Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B 12  in combination on progression to severe outcomes in older patients with coronavirus (COVID-19)

Author(s): Chuen Wen Tan , M.R.C.P., F.R.C.Path ^a ^, ¹ , Liam Pock Ho , F.R.C.P.A. ^a ^, ^b ^, ^c ^, ¹ , Shirin Kalimuddin , M.B.B.S., M.R.C.P., M.P.H. ^d ^, ^e , Benjamin Pei Zhi Cherng , M.B.B.S., M.R.C.P. ^d , Yii Ean Teh , M.B.B.S., M.R.C.P.(UK) ^d , Siew Yee Thien , M.R.C.P.(UK) ^d , Hei Man Wong , M.R.C.P.(UK), M.Med(NUS) ^d , Paul Jie Wen Tern , M.B B.Chir ^d , Manju Chandran , M.D., F.A.C.P., F.A.C.E., F.A.M.S., C.C.D. ^f , Jason Wai Mun Chay , M.R.C.P., F.R.C.Path(UK) ^b ^, ^c , Chandramouli Nagarajan , F.R.C.P.(Edin), F.R.C.Path(UK) ^a , Rehena Sultana , M.Sc. (Statistics), MBA (Systems Management) ^g , Jenny Guek Hong Low , M.R.C.P.(UK), M.P.H.(US) ^d ^, ^e , Heng Joo Ng , M.R.C.P.(UK), F.R.C.Path(UK) ^a ^, ^*

Publication date (Electronic): 8 September 2020

Journal: Nutrition (Burbank, Los Angeles County, Calif.)

Publisher: Elsevier Inc.

Keywords: Vitamin D, Magnesium, Vitamin B12COVID-19

Read this article at

ScienceOpenPublisher PMC

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Highlights

•

Use of a combination of vitamin D, magnesium, and vitamin B ₁₂ (DMB) in patients with coronavirus disease (COVID-19) was studied.
•

Fewer patients ≥50 y of age with COVID-19 on DMB suffered clinical deterioration.
•

Further studies are warranted to ascertain the full benefit of DMB in patients with COVID-19.

Abstract

Objectives

The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B ₁₂ (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not.

Methods

This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D ₃, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B ₁₂ upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both.

Results

Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03–0.59) and 0.20 (95% CI, 0.04–0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively.

Conclusions

A vitamin D / magnesium / vitamin B ₁₂ combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

Related collections

Most cited references 10

Record: found
Abstract: found
Article: not found

Estimates of the severity of coronavirus disease 2019: a model-based analysis

Robert Verity, Lucy C Okell, Ilaria Dorigatti … (2020)

Summary Background In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. Methods We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. Findings Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older. Interpretation These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death. Funding UK Medical Research Council.

0 comments Cited 1781 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study

Lei Pan, Mi Mu, Pengcheng Yang … (2020)

OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

0 comments Cited 850 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: found

Is Open Access

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Adrian Martineau, David A. Jolliffe, Richard Hooper … (2017)

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.

0 comments Cited 615 times – based on 0 reviews      Review now

All references

Author and article information

Journal

Journal ID (nlm-ta): Nutrition

Journal ID (iso-abbrev): Nutrition

Title: Nutrition (Burbank, Los Angeles County, Calif.)

Publisher: Elsevier Inc.

ISSN (Print): 0899-9007

ISSN (Electronic): 1873-1244

Publication date PMC-release: 8 September 2020

Publication date (Print): November-December 2020

Publication date (Electronic): 8 September 2020

Volume: 79

Page: 111017

Affiliations

[a ]Department of Hematology, Singapore General Hospital, Singapore

[b ]Department of Clinical Pathology, Singapore General Hospital, Singapore

[c ]Department of Pathology, Sengkang General Hospital, Singapore

[d ]Department of Infectious Diseases, Singapore General Hospital, Singapore

[e ]Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore

[f ]Department of Endocrinology, Singapore General Hospital, Singapore

[g ]Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore

Author notes

[* ]Corresponding author. Tel : +65-63266604. Fax : +65-62260237.

[1]

Contributed equally

Article

Publisher Item ID: S0899-9007(20)30300-2 Publisher ID: 111017

DOI: 10.1016/j.nut.2020.111017

PMC ID: 7832811

PubMed ID: 33039952

SO-VID: 96247ec3-0dcc-45bc-8468-589b4f837965

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

History

Date received : 24 June 2020

Date revision received : 25 August 2020

Date accepted : 1 September 2020

Comments

Comment on this article

Cited by 117

See all cited by

Most referenced authors 495

See all reference authors

- Version 1

Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B ₁₂ in combination on progression to severe outcomes in older patients with coronavirus (COVID-19)