ArticlePDF Available

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.
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
Ddecient. 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 deciency 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 conrmed via viral reverse
transcriptase PCR swab or supporting radiological evidence.
COVID-19-positive arm (n=70) was sub-divided into
vitamin D-decient (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=2047 nmol/L) compared with COVID-19-negative
arm, with median level of 52 nmol/L
(IQR=31.571.5 nmol/L) (p value=0.0008). Among
patients with vitamin D deciency, 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 deciency 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 NorthernSouthern 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;0:16. doi:10.1136/postgradmedj-2020-138712 1
Original research
on August 28, 2020 by guest. Protected by copyright.http://pmj.bmj.com/Postgrad Med J: first published as 10.1136/postgradmedj-2020-138712 on 27 August 2020. Downloaded from
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 hospitals 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 ² 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 65102; 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;0:16. doi:10.1136/postgradmedj-2020-138712
Original research
on August 28, 2020 by guest. Protected by copyright.http://pmj.bmj.com/Postgrad Med J: first published as 10.1136/postgradmedj-2020-138712 on 27 August 2020. Downloaded from
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
DAvolio 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(67) 5 (56) 5 (56) 0.1 0.66
Median body mass index
(IQR)
25 (2332) 24 (2027) 25 (2229) 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 brillation 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(36) 4 (45) 4 (46) 0.81 0.76
COVID-19-positive (N=70) COVID-19-negative
(N=35
Difference P value
Vitamin D concentration
(nmol/L)
27.00 (20.0047.00) 52.00 (31.5071.50) 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;0:16. doi:10.1136/postgradmedj-2020-138712 3
Original research
on August 28, 2020 by guest. Protected by copyright.http://pmj.bmj.com/Postgrad Med J: first published as 10.1136/postgradmedj-2020-138712 on 27 August 2020. Downloaded from
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.
2527
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-decient and -replete groups
Outcome measures
Median value (IQR)
Serum markers
Vitamin
D30 nmol/L
Vitamin
D >30 nmol/L Difference P value
Peak CRP (mg/L) 191.00
(108.00274.00)
155.00
(96.00252.00)
36 0.32
Peak LDH (IU/L) 272.50
(217.25367.50)
239.50
(180.50333.00)
33 0.17*
Peak ferritin (μg/
L)
518.50
(894.001109.25)
484.50
(221.00715.50)
34 0.40*
Peak D-dimer
(μgFEU/L)
1914.00
(1323.753131.50)
1268.00
(1003.502273.00)
646 0.034
Peak troponin
(ng/L)
37.00
(26.0095.00)
42.00
(25.0088.00)
5 0.83*
Trough
lymphocyte count
(×10
9
/L)
0.56 (0.440.78) 0.68 (0.540.95) 0.12 0.15*
N (%) OR (CI) P value
Chest X-ray
changes
11 (28.20) 8 (25.80) 1.13
(0.393.28)
0.82
Ventilation
requirement
12 (30.77) 3 (9.68) 4.15
(1.0516.34)
0.042
Mortality 6 (15.38) 4 (12.90) 1.40
(0.365.47)
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;0:16. doi:10.1136/postgradmedj-2020-138712
Original research
on August 28, 2020 by guest. Protected by copyright.http://pmj.bmj.com/Postgrad Med J: first published as 10.1136/postgradmedj-2020-138712 on 27 August 2020. Downloaded from
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 consideredonly 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 36 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 nal approval of the manuscript.
Funding This research received no specic grant from any funding agency in the
public, commercial or not-for-prot 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-identiable 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 materialsection 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
REFERENCES
1 Panarese A, Shahini E. COVID19, and vitamin D. Aliment Pharm Ther 2020;51:993.
2 Alipio M. Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of
Patients Infected with Coronavirus-2019 (COVID-2019). SSRN Journal.
3 Cantorna MT. Mechanisms underlying the effect of vitamin D on the immune system.
Proc Nutr Soc 2010;69:2869.
4 GOV.UK. SACN vitamin D and health report. 2016. Available https://www.gov.uk/
government/publications/sacn-vitamin-d-and-health-report (accessed 24th
Jun 2020)
5 British Nutrition Foundation. BNF busts the myths on nutrition and COVID-19. 2020.
Available https://www.nutrition.org.uk/press-ofce/pressreleases/covid (accessed 24th
Jun 2020)
6 GOV.UK. COVID-19: investigation and initial clinical management of possible cases.
2020. Available https://www.gov.uk/government/publications/wuhan-novel-
coronavirus-initial-investigation-of-possible-cases (accessed 26th Jun 2020)
7 Giustina A, Adler RA, Binkley N, et al. Controversies in vitamin D: summary statement
from an international conference. J Clin Endocrinol Metab 2019;104:23440.
8 Rockwood K, Song X, MacKnight C, et al. Global clinical measure of tness and frailty
in elderly people. CMAJ 2005;173:48995.
9 Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic
comorbidity in longitudinal studies: development and validation. J Chronic Dis
1987;40:37383.
10 Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection.
Clin Chem Lab Med 2020;58:11314.
11 Wong HYF, Lam HYS, Fong AHT, et al. Frequency and distribution of chest radiographic
ndings in COVID-19 positive patients. Radiology 2020;296:E72E78.
12 Shi H, Han X, Jiang N, et al. Radiological ndings from 81 patients with COVID-19
pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020;20:42534.
13 DAvolio A, Avataneo V, Manca A, et al. 25-hydroxyvitamin D concentrations are lower
in patients with positive PCR for SARS-CoV-2. Nutrients 2020;12:1359.
Main messages
Older patients with COVID-19 infection and vitamin D deciency
(30 nmol/L) have higher peak D-dimer level and higher incidence
of NIV support and HDU admission.
Vitamin D deciency may be associated with worse outcomes
from COVID-19, and vitamin D status may be a useful
prognosticator.
What is already known on the subject
There appears to be an association between increased COVID-19
incidence and mortality and countries with an increased
prevalence of vitamin D deciency.
Vitamin D plays an important role in the modulation of the
immune system through promotion of anti-inammatory
cytokines and down-regulation of pro-inammatory T cells.
The occurrence of an inammatory cytokine stormduring COVID-19
has been associated with poorer outcomes and increased disease
severity.
Baktash V, et al. Postgrad Med J 2020;0:16. doi:10.1136/postgradmedj-2020-138712 5
Original research
on August 28, 2020 by guest. Protected by copyright.http://pmj.bmj.com/Postgrad Med J: first published as 10.1136/postgradmedj-2020-138712 on 27 August 2020. Downloaded from
14 Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus
disease 2019 infection and mortality. Aging Clin Exp Res 2020;32:11958.
15 Hastie CE, Mackay DF, Ho F, et al. Vitamin D concentrations and COVID-19 infection in
UK Biobank. Diabetes Metab Syndr 2020;14:5615.
16 Almerighi C, Sinistro A, Cavazza A, et al. 1Alpha,25-dihydroxyvitamin D3 inhibits
CD40L-induced pro-inammatory and immunomodulatory activity in human
monocytes. Cytokine 2009;45:1907.
17 Mattner F, Smiroldo S, Galbiati F, et al. Inhibition of Th1 development and treatment of
chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic
analogue of 1,25-dihydroxyvitamin D(3). Eur J Immunol 2000;30:498508.
18 Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent
acute respiratory tract infections: systematic review and meta-analysis of individuals
participant data. BMJ 2017;i6583.
19 Levi M, Thachil J, Iba T, Levy JH. (2020). Coagulation abnormalities and thrombosis in
patients with COVID-19.. Lancet Haematol. 7(6), e438e440.
20 Jose RJ, Manuel A. (2020). COVID-19 cytokine storm: the interplay between inam-
mation and coagulation. The Lancet Respiratory Medicine. 8(6), e46e47.
21 Shorr AF, Thomas SJ, Alkins SA, et al. D-dimer correlates with proinammatory cytokine
levels and outcomes in critically ill patients. Chest 2002;121:12628.
22 Boonstra A, Barrat FJ, Crain C, et al. 1alpha,25-Dihydroxyvitamin d3 has a direct effect
on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol
2001;167:497480.
23 Tang J, Zhou R, Luger D, et al. Calcitriol suppresses antiretinal autoimmunity through
inhibitory effects on the Th17 effector response. J Immunol 2009;182:462432.
24 Daniel C, Sartory NA, Zahn N, et al. Immune modulatory treatment of trinitrobenzene
sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17
to a Th2 and regulatory T cell prole. J Pharmacol Exp Ther 2008;324:2333.
25 Barrat FJ, Cua DJ, Boonstra A, et al. In vitro generation of interleukin 10-
producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and
inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. JExpMed
2002;195:60316.
26 Gorman S, Kuritzky LA, Judge MA, et al. Topically applied 1,25-dihydroxyvitamin D3
enhances the suppressive activity of CD4+CD25+ cells in the draining lymph nodes.
J Immunol 2007;179:627383.
27 Penna G, Roncari A, Amuchastegui S, et al. Expression of the inhibitory receptor ILT3 on
dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-
dihydroxyvitamin D3. Blood 2005;106:34907.
28 Dancer RCA, Parekh D, Lax S, et al. Vitamin D deciency contributes directly to the
acute respiratory distress syndrome (ARDS). Thorax 2015;70:61724.
29 Gibson CC, Davis CT, Zhu W, et al. Dietary vitamin D and its metabolites
non-genomically stabilize the endothelium. PLoS One 2015;10:e0140370.
30 Kuka K, Imai Y, Penninger JM. Angiotensin-converting enzyme 2 in lung diseases. Curr
Opin Pharmacol 2006;6:2716.
31 National Institute for Health and Care Excellence (NICE). COVID-19 rapid guideline:
critical care in adults [NG159]. 2020. Available https://www.nice.org.uk/guidance/
ng159 (accessed 30 Jun 2020)
32 Francis RM, Aspray TJ, Bowring CE, et al. National osteoporosis society practical clinical
guideline on vitamin D and bone health. Maturitas 2015;80:11921.
6 Baktash V, et al. Postgrad Med J 2020;0:16. doi:10.1136/postgradmedj-2020-138712
Original research
on August 28, 2020 by guest. Protected by copyright.http://pmj.bmj.com/Postgrad Med J: first published as 10.1136/postgradmedj-2020-138712 on 27 August 2020. Downloaded from
... Persons with vitamin D deficiency tend to be more vulnerable to infectious diseases. Notably, vitamin D deficiency has been associated with increased risk of SARS-CoV-2 infection and worse clinical outcomes of COVID-19 (Baktash et al., 2021). However, whether poor vitamin D status per se or factors associated with vitamin D deficiency, such as advanced age and comorbidities, is related to COVID-19 severity is still a matter of debate (Rubin, 2021). ...
... It is noteworthy that, in post-COVID-19 patients, the prevalence of vitamin D deficiency shows a sex distribution different from the general population of the same geographic areas, in which lower vitamin D levels were found among adolescent girls, adult and older women compared with their male counterparts (Manios et al., 2018). Findings on the association between serum vitamin D levels and COVID-19 are mixed (Baktash et al., 2021;Bassatne et al., 2021;Teshome et al., 2021). In older adults hospitalized with symptoms consistent with COVID-19, serum vitamin D levels were found to be lower in those who eventually tested positive for SARS-CoV-2 infection (Rubin, 2021). ...
... However, SARS-CoV-2 seropositivity was not independently associated with vitamin D deficiency. As for COVID-19 severity, low serum vitamin D levels have been associated with worse clinical outcomes, including more severe lung involvement (Sulli et al., 2021), need of NIV, ICU admission, and mortality (Baktash et al., 2021). ...
Article
Aim To determine the prevalence and associated factors of vitamin D deficiency in COVID-19 survivors and the relationship between vitamin D status and physical performance. Methods Vitamin D status was assessed in a sample of patients who had recovered from COVID-19 and were admitted to a post-acute outpatient service at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy). Participants were offered comprehensive medical assessment, including physical performance and muscle strength tests. Self-rated health was assessed. Vitamin D deficiency was defined as a serum concentration of 25-OH vitamin D <20 ng/mL. Results Mean age of 681 participants was 53.4 ± 15.2 years and 49% were women. Vitamin D deficiency was detected in 35.6% of the whole study population, and in 40.2% of those 65 and older. Vitamin D deficiency was associated with diabetes, higher body mass index, and COVID-19 severity, and showed a seasonal pattern with a peak in autumn/winter. Participants with vitamin D deficiency performed poorer on the six-minute walking test, with the lowest performance observed in those 65 and older. No significant associations with any other parameters were found. Conclusion Our findings indicate that vitamin D deficiency is frequent in COVID-19 survivors, especially in older adults. Low vitamin D levels are associated with poor physical performance, in particular in old age.
... Since the beginning of the pandemic, its use as a supplement has been suggested around the world, due to its potential preventive effects. These theories arise from different studies that have reported Vit D deficiency in patients with COVID-19, in association with the severity of disease and with the admission to ICU, being a more pronounced deficiency in adults older than 70 years [39,63,64]. In addition to age, ethnicity is another factor that has been associated with Vit D deficiency and the possibility of being a risk factor for COVID-19. ...
... Their review gathers evidence that meets Hill's criteria for temporality, strength of association, dose-response relationship, consistency of findings, plausibility, accounting for alternate explanations, and consistency with known facts. However, there is a lack of clinical trials to experimentally confirm these associations, which makes associations inconclusive [39,63,64]. For example, in an observational study in the USA with 191,779 patients [66], a higher percentage of positivity for SARS-CoV-2 was found in those with Vit D levels below 20 ng/mL (12.5%, 95% CI, 12.2-12.8%) ...
Article
Full-text available
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection can activate innate and adaptive immune responses and result in massive inflammatory responses in the disease. A comprehensive understanding of the participation of micronutrients in the immune response to COVID-19 will allow the creation of prevention and supplementation scenarios in malnutrition states. Microelement deficiency can be decisive in the progression of diseases and their optimal levels can act as protective factors, helping to maintain homeostasis. Vitamin A, B, D, selenium, zinc, and copper, through their complementary and synergistic effects, allow the components of innate and adaptive immunity to counteract infections like those occurring in the respiratory tract. Thus, alterations in nutritional status are related to metabolic diseases, systemic inflammation, and deterioration of the immune system that alter the response against viral infections, such as COVID-19. The aim of this review is to describe the micronutrients that play an important role as immunomodulators and its relationship between malnutrition and the development of respiratory infections with an emphasis on severe and critical COVID-19. We conclude that although an unbalanced diet is not the only risk factor that predisposes to COVID-19, a correct and balanced diet, which provides the optimal amount of micronutrients and favors an adequate nutritional status, could confer beneficial effects for prevention and improvement of clinical results. The potential usefulness of micronutrient supplementation in special cases is highlighted.
... With respect to COVID-19, deficiencies in different micronutrients, including vitamin D [15,16], zinc [17,18], and selenium [19,20], have been discussed as risk factors for a more severe disease course, with need for ICU admission and mechanical ventilation, or higher incidence of death. Based on these observations, there has been a call for more wide-spread supplementation of the above-mentioned micronutrients during the COVID-19 pandemic to prevent and improve courses of infected patients [7,21]. ...
... Both patients with mild and severe courses of the disease had levels that were only slightly above the cut-off for deficiency (i.e., 30 nmol/L), similar to insufficient vitamin D levels in both patients with COVID-19 and healthy controls in a study by Elham et al. [33]. Compared to our study, studies that found an association of vitamin D deficiency and adverse outcomes in COVID-19 had different outcomes defined, including the need for non-invasive ventilation in one study [15] and a composite of invasive mechanical Nutrients 2022, 14, 1862 9 of 12 ventilation and/or death in another study [34]. The lack of an association in our study may be explained by the small sample size with risk for a type II error and the lack of a healthier control group with higher vitamin D baseline levels. ...
Article
Full-text available
Background: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. Methods: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. Results: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05-0.69, p = 0.01), zinc (0.73, 95% CI 0.55-0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78-0.98, p = 0.02). Conclusions: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.
... 155 Vitamin D deficiency has been associated with increased risk of SARS-CoV-2 infection and worse clinical outcomes, including more severe lung impairment, need for respiratory support and intensive care, and mortality. 156,157 Hence, vitamin D supplementation has been tested as a candidate adjunctive treatment for COVID-19. In asymptomatic or mildly symptomatic individuals with SARS-CoV-2 and vitamin D deficiency, a 7-day administration of high-dose vitamin D (60,000 IU of cholecalciferol per day) accelerated viral clearance compared with placebo. ...
Article
Long COVID affects a large share of persons of all age groups but may be especially burdensome for vulnerable older adults. Long COVID has a complex pathophysiology encompassing inflammatory and autoimmune processes, perturbations in metabolic pathways, and alterations in endothelial function and redox homeostasis. The management of long COVID requires a multidimensional approach that should include a comprehensive nutritional assessment. Several food bioactive compounds, nutraceuticals, and supplements may target specific pathways involved in long COVID and may, therefore, be used as an adjunctive therapy to manage the condition.
... Evidence has suggested that vitamin D deficiency is associated with susceptibility to COVID-19 infection (52)(53)(54)(55). Most studies suggested that low vitamin D levels among COVID-19 patients increase the probability of hospitalization, severity of disease, and risk of mortality (56)(57)(58)(59)(60)(61). In contrast, other studies did not find any correlation between vitamin D and COVID-19 (62)(63)(64). ...
Article
Full-text available
The severity of coronavirus disease 2019 (COVID-19) is determined not only by viral damage to cells but also by the immune reaction in the host. In addition to therapeutic interventions that target the viral infection, immunoregulation may be helpful in the management of COVID-19. Vitamin D exerts effects on both innate and adaptive immunity and subsequently modulates immune responses to bacteria and viruses. Patients with chronic kidney disease (CKD) frequently have vitamin D deficiency and increased susceptibility to infection, suggesting a potential role of vitamin D in this vulnerable population. In this paper, we review the alterations of the immune system, the risk of COVID-19 infections and mechanisms of vitamin D action in the pathogenesis of COVID-19 in CKD patients. Previous studies have shown that vitamin D deficiency can affect the outcomes of COVID-19. Supplementing vitamin D during treatment may be protective against COVID-19. Future studies, including randomized control trials, are warranted to determine the effect of vitamin D supplementation on the recovery from COVID-19 in CKD patients.
... These effects may help preventing the cytokine storm that contributes to the severe forms of COVID-19 [6]. Several observational studies have confirmed that, while accounting for potential confounders, participants with lower serum 25-hydroxyvitamin D (25(OH)D) concentrations were more likely to progress to severe forms of COVID-19 [7], to resort to noninvasive ventilation [8], and, ultimately, to die from COVID-19 [9]. Vitamin D3 supplementation prior to COVID-19 [10,11] and during COVID-19 [12][13][14] was associated with improved survival in older adults with COVID-19. ...
Article
Background: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Methods and findings: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. Conclusions: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. Trial registration: ClinicalTrials.gov NCT04344041.
... Studies have also linked vitamin-D deficiency as a risk factor for corona virus disease 6,7 . COVID-19 disease predispose the patients to thrombotic events. ...
Article
Full-text available
Introduction: Objectives: To determine the effect of vitamin-D supplementation in patients of the acute coronary syndrome and its role if any in preventing COVID-19 infection. Study design: Prospective clinical trial Place and duration: Armed Forces Institute of Cardiology in collaboration with Riphah International University Material and methods: The study was conducted by recruiting 40 patients, diagnosed with the acute coronary syndrome. After the PCI procedure during their hospital stay, 20 of them were given a single shot of vitamin-D supplement in a dose of 200000 IU while the rest of 20 were allocated as controls. Patients were instructed to follow the SOPs strictly and were followed up for incidence of coronavirus disease after 2 months. Detailed history regarding their stay during lockdown was taken. Independent sample t-test was used to compare the two groups with p≤0.05 considered as significant. Results: The patients enrolled in the study were assessed for pre and post-intervention levels for vitamin-D. After the intervention the levels in the experimental group were increased to 30.74±18.40 ng/ml (p=0.000***) from a mean value of 18.27 ±8.98 ng/ml. Among the control group, eight out of 40 patients tested positive for COVID-19 while none among the experimental group got the disease (p=0.016*). The results of the follow-up interview showed that the patients followed the precautions for COVID protection during the pandemic. Conclusion: Vitamin-D supplementation during lockdown may prove beneficial in protection against COVID-19. Keywords: Vitamin-D, COVID-19, acute coronary syndrome
Article
Full-text available
Background Serum vitamin D levels may have a protective role against severe coronavirus disease 2019 (COVID-19). Studies have shown that deficiency in vitamin D may be a significant risk factor for poor outcomes. This study aims to compare the outcome and clinical condition of patients diagnosed with COVID-19 infection considering serum vitamin D levels. Methods In this cross-sectional study, 202 COVID-19 patients without known cardiovascular disease (reduced ejection fraction, uncontrolled arrhythmia, pericardial effusion, cardiac block, valvular disease, or hypertension) were included. Patients were divided into three groups of insufficient (< 30 ng/mL), normal (30 to 50 ng/mL), and high (> 50 ng/mL) serum vitamin D levels. Clinical outcome was defined as severe if invasive respiratory intervention and ICU admission was required. Results The patients were divided into three groups based on their vitamin D level: 127 cases in the insufficient vitamin D group, 53 cases in the normal vitamin D group, and 22 cases in the high vitamin D group. The mean age of the population study was 56 years. Thirty-four patients had severe clinical outcomes. The distribution of this group was as follows: 21 patients in the insufficient vitamin D group (16.5%), eight patients in the normal vitamin D group (15.1%), and five patients in the high vitamin D group (22.7%); P = 0.74. No significant differences were found between the groups in terms of mortality rate (P = 0.46). Moreover, the mean of leukocytes (mean ± SD = 6873.5 ± 4236.2), ESR (mean ± SD = 38.42 ± 26.7), and CPK-MB (mean ± SD = 63 ± 140.7) were higher in the insufficient vitamin D group, but it was not statistically significant (P > 0.05). Conclusion The finding of the present study showed that vitamin D could not make a significant difference in cardiovascular systems, laboratory results, and severity of the disease in COVID-19 patients.
Article
Full-text available
Objective: Post-COVID-19 syndrome appears to be a multi-organ illness with a broad spectrum of manifestations, occurring after even mild acute illness. Limited data currently available has suggested that vitamin D deficiency may play a role in COVID-19 cases. However, to our knowledge, no study has examined the frequency of vitamin D deficiency in post-COVID-19 cases and its effect on the symptom severity. The aim of this study is to both screen the frequency of vitamin D deficiency in post-COVID-19 syndrome patients and to study its relation to persistent symptoms. Patients and methods: A cross-sectional, single-center study was conducted involving all cases attending post-COVID-19 follow-up clinic from November 2020 to May 2021. Complete history, clinical examination, and laboratory analysis [kidney functions, serum calcium, C-reactive protein, serum ferritin, Serum 25-(OH) vitamin D] was done as well as HRCT chest. Results: The study included 219 post-COVID-19 cases, 84% had deficient vitamin D levels (< 20 ng/dL); 11.4% had insufficient level (20-30 ng/dL) and only 4.9 % reported normal level. There was no link between levels of vitamin D with either the acute or post-COVID-19 symptoms in the studied groups. Conclusions: Despite the prevalence of vitamin D deficiency among the study population, no association was observed between the levels of vitamin D and post-COVID-19 symptoms. It appears that post-COVID-19 syndrome pathophysiology involves a more complex interaction with the immune system. Dedicated clinical trials are advised to better study vitamin D levels and the related disease severity in COVID-19 patients.
Article
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.
Article
Full-text available
Background and aims COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people. Methods UK Biobank recruited 502,624 participants aged 37–73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19. Results Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99–0.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998–1.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68–7.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65–4.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association. Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.
Article
Full-text available
LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15764.
Article
Full-text available
Background Current COVID-19 radiological literature is dominated by CT and a detailed description of chest x-ray (CXR) appearances in relation to the disease time course is lacking. Purpose To describe the time course and severity of the CXR findings of COVID-19 and correlate these with real time reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-Cov-2 nucleic acid. Materials and Methods Retrospective study of COVID-19 patients with RT-PCR confirmation and CXRs admitted across 4 hospitals evaluated between January and March 2020. Baseline and serial CXRs (total 255 CXRs) were reviewed along with RT-PCRs. Correlation with concurrent CTs (total 28 CTs) was made when available. Two radiologists scored each CXR in consensus for: consolidation, ground glass opacity (GGO), location and pleural fluid. A severity index was determined for each lung. The lung scores were summed to produce the final severity score. Results There were 64 patients (26 men, mean age 56±19 years). Of these, 58, 44 and 38 patients had positive initial RT-PCR (91%, [CI: 81-96%]), abnormal baseline CXR (69%, [CI: 56-80%]) and positive initial RT-PCR with abnormal baseline CXR (59 [CI:46-71%]) respectively. Six patients (9%) showed CXR abnormalities before eventually testing positive on RT-PCR. Sensitivity of initial RT-PCR (91% [95% CI: 83-97%]) was higher than baseline CXR (69% [95% CI: 56-80%]) (p = 0.009). Radiographic (mean 6 ± 5 days) and virologic recovery (mean 8 ± 6 days) were not significantly different (p= 0.33). Consolidation was the most common finding (30/64, 47%), followed by GGO (21/64, 33%). CXR abnormalities had a peripheral (26/64, 41%) and lower zone distribution (32/64, 50%) with bilateral involvement (32/64, 50%). Pleural effusion was uncommon (2/64, 3%). The severity of CXR findings peaked at 10-12 days from the date of symptom onset. Conclusion Chest x-ray findings in COVID-19 patients frequently showed bilateral lower zone consolidation which peaked at 10-12 days from symptom onset.
Article
Full-text available
The currently available data suggests that many laboratory parameters are deranged in patients with COVID-19, and some of these may also be considered significant predictors of adverse clinical outcomes. The most frequent abnormalities were lymphopenia (35–75% of cases), increased values of CRP (75–93% of cases), LDH (27–92% of cases), ESR (up to 85% of cases) and D-dimer (36–43% of cases), as well as low concentrations of serum albumin (50–98% of cases) and hemoglobin (41–50%). Many laboratory abnormalities were instead predictive of adverse outcome, including increased white blood cell count, increased neutrophil count, decreased lymphocyte count, decreased albumin, increased LDH, ALT, AST, bilirubin, creatinine, cardiac troponins, D-dimer, prothrombin time, procalcitonin and CRP values.
Article
WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.
Article
Background: A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods: Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings: 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation: COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1-3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding: None.