, albumin, MAP, and O2 sat. |
Hamulka et al. (2021) [26] | Worldwide and Poland | First wave: 2296 Second wave: 978 |
Online cross-sectional | ≥18 | (1) in April and May 2020 (2) in November 2020 during the second wave |
Good | Spearman rank's coefficients Omega-3 fatty acids and Worldwide: COVID-19 cases: 0.06; Deaths: 0.06 Coronavirus relative search value (RSV): −0.74; p ≤ 0.01 Poland: COVID-19 cases: 0.21; Deaths: 0.21, coronavirus relative search value (RSV): −0.26 - Omega-3 fatty acids supplement consumption: increase from 2.8% to 8.2% |
Jontez et al. (2021) [41] | Slovenia | 38 (14 m , 24 f) |
web survey |
36.3 ± 10.1 | December 2019 | Fair | Mean ± SD fatty acids intake ratio (PUFA+MUFA)/SFA) in healthy Adults: Baseline 1.98 ± 1.34, During Lockdown 1.77 ± 1.20 and Post-Lockdown 1.54 ± 0.78 |
Julkunen et al. (2021) [42] | UK |
Pneumonia participants: n = 105,142; 102,639 controls, 2507 severe incident cases COVID-19 Participants: n = 92,725; 92,073 control, 653 severe incident cases |
Retrospective cohort | 49–84 | blood samples collected 2007–2010 | Good | - multi-biomarker score for fatty acids and susceptibility to severe COVID-19: odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile; p-value<0.001 |
Mei et al. (2021) [39] | China | 223: 91 discharged and 132 deceased | multi-center study | ≥65 years old | Between January and March 2020 | Good | - Fatty acid: lower flux in the survivors vs. the deceased subgroup, AOR = 15.61 [95% CI: 6.66–36.6], p < 0.001. |
Nguyen et al. (2021) [27] | France | 61: 34 non-COVID-19,27 COVID-19 |
prospective | non-COVID-19: 69 (± 12) COVID-19: 62 (± 11) |
– | Good |
In COVID-19 patients vs. non-COVID-19 patients: - Linoleic acid (C18:2 n-6): significantly increased 207 ± 109 vs. 113 ± 67 nmol/ml; p < 0.01. - Arachidonic acid (C20:4 n-6): significantly increased 16 ± 6 vs 12 ± 5 nmol/ml p < 0.01 - Relative proportion of linoleic acid: significantly higher 12.8 ± 3.6 vs. 8.3 ± 2.3%; p < 0.01 - Linoleic acid proportion and ventilator-free days: r = − 0.404, p = 0.001) |
Perez-Torres et al. (2021) [28] | Mexico | COVID-19 patients n = 42: 31 m, 11 f (healthy subjects n = 22) |
– | over 18 years 62 ± 13 years |
– | Good | - Increased in COVID-19 patients: oleic (OA), p = 0.001; linoleic (LA), p = 0.03 and arachidonic acid (AA), p = 0.02. - Mean ± SE of Fatty acids in Healthy subjects vs. COVID-19 patients - Monounsaturated fatty acids (MUFA): 23.82 ± 0.70 vs. 32.09 ± 0.61; p = 0.001 - Omega 3 polyunsaturated fatty acids (PUFA (n-3)): 0.91 ± 0.11 vs. 0.31 ± 0.05; p = 0.001 - Omega 6 polyunsaturated fatty acids (PUFA (n-6)): 25.94 ± 0.53 vs. 28.19 ± 0.82; p = 0.02 |
Vivar-Sierra et al. (2021) [29] | worldwide | – | Web based | – | – | Fair | - Eastern Mediterranean region: higher mean fatality rate (3.52%) and the lowest omega −3 intake from marine sources (45.14 mg/day) - South-East Asia: lowest fatality rate (1.01%) and the highest average consumption (634.00 mg/day) from marine sources - In nations with a consumption <250 mg/day from marine products, differences among regions were observed (chi2 = 59.361; p = 0.000), as well as a trend for higher fatality rates, >2.5 and 4% (chi2 = 10.432; p = 0.064) and (chi2 = 10.367; p = 0.066), - Omega −3 intake from plants and cumulative cases: rSpearman = 0.321; p < 0.001 - Omega −3 intake from plants and total cumulative cases per 1 million population: rSpearman = 0.329; p < 0.001 - Omega −3 intake from plants and fatality rates: rSpearman = 165; p > 0.05 |
Bejan. (2021) [36] | USA | 7768 COVID-19 patients, 509 (6.55%) hospitalized, 82 (1.06%) admitted to ICU, 64 (0.82%) mechanical ventilation, and 90 (1.16%) died |
retrospective cohort | Median = 42 | Patient exposure to a drug during 1-year prior to the pandemic and COVID-19 diagnosis |
Good | - Hospitalized-mild, cumulative severity: supplement of Omega-3 fatty acids: Total exposed: 475 Total unexposed: 7293 Severity rate exposed: 10.7 Severity rate unexposed: 15.7 OR = 0.60, 95% CI: 0.39–0.94 - Hospitalized-mild, exclusive severity supplement of Omega-3 fatty acids: Total exposed: 456 Total unexposed: 7168 Severity rate exposed: 7.2 Severity rate unexposed: 11.5 OR = 0.56, 95% CI: 0.33–0.95(Lower risk for COVID-19 outcomes) |
Hao et al. (2021) [33] | China | 89 asymptomatic COVID-19 patients and 178 healthy controls | – | 19 to 91 Mean ± SD: Asymptomatic: 45 ± 13; healthy controls: 45 ± 13 |
- |
Good | - FAs (including FA 18:1 and FA 20:0) decreased in asymptomatic COVID-19 patients. -Z-scored log 2-scaled peak area value for relative intensity of FA 18:1: 0.42, (95%CI: −0.31 to 1.09) in healthy controls and − 0.73, (95%CI: −1.1 to −0.14) in COVID-19 patients; adjusted p-value = 1.23e-12 - FA 18:1 (asymptomatic/healthy): 0.44 -Z-scored log 2-scaled peak area value for relative intensity of FA 20:0:0.068, (95%CI: −0.34 to 0.89) in healthy controls and − 0.50, (95%CI: −0.99 to −0.17) in COVID-19 patients; adjusted p-value = 8.74e-10 - FA 20:0 (asymptomatic/healthy): 0.65 |
Louca et al. (2021) [30] | UK, USA, Sweden |
UK: n = 372,720: 39263 supplement users and 333,457 non-users. USA: n = 45,757, 8663 supplement users and 37,094 non-users Sweden: n = 27,373, 3039 supplement users and 24,334 non-users |
App-based community survey | aged 16–90 years | in the first waves of the pandemic up to 31 July 2020 |
Fair | - SARS-CoV-2 positive, n (%): UK: 10508 (6%) USA: 2002 (6.2%) Sweden: 1806 (13.5%) - UK cohort: users regularly supplementing their diet with omega-3 fatty acids had a lower risk of testing positive for SARS-CoV-2 by 12% (OR = 0.88, (95%CI: 0.84 to 0.92), p = 5.8 × 10−8) after adjusting for age, sex, BMI, sign-up health status and multiple testing - omega-3 supplement use was not associated with testing positive in Swedish females - Swedish men taking probiotics, omega-3 fatty acids had a decreased risk of infection - protective effect in omega-3 fatty acid supplements users with a 12% reduction in risk of testing positive for SARS-CoV-2 in the overall UK cohort, 21% in the US cohort and 16% in the SE cohort. - women taking multivitamins, omega-3 fatty acids have a slightly lower risk of SARS-CoV-2 infection in the UK, US and SE cohorts |
El-Kurdi et al. (2020) [40] | 61 countries With >1000 COVID-19 death |
1,476,418 patients | Web survey | – | between 3/25/2020 and 04/08/2020 | Good | - %UFA intake was positively associated with mortality: Rate Ratio = 1.02, 95% CI: 1.01–1.03; (p < 0.001) - Multivariate analysis showed only %UFA as significantly associated with mortality (p < 0.0001). |
Barberis et al. (2020) [37] | Italy |
Non-COVID-19 Patients:26 Healthy Control, 32 non-COVID-19 with symptom COVID-19 Patients:103 |
– | (Mean ± SD) Healthy Control: 50.1 ± 5.3 non-COVID-19 with symptoms: 68.6 ± 8.9 COVID-19 Patients: 67.3 ± 18.0 |
– | Good | - Free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease; p value <0.0001. - By using ROC curves, the quantification in the negative mode identified AUC values of 0.99 (SE: 93%, SP: 100%) for arachidonic acid (FA 20:4) and 0.98 (SE: 96%, SP: 88%) for oleic acid (FA 18:1). - Mean ± SD of oleic acid (FA 18:1) in covid-19 patients vs. controls: 2355 ± 1305 vs 0.567 ± 326 pmol/ml plasma - Mean ± SD of arachidonic acid (FA 20:4) in covid-19 patients vs. controls: 415 ± 237 vs. 49.5 ± 24.75.6 pmol/ml plasma - Oleic acid and arachidonic acid levels are directly correlated to the severity of the disease |
Thomas et al. (2020) [31] | USA | COVID-19: n = 33 Controls: n = 16 |
– | (Mean ± SD) COVID-19: 56.5 ± 18.1 Controls: 37.8 ± 11.6 |
– | Fair | - Serum levels of free fatty acids (c18:0–3 and c 20:4–5) were significantly different when comparing COVID-19–positive patients and controls; P < 0.05 |
Dierckx et al. (2020) [34] | Belgium | 581 samples from 480 patients in three different cohorts: UZL, n = 219 and JESSA, n = 164, subset of plasma samples |
retrospective | >18 years old | between March 2020 and September 2020 |
Good | - Increased poly-unsaturated FA (PUFA) content was associated with less severe disease - Increased mono-unsaturated FA (MUFA) content was associated to more severe disease - Linoleic acid (LA) and total Omega-6 FA: stronger and more consistent associations opposite associations with COVID-19 severity than Omega-3 FA. - Opposite associations with COVID-19 severity: - Linoleic acid (LA): OR = 0.55, percentile2.5 = 0.42, percentile97.5 = 0.71; p = 0.000 in UZL and OR = 0.72, percentile2.5 = 0.54, percentile97.5 = 0.96; p = 0.025 in Jessa - total Omega-3 FA: OR = 0.69, percentile2.5 = 0.54, percentile97.5 = 0.89; p = 0.003 in UZL and OR = 1.05, percentile2.5 = 0.75, percentile97.5 = 1.47; p = 0.77 in Jessa - Omega-6 fatty acids: OR = 0.59, percentile2.5 = 0.45, percentile97.5 = 0.75; p < 0.001 in UZL and OR = 0.66, percentile2.5 = 0.47, percentile97.5 = 0.92; p = 0.014 in Jessa - Docosahexaenoic acid (DHA) OR = 0.74, percentile2.5 = 0.57, percentile97.5 = 0.94; p = 0.015 in UZL, OR = 1.1, percentile2.5 = 0.84, percentile97.5 = 1.46; p = 0.48 in Jessa. |
(n = 198, from 97 patients) taken for the CONTAGIOUS observational clinical trial 69 in analyze |
prospective | >18 years old | Samples were taken at the time of admission (within maximum 48 h), at day 7, at the time of hospital discharge and 30 days after hospital discharge (if available). |
Good | - Ratio of omega-6 fatty acids to total fatty acids: median = 35.16; IQR = 34–36.6 in sv3: and median = 32.34; IQR = 30.2–34.7 in sv4; p = 0.002 - Ratio of polyunsaturated fatty acids to monounsaturated fatty acids(PUFA by MUFA): median = 1.4; IQR = 1.26–1.47 in sv3: and median = 1.27; IQR = 1.02–1.37 in sv4; p = 0.022 - Ratio of polyunsaturated fatty acids to total fatty acids (PUFA pct): median = 38.45; IQR = 36.9–40.2 in sv3: and median = 37.05; IQR = 34–38.6 in sv4; p = 0.008 - Higher relative PUFA content and PUFA to MUFA ratio were consistently associated with lower severity, in contrast to increased MUFA levels - Linoleic Acid concentration and total omega-6 fatty acid content (absolute concentration and relative to total FAcontent) were lower in severe COVID-19 cases. |