Abstract: nutrients Review Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19 Patrick Holford 1, *, Anitra C. Carr 2 , Thomas H. Jovic 3,4 , Stephen R. Ali 3,4 , Iain S. Whitaker 3,4 , Paul E. Marik 5 and A. David Smith 6 1 2 3 4 5 6 * Institute for Optimum Nutrition, Ambassador House, Richmond TW9 1SQ, UK Nutrition in Medicine Research Group, Department of Pathology & Biomedical Science, University of Otago, Christchurch 8140, New Zealand; anitra.carr@otago.ac.nz Reconstructive Surgery & Regenerative Medicine Research Group, Institute of Life Sciences, Swansea University Medical School, Swansea University, Swansea SA2 8PY, UK; Thomas.Jovic@wales.nhs.uk (T.H.J.); Stephen.Ali@wales.nhs.uk (S.R.A.); Iain.Whitaker@wales.nhs.uk (I.S.W.) Welsh Centre for Burns & Plastic Surgery, Morriston Hospital, Swansea SA6 6NL, UK Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA; marikpe@evms.edu Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK; david.smith@pharm.ox.ac.uk Correspondence: pat@patrickholford.com; Tel.: +44-(0)-7944-689108 Received: 19 October 2020; Accepted: 3 December 2020; Published: 7 December 2020



 Abstract: There are limited proven therapies for COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2–8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6–24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients’ vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19. Keywords: COVID-19; SARS-CoV-2; coronavirus; vitamin C; ascorbate; colds; pneumonia; sepsis; immunonutrition; supplementation