Pandemic - ‘Action This Day’ – Measure Vitamin D in COVID-19 Patients – Time is of Essence – BAME, Elderly and Obese are Disproportionately Dying
Dear Editor 
Vitamin D is suggested for inclusion in WHO COVID-19 road-map.
Public Health England (PHE) may wish to consider:
BIOLOGICAL PATHWAYS and EVOLUTION - Vitamin D definitively factors in immune function.
Biological / physiological research powerfully evidences Vitamin D factors in disease immune response, through multiple mechanisms and pathways, including transcription and mitochondrial regulation. Multiple pathways have been identified. Vitamin D is unquestionably built very deep into evolutionary biology.[4. 5]
Consequentially, Vitamin D deficiency inevitably must impact both COVID-19 and Kawasaki-like PIMS-TS  progression: the unknowns are quantum and mechanisms.
OBSERVATIONAL EVIDENCE STRIKING – 10-20 greater D deficiency mortality-risk in some.
Nine observational preprints UK Germany, monitoring COVID-19-positive-patients; papers on, infectivity, hypocalcaemia, and a study in Singapore, taken together, strongly suggest Vitamin D deficiency factors in COVID severity and mortality. No RCTs have reported to date.
RCTs / POPULATION STUDIES TAKE TIME, months to years - limited pandemic value.
Most RCTs and wider studies including COVIDENCE, will not report until after main pandemic impact, limiting their application-value.
MEASURE VITAMIN D IN COVID-19 PATIENTS: - quick – easy – cheap: and anonymise – follow NICE.
Immediate widespread measurement of Vitamin D levels in plasma of COVID-19 hospital patients would facilitate deficiency repletion per NICE guidelines; and allow fast determination, of Vitamin D deficiency impact on COVID-19, with sufficient certainty sufficient to support timely public health policy adaptation.
INFECTION AND PROGRESSION - governed by different, albeit related, pathways.
Infection statistics will be impacted both by social factors and biology.
Separation of Vitamin D deficiency effect on; COVID-19 infection; and post diagnosis disease progression in hospitalised patients, is important, as driven by different balances of social and biologic factors.
Whilst infection rates will have a social aspect: asymptomacity, severity, and disease progression, must largely depend on biological factors (given equally standards of care); thus, ultimately on; nutritional status, general health and comorbidities, with possible impact of polymorphic genetic components triggered by extrinsic factors.
Consistent with this, comorbidities such as; hypertension, atherosclerosis, and diabetes, are arguably products of poor nutrition, not ‘poverty per se’. Historically groups subject to ‘poverty’ in China and Africa, had low levels of these diseases.
CONFOUNDERS – comorbidities increase COVID-19 risk
Martineau suggests, implicitly referring to the 7 observational preprints, that ‘confounding may explain associations’. Indeed: however, many such confounders include a vitamin-D-element, and, in the time-urgency of a pandemic, such considerations are arguably a nicety; given vitamin D deficiency is anyway a defined medical condition. Further effects are so large, and results so stark, it is difficult to conceive confounders could materially impact the direction of the basket-of-outcomes.
REVERSE CAUSALITY – an issue for later - this is a pandemic
Martineau noted, “Reverse causality could also be operating”, “Inflammation itself can disturb Vitamin D metabolism, and actually render somebody deficient,”. This is a valid observation, but it is unclear how it obviates the clinical need to urgently replete Vitamin D deficient patients.
If the issue was dehydration, nobody would demand RCTs to determine if dehydration was due to; low-intake-pre-hospitalisation, or fever-in-hospital, before accepting patients deficient or insufficient in water, required hydration.
Surely treatment of Vitamin D deficiency disease patients should be no different. Vitamin D disease is a NICE recognised condition, that requires treatment irrespective of the cause of the deficiency, without exception.
CLINICAL AND NUTRITIONAL ADVICE - determined differently.
Clinical pharmacological applications require RCTs. Current nutritional UK advice restricts itself largely to RCTs, yet decisions on; smoking, handwashing, mask-use, social-distancing, and isolation-polices; as well as historical nutritional policies; were very largely based on judgements, of benefits vs. harms, derived from observation and perceived likely outcomes, rather than RCTs, due to practical difficulties, and ethics of doing human RCT deficiency and infection studies, where potential harm and fatality is involved.
PRAGMATISM - lower Antipodean COVID-19 mortality.
Tasmania, more-widely Australia, and New Zealand, take more pragmatic Vitamin D policy approaches, than the UK, encouraging testing and / or automatic-supplementation (50,000IU month – NZ) for medium-risk patients. Interestingly, Covid -19 mortality per Million, in Australia and New Zealand; and Norway and Finland also with active Vitamin D policies; was much lower than the UK.
NATIONAL AND GLOBAL TRENDS
Infection and mortality incidence, shows signs of both a seasonal and latitudinal aspects, further pointing to Vitamin D factoring in COVID-19 infection and progression.
BAME COVID-19 MORTALITY AND RISK OF VITAMIN D DEFICIENCY – URGENT ISSUES
Facts require facing: BAME Persons including African Americans; Elderly and Obese, are at greatest risk of both, COVID-19 and Vitamin D deficiency: determining if links exists requires urgent measurement of Vitamin D levels in COVID-19 patients.
TIME IS OF ESSENCE in a pandemic.
Evidence based on; Spanish (1918-1920), Asian ‘H2N2’ (1957-1959; 1959 in Peru – seasonal effect?) and Hong Kong ‘H3N2’ (1968-1970), flu pandemics, suggests COVID-19 will likely last 2 years, with a possible 3rd year, latitude-impacted-tail. Historically, the biggest pandemic effect was seen in the second season, suggesting COVID-19 may upsurge this autumn / winter.
DEXAMETHASONE - COMPARE AND CONTRAST
Potential pandemic mitigation strategies, require research and decisive ‘pre-peer-review’ action; as happened with the steroid Dexamethasone; but ironically, not with evolutionary-immune-central-steroid, Vitamin D, despite; high deficiency levels, known biology, low-side-effect-risks and observational studies.
Interestingly, immune pathways activated by Dexamethasone and Vitamin D, overlap, e.g. via VDR; Dexamethasone also changes, Vitamin D and downstream product, levels, logically possibly negatively impacting immune recovery pathways, and time-scales.
CONCLUSION – ‘ACTION THIS COVID-19 DAY’ - Please.
Is failure to collect UK Vitamin D COVID-19 data rational – how can PHE properly and fully consider vitamin D’s role in Covid-19 severity and mortality, without the necessary data?
This is a pandemic – this data is needed now – common sense and pragmatism must prevail – NHS please adopt Churchill’s mantra ‘action this day’- urgently obtain anonymised Vitamin D COVID-19 positive patient data, by addition to testing list / testing of historic samples: record and relate to outcomes - determine if global observational results apply to UK – if the case, PHE please amend Public Health and clinical policy appropriately.
Establishing reduction of Vitamin D deficiency significantly mitigates COVID-19 mortality and severity would be globally ‘game-changing’.
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Competing interests: No competing interests