Mega doses of retinol: A possible immunomodulation in Covid-19 illness in resource-limited settings
Midha et al.
, Mega doses of retinol: A possible immunomodulation in Covid-19 illness in resource-limited settings
, Reviews in Medical Virology, doi:10.1002/rmv.2204 (Review)
Review of the potential benefits of vitamin A for COVID-19, including the effect of vitamin A on ACE2 expression in the respiratory tract, potentially improving the generation of protective immune responses to vaccines, and dosage and safety analysis.
Midha et al., 31 Dec 2020, peer-reviewed, 4 authors.
Abstract: Received: 16 October 2020
- Revised: 30 November 2020
Accepted: 1 December 2020
Mega doses of retinol: A possible immunomodulation in
Covid‐19 illness in resource‐limited settings
Ish K. Midha1
| Nilesh Kumar2 | Amit Kumar3 | Taruna Madan4
Pentamed Hospital, New Delhi, India
Saint Vincent Hospital, Worcester,
Dwight D. Eisenhower VA Medical Center,
Leavenworth, Kansas, USA
Department of Innate Immunity, ICMR‐
National Institute for Research in
Reproductive Health, Mumbai, India
Ish K. Midha, Pentamed Hospital, New Delhi,
Of all the nutrients, vitamin A has been the most extensively evaluated for its
impact on immunity. There are three main forms of vitamin A, retinol, retinal and
retinoic acid (RA) with the latter being most biologically active and all‐trans‐RA
(ATRA) its main derivative. Vitamin A is a key regulator of the functions of various
innate and adaptive immune cells and promotes immune‐homeostasis. Importantly,
it augments the interferon‐based innate immune response to RNA viruses
decreasing RNA virus replication. Several clinical trials report decreased mortality
in measles and Ebola with vitamin A supplementation.
During the Covid‐19 pandemic interventions such as convalescent plasma, antivirals, monoclonal antibodies and immunomodulator drugs have been tried but
most of them are difficult to implement in resource‐limited settings.
The current review explores the possibility of mega dose vitamin A as an
affordable adjunct therapy for Covid‐19 illness with minimal reversible side effects. Insight is provided into the effect of vitamin A on ACE‐2 expression in the
respiratory tract and its association with the prognosis of Covid‐19 patients.
Vitamin A supplementation may aid the generation of protective immune response
to Covid‐19 vaccines. An overview of the dosage and safety profile of vitamin A is
presented along with recommended doses for prophylactic/therapeutic use in
randomised controlled trials in Covid‐19 patients.
Abbreviations: 9‐cisRA, 9‐cis retinoic acid; ACE‐2, angiotensin converting enzyme 2; ACE‐I, angiotensin converting enzyme inhibitor; AID, activation‐induced cytidine deaminase; ALDH1A,
aldehyde dehydrogenase 1A; APCs, antigen presenting cells; ARB, angiotensin‐receptor blockers; ARDS, acute respiratory distress syndrome; ATRA, all‐trans‐retinoic acid; Blimp‐1, B
lymphocyte‐induced maturation protein‐1; BMP, Bone morphogenic protein; BRSV, bovine respiratory syncytial virus; Covid‐19, coronavirus disease 2019; COX‐2, cyclooxygenase‐2; CSIF,
human cytokine synthesis inhibitory factor; CXCL10, C‐X‐C motif chemokine ligand 10; CXCL9, C‐X‐C motif chemokine ligand 9; EBF1, early B cell factor 1; FDA, U.S. Food and Drug
Administration; FDCs, follicular dendritic cells; GATA3, G‐A‐T‐A binding protein 3; GCs, germinal centers; GM‐CSF, granulocyte macrophage colony stimulating factor; IFNγ, interferon
gamma; IL‐1, interleukin‐1; IL‐10, interleukin 10; IL‐12, interleukin 12; IL‐13, interleukin 13; IL‐1β, interleukin 1 beta (leukocytic pyrogen); IL‐23, Interleukin 23; IL‐4, Interleukin 4; IL‐6,
interleukin 6; IL‐6R, interleukin 6 receptor; IL‐8, interleukin 8 (or chemokine [C‐X‐C motif] ligand 8, CXCL8); ILC, innate lymphoid cells; IP‐10, interferon gamma inducible protein 10 kD (or
CXCL10); IRF‐4, interferon regulatory factor 4; LPS, lipopolysaccharide; LTBP, latent TGF‐β binding proteins;..
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation. FLCCC
provide treatment protocols.