Vitamin D status and outcomes for hospitalised older patients with COVID-19

Abstract

Purpose Older adults are more likely to be vitamin D deficient. The aim of the study was to determine whether these patients have worse outcomes with COVID-19.

Methods We conducted a prospective cohort study between 1 March and 30 April 2020 to assess the importance of vitamin D deficiency in older patients with COVID-19. The cohort consisted of patients aged ≥65 years presenting with symptoms consistent with COVID-19 (n=105). All patients were tested for serum 25-hydroxyvitamin D (25(OH)D) levels during acute illness. Diagnosis of COVID-19 was confirmed via viral reverse transcriptase PCR swab or supporting radiological evidence. COVID-19-positive arm (n=70) was sub-divided into vitamin D-deficient (≤30 nmol/L) (n=39) and -replete groups (n=35). Subgroups were assessed for disease severity using biochemical, radiological and clinical markers. Primary outcome was in-hospital mortality. Secondary outcomes were laboratory features of cytokine storm, thoracic imaging changes and requirement of non-invasive ventilation (NIV).

Results COVID-19-positive arm demonstrated lower median serum 25(OH)D level of 27 nmol/L (IQR=20–47 nmol/L) compared with COVID-19-negative arm, with median level of 52 nmol/L (IQR=31.5–71.5 nmol/L) (p value=0.0008). Among patients with vitamin D deficiency, there was higher peak D-dimer level (1914.00 μgFEU/L vs 1268.00 μgFEU/L) (p=0.034) and higher incidence of NIV support and high dependency unit admission (30.77% vs 9.68%) (p=0.042). No increased mortality was observed between groups.

Conclusion Older adults with vitamin D deficiency and COVID-19 may demonstrate worse morbidity outcomes. Vitamin D status may be a useful prognosticator.

Full text

1
Department of Medicine,
Frimley Health NHS Foundation
Trust, Wexham Park Hospital,
Slough, UK
2
Department of Cardiology,
University of Cyprus Medical
School, Nicosia, Cyprus
Correspondence to
Constantinos G Missouris,
Department of Medicine,
Wexham Park Hospital,
Frimley Health NHS
Foundation Trust, Wexham
Street, Slough, UK; dinos.mis
souris@nhs.net
Received 18 July 2020
Accepted 1 August 2020
Revised 1 August 2020
©Author(s)(ortheir
employer(s)) 2020. No
commercial re-use. See
rights and permissions.
Published by BMJ.
To cite: Baktash V, Hosack
T, Patel N, et al. Postgrad
Med J Epub ahead of print:
[please include Day Month
Year]. doi:10.1136/
postgradmedj-2020-
138712
Vitamin D status and outcomes for hospitalised older
patients with COVID-19
Vadir Baktash,
1
Tom Hosack,
1
Nishil Patel,
1
Shital Shah,
1
Pirabakaran Kandiah,
1
Koenraad Van Den Abbeele,
1
Amit K J Mandal ,
1
Constantinos G Missouris
1,2
ABSTRACT
Purpose Older adults are more likely to be vitamin
Ddeficient. The aim of the study was to determine
whether these patients have worse outcomes with
COVID-19.
Methods We conducted a prospective cohort study
between 1 March and 30 April 2020 to assess the
importance of vitamin D deficiency in older patients with
COVID-19. The cohort consisted of patients aged ≥65 years
presenting with symptoms consistent with COVID-19
(n=105). All patients were tested for serum 25-
hydroxyvitamin D (25(OH)D) levels during acute illness.
Diagnosis of COVID-19 was confirmed via viral reverse
transcriptase PCR swab or supporting radiological evidence.
COVID-19-positive arm (n=70) was sub-divided into
vitamin D-deficient (≤30 nmol/L) (n=39) and -replete
groups (n=35). Subgroups were assessed for disease
severity using biochemical, radiological and clinical markers.
Primary outcome was in-hospital mortality. Secondary
outcomes were laboratory features of cytokine storm,
thoracic imaging changes and requirement of non-invasive
ventilation (NIV).
Results COVID-19-positive arm demonstrated lower
median serum 25(OH)D level of 27 nmol/L
(IQR=20–47 nmol/L) compared with COVID-19-negative
arm, with median level of 52 nmol/L
(IQR=31.5–71.5 nmol/L) (p value=0.0008). Among
patients with vitamin D deficiency, there was higher peak
D-dimer level (1914.00 μgFEU/L vs 1268.00 μgFEU/L)
(p=0.034) and higher incidence of NIV support and high
dependency unit admission (30.77% vs 9.68%)
(p=0.042). No increased mortality was observed between
groups.
Conclusion Older adults with vitamin D deficiency and
COVID-19 may demonstrate worse morbidity outcomes.
Vitamin D status may be a useful prognosticator.
INTRODUCTION
The COVID-19 outbreak, which began in China in
late 2019 and then rapidly spread across the world,
has spurred a global effort to tackle the disease and
establish risk factors and prognostic markers; one
such is serum vitamin D deficiency. Vitamin D is
a secosteroid with varied immunomodulatory, anti-
inflammatory, antifibrotic and antioxidant actions.
There is growing evidence that it may play a role in
the pathophysiological processes of COVID-19.
The relationship between vitamin D deficiency
and adverse prognosis has been suggested by the
apparent Northern–Southern latitude gradient,
with mortality and hospitalisation rates for
COVID-19 seen to be higher in northern latitude
countries compared with those closer to the
equator.
1
Furthermore, research by Alipio and
colleagues
2
, in a retrospective study, provides evi-
dence of an association between vitamin
D deficiency and adverse outcome in patients with
COVID-19. Older adults in institutions, such as
hospitals and care homes, are particularly likely to
be vitamin D deficient as a result of a lack of sun
exposure and dietary insufficiency, and may have
worse outcomes with COVID-19.
In the UK, The Royal College of Physicians of
London Commentary
3
reported that patients who
died of COVID-19 were severely vitamin
D deficient. There is also growing concern that the
Black, Asian and Minority Ethnic community who
produce less vitamin D as a result of higher skin
melanin content are inherently more susceptible to
severe presentations of COVID-19.
4
Therefore, the
British Nutrition Found
2
ation,
5
who applied gui-
dance to the public amidst self-isolation for
COVID-19, has suggested that everyone should
consider taking a daily supplement of 400 IU of
vitamin D.
We investigated serum vitamin D levels in older
patients admitted to our institution during the pan-
demic. The aim of our study was to assess the poten-
tial relationship between vitamin D deficiency and
COVID-19 severity in hospitalised older adults. We
conducted a single-centred prospective cohort study
of older patients admitted to a large district general
hospital in the UK, with symptoms in keeping with
a viral infection. Patients were divided into COVID-
19-positive and -negative groups with subsequent
assessment of vitamin D status. A subgroup analysis
of the COVID-19-positive arm was conducted with
analysis of serum markers of infection and clinical
markers of disease severity, such as high dependency
unit (HDU) admission and non-invasive ventila-
tion (NIV).
METHODS AND MATERIALS
Population
All emergency admissions aged ≥65 years admitted
to our hospital with symptoms consistent with
COVID-19 including cough, dyspnoea, fever and/
or anosmia
6
between 1 March and 30 April 2020
were included in the study (figure 1). These patients
were investigated with real-time reverse transcrip-
tase-PCR (RT-PCR) assay for severe acute respira-
tory syndrome coronavirus-2 (SARS-CoV-2) on
nasopharyngeal swab, blood tests including vitamin
D levels (25-hydroxyvitamin D (25(OH)D), basic
Baktash V, et al. Postgrad Med J 2020;0:1–6. doi:10.1136/postgradmedj-2020-138712 1
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observations, and chest X-ray (CXR) and/or chest CT.
Diagnosis of active SARS-CoV-2 infection was based on posi-
tive viral RT-PCR swab or evidence of COVID-19 on a chest
radiograph or chest CT (bilateral peripheral infiltrates/ground-
glass opacities, airspace opacification, traction bronchiectasis,
inter/intralobular septal thickening and organising pneumonia).
Patients who did not meet either of these criteria were enrolled
into the COVID-19-negative group.
The COVID-19-positive group was divided into vitamin
D-deficient (≤30 nmol/L) and -replete (>30 nmol/L) groups,
as per national guidelines and local laboratory standards.
7
Vitamin D-deficient patients were supplemented in accor-
dance with national guidelines and all patients received care
in line with best practice guidance. In addition, patients were
treated with subcutaneous low-molecular-weight heparin
venous thromboembolism (VTE) prophylaxis as per national
guidance.
Data collection
Data were extracted from medical notes and the local hospital
electronic database. These included age, weight, height, ethnicity,
smoking status and comorbidities. Ethnicities were self-assigned.
Rockwood Clinical Frailty Score
8
and Charlson Comorbidity
Index
9
were calculated retrospectively.
The primary outcome measured was in-hospital mortality
secondary to COVID-19. Secondary outcomes were defined
as NIV support and admission to HDU, COVID-19 radio-
graphic changes on CXR and laboratory features of cytokine
storm. All patients had vitamin D levels checked in keeping
with good medical practice. Biochemical/haematological
panels (C reactive protein (CRP), D-dimer, ferritin, high sen-
sitivity troponin T, lactate dehydrogenase (LDH) and lympho-
cyte count) were carried out in accordance with local
guidance on COVID-19 diagnostics and prognostication.
10
In addition, data for specific features consistent with the
COVID-19
11 12
were collected from formal reports of CXR
and/or chest CT. Causes of death were obtained digitally from
mortality reports made by our hospital’s mortality and
bereavement office.
Statistical analysis
All statistical analyses were carried out on GraphPad Prism (ver-
sion 8). For continuous outcome variables, each data set was
assessed for normality using Kolmogorov-Smirnov and Shapiro-
Wilk tests, and tested for significance with either an unpaired
t-test if parametric or a Mann-Whitney test if non-parametric.
Possible outcome sets were normalised by logarithmic transfor-
mation and tested for significance using a parametric method. For
categorical variables, an OR was calculated and tested for signifi-
cance using a Pearson ᵡ² test. P value <0.05 (two-tailed test) was
considered to be statistically significant. In addition, all variables
underwent a Pearson and Spearman analysis to gauge linear
covariance between the outcome measures and the correspond-
ing serum vitamin D concentration.
For binary outcomes, a receiver operating characteristic (ROC)
curve was plotted to assess the prognostic value of serum con-
centrations of vitamin D. Area under the curve (AUC) values
>0.5 were deemed to convey a prognostic value in the measured
variable.
Ethics
This survey was approved by the trust audit department with
reference FH119 and with clinically collected, non-identifiable
data which does not fall under the remit of NHS Research Ethics
Committee. All data were collected locally and handled in accor-
dance with European General Data Protection Regulation
(GDPR) standards, as well as local and NHS standards on data
protection.
All practices conducted as part of this study were done in
accordance with local regulations and best clinical practice pro-
tocols. Serum vitamin D levels were tested alongside the hospital
routine serum COVID-19 panel and did not require any extra
phlebotomy. Patients received care in line with standard practices
for the management of COVID-19 throughout the study period.
RESULTS
A total of 105 patients (mean age 81 years, range 65–102; male
(n=57):female (n=48)) were recruited to the study, with 70
(66.7%) subsequently allocated to the COVID-19-positive
group and 35 (33.3%) allocated to the COVID-19-negative
group. Among the COVID-19-positive group, 39 (55.7%)
patients were found to have 25(OH)D level ≤30 nmol/L and 31
(44.3%) were found to have a level >30 nmol/L.
Demographics (age, sex, ethnicity, frailty, body mass
index, smoking history and comorbidities) between
COVID-19-positive and -negative groups were comparable.
In addition, the characteristics of vitamin D-replete and -
deficient groups in the COVID-19-positive arm were found
to be comparable (table 1). Only three patients were
admitted from a nursing home with one instance in each of
the three study subgroups.
No patients were admitted to the intensive treatment unit, and
ceilings of care were set to NIV support on the HDU. There was
no difference in the average length of stay between vitamin
D subgroups (29 days).
Vitamin D levels in the COVID-19-positive group were overall
significantly lower compared with that in the COVID-19-negative
group (27.00 nmol/L vs 52.00 nmol/L) (p=0.0008). Among
patients with vitamin D deficiency in the COVID-19-positive
group, there was a higher average peak in D-dimer level
(1914.00 μgFEU/L vs 1268.00 μgFEU/L) (p=0.034) and
a higher incidence of NIV support and HDU admission (30.77%
vs 9.68%) (p=0.042). The vitamin D-deficient case group demon-
strated higher peak CRP, LDH and ferritin levels; lower trough
lymphocyte counts; and increased incidence of radiographic
changes, although these were not statistically significant. The
vitamin D-replete case group demonstrated a higher peak tropo-
Figure 1 Flow chart, depicting recruitment of patients upon admission
via the emergency department, with subsequent separation. CRP,
C reactive protein; LDH, lactate dehydrogenase.
2 Baktash V, et al. Postgrad Med J 2020;0:1–6. doi:10.1136/postgradmedj-2020-138712
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nin level that was not statistically significant (table 2). There was
only one confirmed case of pulmonary thrombosis in the vitamin
D-deficient case group. There was no apparent difference in
mortality between the two groups. Ethnicity did not influence
outcomes in this cohort. The outcome measures did not appear
to follow a linear relationship with serum vitamin
D concentrations.
ROC curves were plotted for vitamin D as a distinguisher
between COVID-19-positive and -negative states as well as
between those requiring and not requiring ventilatory support
(figure 2). For the former, AUC was 0.70 (95% CI 0.59 to 0.80) (p
value=0.0009). For the latter, AUC was 0.67 (95% CI 0.54 to
0.80) (p value=0.046).
DISCUSSION
The main findings of our study suggest that older patients with
lower serum concentrations of 25(OH)D, when compared with
aged-matched vitamin D-replete patients, may demonstrate
worse outcomes from COVID-19. Markers of cytokine release
syndrome were raised in these patients and they were more likely
to become hypoxic and require ventilatory support in HDU.
There was no difference in mortality between groups.
Evidence of an association between vitamin D deficiency and
adverse outcome in COVID-19 is provided by Alipio (2020) and
D’Avolio and colleagues.
13
The former study (preprint) observed
an increased disease severity for patients with vitamin D defi-
ciency, while the latter noted a decreased serum vitamin D
Table 1 Population characteristics of COVID-19-positive versus -negative groups, subdivided by serum vitamin D concentrations
Population sample characteristics
COVID-19-positive (N=70) P value
Demographics
Vitamin D ≤30 nmol/
L (N=39)
Vitamin D >30 nmol/
L (N=31)
COVID-19-
negative (N=35)
COVID-19-positive vit D ≤30 nmol/L
vs >30 nmol/L
COVID-19-positive versus
COVID-19-egative
Mean age (SD) 79.46 (±9.52) 81.16 (7.23) 83.44 (±8.08) 0.41 0.064
Male:female 24:15 18:13 15:20 0.77 0.075
Rockwood Clinical Frailty
Score Median (IQR)
6(6–7) 5 (5–6) 5 (5–6) 0.1 0.66
Median body mass index
(IQR)
25 (23–32) 24 (20–27) 25 (22–29) 0.14 0.75
Smoking
status (%)
Current
smoker
1 (2.56) 5 (16.13) 4 (11.43) 0.14 0.65
Ex-smoker 12 (30.77) 11 (35.48) 15 (42.86) 0.66 0.13
Ethnicity (%) Caucasian 29 (74.36) 21 (67.74) 30 (85.71) 0.51* 0.27*
South
Asian
8 (20.51) 10 (32.36) 3 (8.57)
East Asian 2 (5.13) 0 (0) 0 (0)
Afro-
Caribbean
0 (0) 1 (3.26) 3 (8.57)
Comorbidities
N (%) P value
Vitamin D ≤30 nmol/
L (N=39)
Vitamin D >30 nmol/
L (N=31)
COVID-19-
negative (N=35)
COVID-19-positive vit D ≤30 nmol/L
vs >30 nmol/L
COVID-19-positive versus
COVID-19-negative
Hypertension 18 (46.15) 16 (51.61) 20 (55.56) 0.65 0.41
Diabetes mellitus 17 (43.59) 9 (29.03) 8 (22.22) 0.21 0.14
Ischaemic heart disease 7 (17.95) 8 (25.81) 11 (30.56) 0.43 0.27
Chronic respiratory disease 6 (15.38) 7 (22.58) 4 (11.11) 0.44 0.35
Heart failure 6 (15.38) 6 (19.35) 5 (13.89) 0.66 0.71
Stroke 6 (15.38) 3 (9.68) 3 (8.33) 0.48 0.52
Dementia 4 (10.26) 2 (6.45) 1 (2.78) 0.58 0.29
Chronic kidney disease 10 (25.64) 6 (19.35) 6 (16.67) 0.53 0.5
Atrial fibrillation 6 (15.38) 8 (25.81) 8 (22.22) 0.28 0.73
Cancer 2 (5.13) 1 (3.23) 2 (5.56) 0.7 0.75
Endocrinological disease 1 (7.69) 2 (6.45) 2 (5.56) 0.44 0.75
Median value (IQR) P value
Vitamin D ≤30 nmol/
L (N=39)
Vitamin D >30 nmol/
L (N=31)
COVID-19-
negative (N=35)
COVID-19-positive vit D ≤30 nmol/L
vs >30 nmol/L
COVID-19-positive versus
COVID-19-negative
Charlson Comorbidity
Index
5(3–6) 4 (4–5) 4 (4–6) 0.81 0.76
COVID-19-positive (N=70) COVID-19-negative
(N=35
Difference P value
Vitamin D concentration
(nmol/L)
27.00 (20.00–47.00) 52.00 (31.50–71.50) 25 0.0008
*P value for ethnicities calculated by comparing the number of Caucasian patients to all other ethnic groups.
vit, vitamin.
Baktash V, et al. Postgrad Med J 2020;0:1–6. doi:10.1136/postgradmedj-2020-138712 3
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concentration between COVID-19-positive and -negative
patients. These were both retrospective cohort studies encom-
passing a sample size of 212 and 120, respectively.
Ilie and colleagues
14
performed a meta-analysis to study the
association of vitamin D and morbidity and mortality with
COVID-19 in 20 European countries and proposed a possible
correlation between vitamin D levels, the incidence of SARS-
CoV-2 infection and mortality. Hastie and colleagues
15
used
biobank data on 449 people with confirmed SARS-CoV-2 infec-
tion and found no relationship with serum 25(OH)D concentra-
tions. The average age of subjects in this study was 49 years, and
a major limitation was utilisation of historical vitamin D levels of
patients (between 2006 and 2010) rather than vitamin D status at
the time of infection with SARS-CoV-2. In our study, the average
age was older at 81 years and we were able to establish vitamin D
status during active SARS-CoV-2 infection.
In non-communicable diseases, both viral and bacterial, vita-
min D deficiency has been associated with increased morbidity
and mortality as well as a higher incidence of acute respiratory
distress syndrome in critically unwell patients.
16 17
Whether low
vitamin D levels are cause or consequence of disease (reverse
causality) processes remains unclear. However, a meta-analysis
performed in 2017 of 11 321 patients from 25 randomised con-
trolled studies demonstrated that vitamin D supplementation
protected against acute respiratory tract infection and patients
with very low concentrations of 25(OH)D (<25 nmol/L) benefit-
ing most.
18
Cited markers of cytokine storm were elevated in our vitamin D
deficiency subset of patients, and the high peak D-dimer concen-
tration was deemed statistically significant (p=0.034). This was
found in the absence of in situ pulmonary thrombosis and in the
context of standard VTE prophylaxis. Several studies have
explored
19 20
the pro-thrombotic state induced during the cyto-
kine storm phase of inflammatory lung disease. The coagulation
system appears active in critically ill patients, and high D-dimer
levels reflect activation of the proinflammatory cytokine cascade
(and downregulation of the anti-inflammatory cytokine cascade).
Elevated D-dimer levels are associated with amplified risk for
multiple organ failure and death.
21
This may explain the
increased incidence of ventilatory support seen in vitamin
D-deficient patients.
Vitamin D has been shown to condition the innate immune
reaction against both bacterial and viral infections. Calcitriol
(1,25(OH)
2
D
3
), the active form of vitamin D, modulates
macrophage activity by inhibiting the release of pro-
inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-
8, IL-12 and tumour necrosis factor-alpha.
16
Vitamin D shifts
the adaptive immune reaction from a Th1 to a Th2
phenotype,
17 22
downregulating differentiation of naïve
T cells into pro-inflammatory Th17 cells,
23 24
and promotes
T regulatory cell induction.
25–27
Dysregulation of both innate
and adaptive immunity, as a result of vitamin D deficiency,
may therefore be central to precipitating the ‘cytokine storm’
seen in COVID-19 infection.
In addition to anti-inflammatory properties, vitamin D also
exerts a protective effect on human alveolar epithelial cells by
promoting wound repair.
28
Vitamin D has also been shown to
preserve endothelial integrity and deficiencies result in increased
vascular permeability and leak.
29
Vitamin D also increases the expression of ACE-2. While
increased ACE-2 expression in the early pandemic was predicted
to increase the risk of infection, paradoxically, ACE-2 has also
been shown to protect against acute lung injury.
14 30
Disruption
of one or more of these defensive pathophysiological processes
may explain the association we found between vitamin D defi-
ciency and increased requirement of ventilatory support.
Whether this actually represents a causal relationship has not
yet been elucidated.
Limitations
As a single-centre study at a district general hospital, we cannot
generalise our results to other settings. Furthermore, our trust is
based in Southern England, where population demographics and
socioeconomic status may differ from those elsewhere.
We acknowledge that extracting information from medical
notes requires second-hand interpretation and may not be repre-
sentative of the full clinical picture. Patient outcomes may also
have been influenced by current guidelines imposed by the
National Institute of Clinical Excellence committee.
31
We also acknowledge the role that sunlight exposure may have
played in the measured serum levels of 25(OH)D. Unfortunately,
this could not reliably be measured in patients; however, efforts
Table 2 Primary and secondary outcome measures, for vitamin
D-deficient and -replete groups
Outcome measures
Median value (IQR)
Serum markers
Vitamin
D≤30 nmol/L
Vitamin
D >30 nmol/L Difference P value
Peak CRP (mg/L) 191.00
(108.00–274.00)
155.00
(96.00–252.00)
−36 0.32
Peak LDH (IU/L) 272.50
(217.25–367.50)
239.50
(180.50–333.00)
−33 0.17*
Peak ferritin (μg/
L)
518.50
(894.00–1109.25)
484.50
(221.00–715.50)
−34 0.40*
Peak D-dimer
(μgFEU/L)
1914.00
(1323.75–3131.50)
1268.00
(1003.50–2273.00)
−646 0.034
Peak troponin
(ng/L)
37.00
(26.00–95.00)
42.00
(25.00–88.00)
5 0.83*
Trough
lymphocyte count
(×10
9
/L)
0.56 (0.44–0.78) 0.68 (0.54–0.95) 0.12 0.15*
N (%) OR (CI) P value
Chest X-ray
changes
11 (28.20) 8 (25.80) 1.13
(0.39–3.28)
0.82
Ventilation
requirement
12 (30.77) 3 (9.68) 4.15
(1.05–16.34)
0.042
Mortality 6 (15.38) 4 (12.90) 1.40
(0.36–5.47)
0.5
*P value derived using a parametric technique on logarithmically transformed data.
CRP, C reactive protein; LDH, lactate dehydrogenase.
0 20406080100
0
20
40
60
80
100
100% - Specificity%
Sensitivity%
0 20406080100
0
20
40
60
80
100
100% - Specificity%
Sensitivity%
Figure 2 ROC curves for vitamin D and COVID-19 status (left) and
ventilatory support requirement (right). ROC, receiver operating
characteristic.
4 Baktash V, et al. Postgrad Med J 2020;0:1–6. doi:10.1136/postgradmedj-2020-138712
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were made to account for this. Notably, the study was carried out
within a 2-month period which attenuated potential weather
influence on sunlight exposure. In addition, the housing status
of patients was considered—only three nursing home residents
were included in the study, which minimised the risk of institu-
tionalisation and its association with reduced sun exposure bear-
ing influence on the results.
Considerations were made for the utilisation of sample size
calculations to ensure the study was powered appropriately.
No limit was initially set for sample size; however, the final
number was limited by the dwindling numbers of patients
with COVID-19. Despite achieving significant results in sev-
eral outcomes, we acknowledge the risk of a type 2 error
occurring with our experimental sample size. Therefore, we
were unable to discount an association between vitamin
D deficiency and those variables which did not achieve sta-
tistical significance with observed effect sizes.
Length of stay was recorded for all patients in the COVID-19
arm of the study, with no difference found between vitamin
D subgroups. We emphasise, however, concerns on the reliability
of this measure. Given the geriatric population of our study
sample, the overwhelming issues affecting hospital discharge
were social and housing issues. This was further complicated by
infection control measures during the pandemic limiting the
ability of some families to receive their relatives back home.
Therefore, any firm conclusions should not be drawn from this
outcome measure.
Another issue of consideration was vitamin D replacement and
the effect this may have on the outcome measures recorded. In
our study, vitamin D supplementation was only initiated after the
acute phase of illness. Given that steady-state serum concentra-
tions of vitamin D are achieved after 3–6 months with
replacement,
32
it is unlikely that serum levels would significantly
change during the infective and symptomatic phase of admission.
Consequently, we do not believe this would have influenced out-
come measures. We were also unable to establish whether vitamin
D replacement during active SARS-CoV-2 infection results in
favourable outcomes.
CONCLUSION
Our study has demonstrated that patients over the age of 65 years
presenting with symptoms consistent with COVID-19 are more
likely to be vitamin D deficient. There appears to be a clinically
relevant association between this and elevated markers of cyto-
kine release syndrome and increased risk of respiratory failure
requiring ventilatory support. Although there was no apparent
mortality difference between the two groups, this may reflect the
overall poor prognosis associated with the higher prevalence of
frailty and comorbidities in our older cohort of patients. Vitamin
D status may be a prognosticator for COVID-19, and supplemen-
tation might improve outcomes. Further studies in all age groups
are awaited to validate this.
Contributors All authors contributed to the manuscript. All were involved in the
design of the study. VB, PK and NP collected the data. VB and TH were responsible for
the statistical analysis. VB, TH, AKJM, KVDA, SS and CGM wrote the manuscript and
all authors were involved in the final approval of the manuscript.
Funding This research received no specific grant from any funding agency in the
public, commercial or not-for-profit sectors.
Competing interests All authors understand the policy of declaration of interests.
CGM is a former member of the Fellowship of Postgraduate Medicine (FPM) council
and is currently an FPM Fellow. VB, TH, NP, SS, PK, KVDA, AKJM all declare that they
have no competing interests.
Patient consent for publication Not required.
Ethics approval As an audit using clinically collected, non-identifiable data, this
work does not fall under the remit of National Health Service Research Ethics
Committees. This statement is also present in the ‘Methods and material’section of
our manuscript.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
This article is made freely available for use in accordance with BMJ's website terms
and conditions for the duration of the COVID-19 pandemic or until otherwise
determined by BMJ. You may use, download and print the article for any lawful, non-
commercial purpose (including text and data mining) provided that all copyright
notices and trade marks are retained.
ORCID iD
Amit K J Mandal http://orcid.org/0000-0003-0986-5927
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