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Original Article| Volume 48, P55-63, April 2023

The association of dietary approach to stop hypertension (DASH) diet with hospitalization risk in patients with COVID-19

  • Ali Zamanian
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
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  • Zahra Yari
    Correspondence
    Corresponding author.
    Affiliations
    Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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  • Samira Soltanieh
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
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  • Marieh Salavatizadeh
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
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  • Sara Karimi
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
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  • Sussan K. Ardestani
    Affiliations
    Department of Immunology, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
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  • Mohammadreza Salehi
    Affiliations
    Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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  • Soodeh Razeghi Jahromi
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
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  • Tooba Ghazanfari
    Affiliations
    Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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  • Azita Hekmatdoost
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
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Open AccessPublished:March 03, 2023DOI:https://doi.org/10.1016/j.nutos.2023.02.001

      Summary

      Background and aim

      Given the importance of dietary habits in the immune system, the current study aimed at investigating the association between Dietary Approach to Stop Hypertension (DASH) diet and risk of hospitalization due to COVID-19.

      Methods

      Dietary data of 141 patients with COVID-19 were collected using 147-item food frequency questionnaire. DASH score in this cross-sectional study was calculated based on eight components, including fruits, vegetables, legumes and nuts and seeds, whole grains, low-fat dairy, red or processed meats, sweetened beverages, and sodium. Multivariable logistic regression models were applied to estimate the OR and 95% CI for hospitalization due to COVID-19 in each tertile of DASH score.

      Results

      Mean ± SD of DASH score in inpatients (n=74) and outpatients (n= 87) was 22.5 ± 4.57 and 25.34 ± 4.23, respectively. The risk of hospitalization in the highest tertile of DASH score was 81% lower than the lowest tertile (OR=0.19, 95%CI: 0.07–0.55, P trend = 0.001 after adjustment for age, sex, BMI, energy intake). Also, more intake of fruits, vegetables and low-fat dairy products and less intake of sodium, red and processed meat were each significantly associated with reduced risk of hospitalization due to COVID-19.

      Conclusions

      Our data provide evidence that adherence to DASH-style diet was associated with lower risk of hospitalization due to COVID-19.

      Keywords

      Introduction

      One of the global issues that has been emerged in 2019 was Coronavirus disease (COVID-19) that caused severe acute respiratory syndrome (SARS) leading to significant morbidity and mortality in humans [
      • Umakanthan S.
      • Sahu P.
      • Ranade A.V.
      • Bukelo M.M.
      • Rao J.S.
      • Abrahao-Machado L.F.
      • et al.
      Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19).
      ]. Fever, cough, sore throat, and malaise are considered as the primary symptoms. Other symptoms mainly include gastrointestinal upsets, nausea, vomiting, diarrhea, loss of taste and/or smell, muscle pain [
      • Zhu N.
      • Zhang D.
      • Wang W.
      • Li X.
      • Yang B.
      • Song J.
      • et al.
      A Novel Coronavirus from Patients with Pneumonia in China, 2019.
      ]. Furthermore, COVID-19 is allied with serious complications such as acute respiratory distress syndrome (ARDS), cardiac insufficiency, sepsis, and multiple organ dysfunctions (MODS) [
      • Chen T.
      • Wu D.
      • Chen H.
      • Yan W.
      • Yang D.
      • Chen G.
      • et al.
      Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study.
      ]. The burden of mortality and morbidity related to COVID was extraordinary [
      • Nalbandian A.
      • Sehgal K.
      • Gupta A.
      • Madhavan M.V.
      • McGroder C.
      • Stevens J.S.
      • et al.
      Post-acute COVID-19 syndrome.
      ]. Recent evidence has shown that the symptoms and complications of the illness may last for weeks or months after recovery in most patients [
      • Iwu C.J.
      • Iwu C.D.
      • Wiysonge C.S.
      The occurrence of long COVID: a rapid review.
      ], however, attentions are still initially focused on managing the acute symptoms of the disease [
      • Lopez-Leon S.
      • Wegman-Ostrosky T.
      • Perelman C.
      • Sepulveda R.
      • Rebolledo P.A.
      • Cuapio A.
      • et al.
      More than 50 long-term effects of COVID-19: a systematic review and meta-analysis.
      ]. On the one hand, comorbidities such as type 2 diabetes, obesity, chronic lung, kidney and liver diseases, hypertension, and cardiovascular diseases are associated with a poor prognosis and an increased risk of death [
      • Yang J.
      • Zheng Y.
      • Gou X.
      • Pu K.
      • Chen Z.
      • Guo Q.
      • et al.
      Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis.
      ,
      • Simonnet A.
      • Chetboun M.
      • Poissy J.
      • Raverdy V.
      • Noulette J.
      • Duhamel A.
      • et al.
      High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation.
      ]. On the other hand, the presence of these diseases predisposes a person to COVID-19 and exacerbates its complications [
      • Wu C.
      • Chen X.
      • Cai Y.
      • Xia J.
      • Zhou X.
      • Xu S.
      • et al.
      Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.
      ].
      The key missing link in this relationship may be diet. Healthy dietary patterns may play important roles in the treatment and prevention of COVID-19 due to close association with immunity and inflammation [
      • de Araújo Morais A.H.
      • de Souza Aquino J.
      • da Silva-Maia J.K.
      • de Lima Vale S.H.
      • Maciel B.L.L.
      • Passos T.S.
      Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2.
      ,
      • Chaari A.
      • Bendriss G.
      • Zakaria D.
      • McVeigh C.
      Importance of dietary changes during the coronavirus pandemic: how to upgrade your immune response.
      ]. Furthermore, it has been proposed that a balanced diet might improve the immune response to SARS-CoV-2 infection [
      • de Araújo Morais A.H.
      • de Souza Aquino J.
      • da Silva-Maia J.K.
      • de Lima Vale S.H.
      • Maciel B.L.L.
      • Passos T.S.
      Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2.
      ]. Moreover, the adoption of a healthy dietary pattern can reduce the risk factors and complications of COVID-19 [
      • Chaari A.
      • Bendriss G.
      • Zakaria D.
      • McVeigh C.
      Importance of dietary changes during the coronavirus pandemic: how to upgrade your immune response.
      ]. Dietary Approaches to Stop Hypertension (DASH) include foods with anti-inflammatory properties that have positive impacts on improving chronic inflammatory processes and preventing metabolic alterations [
      • Rodríguez-López C.P.
      • González-Torres M.C.
      • Aguilar-Salinas C.A.
      • Nájera-Medina O.
      Dash diet as a proposal for improvement in cellular immunity and its association with metabolic parameters in persons with overweight and obesity.
      ]. DASH diet is characterized by consumption of high amounts of fruits, vegetables, legumes, nuts and seeds, whole grains, low-fat dairy, poultry and fish with reduced amounts of processed meats, sweetened beverages, and sodium [
      • Rodríguez-López C.P.
      • González-Torres M.C.
      • Aguilar-Salinas C.A.
      • Nájera-Medina O.
      DASH Diet as a Proposal for Improvement in Cellular Immunity and Its Association with Metabolic Parameters in Persons with Overweight and Obesity.
      ,
      • Vollmer W.M.
      • Sacks F.M.
      • Ard J.
      • Appel L.J.
      • Bray G.A.
      • Simons-Morton D.G.
      • et al.
      Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial.
      ]. DASH diet not only effectively reduces blood pressure, but has also been reported to be associated with lower risk of chronic diseases and mortality [
      • Soltani S.
      • Arablou T.
      • Jayedi A.
      • Salehi-Abargouei A.
      Adherence to the dietary approaches to stop hypertension (DASH) diet in relation to all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.
      ]. Furthermore, previous research has stated the association between DASH and lower biomarkers of lipid peroxidation and higher antioxidant capacity [
      • Razavi Zade M.
      • Telkabadi M.H.
      • Bahmani F.
      • Salehi B.
      • Farshbaf S.
      • Asemi Z.
      The effects of DASH diet on weight loss and metabolic status in adults with non-alcoholic fatty liver disease: a randomized clinical trial.
      ]. Low sodium content of DASH diet is associated with a reduced systemic inflammation, which can be attribute to a decreased coagulation level [
      • Fogarty A.W.
      • Lewis S.A.
      • McKeever T.M.
      • Britton J.R.
      Is higher sodium intake associated with elevated systemic inflammation? A population-based study.
      ].
      Comprehending the association between DASH diet and COVID-19 disease can highlight the importance of nutrition in viral and infectious diseases. The aim of the current study was to investigate the relationship of DASH dietary pattern with the COVID-19 related risk of hospitalization.

      Method and materials

      Participants

      A COVID-19 case–control study in 53 inpatients and 88 outpatients was conducted to assess the association of DASH dietary pattern with the COVID-19 related risk of hospitalization. Simple consecutive method was used in order to enroll hospitalized patients from Imam Khomeini referral hospital in Tehran, Iran. Simorgh clinical laboratory was designated to enroll outpatients. Sampling methods has been explained in another article more comprehensively [
      • Ghazanfari T.
      • Salehi M.R.
      • Namaki S.
      • Arabkheradmand J.
      • Rostamian A.
      • Rajabnia Chenary M.
      • et al.
      Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.
      ]. Briefly, the diagnosis was made based on the results of nasopharyngeal swabs for SARS-CoV-2 RT-PCR and chest computed tomography scans. Patients admitted to the intensive care unit (ICU) or in need of invasive respiratory support were not included in the study. Those who received noninvasive ventilation masks were categorized as the severe group. Patients with COVID-19 infection who were not sick enough to need hospitalization and were treated at home included as the outpatient group. 24 hours after patient assignment, two physicians independently collected clinical characteristics to increase the accuracy of the collected data. This study is related to the project No. IR. NIMAD.REC.1399.041 from national institute for medical research development entitled “Immunological aspects of COVID-19 in selected provinces of Iran”. The flow chart provides a description of the patients recruited and the sample sizes for analysis (Figure 1).
      Figure 1
      Figure 1Flowchart of participant recruitment.
      The inclusion criterion was positive PCR COVID-19 test result and the exclusion criteria were diabetes, hypertension, kidney disease, cancer, and cardiovascular diseases and also adherence to special diets over the past year, pregnancy and lactation. The consent form was signed by all patients after explaining them the details about the goals and process of the study. The Ethical Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.NNFTRI.REC.1399.046) approved the study protocol.

      Dietary intake assessment

      The 147-item semi-quantitative food frequency questionnaire (FFQ) was used to evaluate dietary intake of patients, the validity and reliability of which have been explained extensively in advance [
      • Mirmiran P.
      • Esfahani F.H.
      • Mehrabi Y.
      • Hedayati M.
      • Azizi F.
      Reliability and relative validity of an FFQ for nutrients in the Tehran lipid and glucose study.
      ]. The Frequency of consumption of each food items during the past year was gathered via person-to-person interviews by expert nutritionists. The amount of consumed food first converted to grams and then the nutrients and energy contents were calculated by using the United States Department of Agriculture (USDA) food composition table. An Iranian FCT was also used for local food items.
      DASH score in this study was calculated based on eight components, including fruits, vegetables, legumes and nuts and seeds, whole grains, low-fat dairy, red or processed meats, sweetened beverages, and sodium [
      • Fung T.T.
      • Chiuve S.E.
      • McCullough M.L.
      • Rexrode K.M.
      • Logroscino G.
      • Hu F.B.
      Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women.
      ]. Energy adjustments were carried out for each food component (g/1000). DASH scores had been computed according Fung et al. [
      • Fung T.T.
      • Chiuve S.E.
      • McCullough M.L.
      • Rexrode K.M.
      • Logroscino G.
      • Hu F.B.
      Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women.
      ]. Briefly, subject's quintile rankings were implemented for whole grains, fruits, vegetables, legumes, nuts and seeds, and low-fat dairy to appoint component scores, e.g. 1 point for the lowest quintile participants and 5 points for the highest. For sodium, red and processed meats and sugar-sweetened beverages, 5 points were assigned for those who received the lowest quintile and consequently 1 point for the highest ones. Then the scores for these eight components were summed up to calculate the DASH score.

      Clinical parameters

      Measuring weight was conducted by a digital scale with an accuracy of 0.1 kg. Also, mechanical, wall-mounted stadiometer, with an accuracy of 0.1 cm was applied for measuring height. Body mass index was computed as weight (kg) divided by height (m2). Serum concentrations of neutrophil-to-lymphocyte ratio (NLR), Interlukin-6, C-reactive protein (CRP), white blood cells were measured.

      Statistical analysis

      Data analyses were carried out using the SPSS software (Statistical Package for the Social Sciences version 20.0; SPSS Inc., Chicago, IL). The level of statistical significance was set at P <0.05. Histogram chart and the Kolmogorov-Smirnov's test were administered in order to monitor the distribution of variables. Classifying the participants was according to tertiles of DASH diet score cutoff points (≤22, 23–26, and ≥27). Baseline characteristics of participants are expressed as mean ± SD or median (25–75 inter-quartile range) for continuous variables, and percentages for categorical variables across tertiles of DASH score. Linear regression was used to examine the trend of continuous variables across tertiles of DASH score, accordingly, P for trend was reported. Logistic regression models were conducted to evaluate the odds ratio (ORs) and 95% confidence intervals (CIs) of COVID-related hospitalization risk across tertiles. The first tertile of each score was considered as the reference. The relationship between the DASH scores and the risk of hospitalization caused by COVID-19 were assessed in three models. Potential confounders were included sex, age, BMI, and daily energy intake.

      Results

      Basic characteristics of study participants based on COVID-19 severity are shown in Table 1. 52.5% of participants in this study were men and 47.5% were women. The mean age of patients was 46.23 ± 15.88 years, but hospitalized patients were older than outpatients (50.17 ± 15.45 vs 43.91 ± 15.77. P= 0.024). The mean ± SD of BMI was 26.95 ± 3.83 kg/m2, and although BMI in hospitalized patients was higher than outpatients, but this difference was not statistically significant. Also, the mean of DASH score of all patients were 23.86 ± 4.4, and in hospitalized patients it was significantly lower than outpatients (P<0.001). Although energy intake in hospitalized patients was significantly lower than outpatients, the percentage of macronutrients did not show a statistically significant difference between the two groups. In terms of biochemical parameters there was no significant difference between the two groups.
      Table 1Basic characteristics of study participants based on COVID-19 severity.
      In-patients (n= 53)Out-patients (n= 88)P-Value
      Age, y50.17 ± 15.4543.91 ± 15.770.024
      Male, N (%)29 (54.7%)45 (51.7%)0.433
      Weight, kg78.77 ± 13.4576.59 ± 11.720.313
      Height, cm1.68 ± 0.11.69 ± 0.10.567
      BMI, kg/m227.66 ± 4.5726.53 ± 3.260.089
      Dietary intakes
      Energy (Kcal/d)1542.83 ± 592.031920.83 ± 648.070.001
      Carbohydrate (%)59.84 ± 8.9860.44 ± 9.520.712
      Protein (%)13.68 ± 2.4813.43 ± 2.430.563
      Fat (%)29.5 ± 829.68 ± 7.850.899
      Biochemical Parameters
      W.B.C (103/μL)6.34 ± 1.976.14 ± 2.240.638
      Lymphocytes (%)30.72 ± 10.4432.62 ± 7.930.326
      Neutrophils (%)57.75 ± 11.1150.09 ± 9.090.437
      NLR2.43 ± 2.061.95 ± 1.140.157
      IL-6 (pg/ml)7.59 ± 15.2211.38 ± 30.990.582
      CRP (mg/L)6.26 ± 7.534.96 ± 6.220.294
      DASH score22.5 ± 4.5725.34 ± 4.23<0.001
      Data are presented as mean (SD) for continuous variable and number (percent) for categorical variables.
      Table 2 presents basic characteristics of study participants based on DASH scores tertile. As shown in Table 2, there were no significant differences in dietary intakes and biochemical parameters across tertiles of DASH diet scores.
      Table 2Basic characteristics of study participants based on DASH scores tertile.
      DASH scoreTertiles
      T1 (n= 53)T2 (n= 47)T3 (n= 41)P trend
      Age, y45.05 ± 16.2845.59 ± 14.8348.46 ± 16.690.561
      Male (%)27 (50.9%)26 (55.3%)21 (52.5%)0.907
      BMI, kg/m227.22 ± 3.9827.63 ± 4.1725.83 ± 2.970.071
      Dietary intakes
      Energy (Kcal/d)1809.99 ± 826.41664.07 ± 499.871869.81 ± 535.60.307
      Carbohydrate (%)58.94 ± 9.7459.26 ± 8.8462.97 ± 8.850.078
      Protein (%)13.63 ± 2.5413.79 ± 2.5713.07 ± 2.150.357
      Fat (%)30.36 ± 8.9530.27 ± 6.9127.90 ± 7.330.257
      Biochemical Parameters
      W.B.C (103/μL)6.08 ± 1.885.92 ± 1.766.77 ± 2.760.230
      NLR2.04 ± 1.12.36 ± 2.121.91 ± 0.990.475
      IL-6 (pg/ml)10.01 ± 17.215.47 ± 41.114.14 ± 3.610.355
      CRP (mg/L)5.66 ± 6.976.62 ± 7.435.45 ± 6.740.145
      DASH score19.60 ± 2.6825.06 ± 0.8429.41 ± 2.42<0.001
      Data are presented as mean (SD) for continuous variable and number (percent) for categorical variables.
      The ORs (95% CIs) of the relationship between DASH score components with the risk of hospitalization are presented in Table 3. Higher intake of fruits (P trend = 0.003), vegetables (P trend = 0.007), and low-fat dairy products (P trend = 0.010) was significantly associated with a reduced risk of hospitalization due to COVID-19. Although the risk of hospitalization associated with COVID-19 in second and third tertiles of legumes, nuts and seeds intake was 39% (OR: 0.61, 95%CI: 0.25–1.46) and 57% (OR: 0.43, 95%CI: 0.18–1.02) lower than the first tertile, respectively, but was not statistically significant. While, higher intake of red and processed meats was associated with nearly 3-fold increase in the risk of hospitalization in patients with COVID-19 (P trend = 0.032). Regression analysis also showed that sodium intake increased the risk of hospitalization by 2.3 times P trend = 0.006).
      Table 395% odds and confidence interval of the relationship between DASH score components with the risk of hospitalization.
      Tertiles
      T1T2T3P trend
      Fruits1 (ref)0.75 (0.2–1.93)0.62 (0.1–1.66)0.003
      Vegetables1 (ref)0.63 (0.14–1.91)0.59 (0.2–1.85)0.007
      Legumes, nuts and seeds1 (ref)0.61 (0.25–1.46)0.43 (0.18–1.02)0.072
      Whole grains1 (ref)1.06 (0.45–2.48)0.79 (0.34–1.81)0.827
      Low fat dairy1 (ref)0.94 (0.39–2.27)0.56 (0.25–1.38)0.010
      Red and processed meats1 (ref)1 (0.44–2.26)3.13 (1.27–7.7)0.032
      Sweet beverages1 (ref)1.12 (0.5–2.5)2.21 (0.92–5.35)0.488
      Sodium1 (ref)0.99 (0.42–2.16)2.3 (0.96–5.53)0.006
      Data are presented as mean (SD) for continuous variable and number (percent) for categorical variables.
      COVID-19-associated hospitalization risk according to tertiles of DASH scores is shown in Table 4. Higher score of DASH was associated with lower disease-associated hospitalization risk. The risk of hospitalization due to COVID-19 in the second and third tertiles of DASH score, after adjusting for all confounders including age and sex, BMI and energy intake was 41% and 81% lower than the first tertiles, respectively.
      Table 4Odds ratio (95% CI) COVID-19-associated hospitalization risk according to tertiles of DASH scores.
      Tertiles of scores
      T1T2T3P trend
      Mean (IQR)20 (18, 21)25 (24, 26)28 (28, 31)
      Model 11 (ref)0.47 (0.17–1.26)0.20 (0.08–0.51)<0.001
      Model 21 (ref)0.42 (0.15–1.15)0.18 (0.06–0.47)0.001
      Model 31 (ref)0.59 (0.2–1.75)0.19 (0.07–0.55)0.001
      Model 1: Crude.
      Model 2: Adjustment for age, sex.
      Model 3: Adjustment for age, sex, BMI, energy intake.

      Discussion

      In this cross-sectional study, higher adherence to DASH-style diet was inversely associated with odds of hospitalization due to COVID-19. Also, greater score of fruits, vegetables and low-fat dairy products and lower score of sodium, red and processed meat were each significantly associated with reduced COVID-19-associated hospitalization risk. Based on our knowledge this is the first study to investigate the relationship between DASH score and risk of hospitalization due to COVID-19.
      Findings of the current study are in agreement with previous researches which suggest greater adherence to higher quality healthy diet is associated with beneficial health effects through reducing systemic inflammation as a potential biological mechanism [
      • Calle M.C.
      • Andersen C.J.
      ,
      • Millar S.R.
      • Navarro P.
      • Harrington J.M.
      • Perry I.J.
      • Phillips C.M.
      Dietary quality determined by the healthy eating index-2015 and biomarkers of chronic low-grade inflammation: A cross-sectional analysis in middle-to-older aged adults.
      ]. There is a close correlation between immune system with inflammation and oxidative stress. Long-lasting inflammation can lead to a weakened immune system. DASH diet with an anti-inflammatory effects might inhibit an inflammatory response and further consequences such as impaired immune response [
      • Liguori I.
      • Russo G.
      • Curcio F.
      • Bulli G.
      • Aran L.
      • Della-Morte D.
      • et al.
      Oxidative stress, aging, and diseases.
      ].
      DASH pattern is characterized with higher intake of fruits and vegetables, whole grains, legumes, poultry, and less intake of red meat, sodium and sugar. Therefore, the content of calcium, potassium, magnesium and fiber in DASH diet is high [
      • Lin P.-H.
      • Aickin M.
      • Champagne C.
      • Craddick S.
      • Sacks F.M.
      • McCarron P.
      • et al.
      Food group sources of nutrients in the dietary patterns of the DASH-Sodium trial.
      ]. Evidence suggests that these nutrients modulate inflammatory status [
      • Phillips C.M.
      • Shivappa N.
      • Hébert J.R.
      • Perry I.J.
      Dietary inflammatory index and biomarkers of lipoprotein metabolism, inflammation and glucose homeostasis in adults.
      ]. On the other hand, less amounts of red and processed meats, refined grains and simple sugar may provide anti-inflammatory benefits [
      • Lankinen M.
      • Uusitupa M.
      • Schwab U.
      Nordic diet and inflammation—A review of observational and intervention studies.
      ,
      • Barbaresko J.
      • Koch M.
      • Schulze M.B.
      • Nöthlings U.
      Dietary pattern analysis and biomarkers of low-grade inflammation: a systematic literature review.
      ]. This dietary pattern is also rich in bioactive compounds that can inhibit pro-inflammatory pathways and reduce the morbidity and mortality risk of an infectious disease by strengthening the immune response [
      • Setiawan B.
      • Masfufatun M.
      Dietary Patterns for Immunity Support and Systemic Inflammation against Infections: A Narrative Review.
      ]. Furthermore, DASH diet may be considered as including several nutraceuticals that favorably influence health. Nutraceuticals comprise active phytochemicals with medicinal properties such as zinc, vitamins, curcumin, resveratrol, and selenium [
      • Pastor N.
      • Collado M.C.
      • Manzoni P.
      Phytonutrient and nutraceutical action against COVID-19: Current review of characteristics and benefits.
      ]. In addition to its immune-boosting properties, the nutrient appears to interact with angiotensin-converting enzyme-2 (ACE2) [
      • Catalano A.
      • Iacopetta D.
      • Ceramella J.
      • Maio A.C.D.
      • Basile G.
      • Giuzio F.
      • et al.
      Are nutraceuticals effective in COVID-19 and post-COVID prevention and treatment?.
      ]. The effects of these natural compounds in reducing ACE2 activity and consequently treating COVID-19 have been shown in several studies [
      • Lordan R.
      • Rando H.M.
      • Greene C.S.
      Dietary supplements and nutraceuticals under investigation for COVID-19 prevention and treatment.
      ,
      • Motti M.L.
      • Tafuri D.
      • Donini L.
      • Masucci M.T.
      • De Falco V.
      • Mazzeo F.
      The role of nutrients in prevention, treatment and Post-Coronavirus Disease-2019 (COVID-19).
      ]. These findings are supported in a meta-analysis of randomized controlled trials which report the beneficial effects of the DASH diet on reducing inflammation [
      • Soltani S.
      • Chitsazi M.J.
      • Salehi-Abargouei A.
      The effect of dietary approaches to stop hypertension (DASH) on serum inflammatory markers: a systematic review and meta-analysis of randomized trials.
      ].
      Inflammation is a known component in the pathophysiology of COVID-19 [
      • Tay M.Z.
      • Poh C.M.
      • Rénia L.
      • MacAry P.A.
      • Ng L.F.
      The trinity of COVID-19: immunity, inflammation and intervention.
      ]. According to the findings of this study, the higher score of the DASH diet was associated with a reduction in the risk of COVID-19-related hospitalization, which could be due to a reduction in inflammation. Consistently, adherence to plant-based diets or pescatarian diets, as anti-inflammatory diets, has been shown to be associated with a 73% and 59% lower risks of moderate-to-severe COVID-19 severity, respectively [
      • Kim H.
      • Rebholz C.M.
      • Hegde S.
      • LaFiura C.
      • Raghavan M.
      • Lloyd J.F.
      • et al.
      Plant-based diets, pescatarian diets and COVID-19 severity: a population-based case–control study in six countries.
      ].
      Findings of the present study showed that higher intakes of Legumes, nuts and seeds were associated with a 57% reduction in disease severity, although it was close to a significant level (P trend: 0.072). Similarly, a recent study of 158 countries across the world showed that increased beans and legumes intake was significantly associated with lower risk of COVID-19 infection [
      • Abdulah D.M.
      • Hassan A.
      Relation of dietary factors with infection and mortality rates of COVID-19 across the world.
      ]. In the present study, comparing the third tertile of fruit and vegetable intake scores with the first tertile showed a 38% and 41% reduction in disease severity, respectively. One of the possible mechanisms of this effect could be the high fiber content of fruits and vegetables, which as influencer of gut health, strengths the integrity of the intestinal mucosa and reduces gut permeability [
      • Parada Venegas D.
      • De la Fuente M.K.
      • Landskron G.
      • González M.J.
      • Quera R.
      • Dijkstra G.
      • et al.
      Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases.
      ,
      • Tan J.
      • McKenzie C.
      • Potamitis M.
      • Thorburn A.N.
      • Mackay C.R.
      • Macia L.
      The role of short-chain fatty acids in health and disease.
      ]. Also, DASH diet increases short chain fatty acid (SCFA) production by promoting the growth of protective gut microflora, which has positive effects on the immune system [
      • Jama H.A.
      • Beale A.
      • Shihata W.A.
      • Marques F.Z.
      The effect of diet on hypertensive pathology: is there a link via gut microbiota-driven immunometabolism?.
      ].
      Gut microbiota is not only directly related to the immune system but is also involved in the etiology of respiratory infections [
      • Dubourg G.
      • Edouard S.
      • Raoult D.
      Relationship between nasopharyngeal microbiota and patient’s susceptibility to viral infection.
      ]. Therefore, since COVID-19 has been shown to be associated with both symptoms of respiratory and gastrointestinal infections [
      • Kan H.
      • Stevens J.
      • Heiss G.
      • Rose K.M.
      • London S.J.
      Dietary fiber, lung function, and chronic obstructive pulmonary disease in the atherosclerosis risk in communities study.
      ], modifying the intestinal microbiota by following a healthy diet can reduce the severity of the disease.
      In this study, unlike usual case-control studies, outpatients and inpatients were compared and the relationship between DASH dietary pattern and the risk of hospitalization due to COVID-19 was assessed. The main limitation of this study was that we were not able to verify the causal relationship between DASH diet and the infection, due to cross-sectional design of the study. Another important limitation was that we could not adjust all potential confounders. Relatively small study population and the use of FFQ which is inevitably allied with recall bias, were other limitations.

      Conclusions

      In conclusion, our data provide evidence that adherence to DASH-style diet was associated with lower risk of hospitalization due to COVID-19. Nevertheless, due to the mediocre quality of evidence, it is required to conduct well-designed clinical trials to confirm and generalize these findings.

      Statement of authorship

      Conceptualization, ZY and AH; Formal analysis, ZY and AZ; Investigation, SS, MS and SK; Methodology, SKA and SRJ; Project administration, ZY and MS; Software, AZ; Validation, TG; Writing – original draft, ZY and AZ; Writing – review & editing, ZY and AH.

      Funding sources

      This research received no specific grant.

      Ethical statements

      The Ethical Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.NNFTRI.REC.1399.046) approved the study protocol.

      Conflict of interest

      The authors declare no conflict of interest.

      Acknowledgements

      This study was funded by the Ministry of Health and Medical Education of Iran and the Immunoregulation Research Centre of Shahed University (grant ID: 1398.411).

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