NUTRITION FOR PREGNANT

WOMEN IN THE COVID 19

PANDEMIC ERA

Putra Wiradnyana
Obstetrician & Gynecologist
Maternal Fetal Medicine Consultant
Udayana University / Sanglah Hospital
Denpasar / Bali
INTRODUCTION
The world is now experiencing its third
major epidemic of coronavirus (CoV)
infections.
A new CoV infection epidemic began in
Wuhan, Hubei, China, in late 2019, originally
called 2019 nCoV and renamed COVID-19 by
the WHO on February 11, 2020.
The direct cause of death is generally due to
ensuing severe atypical pneumonia.
Those epidemics all began with animal to
human infection.
Previous CoV
epidemics include The ongoing Middle
Severe Acute East Respiratory
Respiratory Syndrome COVID-19 / SARS-CoV-
Syndrome (MERS)- 2 by the WHO on
(SARS)-CoV, which CoV in the Middle
started in China in February 11, 2020.
East, first reported in
2002. 2012.
Seasonal influenza has a high health burden.
2002-2011  according to one recent
estimate, 389,000 (uncertainty range 294,000–
518,000) respiratory deaths were associated
with influenza.
According to the U.S. Center for Disease
Control and Prevention, during the period
2010–2019  annual symptomatic illness
affected between 9-45 million people, resulting
in between 4-21 million medical visits,
140,000–810,000 hospitalizations, and 23,000–
61,000 deaths.
THE IMMUNE SYSTEM

The innate response :

Fast.
Non antigen specific.

The adaptive response :

Slower.
Antigen specific.
The innate immune system  skin, gut
epithelium, antimicrobial peptides, the
complement system, a variety of
phagocytic and other cells (neutrophils,
macrophages, natural killer cells) 
recognize the presence of pathogens via
the expression of nonspecific pattern
recognition receptors.
The innate system moves quickly to
recognize and destroy “non-self”
threats, typically via inflammatory
processes, and then resolve the
inflammation and repair the damage
caused by these events.
The adaptive response  T lymphocytes, subsets of which coordinate the
overall adaptive response or kill virally-infected cells, and B lymphocytes,
which can be activated to secrete antibodies specific to the infecting
pathogen.
The adaptive system is responsible for generating immunological
“memory”, whereby a repeated infection with the same pathogen will
generate a vigorous, fast antigen-specific response  the induction of
immunological memory is the mechanism by which vaccines can provide
protection against subsequent exposure.

ACTIVE
IMMUNITY

PASSIVE
IMMUNITY
NUTRITIONAL IMPACT ON
IMMUNITY
Several vitamins (vitamins A, B6, B12, C,
D, E, folate)and trace elements (zinc,
iron, selenium, magnesium, copper) play
important and complementary roles in
supporting both the innate and adaptive
immune systems.
Inadequate intake and status of these
nutrients are widespread, leading to a
decrease in resistance to infections and
as a consequence an increase in disease
burden.
 To support the development
and maintenance of physical
barriers.

Production and activity of

antimicrobial proteins.

Cytokine production.
Innate
Immunity promotion of and recovery
from inflammation.

Antioxidant activity.

Phagocytic and killing

activities of neutrophils and
macrophages

Growth, diferentiation and

motility/chemotaxis of innate
cells.
 Lymphocyte diferentiation,
proliferation, and homing.

Cytokine production.

Adaptive Immunity

Antibody production.

The generation of memory

cells.
VITAMIN D
Several reviews consider the ways in which
vitamin D reduces the risk of infection (viral and
microbial) and death.
A recent review regarding the role of vitamin D
in reducing the risk of the common cold
grouped those mechanisms into three
categories  physical barrier, cellular natural
immunity, and adaptive immunity.
Vitamin D helps maintain tight junctions, gap
junctions, and adherens junctions (by E-
cadherin)  several articles discussed how
viruses disturb junction integrity, increasing
infection by the virus and other
microorganisms.
Vitamin D enhances cellular innate immunity
 the induction of antimicrobial peptides 
human cathelicidin (LL-37) by 1,25-
dihdroxyvitamin D, and defensins.
Cathelicidins exhibit direct antimicrobial
activities against a spectrum of microbes 
Gram-positive and Gram-negative bacteria,
enveloped and nonenveloped viruses, and
fungi.
Those host derived peptides kill the invading
pathogens by perturbing their cell membranes
and can neutralize the biological activities of
endotoxins.
Vitamin D also enhances cellular immunity
 by reducing the cytokine storm induced
by the innate immune system.
The innate immune system generates both
pro-inflammatory and anti-inflammatory
cytokines in response to viral and bacterial
infections, as observed in COVID-19
patients  vitamin D can reduce the
production of pro-inflammatory Th1
cytokines  TNF-α and INF-γ.
Administering vitamin D reduces the
expression of pro-inflammatory cytokines
and increases the expression of anti-
inflammatory cytokines by macrophages.
Vitamin D is a modulator of adaptive
immunity  suppresses responses mediated
by the Th1  primarily repressing
production of IL-2 and INFγ.
Additionally, vitamin D promotes cytokine
production by the Th2 cells, which helps
enhance the indirect suppression of Th1 cells
by complementing this with actions
mediated by a multitude of cell types.
Furthermore, vitamin D promotes induction
of the T regulatory cells, thereby inhibiting
inflammatory processes.
In a mouse model (2011)  the human
cathelicidin, LL-37, and the murine cathelicidin,
mCRAMP  demonstrated significant anti-viral
activity in vivo, reducing disease severity and
viral replication in infected mice to a similar
extent as the well characterized influenza virus
specific antiviral drug zanamivir.
Influenza virus infected mice treated with LL-37
had lower concentrations of pro-inflammatory
cytokines in the lung than did infected animals
that had not been treated with cathelicidin
peptides.
Martineau et al. (2017)  a systematic
review and meta-analysis of individual
participant data (n = 10,933) from 25
randomized, double blind, placebo
controlled trials of vitamin D
supplementation with a specified outcome
of ARI.
They found a 12% reduction for
experiencing at least one ARI irrespective of
dosing schedule, 19% reduction in
individuals taking a daily or weekly dose
without bolus doses and no benefit with
bolus dosing.
Among those receiving a daily or weekly dose  they
observed a 25% reduction for those with baseline 25(OH)D
levels ≥ 25 nmol/L (12 ng/mL) and a 70% reduction for
those with baseline levels < 25 nmol/L.
They concluded that daily or weekly vitamin D
supplementation protected against ARI overall and that it
was safe.
OMEGA-3, EPA, AND DHA

Inflammation is a key component of the immune

response  inflammation typically resolves
quickly at the end of the immune response, due to
activation of specific negative-feedback
mechanisms  the omega-3 fatty acids,
eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA) present at the site of inflammation are
enzymatically converted to specialized pro-
resolving mediators (SPMs)  resolvins,
protectins, and maresins.
Notably, nutritional deficiencies in these essential
fatty acids can result in delayed or suboptimal
resolution of inflammation  this could be very
important in the context of severe COVID-19
which manifests as uncontrolled inflammation 
cytokine storm.
A recent Cochrane review (2019)  significant
improvement in blood oxygenation and
significant reductions in ventilation requirement,
new organ failures, length of stay in the intensive
care unit and mortality at 28 days.
VITAMIN C

Vitamin C affects several aspects of immunity :

Supporting epithelial barrier function, growth and

function of both innate and adaptive immune cells.

White blood cell migration to sites of infection.

Phagocytosis and microbial killing.

Antibody production.
Cochrane systematic review, 2013 :
 A significant reduction in the risk of
pneumonia with vitamin C
supplementation  particularly in
individuals with low dietary intakes.
 In older patients, disease severity
and risk of death were reduced with
supplementation  particularly in
the case where initial plasma levels
of vitamin C were low.
Hemilä, 2017 :
 Decrease the duration and severity of upper
respiratory tract infections, such as the
common cold.
 Significantly decrease the risk of infection
when given prophylactically in people under
enhanced physical stress.
VITAMIN E

Enhances T cell mediated immune function in the face

of age related decline.

Improved natural killer cell activity.

Neutrophil chemotaxis and phagocytosis.

Mitogen induced lymphocyte proliferation.

Clinical demonstrate a role for vitamin E in
respiratory tract infections.
Wu et al. (2014)  randomized clinical trial 617
nursing home residents  daily supplementation
for one year with 200 IU vitamin E reduced the risk
of upper respiratory tract infections, but not lower
respiratory tract infections.
TRACE ELEMENTS

Zinc is important for maintenance and development

of cells in both the innate and adaptive immune
systems.
Zinc deficiency results in :
 Impaired formation, activation and maturation of
lymphocytes.
 Disturbs the intercellular communication via
cytokines.
 Weakens the innate host defense.
Data from animal models and epidemiological
studies in people indicate that deficiency in
specific nutrients  particularly selenium and
vitamin E  can lead to reproducible genetic
mutations and increased virulence of certain
viruses  coxsackievirus, poliovirus, and
murine influenza.
RECOMMENDATIONS AND
CONCLUSIONS
• Astawa, I. N. M. (2018). 'Dasar-dasar Patobiologi Molekuler I: Apoptosis &
Onkogenesis'. Edisi Pertama. Airlangga University Press. Surabaya. pp. 79-107.
• Barazzoni, R., et al. (2020). “ESPEN expert statements and practical guidance for
nutritional management of individuals with SARS-CoV-2 infection, Clinical
Nutrition”. https://doi.org/10.1016/j.clnu.2020.03.022.
• Calder, P.C., Carr, A.C., Gombart, A.F., Eggersdorfer, M. (2020). “Optimal
Nutritional Status for a Well-Functioning Immune System Is an Important Factor
to Protect against Viral Infections”. Nutrients, 12, 1181.
doi:10.3390/nu12041181.
• Caussy, C., Wallet F., Laville M., Disse E. (2020). “ Obesity is associated with
severe forms of COVID-19”. doi: 10.1002/oby.22842.
• Grant, W.B., Lahore, H., McDonnell, S.L., Baggerly, C.A., French, C.B., Aliano, J.L.,
Bhattoa, H.P. (2020). “Evidence that Vitamin D Supplementation Could Reduce
Risk of Influenza and COVID-19 Infections and Deaths”. Nutrients, 12, 988;
doi:10.3390/nu12040988.
• Kalantar-Zadeh, K., Moore, L.W. (2020). “Impact of Nutrition and Diet on COVID-
19 Infection and Implications for Kidney Health and Kidney Disease
Management”. Journal of Renal Nutrition. doi:
https://doi.org/10.1053/j.jrn.2020.03.006.
• Laviano, A., et al. (2020). “Nutrition support in the time of SARS-CoV-2 (COVID-
19)”. Nutrition. https://doi.org/10.1016/j.nut.2020.110834.
• Lobascio, F., Montagna, E., Bruno, R., Ludovisi, S., Corsico, A.G., Di Sabatino, A.,
Belliato, M., D., Calvi, M., Iacona, I., Grugnetti, G., Bonadeo, E., Muzzi, A.,
Cereda, E. (2020). “Early nutritional supplementation in non-critically ill patients
hospitalized for the 2019 novel coronavirus disease (COVID-19): Rationale and
feasibility of a shared pragmatic protocol”. Nutrition, doi:
https://doi.org/10.1016/j.nut.2020.110835.