Nutritional Habits, and Coronavirus Disease 2019 (COVID-19) Outcome

As of May 30th more than 23,000 cases of COVID -19 cases were confirmed in Egypt with total
deaths of 913. There are over six million confirmed cases of COVID-19 and almost 370,000
deaths globally. COVID-19 originated from Wuhan city, China in early 2020, from their
extending to the rest of the world. The virus belong to a large class of viruses known as
β-coronaviruses with a large number of potential natural primary, intermediate and final
hosts. Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is an enveloped RNA
virus that typically spread by droplets causing pulmonary and extra-pulmonary complications.

COVID-19 can result in cytokine storm, which in severe cases can lead to acute respiratory
distress syndrome (ARDS), sepsis and multiple organ dysfunction that can progress to death.
Post SARS-CoV-2 entry, intense immune response against the virus with infiltration of
monocytes and macrophages into alveolar cells with decreasing number of lymphocytes in
peripheral blood along with reduced lymphocytes in lymphoid organs, hypercoagulability,
thrombosis and multiple organ damage. This along with the fact that some patients of this
disease have diarrhea points out towards a distinct possibility of involvement of gut-lung
axis and may be the gut microbiota.

The gut microbiota and immune homeostasis seem to have a back and forth relationship. Also,
gut microbiota derived signals are known to tune the immune cells for pro and
anti-inflammatory responses thereby affecting the susceptibility to various diseases.

Many elderly and immune-compromised patients progress to serious adverse clinical outcomes,
it is therefore tempting to speculate that in COVID-19, there is a possible cross-talk taking
place between the lung and the gut microbiota which might influence the outcome of the
clinical manifestation.

Healthy gut microbiome essentially could be pivotal in maintaining an optimal immune system
to prevent an array of excessive immune reactions that eventually become detrimental to lungs
and vital organ systems.

Several studies have shown that increased D-dimer levels are associated with severe forms of
COVID-19 infection, this might be explained by diffuse alveolar damage, pneumocytes
desquamation, pulmonary edema, interstitial mononuclear cells and lymphocytes infiltration
causing intense inflammatory burden induced in severe COVID-19 infections.

Numerous studies have shown that the patient's nutritional status have a significant effect
on an individual's immunity and over all health status and it has been suggested that
nutritional deficiencies may predispose to severe forms of COVID-19 infections. Adequate
Fruits and vegetables consumption have been studied for their potential protective effects
against respiratory diseases and anti-inflammatory effects, furthermore, fruits and
vegetables are also rich sources of fibers that have favorable effects on gut microbiome. One
of very familiar water-soluble vitamins; Vitamin C (ascorbic acid) , that can be found in
citrus fruits, barriers, leafy greens, tomatoes, and various other fruits and vegetables.
Indeed, 1-2 g supplementation of vitamin C was found to shorten the duration of common cold
by 18%, according to the United states National Institute of health (NIH) the recommended
daily allowances (RDA) of vitamin C for healthy adults is 75-90 mg/d.

The Sunshine vitamin (Vitamin D) which is found in mushrooms, eggs, salmon and milk was found
in a meta-analysis of 25 randomized controlled trails conducted over more than 11,000
participants, an overall protective effect of vitamin D supplementation in acute respiratory
infections and, also, COVID-19, studies also suggested to possible role of Vitamin D as an
antiviral immunomodulator through anti-inflammatory properties, for this reason, Vitamin D
have been suggested to have a beneficial effects against SARS-CoV-2 infection (16), another
study done in Switzerland on SARS-CoV-2 positive patients found to have significant lower
levels (mean value 11.1 ng/mL) of 25-hydroxyvitamin D. The recommended RDA of vitamin D
according to NIH 15-20 ug/d (600-800 IU with tolerable upper limit of 4000 IU). Another
vitamin with anti-inflammatory benefits, fat soluble vitamin E (œ-tocopherol) found in seeds,
green leafy vegetables, nuts, and fortified cereals. Vitamin E has been labeled as
immunoenhancing vitamin by with anti-inflammatory properties by regulating the production of
Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and modulating signal
transduction, thus protecting The polyunsaturated fatty acids (PUFAs) in the cell membranes,
for this reason, it has been suggested that the combination of Vitamins C, D & E may be
useful in COVID-19 patients. The RDA of Vitamin E for healthy adults according to the NIH is
15 mg/d (tolerable upper level 1000 mg/d).

Regarding minerals, Zinc has been found to have a critical role in maintaining immune cells
integrity and important cofactor for numerous enzyme, zinc deficiency can cause impaired
cell-mediated immunity predisposing to various infections, especially respiratory infections,
available food sources of zinc including; meats, legumes and diary products, the RDA of zinc
according to NIH is 8-11 mg/d (with 40 mg/day tolerable upper intake level).

Another essential trace element is Copper that can be found in nuts and offal and, in lesser
concentrations in cereals and fruits, copper has a pivotal role in maintaining DNA integrity
by its antioxidant effects, studies have shown that adequate copper supplementation can
reduce lung inflammation in mice, according to NIH, the RDA of copper is 900 ug/d (tolerable
upper limit of 10 mg/d).

Regular intake of prebiotic foods such as oligosaccharides, fermentable fibers, and resistant
starches can beneficially affect the gut microbiota, prebiotic fibers are considered
selective substrates for specific beneficial colonic bacteria as they are neither hydrolyzed
nor absorbed in the proximal gut. Dietary fibers have been suggested as immunity modulators
as they lower incidence of bacterial translocation by maintaining integrity of the gut
barrier, available sources include; oat, barley, seeds, nuts, peas and some fruits, the
recommended daily intake is 25-38 g/day. Probiotic foods (from dairy products as yogurt& sour
cream) and supplements have the ability to modify the gut microbiota and potentially modulate
gut inflammatory response.

D-dimer is a fibrin degradation product (FDP) that reflects bath thrombin production and
activation, elevated levels have been linked to increased risk of coronary artery disease,
cerebrovascular strokes and total mortality, so far the link between dietary habits and
D-dimer levels has been poorly explored. Studies have reported, that adherence to a
Mediterranean diet was found to be associated with decreased levels of D-dimer, with possible
antithrombotic effects due to high content of fibers, antioxidants, mono and polyunsaturated
fatty acids.

Co-existing non-communicable chronic diseases (NCDs) in COVID-19 patients have been found to
delay patients recovery and worsen their prognosis, the reason may be due to aggravated
inflammatory pathology found in NCDs exacerbating COVID-19 infection. Such patients with
underlying cardiovascular, respiratory disease were found to have worse prognosis, diabetes,
hypertension and hypercholesterolemia are considered major risk factors for thrombotic
complications, which in COVID-19 patients may account for higher risk of serious disease
outcome and is associated with two-folds increase in mortality.

Fish and fish oils are considered very beneficial to individual health especially in patients
with NCDs including cardiovascular diseases. Omega-3-polyunsaturated fatty acids (PUFA) are
integral component of the cell membrane thus having anti-inflammatory effects, however,
substantial human trials in this area are lacking.

For this reason, an effective approach to reduce person's risk of developing NCDs is to halt
underlying inflammation via modifiable risk factors including; diet, exercise and healthy
lifestyle choices. To date, there is no single food or natural remedy that has been used for
preventing COVID-19 infections. Healthy diets containing adequate amounts of necessary macro
and micronutrients, prebiotics and probiotics that can maintain and restore immune system,
therefore increasing protection against chronic inflammation-related NCDs. Foods with
anti-inflammatory and immunomodulatory compounds including essential vitamins (C, D & E) and
minerals (Zinc, Copper, Calcium & Selenium) are considered protective foods, these
micronutrients can act in harmony to prevent thrombotic and reactive oxygen species (ROS)
complications by their anti-inflammatory properties. They are present in fair amounts in
Mediterranean Diet, which is characterized by increased dietary consumption of legumes, olive
oil, whole grains, nuts, and monounsaturated fats, minimally processed fruits, vegetables,
associated with low to moderate consumption of fermented dairy products, fish, poultry.
Antithrombotic advantages of Mediterranean diet have been explained by reduced levels of
factor VII, tissue factor, platelets and leucocytes counts in individuals consuming
Mediterranean diet. On the other hand, The "Western" dietary pattern, which is characterized
by high consumption of saturated fats, refined carbohydrates, red meat, deserts and sweets,
that may be associated with hyperglycemia, hyperlipidemia and chronic inflammatory state.

The aim of the study is to evaluate the role dietary habits among COVID-19 Egyptian patients
and whether type of diet (Mediterranean or Western) will affect disease outcomes.

The current study also trying to determine if balanced diet maintaining healthy gut
microbiota can have a role in avoiding disease progression and deterioration in COVID-19
cases.

Dietary pattern questionnaire for COVID 19 patient Name:- Age :- The work:- height :- Weight
:- BMI :-

- Did you lose weight during the previous 3 months?

- Do you smoke?

- What is your usual breakfast before the injury and when to take it ?

- What is your usual lunch before the injury and when to take it ?

- What is your usual dinner before the injury and when to take it ?

- Did you eat between meals and what you eat?

- How many cups of water you drink daily?

- Do you eat salads or fresh vegetables daily (type and amount)?

- Do you eat fruit daily (type and amount )?

- Do you drink milk daily ?

- Do you eat yogurt daily?

- Do you drink fermented milk daily?

- Do you eat cheese daily(type and amount)?

- Do you eat fish weekly ( type and amount)?

- Do you eat pickles daily(amount) ?

- Are you exposed to the sun daily ( duration and time)?

- Number of spoons of sugar taken per day ( and sweets)?

- Types of drinks daily and their times ?

- Frequency of eating out ( weekly)?

- Do you eat any of these food daily ( cocoa , cashew , cheddar, chicken , meat, Milk ,
almond , salmon , yogurt)?

- Number of times eating eggs per week ?

- The type and amount of fats used in cooking :-

- Number of hours of sleep per day :-

- Antibiotic intake rate:-

- Have you take any supplements and vitamins for the past months?

The analysis of the above food habits questionnaire Will be fitted to a scoring system from 0
to 32 points covering the following

1. Probiotic in food

2. Prebiotic in food

3. Vitamins and minerals in food

4. Mediterranean type of food

5. Antibiotics intake that affect gut microbiota

6. Tea frequency and amount intake with respecting it's role on microbiota

7. Exercise daily and it's effect on immune system and lung capacity

All patients will be followed up for 14 days For disease recovery or progression to severe
category.

Statistical analysis will be done after tabulation of the results to correlate with
microbiome as well as the clinical status of patients.

Aim and Expected outcomes: The novelty of this study is that the investigators will get
information about the role and type of diet on COVID-19 outcome and clarifying the role
certain macro and micronutrients in inducing chronic inflammation, protecting from thrombosis
The investigators also hope through this research to modify dietary habits in the Egyptian
society encouraging healthy nutrition with the pre and probiotics food role to retain normal
healthy life.