key: cord-1035255-3ys59w4e authors: Kien Han Wee, Andrew title: COVID-19’s toll on the elderly and those with diabetes mellitus – is vitamin B12 deficiency an accomplice? date: 2020-11-12 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110374 sha: 870c132b2b5d969c2e1830ee92bae5094f9a6f9c doc_id: 1035255 cord_uid: 3ys59w4e COVID-19 exacts a disproportionate toll on both the elderly and those with diabetes; these patients are more likely to require costly intensive care, longer hospitalisation, and die from complications. Nations would thus find it extremely difficult to either lift or sustain socially-economically-and-politically damaging restrictions that keep this group of people safe. Without a vaccine, there is thus an urgent need to identify potential modifiable risk factors which can help manage overall fatality or recovery rates. Case fatality rates are highly variable between (and even within) nations; nutritional differences have been proposed to account significantly for this disparity. Indeed, vitamin B12 deficiency is a common denominator between the elderly and those with diabetes. The question on hand thus lies on whether managing B12 deficiencies will impact COVID-19 fatality outcome or recovery rates. Herein, we review the latest evidence to support the hypothesis of B12 deficiency as a potential modifiable risk factor in our fight against COVID-19. The COVID-19 pandemic exacts a disproportionate toll on the elderly and those with 96 diabetes mellitus (henceforth used interchangeably with "diabetes"); these patients are more COVID-19 patients with diabetes mellitus (with an 88·5% predominance of type-2 diabetes 115 mellitus (T2DM)) showed a case fatality of 10·6% (by day 7 of hospitalization); combining 116 both outcomes of "death" and "tracheal intubation for assisted mechanical ventilation" 117 (within 7 days of admission), the prevalence rose to 29% (5). Recently, it has been proposed that nutrition is partly responsible for these wide differences 152 in COVID-19 death rates seen between (and even within) countries (27). Nutrition can 153 certainly affect the immune system's ability to protect against viral infections (28, 29); 154 elderly malnutrition in COVID-19 infections has been described in a Chinese study. This 155 study of 182 elderly (age ≥ 65 years) COVID-19 patients using the Mini-Nutritional- Assessment score showed 52·7% to be "malnourished" and a further 27·5% to be "at risk of 157 malnutrition". Regression risk in the study also showed diabetes mellitus to be an To review the state of the art pertaining to vitamin B12 deficiency (henceforth known as 178 "B12" deficiency) and COVID-19, an on-line literature search on "Pubmed", "Google", and 179 the clinical trials register "ClinicalTrials.gov" was done using the following MeSH and free 180 text search terms (associated with B12 deficiency): "B12 deficiency"; "B12"; "folate"; 181 "vitamin"; "homocysteine"; "one-carbon metabolism"; and "metformin", which were first 182 used singly, and subsequently matched, each in turn, with the terms (associated with COVID-183 19): "COVID"; "COVID-19"; and "Sars-Cov-2". A third round of searches ensued with the 184 terms (comprising biomarkers of poor COVID-19 outcomes, or the means by which the virus 185 gains entry): "prognostic factors"; "elderly"; "older"; "diabetes"; "obesity"; "BMI"; "gender"; "tnf alfa"; "interleukin"; "ifn gamma"; "cd4 cd8"; "lymphocyte"; "nk cell"; and antagonists among these patients (38, 53), especially as gastric-acid-reducing adjuncts to 218 aspirin therapy (used in the secondary prevention of cardiovascular events in diabetes (54, 219 55)), could also reduce the ability to digest B12 from food (56). Like us, human gut microbes that support our gut barrier also require B12 as a cofactor for 266 metabolism (29). 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Conflict-of-interest/ financial disclosure statement: 762 The author declares no competing interest