最新消息

2022.05.27

研討會_上線連結_【已報名】 通知時間

各位敬愛的會員您好: 感謝您報名參加協會舉辦各場次研討會, 5月29日(星期日) 09:00~12:00 健康醫學協會(線上)研討會   EMAIL寄發 Zoom上線連結 通知時間如下: 第一次通知_5月27日(五) 會前二日 第二次通知_5月28日(六) 會前一日 第三次通知_5月29日(日) 會前一小時 名額有限歡迎盡早完成註冊及報名程序。 ★申請網路會員連結: http://tahm.com.tw/index.php?action=peo_registered

2022.05.27

【轉知_研討會訊息】5月28日(星期六) 2022年度_肺高壓&高血脂研討會

會議鏈結: https://pulmonaryhypertensionassociationtaiwan.my.webex.com/pulmonaryhypertensionassociationtaiwan.my/j.php?MTID=m0290958d601eb82f3c2b63db4eb02ea6 會議號: 2553 405 1591 會議密碼: eNWDktaM326 視訊系統的會議密碼 36935826  

2022.04.10

【重要通知_線上研討會報名注意事項】

各位敬愛的會員您好: 1. 參加本協會舉辦之研討會需為本會網路會員 (協會網站右上角簡易註冊即可,然註冊報名申請資料皆為必填項目)。完成上線簽到、後測簽退之研討會會員,秘書處將代送有公佈之各專科學會學分之申請,學分認證依各申請學會認證規定。 2. 本協會舉辦之線上研討會官網報名截止期限一律以研討會會前一日24:00為準。 3. 本協會之宗旨乃推廣醫學新知,學分申請服務為免費,但不保證各學會學分之申請責任。若非依循本協會所公告之標準作業流程而需額外使用本協會之人力者(例如,另申請上課證明者、須另外查詢確認等情況),酌收工本費$500 元。 4. 如線上研討會官網報名截止期限前未登錄為本會網路會員或未完成線上報名者,恕難申請任何學分。另提醒申請學分需要身分證號, 只給姓名,各學會皆無法認證。 5. 由於協會人力不足,若有任何問題請用email聯絡報名或學分相關事宜,請勿再使用電話或 line處理。聯絡通知請寄至: servicelipid@lipid.com.tw   匯款資訊如下: 銀行名稱:合作金庫銀行 南門分行 匯款帳號: 5159-717-510485(代碼006) 戶名:台灣健康醫學協會  

2022.04.08

2022年上半年度(線上) 學術研討會

本會將於05/29、06/12、06/26 三天的週日舉行三場111年上半年度 (線上)學術研討會。 主題:Brain-Heart-Gut-Kidney Axis  What's New for Integrative Medicine? 歡迎全國性各醫師、護理、藥師等專業同業人員申請為協會醫師會員參加,本推動學術研究之宗旨與服務,並提供與會會員之最新專業報告與分享,俾推廣健康相關醫學分享與進步。*因應疫情變化狀況,如有調整研討會舉辦型式,將會隨時於官網公告及通知。 線上報名説明: 一、參加資格,需為本會之協會網路會員。 如醫師、護理師、藥師、醫護相關之醫事人員等。如第一次參加本會活動請至本會官網註冊,相關須填寫資料皆為必填項目,網路會員可免費參加本次線上研討會,及日後各項學術研討會活動。 ★申請網路會員連結: http://tahm.com.tw/index.php?action=peo_registered   二、報名是否成功? 可至各場次報名名單公告訊息。 三、線上簽到連結:每場次前一天 會發送EMAIL給已報名完成。   四、學分申請: 1.需為本會網路會員(本年度入會免會費),本會協助參加完成研討會之會員,各專科學會申請學分,學分認證則依各申請學會認證規定。 2.相關報名申請資料皆為必填項目 。 3.研討會當日需完成線上簽到、簽退及後測,後測於當日最後一場演講結束後5分鐘內會顯示。 4.本活動以學術分享研討為主,不保證各學會學分之申請責任。若非依循本協會所公告之標準作業流程而需額外使用本協會之人力者(例如,另申請上課證明者、須另外查詢確認等情況), 酌收工本費$500 元。通知請寄至: servicelipid@lipid.com.tw。   各場次預計申請學會學分參考如下: (1)中華民國心臟學會>5學分 (2)中華民國糖尿病學會>1學分 (3)中華民國醫師公會全國聯合會>3.2學分 (4)台灣內科醫學會>5學分 (5)台灣老年學暨老年醫學會>3學分 (6)台灣家庭醫學醫學會>3學分 (7)台灣腎臟醫學會>2學分 (8)台灣臨床藥學會>3.4學分 (9)糖尿病共照網>1學分  

2022.04.06

2022-5月-線上-學術研討會-注意事項

各位醫師會員 您好: 感謝您報名參加與出席~台灣健康醫學協會2022年度月 (線上)學術研討會 <視訊會議流程與注意事項> 1.建議使用設備:筆電/桌電或平板電腦為主。 2.學分取得條件:需完成 協會網路會員申請、會議時間上線登入 及 完成後測測驗,才能獲得學分申請。 3.Q&A時間:主持人於講師演講結束後,提問時間5分鐘內,主持人可在【發問】欄位,依【醫師會員】 針對講師所提出的問題進行討論。 ~~~ 研討會前一小時,會再次email提醒 ~~ ~上線時數以各學會認定為標準,上、下線時數,系統會自動計算,時數不足或未完成後側 ,不保證學分之申請,謝謝。

2022.04.01

說明-申請會員、報名程序

※為確保您的電子信箱未遭他人冒用,確實可收到本會回信,請 至您的電子信箱 接收認證郵件完成確認。 ※如未收到「認證郵件」,請至您的「垃圾郵件匣」查看。凡未經您確認的信件,本次會員申請將無法完成。 ※本會 網路會員 「免會費」,限 僅限 「醫事人員」申請  ※完成每場次簽到、簽退程序, 請完成 「會後3分鐘內」系統自動 跳出之「後測題目」,點選"送出"使得完成會議之簽到、簽退之條件。 ※ 非本會會員、會後上線 、中途下線、沒填完後測題目者,皆不予申請學會學分。 ※會議連結_「會前一天」及 「會議前一小時」 (共2次),系統會自動 EMAIL 通知 已報名之會員。

2021.06.06

擁有「腎」利人生!!戰「腎」三高~~

  依據國民健康署「96年台灣地區高血壓、高血糖、高血脂之追蹤調查研究」,國內20歲以上成人每10位就有1位患有慢性腎臟疾病。慢性腎臟病發展至後期需要洗腎,108年健保門診透析治療花費達533億元,約占健保總預算6.9%。國民健康署賈淑麗代理署長強調,高血壓、糖尿病及高血脂(簡稱三高)不僅是造成慢性腎臟病的主要原因之一,也是慢性腎臟病的併發症,呼籲已經罹患高血壓、糖尿病的民眾更應該依照醫師處方正確用藥,妥善治療,才不會因為長期血壓、血糖過高,嚴重傷害腎臟,而走上洗腎之路。  一半以上慢性腎臟病病人不注意三高控制     根據國民健康署106年國民健康訪問調查結果,顯示有5成以上(56.0%)的慢性腎臟病人沒有注意量血壓,5成以上(51.0%)沒有注意測血糖,6成以上(64.7%)沒有注意測量膽固醇(表1)。此外,在規則服藥控制三高患者,除糖尿病病人有9成以上規律服藥外,在高血壓與高血脂的按醫囑用藥部份僅占5-7成,且更令人憂心的是,越年輕的慢性腎臟病人越不注意測量三高及規律用藥重要性(表2)。腎臟病、三高不是中老年人的專利,年輕的患者也需要留意三高的問題,勿輕忽,應與專業人員討論,配合適當的疾病自我管理,養成規則用藥與三高監測之健康行為,才是「謹腎顧腎」之道。 善用成人健檢,及早發現三高及慢性腎臟病     根據國民健康署統計108年40歲以上民眾成人預防保健服務利用情形,其中男性受檢民眾占42.2%,女性占57.8%。針對男性利用服務少於女性之情形,健康署提醒全國男性朋友,在顧經濟之餘,可多利用由健康署免費提供的成人預防保健服務(40歲以上未滿65歲之民眾,每3年提供1次,65歲以上則可每年提供1次),及早發現自己三高及慢性腎臟病的問題,以能及早介入與控制。 腎臟保健的八項黃金守則     血糖、血壓與血脂的良好控制是預防和治療早期糖尿病腎臟病變之根本。國際腎臟醫學會(ISN)與國際腎臟基金會(International Federation of Kidney Foundation, IFKF)共同提出腎臟保健的八項黃金守則(表3),簡單來說:就是三高控制、健康飲食、規律運動、體重控制、避免服用不當藥物、多喝水、不抽菸及定期檢查腎功能。賈代理署長呼籲,血糖、血壓過高,會損害腎臟!服用偏方、草藥、來路不明藥品也會傷腎!積極配合醫療團隊,採取藥物、飲食、運動三管齊下的正規治療,將血糖、血壓控制在理想範圍,就能擁有「腎」利人生。

2021.05.13

活性碳有幾種分類?

口服活性碳會吸附腸道內有毒物質, 本身不被人體吸收,過去是使用在緊急治療藥物或化學品中毒之病人。 近年來的研究發現活性碳會吸附干擾胃腸道的細菌性毒素、消化性毒素及其他有機性廢物、解除腸內滯留氣體及有關症狀。  還有實驗證明某些特殊劑型的口服活性碳 (例如: 多孔分散吸附元、微球細粒吸附碳等), 可在腸胃道選擇性的吸附重金屬、indole及p-cresol,以減少人體吸收的機會,進而延緩慢性腎衰竭患者透析起始時間及改善尿毒症狀。​

2021.04.02

學術分享 The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial

The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial Saeid Doaei,  Somayeh Gholami,  Samira Rastgoo,  Maryam Gholamalizadeh,  Fatemeh Bourbour,  Seyedeh Elaheh Bagheri,  Forough Samipoor,  Mohammad Esmail Akbari,  Mahdi Shadnoush,  Fereshteh Ghorat,  Seyed Alireza Mosavi Jarrahi,  Narjes Ashouri Mirsadeghi,  Azadeh Hajipour,  Parvin Joola,  Alireza Moslem &  Mark O. Goodarzi  Journal of Translational Medicine volume 19, Article number: 128 (2021) Cite this article 11k Accesses 290 Altmetric Metricsdetails Abstract Background Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19. Methods A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups. Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention. Results The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 0.05). There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups. Conclusion Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19. Further clinical studies are warranted. Trial registry Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020.5.20; URL of trial registry record: https://en.irct.ir/trial/48213 Introduction In recent years, coronavirus infections have been a significant source of morbidity and mortality around the world [1]. Novel coronavirus 2019 (nCoV-2019), now known as acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the pandemic of coronavirus disease COVID-19 [2]. This infection usually causes a defined pattern of metabolic and clinical changes in affected patients [3]. Leukocytopenia, lymphopenia, and elevated C-reactive protein (CRP) can occur in the primary form of COVID-19. With disease progression, increasing levels of leukocytes, creatine kinase, and creatinine may also occur [4]. Host nutritional status has an important role in defense against viral infections [5]. Numerous studies have reported that malnourished humans are more susceptible to a wide variety of infections [6]. Indeed, proper nutrition can preserve the immune system and improve its function [7]. Nutritional deficiencies influence both immune response and viral pathogenic functions [5, 8]. Moreover, they may lead to oxidative stress in the host which can alter the genome of the virus, so that a normally benign or mildly pathogenic virus can convert to a highly virulent pathogen [6]. Omega-3 polyunsaturated fatty acids (n3-PUFAs) are important mediators of inflammation and acquired immune responses and can amplify anti-inflammatory responses [9]. Recent studies have been shown that n3-PUFAs including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and α-linoleic acid (ALA) can increase the stability of the cell membrane, regulate immune function, block hyper inflammatory reactions, and reduce the incidence of systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and complications of infection [10]. Chen et al. reported a lower mortality rate in septic patients who received total parenteral nutrition containing 100 ml (ml) n3-PUFAs daily for 4 weeks. Also, the treatment group had a higher ratio of T helper to inducer lymphocytes and CD4 to CD8 lymphocytes in comparison with the control group during the first 7 days of follow-up [11]. Pluta et al. found that patients with chronic kidney disease, who daily received one capsule of omega 3 including 1000 mg n3-PUFAs containing 330 mg of EPA, 220 mg of DHA, and 100 mg of other acids such as alpha-linolenic acid (ALA) had lower urinary excretion of monocyte chemoattractant protein-1 (MCP-1) after 6 months of follow-up. However, white blood cell (WBC) count and serum levels of CRP and MCP-1 did not change significantly [12]. Soleimani et al. reported that patients with diabetic nephropathy, who received 1 g omega-3 acids daily had higher circulating nitric oxide (NO) after 12 weeks of follow-up with no change in serum concentrations of high sensitivity (hs)-CRP or total antioxidant capacity (TAC) [13]. Coghill et al. demonstrated that human immunodeficiency virus (HIV) and human herpesvirus-8 (HHV-8) co-infected patients, who received 3 gr of omega-3 fatty acids daily (each pill contained about 230 mg EPA and 150 mg DHA), had lower serum concentrations of the inflammatory cytokine interleukin-6 (IL-6) and higher CD8 + counts at 12 weeks [14]. Omar et al. in a recent study found that end-stage renal disease patients on chronic hemodialysis, who daily received two grams of omega-3 (containing 360 mg EPA and 240 mg DHA) had lower serum levels of IL-6 and CRP at 3 months [15]. On the other hand, Rice et al. conducted a randomized, double-blind, placebo-controlled, multicenter trial and reported that the n-3 supplementation did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. Patients receiving the n-3 supplement had fewer ventilator-free days, intensive care unit–free days, and nonpulmonary organ failure–free days [16] Given suggestive evidence of the beneficial effects of n3-PUFAs on the immune system and the contradictory results of recent studies concerning the effects of omega-3 fatty acids in patients with viral infections, we aimed to examine the effect of omega-3 supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19. Methods Study design and population This study was a double-blind, randomized clinical trial study carried out from May to July 2020 in critically ill patients infected with COVID-19 in Razi Hospital, Rasht, Iran. The inclusion criteria were the age between 35 and 85 years, diagnosis of COVID-19 confirmed by a positive RT-PCR nasopharyngeal swab, as well as symptoms such as severe pneumonia, fever, fatigue, dry cough, respiratory distress, and indicated for enteral nutrition. One hundred thirty five patients were assessed for eligibility and 128 patients met the inclusion criteria. Sample size was calculated using α = 0.95, β = 20%, ratio of unexposed to exposed of 2:1, and power of 0.8. An unequal randomization ratio (2:1) was used because of a fixed and limited budget for this research project. Therefore, more participants were randomized to the cheaper arm in order to facilitate greater overall recruitment in the face of a possibly high drop-out rate. The exclusion criteria included history of cardiovascular and/or lung diseases (n = 4), and diagnosis of malignant tumors (n = 1) because of their effects on current medical treatment and diet, consumption of omega-3 fatty acids during the prior 3 months before the study (n = 1), history of hypersensitivity reactions to fish or its products (n = 1), did not complete the study because of death (n = 14) or no indication for enteral feeding any more (n = 13). The final analysis was performed on 101 critically ill patients infected with COVID-19 who were assigned to the intervention (n = 28) and control (n = 73) groups. Interventions This study was done in form of a double-blind trial. Though no placebo was used, the patients were not aware of their feeding contents, and the patients and researchers were not aware of the arms of the study. Finally, the results were analyzed by a person outside of the treatment team. The allocation to the groups was done through web-based randomization using https://www.randomizer.org. Sealed non-transparent envelopes with randomized sequences were used to hide the allocation. All participants received high protein formula as 30 kcal/kg/d through enteral feeding. The intervention group received one capsule of 1000 mg omega-3 daily (Vita Pharmed, Switzerland) containing 400 mg EPAs and 200 mg DHAs for 14 days through adding the supplement to their enteral formula. Omega-3 fatty acids fortified formula was administered to the case group by a nurse, who was not a member of the research team, for 2 weeks after the first 24 h of hospitalization in ICU. The omega-3 capsules were pierced with a syringe, then its contents were squeezed out into a prepared enteral formula, with thorough mixing. The control group received nutritional support including the isocaloric-isovolemic formula using the same route, except for the intervention. Data collection After collecting the written consent forms, the required information was collected using a pre-determined checklist including the following sub-scales: Anthropometric and medical history Data on age, weight, height, previous illnesses, medications, blood pressure, serum lipids, random blood glucose, and respiratory status was collected using medical records. Dietary intake Data on nutritional intake including caloric intake, type of formula, and dietary supplements were assessed using documents recorded in ICU sheets and patient logs. Biochemical and pathological indices Arterial blood gas (ABG) parameters [i.e., O2 saturation, arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), and base excess (Be)], kidney function parameters [i.e., blood urea nitrogen (BUN), creatinine (Cr), and urine volume], as well as blood glucose, mean arterial pressure, white cell blood count (including neutrophil, lymphocyte, monocyte), the Acute Physiology and Chronic Health Evaluation II (APACHE II), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), the partial thromboplastin time (PTT), serum electrolytes [i.e. sodium (Na), potassium (K), calcium, phosphorus (P)], albumin, and hematocrit (Hct) were measured at baseline and after 14 days of the intervention. These measurements were routinely performed in the hospital using standard kits and the required data were gathered from the lab test section of the ICU sheets. Statistical analyses Quantitative data were presented as the mean ± standard deviation and qualitative data were presented as the percentage and number to describe the status of demographic, social, and anthropometric measurements of the participants. The Kolmogorov–Smirnov test was used to verify the normal distribution. Independent T-test and chi-square test were used to compare results between groups at baseline. The core research question was whether the difference between groups of interest changed from the basal values to the values after treatment. The general linear model repeated measure was used to identify the group-by-time interaction effect of omega-3 supplementation on inflammatory and biochemical markers, comparing the values in intervention and control groups. Confounding factors including age, sex, body mass index (BMI), dietary intake, smoking, presence of background diseases such as diabetes and hypertension, and medication and supplements were adjusted for. Statistical analyses were performed using the SPPS software (version 20). P values less than 0.05 were considered statistically significant. Results Patient characteristics A total of 135 eligible patients were included in this study and randomization was done 1:2. Of these, seven patients were excluded based on the exclusion criteria (Fig. 1). In addition, another seven patients in the treatment group and twenty controls were excluded from analysis after randomization, because they died during the intervention period. Finally, 101 patients were included in the analysis, of which 28 were assigned to the treatment group and 73 were assigned to the control group. All baseline data in Table 1 were normally distributed. The groups were not significantly different in demographic or clinical characteristics at baseline, except for the lymphocyte count, which was lower in the intervention group (11.59 vs 13.26, P = 0.01). Fig. 1 Study flowchart Full size image Table 1 Baseline demographic and clinical data of the study groups Full size table Effects of omega-3 supplementation on 1-month survival rate The intervention group had significantly higher 1-month survival rate compared with the control group (21% vs 3%, P = 0.003). About 21% (n = 6) of the participants in the intervention group and only about 3% (n = 2) of the participants in the control group survived at least for 1 month after the beginning of the study. Effects of omega-3 supplementation on kidney function As summarized in Table 2, 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) were significantly lower and the amount of urine excreted (2101 vs 1877.02, F = 12.26, p = 0.01) was significantly higher in the intervention group compared with the control group. Table 2 Comparison of clinical and biochemical parameters between the intervention group and control group after the intervention Full size table Effects of omega-3 supplementation on arterial blood gas (ABG) parameters After 14 days, the 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) were significantly higher in the intervention group compared with the control group. However, there were no significant differences among PO2 and PCO2 between two groups (Table 2). Effects of omega-3 supplementation on the Glasgow coma scale (GCS) On admission to the study, the mean GCS was 8.37 in the intervention group and 7.90 in the control group (P > 0.05). As shown in Table 2, it was significantly lower after 14 days of the study in both groups (7.90 vs 7.49, F = 6.07, P = 0.05). No significant difference was found in APACHE II score between the groups (15.54 ± 1.73 vs 15.42 ± 1.92., P = 0.78). Effects of omega-3 supplementation on serum electrolytes As shown in Table 2, the level of K was significantly reduced in the intervention group compared to the control group (4.00 vs 4.14, F = 10.15, P = 0.01) after 14 days. No significant differences were found between the levels of serum electrolytes including Na, Ca, and P in between two groups after intervention. Effects of omega-3 supplementation on blood clotting function and cell blood count (CBC) The lymphocyte count increased in the omega-3 group compared to the control group, though this effect was marginally significant (11.59 vs 11.80, F = 4.08, P = 0.05). There were no significant differences in levels of PTT, hematocrit, neutrophil, monocyte, hemoglobin, and Plt between the two groups (Table 2). Effects of omega-3 supplementation on the other blood factors As shown in Table 2, no significant differences were observed in the other factors including blood glucose, albumin, MAP, and O2 sat between two groups after intervention. Discussion To our knowledge, this is the first randomized clinical trial assessing the effect of omega-3 fatty acid supplementation in ICU patients with COVID-19. We found that administration of omega-3 PUFA significantly improved arterial PH, HCO3, and Be. This trial also supports our hypothesis that omega-3 supplementation can improve the level of indicators of kidney function including BUN, Cr, K, and urine volume. The results have indicated that omega-3 supplementation may increase the lymphocyte count and GCS. However, these increases were not statistically significant. In our study, omega-3 supplementation had a positive effect on 1-month survival rate of the critically ill patients with COVID-19. Many severely or critically ill COVID-19 patients have been reported to develop severe metabolic and respiratory acidosis [17, 18], indicating possible microcirculation dysfunction [18]. This study identified that omega-3 supplementation improved arterial PH, HCO3, and Be, which may be related to the effect of omega-3 supplementation on microcirculatory function. Several studies [19,20,21] have reported that omega-3 supplementation improved endothelial function and microcirculation. Vasil'ev et al. reported that therapy with omega-3 PUFAs increased tissue hemoperfusion, capillary blood flow, and tissue blood flow and generally improved microcirculation. Trevor et al. studied the effects of DHA and EPA supplementation on vascular reactivity and microcirculation. They found that DHA significantly enhanced vasodilator mechanisms, attenuated constrictor responses, and improved endothelium reactivity and microcirculation [22] It has been reported that renal abnormalities occurred in the majority of patients with COVID-19 [18, 23,24,25], and microemboli in renal vessels as a consequence of the prothrombotic state results in kidney damage. Furthermore, hypertension induced by pro-inflammatory status, increasing IFN-γ, IL-6, and IL-17 expression and CD8 + T cells in the kidney, angiotensin II-induced hypertension, and the endothelial dysfunction caused by the innate immune response seems to be involved in the kidney injury [26]. Renal involvement in COVID-19 was reported to be associated with higher mortality [18, 23,24,25]. Hence, it is crucial to identify adjuvant and protective therapies that improve kidney function in patients with severe COVID-19. The present study found that the administration of omega-3 PUFAs significantly decreased BUN, Cr, and K and increased urine volume in ICU patients infected with COVID-19. These findings suggest that omega-3 supplementation may be protective against progression to renal impairment, consistent with observations from animal models that showed that omega-3 PUFA supplementation reduces the progression of renal disease [27,28,29,30,31]. Moreover, studies in human subjects suggested that a higher dietary intake of PUFAs may improve creatinine clearance [32] and also may have a role in maintaining healthy kidney function [33]. In contrast, some studies have reported that omega-3 treatment did not protect renal function. Higashihara et al. assessed the effects of omega-3 PUFAs on kidney function in 41 patients with stages two or three chronic kidney disease (CKD); omega-3 supplementation did not alter kidney function, assessed using 24-h urine creatinine clearance. Another study demonstrated that omega-3 PUFA pre-treatment did not protect against renal function deterioration or ischemia-induced renal inflammation; however, tubular transport was improved [30]. Previous studies that have evaluated omega-3 PUFAs in the treatment of kidney disease have yielded contradictory results, which may reflect differences in study duration, dosage of omega-3, route of administration, and type of omega-3 fatty acids. Omega-3 PUFAs can change the lipid composition and cell function of lymphocytes and affect cellular immune function [10, 34, 35]. There is no consensus regarding the efficacy of omega-3 PUFAs on lymphocyte count. A meta-analysis of randomized control trials found that the value of postoperative lymphocyte count increased in response to omega-3 PUFAs supplementation [10]. Consistent with this finding, the results of the present study identified a marginal increase in lymphocyte count after omega-3 PUFAs supplementation. The results of the current study identified a significant difference in 1-month survival rate between two groups. Supplementation with omega-3 fatty acids may have immune-modulating [36,37,38] and organ-protective effects [39, 40]. Previous studies have reported that higher plasma levels of omega-3 PUFAs are associated with survival [41,42,43]. Moreover, a recent systematic review found that omega-3 supplements can improve survival in critically ill patients [44]. However, another recent review article concluded that there is weak evidence for beneficial effects of omega-3 supplementation on ICU or hospitalized survival in critically ill patients [45]. Heller et al. have reported that the effects and effect sizes of omega-3 on clinical outcome is dependent on the disease [46]. Our study had some limitations. Although the sample size was calculated with an acceptable power for the study, the results need to be confirmed in larger studies. Moreover, only one dosage of omega-3 was used, which makes it difficult to discuss the dose–response efficacy of the supplement. It is possible that we may have seen more benefit with a higher dose. Another limitation of this study was the short duration of the study. Furthermore, prognostic biochemical markers in COVID-19 including the inflammatory cytokines C-reactive protein (CRP), interleukin-6, and interleukin-10, were not measured due to limited resources. Another limitation of this study was that there was no access to an omega-3 fatty acid enriched formula, and therefore we had to add it manually. Conclusion In conclusion, this randomized, double-blind, clinical trial has shown that omega-3 supplementation has promising effects on acidosis and renal function and possibly can improve clinical outcomes of patients infected with COVID-19. Further clinical studies with different dosages of n-3 PUFAs, larger sample sizes, and longer duration are warranted. Availability of data and materials All data will be made available upon request. Abbreviations n3-PUFAs: Omega-3 polyunsaturated fatty acids Na: Sodium K: Potassium BUN: Blood urea nitrogen Cr: Creatinine HCT: Hematocrit Ca: Calcium P: Phosphorus MAP: Mean arterial pressure O2 sat: O2 saturation PCO2 : Partial pressure of oxygen WBC: White blood cells References 1. Al-Osail AM, Al-Wazzah MJ. The history and epidemiology of middle east respiratory syndrome corona virus. Multidiscip Respir Med. 2017;12(1):1–6. Article Google Scholar  2. Ye Z-W, Yuan S, Yuen K-S, Fung S-Y, Chan C-P, Jin D-Y. Zoonotic origins of human coronaviruses. Int J Biol Sci. 2020;16(10):1686–97. CAS PubMed PubMed Central Article Google Scholar  3. Kurpad AV. The requirements of protein & amino acid during acute & chronic infections. Indian J Med Res. 2006;124(2):129–48. CAS PubMed PubMed Central Google Scholar  4. Han Q, Lin Q, Jin S, You L. Recent insights into 2019-nCoV: a brief but comprehensive review. J Infect. 2020;80(4):373–7. CAS PubMed PubMed Central Article Google Scholar  5. Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systemic review. J Med Virol. 2020;92(5):479–90. CAS PubMed PubMed Central Article Google Scholar  6. Beck MA, Levander OA, Handy J. Selenium deficiency and viral infection. J Nutr. 2003;133(5):1463S-7S. CAS PubMed Article PubMed Central Google Scholar  7. López Plaza B, Bermejo López LM. Nutrición y trastornos del sistema inmune. Nutr Hosp. 2017;34:68–71. PubMed Article PubMed Central Google Scholar  8. BourBour F, Mirzaei Dahka S, Gholamalizadeh M, Akbari ME, Shadnoush M, Haghighi M, Taghvaye-Masoumi H, Ashoori N, Doaei S. Nutrients in prevention, treatment, and management of viral infections; special focus on coronavirus. Arch Physiol Biochem. 2020;7:1–10. Article CAS Google Scholar  9. Bheliya VK, Pathak AK. clinical research and role of dietary supplement in the treatment of middle east respiratory syndrome current status. J Pharm Pharm Sci. 2020;9(3):823–39. CAS Google Scholar  10. Zhao Y, Wang C. Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy: a meta-analysis of randomized control trials in China. Medicine. 2018;97(16):e0472. CAS PubMed PubMed Central Article Google Scholar  11. Chen H, Wang W, Hong Y, Zhang H, Hong C, Liu X. Single-blinded, randomized, and controlled clinical trial evaluating the effects of omega-3 fatty acids among septic patients with intestinal dysfunction: a pilot study. Exp Ther Med. 2017;14(2):1505–11. CAS PubMed PubMed Central Article Google Scholar  12. Pluta A, Stróżecki P, Kęsy J, Lis K, Sulikowska B, Odrowąż-Sypniewska G, Manitius J. Beneficial effects of 6-month supplementation with omega-3 acids on selected inflammatory markers in patients with chronic kidney disease stages 1–3. Biomed Res Int. 2017;2017:1680985. PubMed PubMed Central Article CAS Google Scholar  13. Soleimani A, Taghizadeh M, Bahmani F, Badroj N, Asemi Z. Metabolic response to omega-3 fatty acid supplementation in patients with diabetic nephropathy: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2017;36(1):79–84. CAS PubMed Article PubMed Central Google Scholar  14. Coghill AE, Schenk JM, Mahkoul Z, Orem J, Phipps W, Casper C. Omega-3 decreases interleukin-6 levels in HIV and HHV-8 co-infected patients: results from a randomized supplementation trial in Uganda. AIDS. 2018;32(4):505–12. CAS PubMed PubMed Central Article Google Scholar  15. Omar ZA, Montser BA, Farahat MAR. Effect of high-dose omega 3 on lipid profile and inflammatory markers in chronic hemodialysis children. Ren Fail. 2010;32(9):1031–5. Article CAS Google Scholar  16. Rice TW, Wheeler AP, Thompson BT, DeBoisblanc BP, Steingrub J, Rock P. Enteral omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011;306(14):1574–81. CAS PubMed PubMed Central Article Google Scholar  17. Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther. 2020;26(5):499–501. CAS PubMed PubMed Central Article Google Scholar  18. Li H, Liu L, Zhang D, Xu J, Dai H, Tang N, Su X, Cao B. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020;395(10235):1517–20. CAS PubMed PubMed Central Article Google Scholar  19. Heller A, Koch T. Immunonutrition with omega-3-fatty acids. Are new anti-inflammatory strategies in sight? Zentralbl Chir. 2000;125(2):123–36. CAS PubMed PubMed Central Google Scholar  20. Vasil’ev A, Strel’tsova N, Sekisova M. Effect of omega-3 fatty acids on the serum lipid profile and microcirculation in patients with metabolic syndrome and hypertensive disease. Klin Med. 2009;87(4):37–41. CAS Google Scholar  21. Weitzel L-RB, Mayles WJ, Sandoval PA, Wischmeyer PE. Effects of pharmaconutrients on cellular dysfunction and the microcirculation in critical illness. Curr Opin Anaesthesiol. 2009;22(2):177–83. PubMed Article PubMed Central Google Scholar  22. Mori TA, Watts GF, Burke V, Hilme E, Puddey IB, Beilin LJ. Differential effects of eicosapentaenoic acid and docosahexaenoic acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, overweight men. Circulation. 2000;102(11):1264–9. CAS PubMed Article PubMed Central Google Scholar  23. Pei G, Zhang Z, Peng J, Liu L, Zhang C, Yu C, Ma Z, Huang Y, Liu W, Yao Y. Renal involvement and early prognosis in patients with COVID-19 pneumonia. J Am Soc Nephrol. 2020;31(6):1157–65. CAS PubMed Article PubMed Central Google Scholar  24. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97(5):829–38. CAS PubMed PubMed Central Article Google Scholar  25. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017–32. CAS PubMed Article PubMed Central Google Scholar  26. Robba C, Battaglini D, Pelosi P, Rocco PR. Multiple organ dysfunction in SARS-CoV-2: MODS-CoV-2. Expert Rev Respir Med. 2020. https://doi.org/10.1080/17476348.2020.1778470. Article PubMed PubMed Central Google Scholar  27. Simopoulos A, Leaf A, Salem N Jr. Workshop statement on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2000;63(3):119–21. CAS PubMed Article PubMed Central Google Scholar  28. Brown SA, Finco DR, Brown CA. Is there a role for dietary polyunsaturated fatty acid supplementation in canine renal disease? J Nutr. 1998;128:2765S-7S. CAS PubMed Article PubMed Central Google Scholar  29. Garman JH, Mulroney S, Manigrasso M, Flynn E, Maric C. Omega-3 fatty acid rich diet prevents diabetic renal disease. Am J Physiol Renal Physiol. 2009;296(2):F306-16. CAS PubMed Article PubMed Central Google Scholar  30. Rund KM, Peng S, Greite R, Claaßen C, Nolte F, Oger C, Galano J-M, Balas L, Durand T, Chen R. Dietary omega-3 PUFA improved tubular function after ischemia induced acute kidney injury in mice but did not attenuate impairment of renal function. Prostaglandins Other Lipid Mediat. 2020;146:106386. CAS PubMed Article PubMed Central Google Scholar  31. Hassan IR, Gronert K. Acute changes in dietary ω-3 and ω-6 polyunsaturated fatty acids have a pronounced impact on survival following ischemic renal injury and formation of renoprotective docosahexaenoic acid-derived protectin D1. J Immunol. 2009;182(5):3223–32. CAS PubMed Article PubMed Central Google Scholar  32. Lauretani F, Maggio M, Pizzarelli F, Michelassi S, Ruggiero C, Ceda G, Bandinelli S, Ferrucci L. Omega-3 and renal function in older adults. Curr Pharm Des. 2009;15(36):4149–56. CAS PubMed PubMed Central Article Google Scholar  33. Gopinath B, Harris DC, Flood VM, Burlutsky G, Mitchell P. Consumption of long-chain n-3 PUFA, α-linolenic acid and fish is associated with the prevalence of chronic kidney disease. Br J Nutr. 2011;105(9):1361–8. CAS PubMed Article PubMed Central Google Scholar  34. Fan Y-Y, McMurray DN, Ly LH, Chapkin RS. Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr. 2003;133(6):1913–2035. CAS PubMed Article PubMed Central Google Scholar  35. Gutiérrez S, Svahn SL, Johansson ME. Effects of omega-3 fatty acids on immune cells. Int J Mol Sci. 2019;20(20):5028. PubMed Central Article CAS Google Scholar  36. Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep. 2004;6(6):461–7. PubMed Article PubMed Central Google Scholar  37. Berger MM, Delodder F, Liaudet L, Tozzi P, Schlaepfer J, Chiolero RL, Tappy L. Three short perioperative infusions of n-3 PUFAs reduce systemic inflammation induced by cardiopulmonary bypass surgery: a randomized controlled trial. Am J Clin Nutr. 2013;97(2):246–54. CAS PubMed Article PubMed Central Google Scholar  38. Gogos CA, Ginopoulos P, Salsa B, Apostolidou E, Zoumbos NC, Kalfarentzos F. Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Cancer. 1998;82(2):395–402. CAS PubMed Article PubMed Central Google Scholar  39. Hall TC, Bilku DK, Al-Leswas D, Neal CP, Horst C, Cooke J, Metcalfe MS, Dennison AR. A randomized controlled trial investigating the effects of parenteral fish oil on survival outcomes in critically ill patients with sepsis: a pilot study. JPEN J Parenter Enteral Nutr. 2015;39(3):301–12. CAS PubMed Article Google Scholar  40. Pontes-Arruda A, DeMichele S, Seth A, Singer P. The use of an inflammation-modulating diet in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of outcome data. JPEN J Parenter Enteral Nutr. 2008;32(6):596–605. CAS PubMed Article PubMed Central Google Scholar  41. Mozaffarian D, Lemaitre RN, King IB, Song X, Huang H, Sacks FM, Rimm EB, Wang M, Siscovick DS. Plasma phospholipid long-chain ω-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Ann Intern Med. 2013;158(7):515–25. PubMed PubMed Central Article Google Scholar  42. Nagata C, Takatsuka N, Shimizu H. Soy and fish oil intake and mortality in a Japanese community. Am J Epidemiol. 2002;156(9):824–31. PubMed Article PubMed Central Google Scholar  43. Eide IA, Jenssen T, Hartmann A, Diep LM, Dahle DO, Reisæter AV, Bjerve KS, Christensen JH, Schmidt EB, Svensson M. The association between marine n-3 polyunsaturated fatty acid levels and survival after renal transplantation. Clin J Am Soc Nephrol. 2015;10(7):1246–56. CAS PubMed PubMed Central Article Google Scholar  44. Manzanares W, Dhaliwal R, Jurewitsch B, Stapleton RD, Jeejeebhoy KN, Heyland DK. Parenteral fish oil lipid emulsions in the critically ill: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr. 2014;38(1):20–8. PubMed Article CAS PubMed Central Google Scholar  45. Koekkoek WK, Panteleon V, van Zanten AR. Current evidence on ω-3 fatty acids in enteral nutrition in the critically ill: a systematic review and meta-analysis. Nutrition. 2019;59:56–68. CAS Article Google Scholar  46. Heller AR, Rössler S, Litz RJ, Stehr SN, Heller SC, Koch R, Koch T. Omega-3 fatty acids improve the diagnosis-related clinical outcome. J Clin Med. 2016;5(3):34. Article CAS Google Scholar  Download references Acknowledgements This study was conducted at Guilan University of Medical Sciences, Rasht, Iran. We acknowledge the staff of the mentioned centers for their kind cooperation. Funding Funding for this study was provided by Sabzevar University of Medical Sciences (code: 99068), Sabzevar, Iran. Author information Affiliations Research Center of Health and Environment, School of Health, Guilan University of Medical Sciences, Rasht, Iran Saeid Doaei Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Saeid Doaei, Mohammad Esmail Akbari & Seyed Alireza Mosavi Jarrahi Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran Somayeh Gholami & Forough Samipoor National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran Samira Rastgoo, Fatemeh Bourbour & Narjes Ashouri Mirsadeghi Student Research Committee, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Gholamalizadeh School of Paramedicine, Guilan University of Medical Sciences, Langroud, Iran Seyedeh Elaheh Bagheri Department of Clinical Nutrition, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mahdi Shadnoush Traditional and Complementary Medicine Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran Fereshteh Ghorat School of Health, Qazvin University of Medical Sciences, Qazvin, Iran Azadeh Hajipour Department of Non-Communicable Disease, Deputy of Health Services, Dezful University of Medical Sciences, Dezful, Iran Parvin Joola Iranian Research Center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, Iran Alireza Moslem Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA Mark O. Goodarzi Contributions SD, SG, SR, MGH, FM, SEB, FS and MEA designed the study, involved in the data collection, analysis, and drafting of the manuscript. MSH, FGH, AMJ, NA, HTM, AH, PJ, AM and MG were involved in the design of the study, analysis of the data, and critically reviewed the manuscript. All authors read and approved the final manuscript. Corresponding author Correspondence to Alireza Moslem. Ethics declarations Ethics approval and consent to participate The study was approved by the ethics committee of Sabzevar University of Medical Sciences and Health Services, Khorasan Razavi, Iran (Ethical code: IR.MEDSAB.REC.1399.054). Furthermore, the necessary details of the project were explained clearly to the patients or their first-degree relatives and written informed consent was obtained from them before they joined the study. All participants were free to decide whether or not to participate or to withdraw at any time and for any reason without further penalty either personal or professional or affecting their future medical care. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Reprints and Permissions About this article Cite this article Doaei, S., Gholami, S., Rastgoo, S. et al. The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial. J Transl Med 19, 128 (2021). https://doi.org/10.1186/s12967-021-02795-5 Download citation Received10 November 2020 Accepted18 March 2021 Published29 March 2021 DOIhttps://doi.org/10.1186/s12967-021-02795-5 Share this article Anyone you share the following link with will be able to read this content: https://rdcu.be/cm28i Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative Keywords Omega-3 fatty acids Coronavirus Kidney function Respiratory function   Download PDF Section Nutrition & metabolism Sections Figures References Abstract Introduction Methods Results Discussion Conclusion Availability of data and materials Abbreviations References Acknowledgements Funding Author information Ethics declarations Additional information Rights and permissions About this article Journal of Translational Medicine ISSN: 1479-5876 Contact us Submission enquiries: Access here and click Contact Us General enquiries: info@biomedcentral.com

2021.03.06

學術分享 Blood omega-3 fatty acids and death from COVID-19: A pilot study

Prostaglandins, Leukotrienes and Essential Fatty Acids Volume 166, March 2021, 102250   Short communication Blood omega-3 fatty acids and death from COVID-19: A pilot study Author links open overlay panelArashAsheraNathan L.TintlebcMichaelMyersdLauraLockshonaHeribertBacarezaeWilliam S.Harrisbf a Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA b Fatty Acid Research Institute, Sioux Falls, SD c Department of Mathematics and Statistics, Dordt University, Sioux Center, IA d Los Alamitos Medical Center, Los Alamitos, CA e Department of Medical Affairs, Cedars-Sinai Medical Center, Los Angeles, CA f Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD Received 6 January 2021, Revised 17 January 2021, Accepted 17 January 2021, Available online 20 January 2021. Show less Add to Mendeley Share Cite https://doi.org/10.1016/j.plefa.2021.102250Get rights and content       Highlights   • Nutrition-based interventions to reduce COVID-19 morbidity/mortality are needed. • The Omega-3 Index (O3I) was measured in banked blood from 100 COVID-19 patients. • Risk for death was analyzed as a function of quartiles (Q) of the O3I. • Patients in Q4 (O3I ≥ 5.7%) vs. Q1–3 were 75% less likely to die (p = 0.07). • These pilot data suggest that a higher O3I may lower risk for death from COVID-19.   Abstract Very-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked blood samples drawn at hospital admission. Fourteen patients died, one of 25 in quartile 4 (Q4) (O3I ≥5.7%) and 13 of 75 in Q1–3. After adjusting for age and sex, the odds ratio for death in patients with an O3I in Q4 vs Q1–3 was 0.25, p = 0.07. Although not meeting the classical criteria for statistical significance, this strong trend suggests that a relationship may indeed exist, but more well-powered studies are clearly needed. Previous article in issue Next article in issue Keywords Omega-3 fatty acids Eicosapentaenoic acid Docosahexaenoic acid COVID-19 Total mortality Omega-3 index Inflammation 1. Introduction COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been diagnosed in over 80 million people worldwide as of the end of 2020, and over 1.8 million have died [1]. Although 81% of symptomatic individuals have relatively mild disease, 14% will develop severe disease characterized by dyspnea, hypoxia, or >50 percent lung involvement by imaging, with the remaining 5% developing critical disease characterized by respiratory failure, shock, and/or multiorgan dysfunction [2]. Severe and critical disease from COVID-19 is associated with advancing age (especially over 65 years), male gender, chronic lung disease, obesity, cardiovascular disease including hypertension, diabetes, and other chronic medical conditions. Severe COVID-19 disease and death is, in part, mediated by rapid elevations of inflammatory cytokines including TNF-alpha, IL-1β, and IL-6 leading to a cytokine release syndrome or “cytokine storm.” [3] Accordingly, an attractive preventative approach to COVID-19 infection is to minimize cytokine release. Very long-chain omega-3 s (DHA and EPA) found in fish oils have a plethora of biological activities including directly and indirectly modulating inflammatory responses and cytokine release [4], [5], [6]. In non-COVID-19 ettings, higher intakes [7], [8] and blood levels [9], [10] of these omega-3 s are associated with lower levels of circulating inflammatory cytokines, and intervention with fish oils reduces levels [11], [12]. EPA and DHA are precursors to a suite of inflammation-resolving mediators (IRMs; resolvins, maresins and protectins [13]) that actively regulate the resolution of acute inflammation. IRMs down-regulate cytokine production and promote a return to homeostasis via monocyte/macrophage-mediated uptake of debris, apoptosis of neutrophils, and clearing of microbes. Accordingly, higher intakes of EPA and DHA (which result in higher RBC EPA+DHA levels, hereafter called the Omega-3 Index, O3I [14], [15]) have been proposed to lower the risk for adverse outcomes from COVID-19 [16], [17], [18], [19], [20], [21], [22], and case reports suggesting benefit have been published [23], [24]. Given the profound public health concerns related to the current COVID-19 pandemic, modifiable risk factors for developing severe and critical complications are urgently needed, especially ones that may be easily implemented and nutritionally based. Despite the known mechanisms by which IRMs and omega-3 fatty acids support the active, endogenous resolution of inflammatory mechanisms, to our knowledge no study has explored the relationship between omega-3 tissue levels and COVID-19 outcomes. The primary objective of this pilot study was to define the relationship between O3I and death from COVID-19. We hypothesize that a higher O3I is associated with lower risk for death in these patients. 2. Methods 2.1. Subjects We studied 100 patients hospitalized at Cedars-Sinai Medical Center from March 1, 2020 onwards with confirmed COVID-19 infection who met the criteria for inclusion, which were the availability of basic demographic data, clinical outcomes and an EDTA blood sample (drawn within 10 days of diagnosis) stored at −80 °C at the Cedars-Sinai biorepository. If more than one sample was available, the first sample drawn after the time of diagnosis was utilized. We utilized sample remnant protocol Pro00036514 to obtain blood samples for this study. Briefly, a protocol was submitted to the Enterprise Information Service (EIS) team and staff members of the Biobank. After review and approval, the EIS/Biobank team pulled the samples and the data, de-identifying each sample by assigning a study-specific number. Using this protocol, we obtained a limited data and blood sample set to conduct this pilot investigation. The study was approved by the IRB of Cedars-Sinai Medical Center (STUDY-00,000,779). 2.2. Clinical outcomes The primary outcome was death from COVID-19 infection. 2.3. Laboratory Blood samples were thawed at the biorepository and one drop was placed on a dried blood spot collection card pre-treated with antioxidants to protect the fatty acids from degradation. The cards were then shipped overnight in batch to OmegaQuant Analytics (Sioux Falls, SD) for analysis of fatty acids and calculation of the Omega-3 Index [25]. Briefly, blood spots were transferred to a reaction vial and FA methyl esters (FAMEs) were generated using boron trifluoride in methanol by heating for 45 min at 100 °C. FAMEs were extracted into hexane (after the addition of water) and analyzed using a GC2010 Gas Chromatograph (Shimadzu Corporation, Columbia, MD) equipped with a SP2560, 100-m column (Supelco, Bellefonte, PA). FAMEs were identified by comparison with a standard mixture (GLC, Nucheck Prep, Elysian, MN). Analysis was conducted using an internal-standard-based, three-point calibration curve to quantify levels of 24 FAMEs which were each expressed as a percent of total FAs. The O3I was calculated from the dried blood spot EPA+DHA value as described previously [25]. The analytical coefficient of variation for the O3I is <5%. 2.4. Statistical methods The study sample is described using standard descriptive statistics (means and standard deviations, medians and ranges, and counts and percentages). Additional descriptive summary of the sample is provided by stratifying using quartiles of the O3I or by comparing Q4 to Q1–3. The distribution of age, sex and do not resuscitate (DNR) status by O3I quartiles or top 25%/bottom 75% was tested using an F-test (age) or Chi-squared test (sex, DNR status). The primary analysis examined the hypothesis that O3I is associated with risk for death. We first predicted death using unadjusted logistic regression models by quartiles of the O3I using a Chi-squared test to evaluate overall (4-group) association. We also predicted death by age, sex and DNR status to evaluate and confirm known associations between risk for death and these factors. Subsequently, significant association between O3I quartiles and death was tested using logistic regression and by comparing Q4 with Q1–3 in both unadjusted models and models adjusted for age and sex. To account for the small sample sizes present in this study, primary model results use Firth's adjustment for small sample sizes in logistic regression using the logistf package in R [26]. We also report conventional logistic regression F-test results for comparison. A 2-tailed p-value of 0.05 was used for statistical significance. 3. Results 3.1. Sample description The study sample is described in Table 1. They were predominantly men, the mean age was over 70, and they were admitted between April and July 2020. Nearly 40% were under a DNR order instituted at some point during the hospitalization, and 14% died during hospitalization. The average O3I was 5.09%, and the median was 4.75%. Table 1. Descriptive statistics. Characteristics of sample % (X/N) or Mean (SD; min,max) Sex – Male 59% (59/100) Age 72.5 (16.5; 25,100) Month of data collection April – 47% (47/100) May – 25% (25/100) June – 15% (15/100) July – 13% (13/100) Red blood cell EPA+DHA (% of RBC fatty acids; the Omega-3 Index, O3I) 5.09% (1.62%; 2.87%, 13.79%) Died 14% (14/100) DNR orders 38% (38/100) Table 2 illustrates the association of the O3I by age, sex and do not resuscitate (DNR) status. Higher O3I values were significantly related to older age, with the highest mean age in the third quartile (79.8 years). Men and those who were not DNR tended to have higher O3I values, but these trends were not statistically significant. Table 2. Demographic profile of participants by category of the O3I. Categorical by O3I Quartile Age Mean (SD) Sex - Male% (x/n) DNR% (x/n) Q1 (O3I<4.0%) 63.0 (18.9) 64% (16/25) 44% (11/25) Q2 (4.0%<O3I<4.7%) 71.0 (16.1) 56% (14/25) 28% (7/25) Q3 (4.7<O3I<5.7%) 79.8 (13.3) 52% (13/25) 52% (13/25) Q4 (O3I≥5.7%) 76.3 (12.7) 64% (16/25) 28% (7/25) P-valuea 0.0014 0.77 0.20 Comparing O3I Q4 vs Q1–3       Q1–3: O3I<5.7% 71.3 (17.5) 57.3% (43/75) 41.3% (31/75) Q4: O3I≥5.7% 76.3 (12.7) 64% (16/25) 28% (7/25) P-valuea 0.19 0.56 0.23 a F-test (age and O3I) or Chi-square test (sex, DNR and O3I). 3.2. Unadjusted analyses Relationships between omega-3 status and fatal outcomes are shown in Table 3. As expected, older patients and those under a DNR order were more likely to die. In O3I Q4, there was one death (a 66-year-old male under a DNR order), whereas there were 13 deaths among the 75 patients in Q1–3. In the unadjusted model (and focusing on the small-sample size p-values), there was a significant difference in risk for death across quartiles of the O3I (p = 0.047), with those in the highest O3I quartile (Q4) having an odds ratio (OR) of 0.39 (p = 0.34) relative to Q1. In an unadjusted comparison between Q4 and Q1–3, the OR for death in Q4 was 0.28 (p = 0.11) or 3.6-fold higher (1/0.28) higher risk in Q1–3 vs. Q4. For comparison, the risk for death from COVID-19 associated with being 1-decade older was about 1.3-fold higher (p = 0.14). Hence, a low O3I appeared to be at least as predictive of risk for death as being 10-years older.  The higher OR for death in Q3 was largely accounted for by age as the mean age in Q3 was the highest of all. The OR in Q3 was markedly attenuated in the adjusted analysis (Table 4). Table 3. Unadjusted associations of the Omega-3 Index and demographic variables with death. Risk factor Death% (x/N) Unadjusted Models OR (95% CI)a Firth's test P-valuea F-test P-valueb Female 14.6% (6/41) 1.00     Male 13.6% (8/59) 0.90 (0.30, 2.83) 0.85 0.88 Age         Per decade – 1.33 (0.92, 2.08) 0.14 0.13 DNR         Yes 34.2% (13/38) 21.76 (4.90, 206.44) <0.0001 0.001 No 1.6% (1/62)       Categorical by O3I Quartile   Overall model F-test 0.047 0.03 Q1 (O3I<4.0%) 12.0% (3/25) 1.00     Q2 (4.0%<O3I<4.7%) 8.0% (2/25) 0.68 (0.11, 3.86) 0.66 0.64 Q3 (4.7<O3I<5.7%) 32.0% (8/25) 3.13 (0.82, 14.30) 0.10 0.10 Q4 (O3I≥5.7%) 4.0% (1/25) 0.39 (0.04, 2.61) 0.34 0.32 Comparing O3I Q4 vs Q1–3         Q1–3: O3I<5.7% 17.3% (13/75) 1.00     Q4: O3I≥5.7% 4.0% (1/25) 0.28 (0.03, 1.26) 0.11 0.13   Bold and italics is used for p-values less than the significance level of 0.05.   a Using the Firth's modified score procedure for small sample sizes. b Standard F-test from Logistic Regression ignoring small sample sizes. Table 4. Associations of the omega-3 index with death adjusted for age and sex. Risk factor Adjusted Models OR (95% CI)a Firth's test P-valuea F-test P-valueb Categorical by O3I Quartile Overall model F-test 0.078 0.0499 Q1 (O3I<4.0%) 1.00     Q2 (4.0%<O3I<4.7%) 0.58 (0.09, 3.35) 0.54 0.52 Q3 (4.7<O3I<5.7%) 2.18 (0.52, 10.80) 0.29 0.28 Q4 (O3I≥5.7%) 0.30 (0.03, 2.08) 0.22 0.22 Comparing O3I Q4 vs Q1–3       Q1–3: O3I<5.7% 1.00     Q4: O3I≥5.7% 0.25 (0.03, 1.11) 0.071 0.099   Bold and italics is used for p-values less than the significance level of 0.05.   a Using the Firth's modified score procedure for small sample sizes. b Standard F-test from Logistic Regression ignoring small sample sizes. 3.3. Adjusted analyses In models adjusted for age and sex (Table 4), the overall relationship across quartiles became somewhat weaker (i.e., from p = 0.047 to 0.078), although the OR at Q4 (vs Q1) decreased slightly (0.39 to 0.30; p-value also decreased somewhat from 0.34 to 0.22). Comparing Q4 to Q1–3, the OR decreased slightly (from 0.28 to 0.25), and the p-value also decreased from 0.11 to 0.07. An OR of 0.25 implies that risk for death in COVID-19 patients with an O3I >5.7% was ~75% less than it was for patients with an O3I<5.7%. 4. Discussion The 2020 COVID-19 pandemic has had devasting effects on morbidity and mortality worldwide. While vaccines may soon slow the spread and drugs may help diminish the adverse effects of infection, preventative measures – ideally ones that are cheap, safe, and readily accessed by large numbers of people – that modulate the most severe disease outcomes are desperately needed. Some evidence is accumulating for a potential benefit of vitamin D [27], and here we examined another nutrient, omega-3 fatty acids, which like vitamin D, have multiple anti-inflammatory effects and may also reduce risk for adverse COVID-19 outcomes. In this pilot study we compared the associations between the O3I and risk for death from COVID-19 in 100 patients. We found (in age and sex-adjusted models) that those patients with an O3I at 5.7% or greater were at about 75% lower risk for death compared with those below that value (p = 0.071). Although not meeting the criteria for classical statistical significance, this strong trend suggests that a relationship may indeed exist, but more well-powered studies are clearly needed. The OR for death was higher in Q3 than in the other quartiles including Q4. Part of the reason for this was the mean age (and the percent of patients with DNR orders) was the highest in Q3. Accordingly, in the age-adjusted model the OR in Q3 dropped by a third. The comparison of Q4 to Q1–3 has historical precents. For example, in the Framingham Heart Study, significantly larger brain volumes and better cognitive function were observed in Q4 vs Q1–3 [28], and 10-year risk for dementia was 47% lower in subjects with omega-3 levels in Q4 vs Q1-Q3 [29]. More generally, higher omega-3 FA blood levels have been associated with the better clinical outcomes for cardiovascular disease [30,31], post-MI cardiac remodeling [32], telomere attrition [33], attempted suicide [34] and total mortality [35]. These data suggest that in some settings there may be threshold effects of the O3I. This study used the O3I as a biomarker of omega-3 FA status. This RBC-based metric has advantages, particularly in the acute hospitalization setting. This is because, much like a hemoglobin A1C versus plasma glucose, the O3I is a better long-term reflection of tissue omega-3 levels versus plasma omega-3 levels [36], and it would thus be less affected by an acute change in omega-3 intake, as might happen with hospitalization for an acute illness [37]. The O3I has been validated [25] and used in several interventional [14] and prospective cohort studies such as the Framingham Heart Study [31] and the Women's Health Initiative Memory Study [38]. The O3I is also easily modified by increasing the intake of oily fish (e.g., salmon, herring, mackerel, albacore tuna, etc.) which are rich in EPA and DHA, and dietary supplements of omega-3 will also raise levels [15]. The average O3I in this study was 5.1% which is similar to that seen other US-based studies [39], [40]. We also examined the associations between risk for death and EPA and DHA individually and with the omega-6:omega-3 ratio. We found the same directional relationships as with the O3I but they were not as statistically strong (data not shown). Multiple randomized clinical trials (RCTs) are currently (as of January 2021) underway testing the hypothesis that treatment with omega-3 fatty acids (EPA and DHA) will have beneficial effects on a variety of aspects of COVID-19 infection. Although their outcomes are not yet known, there are compelling scientific reasons to expect that these studies will be positive (and these same reasons formed the foundation for the present study). The data supporting a possible beneficial role for omega-3 fatty acids in COVID-19 infection come from past epidemiological, interventional, therapeutic, and basic science studies. For example, in the Framingham Offspring study [41], the O3I was inversely associated with 10 separate inflammatory biomarkers (e.g., CRP, IL-6, ICAM-1, LpPLA2, TNF receptor 2, and osteoprotegerin). In intervention studies [11], EPA supplementation alone (3 g/d for 10 weeks) significantly reduced the expression of TNFα from LPS-stimulated monocytes as did a similar dose of DHA which, in addition, lowered IL-6 and MCP-1. EPA+DHA supplements had similar effects [42]. Meta-analyses of multiple RCTs confirmed that treatment with omega-3 fatty acids routinely lowers cytokine levels [43], [44], [45]. More important than studies of effects on intermediate markers are clinical findings from RCTs. Langlois et al. [5] summarized the results of 12 RCTs of omega-3 treatment in 1280 intensive-care-unit patients with acute respiratory distress syndrome. There was a significant improvement in measures of blood oxygenation in the treated patients and strong trends (p ≤ 0.08) for reduced ICU length of stay and duration of mechanical ventilation. Overall mortality, hospital length of stay and infectious complications were unaffected. As noted earlier, the potential mechanisms underlying these actions are multiple. EPA/DHA are substrates for the production of IRMs which cannot be made if the parent compounds are not present. Examples of some of the functions of IRMs were summarized by Calder as, “Resolvin E1, resolvin D1 and protectin D1 all inhibit trans-endothelial migration of neutrophils, so preventing the infiltration of neutrophils into sites of inflammation; resolvin D1 inhibits IL-1β production and protectin D1 inhibits TNF-α and IL-1β production.” [46] Higher EPA/DHA levels reduce arachidonic acid (the omega-6 cousin of EPA) membrane levels [47] for the production of some pro-inflammatory oxylipins (certain prostaglandins and leukotrienes). Quite independently of the synthesis of these mediators, the presence of EPA/DHA in inflammatory cells blocks the activation of the key pro-inflammatory transcription factor, nuclear factor kappa B thus retarding the entire intracellular inflammatory cascade [48,49]. This effect is downstream from the action of these fatty acids on membrane G-protein coupled receptors GPR40 and GPR120 and nuclear peroxisome proliferator-activated receptors (reviewed in [50]). Finally, EPA/DHA insert into cell membrane phospholipids and disrupts lipid rafts so as to disassemble surface receptors thereby blocking incoming inflammatory signals [51]. All of these actions together result in a muted “cytokine storm” which, in alveolar macrophages and elsewhere, can result in death from COVID-19 [3]. 4.1. Limitations Given the pilot nature of this exploratory study, a number of limitations are acknowledged. Firstly, the sample size was small and further studies are needed to replicate this finding and to explore potential risk thresholds of the O3I. Secondly, the limited resources and resulting access to the full electronic medical record for more detailed chart review significantly reduced the amount of potentially relevant information on comorbidities and other demographic data besides age and sex (e.g., BMI). Although data on maximal interventions applied during hospitalization were available, the reasons why any given patient was administered a given treatment are not known and could obviously have been influenced by external factors (e.g., ventilator availability) or internal factors (e.g., a DNR order). Accordingly, such information was deemed to be of little utility in this pilot study. The population of patients in this study had an O3I that was typical of the US[39], which unfortunately means that levels were generally low. Future studies should endeavor to include patients with a wider range of O3I to examine these relationships more clearly. 4.2. Conclusions Given the profound public health concerns related to the current COVID-19 pandemic, modifiable risk factors for developing severe and critical complications are urgently needed. Despite the known mechanisms by which IRMs and omega-3 fatty acids support the active, endogenous resolution of inflammatory mechanisms, to our knowledge this is the first study that has explored the relationship between omega 3 tissue levels and the most severe COVID-19 outcome, death. Larger studies are urgently needed to confirm these findings. If an association is confirmed with a larger sample size, then this would lay the groundwork for testing the effects of increased oily fish intake and/or an inexpensive, safe, and widely available dietary supplement (DHA/EPA capsules) to optimize outcomes during this public health crisis. Author disclosure statements WSH holds an interest in OmegaQuant Analytics, LLC; and is a member of the Schiff Science and Innovation Advisory Board. The other authors have no conflicts of interest to disclose. Data availability statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding statement This study was supported in part by Cedars-Sinai Medical Center (through the Cancer Clinical Trials Office), by the Fatty Acid Research Institute (for biostatistical support), and by a donation from Michael Myers (for blood analysis). CRediT authorship contribution statement Arash Asher: Conceptualization, Investigation, Methodology, Project administration, Supervision, Writing - original draft. Nathan L. Tintle: Formal analysis, Writing - review & editing. Michael Myers: Conceptualization, Resources, Methodology, Writing - review & editing. Laura Lockshon: Project administration, Writing - review & editing. Heribert Bacareza: Project administration, Writing - review & editing. William S. Harris: Conceptualization, Methodology, Resources, Writing - original draft.   References [1] World Health Organization Coronavirus Disease (COVID-19) Dashboard. https://covid19.who.int/. Last accessed 01/20/2021. Google Scholar [2] Z. Wu, J.M. McGoogan Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention JAMA, 323 (2020), pp. 1239-1242 CrossRefView Record in ScopusGoogle Scholar [3] D.C. Fajgenbaum, C.H. June Cytokine storm NEJM, 383 (2020), pp. 2255-2273 CrossRefView Record in ScopusGoogle Scholar [4] P.C. Calder Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance Biochim. Biophys. Acta, 1851 (2015), pp. 469-484 ArticleDownload PDFView Record in ScopusGoogle Scholar [5] P.L. Langlois, F. D’Aragon, G. Hardy, W. Manzanares Omega-3 polyunsaturated fatty acids in critically ill patients with acute respiratory distress syndrome: a systematic review and meta-analysis Nutrition, 61 (2019), pp. 84-92 ArticleDownload PDFView Record in ScopusGoogle Scholar [6] M.O. Husson, D. Ley, C. Portal, M. Gottrand, T. Hueso, J.L. Desseyn, F. Gottrand Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids J Infect, 73 (2016), pp. 523-535 ArticleDownload PDFView Record in ScopusGoogle Scholar [7] E. Lopez-Garcia, M.B. Schulze, J.E. Manson, J.B. Meigs, C.M. Albert, N. Rifai, W.C. Willett, F.B. Hu Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women J. Nutr., 134 (2004), pp. 1806-1811 CrossRefView Record in ScopusGoogle Scholar [8] K. Niu, A. Hozawa, S. Kuriyama, K. Ohmori-Matsuda, T. Shimazu, N. Nakaya, K. Fujita, I. Tsuji, R. Nagatomi Dietary long-chain n-3 fatty acids of marine origin and serum C-reactive protein concentrations are associated in a population with a diet rich in marine products Am. J. Clin. Nutr., 84 (2006), pp. 223-229 View Record in ScopusGoogle Scholar [9] R. Farzaneh-Far, W.S. Harris, S. Garg, B. Na, M.A. Whooley Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: The Heart and Soul Study Atherosclerosis, 205 (2009), pp. 538-543 ArticleDownload PDFView Record in ScopusGoogle Scholar [10] S.M. Grenon, M.S. Conte, E. Nosova, H. Alley, K. Chong, W.S. Harris, E. Vittinghoff, C.D. Owens Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease J. Vascular Surgery, 58 (2013), pp. 1283-1290 ArticleDownload PDFView Record in ScopusGoogle Scholar [11] J. So, D. Wu, A.H. Lichtenstein, A.K. Tai, N.R. Matthan, K.R. Maddipati, S. Lamon-Fava EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: a randomized, double-blind, crossover study Atherosclerosis (2020) 316:90-98 Google Scholar [12] J. Allaire, P. Couture, M. Leclerc, A. Charest, J. Marin, M.C. Lepine, D. Talbot, A. Tchernof, B. Lamarche A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study Am. J. Clin. Nutr., 104 (2016), pp. 280-287 CrossRefView Record in ScopusGoogle Scholar [13] C.N. Serhan, B.D. Levy Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators J. Clin. Invest., 128 (2018), pp. 2657-2669 View Record in ScopusGoogle Scholar [14] R.E. Walker, K.H. Jackson, N.L. Tintle, G.C. Shearer, A. Bernasconi, S. Masson, R. Latini, B. Heydari, R.Y. Kwong, M. Flock, P.M. Kris-Etherton, A. Hedengran, R.M. Carney, A. Skulas-Ray, S.S. Gidding, A. Dewell, C.D. Gardner, S.M. Grenon, B. Sarter, J.W. Newman, T.L. Pedersen, M.K. Larson, W.S. Harris Predicting the effects of supplemental EPA and DHA on the omega-3 index Am. J. Clin. Nutr., 110 (2019), pp. 1034-1040 CrossRefView Record in ScopusGoogle Scholar [15] K.H. Jackson, J.M. Polreis, N.L. Tintle, P.M. Kris-Etherton, W.S. Harris Association of reported fish intake and supplementation status with the omega-3 index Prostaglandins Leukot. Essent. Fatty Acids, 142 (2019), pp. 4-10 ArticleDownload PDFView Record in ScopusGoogle Scholar [16] D. Panigrahy, M.M. Gilligan, S. Huang, A. Gartung, I. Cortés-Puch, P.J. Sime, R.P. Phipps, C.N. Serhan, B.D. Hammock Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? Cancer Metastasis Rev., 39 (2020), pp. 337-340 CrossRefView Record in ScopusGoogle Scholar [17] K.S.D. Kothapalli, H.G. Park, J.T. Brenna Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19 Prostaglandins Leukot. Essent. Fatty Acids, 162 (2020), Article 102183 ArticleDownload PDFView Record in ScopusGoogle Scholar [18] D. Hathaway, K. Pandav, M. Patel, A. Riva-Moscoso, B.M. Singh, A. Patel, Z.C. Min, S. Singh-Makkar, M.K. Sana, R. Sanchez-Dopazo, R. Desir, M.M.M. Fahem, S. Manella, I. Rodriguez, A. Alvarez, R. Abreu Omega 3 Fatty Acids and COVID-19: a comprehensive review Infect. Chemother., 52 (2020), pp. 478-495 CrossRefView Record in ScopusGoogle Scholar [19] P. Weill, C. Plissonneau, P. Legrand, V. Rioux, R. Thibault May omega-3 fatty acid dietary supplementation help reduce severe complications in Covid-19 patients? Biochimie, 179 (2020), pp. 275-280 ArticleDownload PDFView Record in ScopusGoogle Scholar [20] J.P. Chang, C.M. Pariante, K.P. Su Omega-3 fatty acids in the psychological and physiological resilience against COVID-19 Prostaglandins Leukot. Essent. Fatty Acids, 161 (2020), Article 102177 ArticleDownload PDFView Record in ScopusGoogle Scholar [21] P.A. Regidor, F.G. Santos, J.M. Rizo, F.M. Egea Pro resolving inflammatory effects of the lipid mediators of omega 3 fatty acids and its implication in SARS COVID-19 Med. Hypotheses, 145 (2020), Article 110340 ArticleDownload PDFView Record in ScopusGoogle Scholar [22] M.M. Rogero, M.C. Leão, T.M. Santana, M. Pimentel, G.C.G. Carlini, T.F.F. da Silveira, R.C. Gonçalves, I.A. Castro Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19 Free Radic. Biol. Med., 156 (2020), pp. 190-199 ArticleDownload PDFView Record in ScopusGoogle Scholar [23] A.A. Berger, R. Sherburne, I. Urits, H. Patel, J. Eskander Icosapent ethyl - a successful treatment for symptomatic COVID-19 infection Cureus, 12 (2020), p. e10211 View Record in ScopusGoogle Scholar [24] W. Suh, I. Urits, O. Viswanath, A.D. Kaye, H. Patel, W. Hall, J.P. Eskander Three cases of COVID-19 pneumonia that responded to icosapent ethyl supportive treatment Am. J. Case. Rep., 21 (2020), Article e928422 Google Scholar [25] W.S. Harris, J. Polreis Measurement of the Omega-3 Index in Dried Blood Spots Ann Clin Lab Res, 4 (2016), pp. 137-144 CrossRefGoogle Scholar [26] R-Project, version 3. www.r-project.org. Google Scholar [27] N. Liu, J. Sun, X. Wang, T. Zhang, M. Zhao, H. Li Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis Int. J. Infect. Dis. (2021) 104:58-64 Google Scholar [28] Z.S. Tan, W.S. Harris, A.S. Beiser, R. Au, J.J. Himali, S. Debette, A. Pikula, C. Decarli, P.A. Wolf, R.S. Vasan, S.J. Robins, S. Seshadri Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging Neurology, 78 (2012), pp. 658-664 CrossRefView Record in ScopusGoogle Scholar [29] E.J. Schaefer, V. Bongard, A.S. Beiser, S. Lamon-Fava, S.J. Robins, R. Au, K.L. Tucker, D.J. Kyle, P.W. Wilson, P.A. Wolf Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study Arch.Neurol., 63 (2006), pp. 1545-1550 CrossRefView Record in ScopusGoogle Scholar [30] L.C. Del Gobbo, F. Imamura, S. Aslibekyan, M. Marklund, J.K. Virtanen, M. Wennberg, M.Y. Yakoob, S.E. Chiuve, L. Dela Cruz, A.C. Frazier-Wood, A.M. Fretts, E. Guallar, C. Matsumoto, K. Prem, T. Tanaka, J.H. Wu, X. Zhou, C. Helmer, E. Ingelsson, J.M. Yuan, P. Barberger-Gateau, H. Campos, P.H. Chaves, L. Djousse, G.G. Giles, J. Gomez-Aracena, A.M. Hodge, F.B. Hu, J.H. Jansson, I. Johansson, K.T. Khaw, W.P. Koh, R.N. Lemaitre, L. Lind, R.N. Luben, E.B. Rimm, U. Riserus, C. Samieri, P.W. Franks, D.S. Siscovick, M. Stampfer, L.M. Steffen, B.T. Steffen, M.Y. Tsai, R.M. van Dam, S. Voutilainen, W.C. Willett, M. Woodward, D. Mozaffarian Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies JAMA Intern. Med., 176 (2016), pp. 1155-1166 CrossRefView Record in ScopusGoogle Scholar [31] W.S. Harris, N.L. Tintle, M.R. Etherton, R.S. Vasan Erythrocyte long-chain omega-3 fatty acid levels are inversely associated with mortality and with incident cardiovascular disease: the Framingham Heart Study J. Clin. Lipidol., 12 (2018), pp. 718-724 View Record in ScopusGoogle Scholar [32] B. Heydari, S. Abdullah, J.V. Pottala, R. Shah, S. Abbasi, D. Mandry, S.A. Francis, H. Lumish, B.B. Ghoshhajra, U. Hoffmann, E. Appelbaum, J.H. Feng, R. Blankstein, M. Steigner, J.P. McConnell, W. Harris, E.M. Antman, M. Jerosch-Herold, R.Y. Kwong Effect of omega-3 acid ethyl esters on left ventricular remodeling after acute myocardial infarctionclinical perspective: the OMEGA-REMODEL randomized clinical trial Circulation, 134 (2016), pp. 378-391 View Record in ScopusGoogle Scholar [33] R. Farzaneh-Far, J. Lin, E.S. Epel, W.S. Harris, E.H. Blackburn, M.A. Whooley Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease JAMA, 303 (2010), pp. 250-257 CrossRefView Record in ScopusGoogle Scholar [34] M. Huan, K. Hamazaki, Y. Sun, M. Itomura, H. Liu, W. Kang, S. Watanabe, K. Terasawa, T. Hamazaki Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China Biol. Psychiatry, 56 (2004), pp. 490-496 ArticleDownload PDFView Record in ScopusGoogle Scholar [35] M.E. Kleber, G.E. Delgado, S. Lorkowski, W. Marz, C. von Schacky Omega-3 fatty acids and mortality in patients referred for coronary angiography. The Ludwigshafen risk and cardiovascular health study Atherosclerosis, 252 (2016), pp. 175-181 ArticleDownload PDFView Record in ScopusGoogle Scholar [36] W.S. Harris, R.M. Thomas Biological variability of blood omega-3 biomarkers Clin. Biochem., 43 (2010), pp. 338-340 ArticleDownload PDFView Record in ScopusGoogle Scholar [37] W.S. Harris, S.A. Varvel, J.V. Pottala, G.R. Warnick, J.P. McConnell Comparative effects of an acute dose of fish oil on omega-3 fatty acid levels in red blood cells versus plasma: implications for clinical utility J Clin Lipidol, 7 (2013), pp. 433-440 ArticleDownload PDFView Record in ScopusGoogle Scholar [38] W.S. Harris, J. Luo, J.V. Pottala, M.A. Espeland, K.L. Margolis, J.E. Manson, L. Wang, T.M. Brasky, J.G. Robinson Red blood cell polyunsaturated fatty acids and mortality in the Women's Health Initiative Memory Study J Clin Lipidol, 11 (2017), pp. 250-259 View Record in ScopusGoogle Scholar [39] W.S. Harris, J.V. Pottala, S.A. Varvel, J.J. Borowski, J.N. Ward, J.P. McConnell Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients Prostaglandins Leukot. Essent. Fatty Acids, 88 (2013), pp. 257-263 ArticleDownload PDFView Record in ScopusGoogle Scholar [40] J.V. Pottala, M.A. Espeland, J. Polreis, J. Robinson, W.S. Harris Correcting the effects of -20 °C storage and aliquot size on erythrocyte fatty acid content in the women’s health initiative Lipids, 47 (2012), pp. 835-846 CrossRefView Record in ScopusGoogle Scholar [41] J.D. Fontes, F. Rahman, S. Lacey, M.G. Larson, R.S. Vasan, E.J. Benjamin, W.S. Harris, S.J. Robins Red blood cell fatty acids and biomarkers of inflammation: a cross-sectional study in a community-based cohort Atherosclerosis, 240 (2015), pp. 431-436 ArticleDownload PDFView Record in ScopusGoogle Scholar [42] A. Tan, B. Sullenbarger, R. Prakash, J.C. McDaniel Supplementation with eicosapentaenoic acid and docosahexaenoic acid reduces high levels of circulating proinflammatory cytokines in aging adults: a randomized, controlled study Prostaglandins Leukot. Essent. Fatty Acids, 132 (2018), pp. 23-29 ArticleDownload PDFView Record in ScopusGoogle Scholar [43] S. AbuMweis, S. Jew, R. Tayyem, L. Agraib Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials J. Hum. Nutr. Diet., 31 (2018), pp. 67-84 CrossRefView Record in ScopusGoogle Scholar [44] L.L. O’Mahoney, J. Matu, O.J. Price, K.M. Birch, R.A. Ajjan, D. Farrar, R. Tapp, D.J. West, K. Deighton, M.D. Campbell Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials Cardiovasc. Diabetol., 17 (2018), p. 98 View Record in ScopusGoogle Scholar [45] K. Li, T. Huang, J. Zheng, K. Wu, D. Li Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor alpha: a meta-analysis PLoS ONE, 9 (2014), p. e88103 CrossRefView Record in ScopusGoogle Scholar [46] P.C. Calder Omega-3 fatty acids and inflammatory processes: from molecules to man Biochem. Soc. Trans., 45 (2017), pp. 1105-1115 View Record in ScopusGoogle Scholar [47] J. Allaire, W.S. Harris, C. Vors, A. Charest, J. Marin, K.H. Jackson, A. Tchernof, P. Couture, B. Lamarche Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid Prostaglandins Leukot. Essent. Fatty Acids, 120 (2017), pp. 8-14 ArticleDownload PDFView Record in ScopusGoogle Scholar [48] A. Denys, A. Hichami, N.A. Khan n-3 PUFAs modulate T-cell activation via protein kinase C-alpha and -epsilon and the NF-kappaB signaling pathway J. Lipid Res., 46 (2005), pp. 752-758 ArticleDownload PDFView Record in ScopusGoogle Scholar [49] T.E. Novak, T.A. Babcock, D.H. Jho, W.S. Helton, N.J. Espat NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription Am. J. Physiol. Lung Cell Mol. Physiol., 284 (2003), pp. L84-L89 CrossRefView Record in ScopusGoogle Scholar [50] P.C. Calder Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br. J. Clin. Pharmacol., 75 (2013), pp. 645-662 CrossRefView Record in ScopusGoogle Scholar [51] S.R. Shaikh, J.J. Kinnun, X. Leng, J.A. Williams, S.R. Wassall How polyunsaturated fatty acids modify molecular organization in membranes: insight from NMR studies of model systems Biochim. Biophys. Acta, 1848 (2015), pp. 211-219 ArticleDownload PDFView Record in ScopusGoogle Scholar View Abstract © 2021 Elsevier Ltd. All rights reserved.

TOP