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co
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Sy
ndemics
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co
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v
iurs disea
se a
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ing
:
the
i
nt
erpla
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a
mo
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utrit
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i
mm
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ne
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r
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a
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t
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Art
icle
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nfo
AB
S
T
RAC
T
A
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ticle
his
to
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y:
R
ec
eiv
ed
Ma
r
2
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,
2
0
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ev
is
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g
1
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Acc
ep
ted
Oct
1
5
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2
0
2
4
Th
e
c
o
r
o
n
a
v
iru
s
d
ise
a
se
2
0
1
9
(
COV
ID
-
19
)
p
a
n
d
e
m
ic
re
v
e
a
led
“
m
a
n
y
p
a
n
d
e
m
ics
”
.
Rig
h
t
fr
o
m
th
e
b
e
g
i
n
n
i
n
g
of
t
h
e
COV
ID
p
a
n
d
e
m
ic
a
n
d
v
a
rio
u
s
in
ti
m
id
a
ti
n
g
wa
v
e
s
of
n
e
w
v
a
rian
t
s
se
rio
u
sly
a
ffe
c
ted
v
u
l
n
e
ra
b
le
p
o
p
u
lati
o
n
s
,
in
c
lu
d
in
g
th
e
e
ld
e
rl
y
.
T
h
is
sc
o
p
i
n
g
re
v
iew
a
ime
d
to
su
m
m
a
rize
th
e
a
v
a
il
a
b
le
d
a
ta
on
n
u
tri
ti
o
n
a
n
d
imm
u
n
e
re
sp
o
n
se
d
u
rin
g
a
g
i
n
g
a
n
d
a
ss
o
c
iati
o
n
s
b
e
twe
e
n
th
e
imm
u
n
e
sy
ste
m
a
n
d
v
iral
i
n
f
e
c
ti
o
n
s
in
t
h
e
o
l
d
e
r
p
o
p
u
lati
o
n
.
T
h
e
re
v
iew
p
a
rti
c
u
larly
e
m
p
h
a
siz
e
s
m
icro
n
u
tri
e
n
ts
i
n
c
lu
d
in
g
v
it
a
m
in
s
C,
D,
z
in
c
,
a
n
d
se
len
iu
m
a
n
d
th
e
ir
re
latio
n
s
to
COV
ID
-
1
9
i
n
fe
c
ti
o
n
.
We
h
a
v
e
su
m
m
a
rize
d
th
e
a
v
a
il
a
b
le
li
tera
tu
re
re
late
d
to
t
h
e
n
u
tri
ti
o
n
a
l
m
a
n
a
g
e
m
e
n
t
of
COV
ID
-
19
in
fe
c
ti
o
n
to
re
d
u
c
e
a
d
v
e
rse
d
ise
a
se
o
u
tco
m
e
s.
Th
e
re
v
iew
fo
u
n
d
th
a
t
t
h
e
c
o
e
x
isten
c
e
of
m
icro
n
u
tri
e
n
t
d
e
ficie
n
c
ies
,
imm
u
n
e
d
y
sf
u
n
c
ti
o
n
,
a
n
d
h
i
g
h
in
fe
c
ti
o
n
e
x
p
o
su
re
i
n
c
re
a
se
s
th
e
risk
of
m
o
rtalit
y
in
o
ld
e
r
p
e
o
p
le
wit
h
COV
ID
-
19.
M
o
st
stu
d
ies
c
o
n
firm
e
d
a
p
o
siti
v
e
a
ss
o
c
iatio
n
b
e
twe
e
n
v
it
a
m
in
D
sta
tu
s
or
s
u
p
p
lem
e
n
tatio
n
a
n
d
its
e
ffe
c
t
on
COV
ID
-
1
9
,
w
h
e
re
a
s
a
fe
w
o
th
e
r
stu
d
ies
re
p
o
rted
a
l
o
w
z
in
c
a
n
d
se
len
iu
m
sta
tu
s
in
COV
ID
-
19
i
n
fe
c
ted
p
e
o
p
le
.
Im
m
e
d
iate
a
n
d
a
d
e
q
u
a
te
n
u
tr
it
io
n
a
l
m
a
n
a
g
e
m
e
n
t
c
o
u
ld
h
e
l
p
tac
k
le
t
h
e
a
d
v
e
rse
h
e
a
lt
h
c
o
n
se
q
u
e
n
c
e
s
in
e
l
d
e
rly
.
He
n
c
e
,
th
e
p
a
n
d
e
m
ic
li
k
e
th
is
r
e
q
u
ires
a
c
o
m
p
re
h
e
n
siv
e
a
p
p
r
o
a
c
h
to
u
n
d
e
rsta
n
d
a
ll
re
late
d
a
sp
e
c
ts
a
n
d
n
e
e
d
s
fu
rt
h
e
r
in
-
d
e
p
th
i
n
v
e
sti
g
a
ti
o
n
s
re
late
d
to
m
icro
n
u
tri
e
n
t
s
u
p
p
lem
e
n
ts
to
e
n
h
a
n
c
e
imm
u
n
it
y
in
COV
ID
-
19
i
n
fe
c
ted
o
ld
e
r
p
o
p
u
lati
o
n
.
K
ey
w
o
r
d
s
:
C
OVI
D
-
19
I
m
m
u
n
e
s
y
s
tem
Ma
ln
u
tr
itio
n
Old
er
p
o
p
u
latio
n
Pan
d
em
ic
T
h
is
is
an
o
p
e
n
a
c
c
e
ss
a
rticle
u
n
d
e
r
th
e
CC
BY
-
SA
li
c
e
n
se
.
C
o
r
r
e
s
p
o
nd
ing
A
uth
o
r
:
I
n
ay
at
Ali
Dep
ar
tm
en
t o
f
An
th
r
o
p
o
lo
g
y
,
Fatim
a
J
in
n
ah
W
o
m
en
Un
iv
er
s
ity
R
awa
lp
in
d
i,
Pak
is
tan
E
m
ail:
in
ay
at_
q
au
@
y
ah
o
o
.
co
m
1.
I
NT
RO
D
UCT
I
O
N
Hu
m
an
co
r
o
n
av
ir
u
s
es
wer
e
f
ir
s
t
d
escr
ib
ed
in
th
e
1
9
6
0
s
as
b
ein
g
r
esp
o
n
s
ib
le
f
o
r
a
s
u
b
s
tan
tial
p
r
o
p
o
r
tio
n
of
u
p
p
er
r
esp
ir
ato
r
y
tr
ac
t
in
f
ec
tio
n
s
an
d
s
ev
er
e
r
esp
ir
ato
r
y
d
is
ea
s
es
in
th
e
eld
er
ly
[
1
]
.
T
h
e
“
C
o
r
o
n
av
ir
id
ae
f
am
ily
,
”
r
ec
o
g
n
ized
as
s
in
g
le
-
s
tr
an
d
e
d
p
o
s
itiv
e
-
s
en
s
e
R
N
A
v
ir
u
s
es,
in
clu
d
es
s
ev
er
e
ac
u
te
r
esp
ir
ato
r
y
s
y
n
d
r
o
m
e
(
SAR
S)
an
d
th
e
m
id
d
le
ea
s
t
r
esp
ir
at
o
r
y
s
y
n
d
r
o
m
e
(
ME
R
S)
co
r
o
n
av
ir
u
s
es,
wh
ich
ar
e
ass
o
ciate
d
with
h
u
m
an
r
esp
ir
ato
r
y
d
is
ea
s
es
[
2
]
.
Sin
ce
2
0
0
3
,
f
i
v
e
n
ew
h
u
m
a
n
co
r
o
n
av
ir
u
s
es
h
av
e
b
ee
n
d
is
co
v
er
ed
[
1
]
.
No
n
et
h
eless
,
th
is
at
-
f
ir
s
t
n
o
v
el
co
r
o
n
av
ir
u
s
(
SAR
S
-
C
o
V
-
2)
as
a
ca
u
s
ativ
e
ag
en
t
of
C
OVI
D
-
19
h
as
s
h
o
wn
s
u
b
s
tan
tial
e
f
f
ec
ts
wo
r
ld
wid
e.
In
h
ea
lth
y
a
d
u
lts
,
th
o
s
e
with
a
c
o
r
o
n
av
ir
u
s
i
n
f
ec
tio
n
h
a
v
e
r
e
p
o
r
ted
s
y
m
p
to
m
s
of
f
lu
,
m
alaise,
an
d
lo
w
-
g
r
ad
e
f
ev
er
,
wh
ils
t
a
p
r
e
v
a
len
ce
of
p
n
eu
m
o
n
ia
is
c
o
m
m
o
n
ly
f
o
u
n
d
in
eld
e
r
ly
an
d
im
m
u
n
o
co
m
p
r
o
m
is
ed
p
at
ien
ts
.
In
th
e
p
r
esen
ce
of
o
th
e
r
ch
r
o
n
ic
d
is
ea
s
es,
C
OVI
D
-
19
-
d
er
iv
e
d
s
y
s
tem
ic
in
f
lam
m
atio
n
ten
d
ed
to
m
ak
e
th
e
r
esp
ir
ato
r
y
s
y
m
p
to
m
s
of
t
h
e
in
f
ec
tio
n
more
s
ev
er
e,
lead
in
g
to
m
o
r
tality
[
3
]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
S
yn
d
emic
s
o
f c
o
r
o
n
a
viu
r
s
d
is
ea
s
e
a
n
d
a
g
in
g
:
th
e
in
terp
la
y
a
mo
n
g
n
u
tr
itio
n
,
th
e
immu
n
e
…
(
S
eh
a
r
I
q
b
a
l
)
887
T
h
e
C
OVI
D
-
19
p
an
d
em
ic
s
ig
n
if
ican
tly
a
f
f
ec
ted
th
e
w
o
r
ld
in
m
u
ltip
le
way
s
an
d
s
et
out
ca
tast
r
o
p
h
ic
co
n
s
eq
u
en
ce
s
on
th
e
g
lo
b
al
e
co
n
o
m
y
.
T
h
ese
ef
f
ec
ts
h
av
e
b
ee
n
f
elt
at
v
ar
io
u
s
le
v
els:
tem
p
o
r
ally
as
well
as
s
p
atially
.
An
alr
ea
d
y
o
v
er
wh
elm
ed
wo
r
l
d
wer
e
u
n
d
er
n
e
w
s
tr
ess
o
r
s
due
to
m
o
r
e
in
ti
m
id
atin
g
wav
es
[
4
]
,
esp
ec
ially
of
n
ew
v
ar
ian
ts
s
u
c
h
as
Delta
an
d
Om
icr
o
n
.
Star
tin
g
f
r
o
m
Dec
em
b
er
31
,
2
0
1
9
,
t
h
e
v
ir
u
s
in
its
v
ar
io
u
s
f
o
r
m
s
h
ad
in
f
ec
ted
n
ea
r
ly
4
5
0
m
illi
o
n
p
o
p
u
latio
n
with
in
f
ir
s
t
two
y
ea
r
s
at
th
e
g
lo
b
al
le
v
el
[
5
]
.
Desp
ite
b
ein
g
a
g
lo
b
al
p
an
d
em
ic,
th
er
e
wer
e
v
ar
io
u
s
s
p
ec
if
icities
to
its
ef
f
ec
t
s
at
v
ar
io
u
s
s
ca
les,
p
ar
ticu
lar
ly
f
o
r
s
o
m
e
c
o
u
n
tr
ies,
co
m
m
u
n
ities
,
a
n
d
in
d
iv
id
u
als,
due
to
th
e
in
ter
p
lay
am
o
n
g
th
e
p
r
e
-
ex
is
tin
g
s
o
cio
-
cu
ltu
r
al,
ec
o
n
o
m
ic,
p
o
liti
ca
l
an
d
en
v
ir
o
n
m
en
tal
co
n
d
itio
n
s
t
h
at
r
esu
lt
in
u
n
iq
u
e
h
u
m
an
b
o
d
ies
th
at
an
th
r
o
p
o
lo
g
is
t
Ma
r
g
ar
et
L
o
ck
ca
lls
“
lo
ca
l
b
io
lo
g
ies
”
[
6
]
.
B
ec
au
s
e
o
f
th
e
s
e
lo
ca
l
b
io
l
o
g
ies
—
a
r
esu
lt
o
f
an
in
ter
ac
tio
n
b
etwe
en
b
io
l
o
g
ical
p
r
o
ce
s
s
es
an
d
s
o
cial
co
n
tex
ts
,
ce
r
tain
p
o
p
u
la
tio
n
s
an
d
in
d
iv
id
u
als
wer
e
m
o
r
e
v
u
ln
er
ab
le
th
an
o
th
er
s
in
th
e
f
ac
e
of
C
OVI
D
-
19,
wh
ich
is
wh
y
m
ed
ical
an
th
r
o
p
o
l
o
g
is
ts
p
r
o
p
o
s
ed
s
y
n
d
e
m
ics
th
eo
r
y
an
d
r
ejec
tin
g
th
e
n
o
tio
n
of
“
g
lo
b
al
s
y
n
d
em
ics
”
[
7
]
.
T
h
e
ter
m
“
s
y
n
d
em
ics,
”
cr
ea
ted
by
cr
itical
m
ed
ical
an
th
r
o
p
o
lo
g
is
t
Me
r
r
ill
Sin
g
er
,
is
a
co
m
b
in
atio
n
of
“
s
y
n
er
g
y
”
a
n
d
“
ep
i
d
em
ics.
”
T
h
is
a
n
aly
tical
“
b
io
s
o
cial
s
y
n
d
em
ics
th
e
o
r
y
”
c
o
n
s
id
er
s
th
e
in
ter
p
lay
am
o
n
g
v
ar
io
u
s
b
io
-
s
o
cial
f
ac
to
r
s
an
d
b
r
id
g
es
“
th
e
cr
itical
k
n
o
wled
g
e
g
ap
”
[
8
]
in
o
r
d
er
to
a
p
p
l
y
h
o
lis
tically
p
r
o
d
u
ce
d
ev
id
e
n
c
e
f
o
r
in
f
e
ctio
n
p
r
ev
en
tio
n
a
n
d
ca
r
e.
T
h
is
is
an
ex
ten
s
io
n
of
o
u
r
p
r
ev
io
u
s
u
n
p
u
b
lis
h
ed
wo
r
k
f
o
cu
s
in
g
m
o
r
e
on
a
g
e
-
C
OVI
D
-
19
s
y
n
d
e
m
ic
[
9
]
.
In
th
is
r
ev
iew
ar
ticle,
we
f
o
llo
w
th
is
t
h
eo
r
y
to
p
ay
atten
tio
n
to
wh
at
we
ca
ll
th
e
“
ag
e
-
C
OVI
D
-
19
s
y
n
d
em
ic
”
with
a
f
o
cu
s
on
th
e
ass
o
ciatio
n
s
am
o
n
g
n
u
tr
itio
n
,
ag
e
,
im
m
u
n
e
s
y
s
te
m
s
,
an
d
C
OVI
D
-
19.
As
p
ar
t
of
our
r
esear
ch
f
o
r
th
is
ar
ticle,
we
r
ev
iewe
d
th
e
av
ailab
le
p
u
b
lis
h
ed
liter
atu
r
e
to
ev
alu
ate
t
h
e
ef
f
ec
ts
of
n
u
tr
it
io
n
on
im
m
u
n
ity
am
o
n
g
th
e
el
d
er
ly
in
r
elatio
n
to
C
OVI
D
-
19.
T
h
is
s
co
p
in
g
r
ev
i
ew
aim
ed
to
s
u
m
m
ar
ize
th
e
a
v
ailab
le
d
ata
on
n
u
tr
itio
n
a
n
d
im
m
u
n
e
r
esp
o
n
s
e
d
u
r
in
g
a
g
in
g
an
d
ass
o
ciatio
n
s
b
etwe
en
th
e
im
m
u
n
e
s
y
s
te
m
an
d
v
ir
al
in
f
ec
tio
n
s
in
th
e
o
ld
er
p
o
p
u
latio
n
,
h
o
wev
er
,
th
e
lim
ited
liter
atu
r
e
an
d
ev
id
en
ce
f
r
o
m
ca
s
e
co
n
tr
o
l
or
in
ter
v
en
tio
n
al
s
tu
d
ies
war
r
an
ts
f
u
tu
r
e
s
tu
d
ies.
2.
M
E
T
H
O
D
T
h
e
p
r
o
p
o
s
ed
s
co
p
in
g
r
ev
iew
s
u
m
m
ar
ized
th
e
av
ailab
le
lit
er
atu
r
e
by
u
s
in
g
s
ea
r
ch
s
o
u
r
c
es
s
u
ch
as
Go
o
g
le
Sch
o
lar
,
Pu
b
Me
d
,
a
n
d
Sco
p
u
s
d
atab
ases
to
co
m
p
ly
with
our
m
ain
o
b
jectiv
e
f
o
c
u
s
in
g
on
n
u
tr
itio
n
an
d
im
m
u
n
ity
in
o
ld
er
p
o
p
u
latio
n
in
r
elatio
n
to
C
OVI
D
-
19
as
s
h
o
wn
in
F
ig
u
r
e
1
.
Sin
ce
,
th
is
r
ev
iew
is
m
ain
ly
n
ar
r
ativ
e
an
d
d
o
es
not
in
clu
d
e
an
y
s
y
s
tem
atic
ap
p
r
o
ac
h
,
h
o
wev
er
,
th
e
au
th
o
r
s
s
ea
r
ch
ed
f
o
r
a
b
r
o
ad
e
r
s
ea
r
ch
ter
m
s
u
ch
as
:
i
)
C
OVI
D
in
o
l
d
er
p
o
p
u
latio
n
;
ii
)
C
OVI
D
an
d
im
m
u
n
it
y
in
o
ld
er
p
o
p
u
latio
n
;
iii
)
C
OVI
D
an
d
m
aln
u
tr
itio
n
in
o
ld
er
p
o
p
u
latio
n
;
an
d
iv
)
C
OVI
D
m
o
r
tality
in
o
ld
er
p
o
p
u
latio
n
to
r
etr
iev
e
m
o
s
t
ap
p
r
o
p
r
iate
d
ata.
T
h
e
au
th
o
r
s
in
d
ep
en
d
en
tl
y
id
en
tifie
d
th
e
m
o
s
t
r
elev
a
n
t
E
n
g
lis
h
lit
er
atu
r
e
in
clu
d
in
g
o
r
i
g
in
al
p
ap
er
s
,
r
ev
iew
ar
ticles,
clin
ical
tr
ials
,
ca
s
e
s
tu
d
ies
an
d
s
er
ies
of
letter
s
(
f
l
o
w
ch
ar
t
of
s
tu
d
y
s
elec
tio
n
)
.
An
y
g
r
ey
liter
atu
r
e,
p
r
ep
r
in
ts
,
an
d
ar
ticles
o
th
e
r
th
an
E
n
g
lis
h
wer
e
ex
clu
d
ed
.
We
tr
ied
to
ac
c
u
m
u
late
r
elev
an
t
liter
atu
r
e
th
at
s
ee
m
s
ap
p
r
o
p
r
iate
f
o
r
ass
ess
in
g
our
s
tu
d
y
o
b
jectiv
e
a
n
d
ac
q
u
ir
e
a
n
ar
r
ativ
e
ap
p
r
o
ac
h
f
o
cu
s
in
g
on
our
s
tu
d
y
o
b
jectiv
e.
Sin
ce
,
it
is
s
co
p
in
g
r
ev
iew
of
p
r
ev
io
u
s
s
tu
d
ies.
E
th
ical
ap
p
r
o
v
al
or
p
ar
ticip
an
ts
co
n
s
en
t
was
not
n
ee
d
ed
.
B
y
th
e
tim
e
we
co
n
d
u
cted
th
is
r
ev
iew
,
th
e
liter
atu
r
e
was
s
till
b
ein
g
p
r
o
d
u
ce
d
,
an
d
s
tu
d
ies
wer
e
o
n
g
o
in
g
,
c
o
n
tin
u
o
u
s
ly
ex
p
lo
r
in
g
an
d
an
al
y
zin
g
th
e
e
f
f
ec
ts
an
d
af
te
r
ef
f
ec
ts
o
f
C
OVI
D
-
1
9
o
n
d
if
f
er
e
n
t
p
o
p
u
latio
n
s
.
T
h
er
ef
o
r
e,
n
o
t
all
s
tu
d
ies
co
u
ld
b
e
in
clu
d
ed
in
th
is
r
ev
iew.
Ad
d
itio
n
ally
,
th
e
r
a
p
id
p
ac
e
o
f
em
er
g
in
g
r
esear
c
h
p
o
s
ed
ch
allen
g
es
in
m
ain
tain
in
g
a
co
m
p
r
e
h
en
s
iv
e
o
v
er
v
iew
o
f
n
ew
f
in
d
in
g
s
.
T
h
e
f
in
al
d
r
af
t
cr
itically
c
h
ec
k
ed
an
d
d
is
cu
s
s
ed
with
all
au
th
o
r
s
by
r
eso
lv
in
g
an
y
d
i
s
cr
ep
an
cies.
3.
RE
SU
L
T
S
AND
D
I
SCU
SS
I
O
N
T
h
e
r
ev
iew
f
o
u
n
d
th
at
th
e
c
o
e
x
is
ten
ce
of
m
icr
o
n
u
tr
ien
t
d
ef
i
cien
cies,
im
m
u
n
e
d
y
s
f
u
n
ctio
n
,
an
d
h
ig
h
in
f
ec
tio
n
ex
p
o
s
u
r
e
in
c
r
ea
s
es
th
e
r
is
k
of
m
o
r
tality
in
o
l
d
er
p
eo
p
le
with
C
OVI
D
-
19.
Mo
s
t
s
tu
d
ies
co
n
f
ir
m
ed
a
p
o
s
itiv
e
ass
o
ciatio
n
b
etwe
en
v
itam
in
D
s
tatu
s
or
s
u
p
p
lem
e
n
t
atio
n
an
d
it
i
s
ef
f
ec
t
on
C
OVI
D
-
19,
wh
e
r
ea
s
a
f
ew
o
th
er
s
tu
d
ies
r
ep
o
r
ted
a
lo
w
z
in
c
an
d
s
elen
iu
m
s
tatu
s
in
C
OVI
D
-
19
in
f
ec
ted
p
eo
p
le.
T
h
e
f
o
llo
win
g
s
ec
tio
n
s
p
r
o
v
id
e
s
u
ch
d
etails.
3
.
1
.
Ag
e
-
CO
VID
-
19
s
y
nd
emics
T
h
e
m
o
s
t
s
ev
er
e
co
n
s
eq
u
en
ce
s
of
co
r
o
n
av
ir
u
s
in
f
ec
tio
n
o
cc
u
r
r
ed
in
o
ld
e
r
p
o
p
u
latio
n
s
,
s
in
ce
p
eo
p
le
ab
o
v
e
65
y
ea
r
s
of
ag
e
wer
e
m
o
r
e
lik
ely
to
d
e
v
elo
p
ac
u
te
r
esp
ir
ato
r
y
d
is
tr
ess
s
y
n
d
r
o
m
e
lead
in
g
to
d
ea
t
h
.
Fo
r
ex
am
p
le,
a
co
m
p
ar
ativ
e
s
tu
d
y
f
r
o
m
C
h
in
a
an
d
I
taly
r
ep
o
r
ted
a
h
ig
h
m
o
r
tality
r
ate
in
th
e
C
OVI
D
-
in
f
ec
ted
o
ld
e
r
p
o
p
u
latio
n
s
co
m
p
a
r
ed
to
o
th
er
ag
e
g
r
o
u
p
s
[
1
0
]
.
Ag
e
of
in
f
ec
tio
n
,
d
o
s
e
an
d
r
o
u
te
of
in
f
ec
tio
n
,
g
en
etic
s
u
s
ce
p
tib
ilit
y
,
an
d
p
o
o
r
im
m
u
n
e
s
y
s
tem
s
wer
e
a
f
ew
i
m
p
o
r
tan
t
f
ac
to
r
s
t
h
at
in
co
m
b
in
atio
n
in
cr
ea
s
e
d
s
u
s
ce
p
tib
ilit
y
to
v
ir
al
in
f
ec
tio
n
s
in
o
ld
er
p
eo
p
le
[
1
1
]
.
Ag
e
-
r
elate
d
p
h
y
s
io
lo
g
ical
c
h
an
g
es,
tis
s
u
e
d
estru
ctio
n
,
an
d
th
e
p
r
esen
ce
of
co
n
cu
r
r
en
t
in
f
ec
tio
n
s
,
in
clu
d
in
g
u
r
i
n
ar
y
an
d
g
astro
in
test
in
al
tr
ac
t
in
f
ec
tio
n
s
,
also
p
lay
ed
a
p
iv
o
tal
r
o
le
in
th
is
r
eg
ar
d
.
Oth
er
co
m
o
r
b
i
d
ities
lik
e
d
iab
etes,
h
y
p
er
ten
s
io
n
,
k
id
n
e
y
,
an
d
ca
r
d
io
v
ascu
lar
d
is
ea
s
es
d
u
r
in
g
ag
in
g
also
in
ter
r
u
p
t
ed
th
e
n
o
r
m
al
h
o
m
eo
s
tasi
s
of
i
n
n
ate
an
d
ad
a
p
tiv
e
im
m
u
n
ity
,
lead
in
g
to
ad
v
er
s
e
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
2
,
J
u
n
e
20
25
:
8
8
6
-
8
9
7
888
d
is
ea
s
e
o
u
tco
m
es
in
o
ld
er
C
OVI
D
p
atien
ts
[
1
2
]
.
C
o
n
c
o
m
itan
tly
,
th
e
v
icio
u
s
cy
cle
of
m
aln
u
tr
itio
n
f
u
r
th
er
r
ed
u
ce
d
o
ld
e
r
in
d
iv
id
u
als’
ca
p
ac
ities
to
f
ig
h
t
ag
ain
s
t
v
i
r
al
in
f
ec
tio
n
by
c
o
m
p
r
o
m
is
in
g
t
h
eir
im
m
u
n
e
s
y
s
tem
s
.
Simu
ltan
eo
u
s
ly
,
ag
e
-
r
elate
d
c
h
an
g
es
in
b
o
th
t
h
e
in
n
ate
an
d
ad
ap
tiv
e
im
m
u
n
e
s
y
s
tem
s
ma
de
o
ld
er
ad
u
lts
m
o
r
e
p
r
o
n
e
to
C
OVI
D
-
19
in
f
ec
tio
n
s
[
1
3
]
.
T
h
ese
co
m
o
r
b
id
ities
an
d
s
itu
atio
n
s
s
y
n
er
g
is
ticall
y
af
f
ec
t
ea
ch
o
th
er
s
h
o
win
g
a
s
y
n
d
e
m
ic
in
ter
ac
tio
n
am
o
n
g
th
em
.
An
ad
ap
tiv
e
im
m
u
n
e
r
esp
o
n
s
e
ag
ain
s
t
co
r
o
n
a
v
ir
u
s
r
e
q
u
ir
es
s
tim
u
latio
n
of
B
an
d
T
ce
ll
e
p
i
to
p
es
[
1
4
]
.
Ho
wev
er
,
C
OVI
D
-
19
r
elate
d
f
r
ailty
,
alo
n
g
with
m
aln
u
tr
i
tio
n
,
c
o
u
ld
p
o
s
e
ad
v
er
s
e
ef
f
ec
ts
on
r
eg
u
lato
r
y
T
-
ce
lls
an
d
s
en
escen
t
n
atu
r
al
k
iller
ce
lls
,
lead
in
g
to
ad
v
er
s
e
C
OVI
D
-
19
o
u
tco
m
es
in
t
h
e
o
l
d
er
p
o
p
u
latio
n
[
1
5
]
.
R
ec
en
t
s
tu
d
ies
h
av
e
s
u
m
m
ar
ized
th
e
b
en
ef
icial
ef
f
ec
ts
of
m
icr
o
n
u
tr
ie
n
ts
in
clu
d
in
g
v
itam
in
C,
D,
zin
c,
an
d
s
elen
iu
m
f
o
r
im
m
u
n
e
s
u
p
p
o
r
t
an
d
to
r
ed
u
ce
th
e
r
is
k
of
in
f
ec
tio
n
[
1
6
]
.
An
tio
x
i
d
an
t
p
r
o
p
er
ties
of
th
ese
m
icr
o
n
u
tr
ie
n
ts
co
n
tain
in
g
en
z
y
m
es
s
u
ch
as
s
u
p
er
o
x
id
e
d
is
m
u
tase,
ca
talase,
an
d
g
lu
tath
io
n
e
p
er
o
x
id
ase
h
elp
to
s
u
p
p
o
r
t
th
e
im
m
u
n
e
s
y
s
tem
[
1
7
]
.
T
h
er
ef
o
r
e,
d
if
f
e
r
en
t
tr
ea
t
m
en
t
s
tr
ateg
ies,
ef
f
ec
tiv
e
v
ac
ci
n
es,
an
d
n
u
tr
itio
n
al
m
an
ag
em
en
t
of
in
f
ec
ted
p
ati
en
ts
wer
e
u
n
d
er
co
n
s
id
er
atio
n
as
th
er
ap
eu
tic
m
ea
s
u
r
es
ag
ain
s
t
th
e
ev
o
lv
in
g
co
r
o
n
a
v
ir
u
s
.
We
em
p
h
asize
th
ese
m
icr
o
n
u
tr
ien
ts
an
d
th
eir
r
elatio
n
to
C
OVI
D
-
19
-
in
f
e
cted
o
ld
er
p
eo
p
le.
Her
ein
,
we
b
r
ief
ly
s
u
m
m
ar
ize
th
e
av
ailab
le
liter
atu
r
e
r
elate
d
to
th
e
n
u
tr
itio
n
al
m
an
a
g
em
en
t
of
a
n
o
v
el
C
OVI
D
-
19
in
f
ec
tio
n
,
wh
ic
h
m
ig
h
t
h
el
p
to
b
o
o
s
t
th
e
im
m
u
n
e
s
y
s
tem
an
d
to
p
r
ev
en
t
a
d
v
er
s
e
o
u
t
co
m
es
in
th
e
o
ld
er
p
o
p
u
latio
n
.
Ho
wev
e
r
,
d
u
e
to
th
e
d
ea
r
t
h
of
clin
ical,
in
ter
v
en
tio
n
al,
a
n
d
r
an
d
o
m
ized
c
o
n
tr
o
lled
t
r
ials
,
th
e
in
f
o
r
m
atio
n
p
r
o
v
id
ed
m
ay
n
ee
d
to
be
u
p
d
ate
d
in
th
e
f
u
tu
r
e
.
Fig
u
r
e
1
.
Flo
w
ch
a
r
t o
f
s
cr
ee
n
in
g
p
r
o
ce
s
s
3
.
2
.
Vira
l
infe
ct
i
o
n
a
nd
im
mu
ne
re
s
po
n
s
es
in
t
he
o
lder
p
o
pu
la
t
io
n
V
i
r
a
l
r
es
p
i
r
at
o
r
y
p
a
t
h
o
g
e
n
s
i
n
c
l
u
d
i
n
g
i
n
f
l
u
e
n
z
a
,
r
es
p
i
r
at
o
r
y
s
y
n
c
y
t
i
a
l
v
i
r
u
s
,
h
u
m
a
n
m
e
t
a
p
n
e
u
m
o
v
i
r
u
s
,
a
n
d
c
o
r
o
n
a
v
i
r
u
s
e
s
h
a
v
e
b
e
e
n
r
e
c
o
g
n
i
z
e
d
as
s
i
g
n
i
f
ic
a
n
t
c
a
u
s
es
of
h
o
s
p
i
t
a
li
z
a
ti
o
n
s
in
t
h
e
o
l
d
e
r
p
o
p
u
l
a
t
i
o
n
[
1
8
]
.
A
s
tu
d
y
of
195
co
u
n
tr
ies
h
as
esti
m
ated
1
,
0
8
0
,
9
5
8
d
ea
th
s
in
th
e
o
ld
er
p
o
p
u
latio
n
due
to
lo
wer
r
esp
ir
ato
r
y
in
f
ec
tio
n
s
[
1
9
]
.
A
h
ig
h
b
u
r
d
en
of
p
n
eu
m
o
n
ia,
lo
wer
r
esp
ir
ato
r
y
tr
ac
t
in
f
ec
tio
n
s
,
an
d
s
ev
er
e
o
u
tc
o
m
es
of
r
esp
ir
ato
r
y
s
y
n
cy
tial
v
ir
u
s
i
n
f
ec
tio
n
ar
e
s
ee
n
in
eld
er
l
y
p
e
o
p
le.
C
o
r
r
esp
o
n
d
in
g
ly
,
in
t
h
e
Un
ited
States
,
p
eo
p
le
ag
ed
85
y
ea
r
s
or
o
ld
e
r
h
av
e
s
h
o
wn
a
32
tim
es
h
ig
h
er
d
ea
th
r
ate
due
to
in
f
lu
e
n
za
-
ass
o
ciate
d
d
ea
th
s
th
an
th
e
y
o
u
n
g
er
p
o
p
u
latio
n
[
2
0
]
.
B
o
th
in
n
ate
a
n
d
a
d
ap
tiv
e
im
m
u
n
ity
as
a
p
ar
t
of
o
u
r
im
m
u
n
e
s
y
s
te
m
s
h
elp
s
to
c
o
n
tr
o
l
v
ir
al
in
f
ec
tio
n
s
.
Ma
c
r
o
p
h
ag
es,
m
o
n
o
c
y
tes,
an
d
d
en
d
r
itic
ce
lls
as
p
ar
ts
of
th
e
i
n
n
ate
im
m
u
n
e
s
y
s
tem
r
ec
o
g
n
ize
th
e
in
v
ad
in
g
p
ath
o
g
en
s
in
th
e
p
r
esen
ce
of
p
atter
n
r
ec
o
g
n
itio
n
r
ec
ep
to
r
s
(
PR
R
s
)
an
d
m
icr
o
b
e
-
ass
o
ciate
d
m
o
lecu
lar
p
atter
n
s
(
MA
MPs).
Fu
r
th
er
m
o
r
e,
ac
tiv
atio
n
of
B
ce
ll
s
v
ia
v
ir
al
an
tig
en
-
s
p
ec
if
ic
h
elp
er
T
ce
lls
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
S
yn
d
emic
s
o
f c
o
r
o
n
a
viu
r
s
d
is
ea
s
e
a
n
d
a
g
in
g
:
th
e
in
terp
la
y
a
mo
n
g
n
u
tr
itio
n
,
th
e
immu
n
e
…
(
S
eh
a
r
I
q
b
a
l
)
889
p
r
o
d
u
ce
s
an
tib
o
d
ies
to
f
ig
h
t
a
g
ain
s
t
th
e
v
ir
u
s
an
d
to
n
eu
tr
ali
ze
th
e
in
f
ec
ti
o
n
.
H
o
wev
er
,
ag
i
n
g
in
d
u
ce
s
ad
v
er
s
e
ef
f
ec
ts
on
in
n
ate
an
d
ad
ap
tiv
e
im
m
u
n
ity
,
r
esu
ltin
g
in
im
p
air
ed
v
ir
u
s
c
o
n
tr
o
l
a
n
d
p
r
o
te
ctiv
e
im
m
u
n
o
l
o
g
ic
m
em
o
r
y
[
2
1
]
.
Mo
r
eo
v
e
r
,
th
e
f
u
n
ctio
n
in
g
an
d
co
o
r
d
in
at
io
n
of
in
n
ate
an
d
ad
ap
tiv
e
im
m
u
n
ity
s
tar
t
to
d
o
wn
r
eg
u
late
with
a
g
e
p
r
o
g
r
ess
io
n
as
s
h
o
wn
in
Fig
u
r
e
2
[
1
6
]
.
Owin
g
to
ag
in
g
,
s
ev
e
r
al
f
ac
to
r
s
af
f
ec
t
th
e
n
o
r
m
al
f
u
n
ctio
n
in
g
of
th
e
im
m
u
n
e
s
y
s
tem
:
i
)
C
D4
+T
h
ce
lls
r
ed
u
ce
t
h
e
an
tig
en
r
esp
o
n
s
e
an
d
in
cr
e
ased
d
if
f
er
en
tiatio
n
in
to
T
h
1
7
ce
lls
;
ii
)
d
ec
lin
e
in
th
e
p
r
o
d
u
ctio
n
of
B
ce
lls
lead
s
to
r
ed
u
ce
d
a
n
tib
o
d
y
av
id
ity
an
d
m
an
y
r
esp
o
n
d
in
g
ce
lls
;
an
d
iii
)
ex
p
a
n
s
io
n
of
C
D8
+CD2
8
−T
ce
lls
im
p
air
th
e
n
o
r
m
al
im
m
u
n
e
f
u
n
ctio
n
s
.
I
n
cr
e
ased
f
r
eq
u
e
n
cies
of
C
D2
8
−T
ce
lls
ar
e
d
ir
ec
tly
or
in
d
ir
ec
tly
r
esp
o
n
s
ib
le
f
o
r
t
h
e
im
m
u
n
e
d
y
s
f
u
n
ctio
n
s
in
th
e
eld
er
ly
th
r
o
u
g
h
co
m
p
r
o
m
is
in
g
T
ce
ll
h
o
m
eo
s
tasi
s
,
th
er
eb
y
in
cr
ea
s
in
g
th
e
r
is
k
of
v
ir
al
in
f
ec
tio
n
s
.
Si
m
ilar
ly
,
ch
a
n
g
es
in
m
o
n
o
c
y
te
f
u
n
ctio
n
(
cir
c
u
latin
g
in
n
ate
im
m
u
n
e
ce
lls
)
an
d
p
h
en
o
ty
p
e
d
u
e
to
a
g
in
g
in
c
r
ea
s
e
th
e
r
is
k
of
ag
e
-
r
elate
d
co
m
o
r
b
i
d
ities
[
2
2
]
.
T
h
u
s
,
th
e
p
r
o
tectiv
e
m
ec
h
an
is
m
s
ag
ain
s
t
v
ir
al
in
f
ec
tio
n
ar
e
s
er
io
u
s
ly
co
m
p
r
o
m
is
ed
in
o
ld
er
p
eo
p
le
due
to
t
h
e
in
ter
r
u
p
tio
n
of
im
m
u
n
e
r
esp
o
n
s
es.
I
m
m
u
n
e
s
en
escen
ce
(
ch
a
n
g
es
in
a
d
ap
tiv
e
im
m
u
n
ity
m
e
d
iated
by
T
an
d
B
ce
lls
)
due
to
o
l
d
ag
e
r
ed
u
ce
th
e
r
esis
tan
ce
to
n
ew
in
f
ec
tio
u
s
ag
en
ts
an
d
c
o
n
tr
o
l
of
v
ir
al
ex
p
o
s
u
r
e.
Fu
r
th
er
m
o
r
e
,
a
lo
w
b
aselin
e
of
C
D4
/C
D8
r
atio
,
r
e
d
u
ctio
n
of
n
aïv
e
T
ce
lls
,
an
d
n
at
u
r
al
k
iller
ce
lls
in
cr
ea
s
e
v
ir
al
s
u
s
ce
p
tib
ilit
y
in
o
ld
er
p
eo
p
le
[
2
3
]
.
Ad
d
itio
n
ally
,
due
to
d
ec
r
e
ased
r
esp
ir
ato
r
y
m
u
s
cle
s
tr
en
g
t
h
,
lu
n
g
co
m
p
lian
ce
,
an
d
ce
llu
lar
im
m
u
n
ity
,
B
ce
lls
f
ail
to
r
esp
o
n
d
to
n
ew
an
tig
en
s
an
d
in
cr
ea
s
ed
lev
els
of
in
f
la
m
m
ato
r
y
m
e
d
iato
r
s
in
th
e
o
ld
er
p
o
p
u
latio
n
[
2
4
]
.
Giv
en
th
at,
o
ld
er
ad
u
lts
m
ig
h
t
not
ef
f
ec
tiv
ely
s
witch
f
r
o
m
in
n
ate
to
ad
ap
tiv
e
im
m
u
n
ity
d
u
e
to
little
or
no
a
n
tib
o
d
y
p
r
o
d
u
ctio
n
,
m
ak
in
g
th
e
m
more
s
u
s
ce
p
tib
le
to
e
m
er
g
i
n
g
in
f
ec
tio
n
s
[
1
2
]
.
Fig
u
r
e
2
.
Ag
e
-
r
elate
d
ch
a
n
g
es
o
f
th
e
im
m
u
n
e
s
y
s
tem
an
d
ef
f
ec
ts
o
n
v
ir
al
in
f
ec
tio
n
in
th
e
o
l
d
er
p
o
p
u
latio
n
3
.
3
.
Nut
rit
io
n
a
nd
imm
un
e
re
s
po
ns
e
in
t
he
o
lder
po
pu
la
t
io
n
In
o
ld
er
p
eo
p
le,
u
n
d
er
n
u
tr
itio
n
in
s
tead
of
o
v
e
r
n
u
tr
itio
n
is
th
e
m
ain
ca
u
s
e
f
o
r
c
o
n
ce
r
n
d
u
e
to
lo
w
d
ietar
y
in
tak
e,
ch
an
g
es
in
m
e
tab
o
lic
d
em
an
d
s
,
m
alab
s
o
r
p
ti
o
n
of
n
u
tr
ie
n
ts
,
an
d
due
to
n
u
tr
ien
t
lo
s
s
es.
Ag
e
-
r
elate
d
m
aln
u
tr
itio
n
can
f
u
r
t
h
er
ag
g
r
a
v
ate
th
e
g
en
e
r
al
r
is
k
of
v
ir
al
in
f
ec
tio
n
s
an
d
r
el
ated
co
m
o
r
b
id
ities
,
in
clu
d
in
g
d
iar
r
h
ea
,
p
n
eu
m
o
n
i
a,
ac
u
te
r
esp
ir
at
o
r
y
in
f
ec
tio
n
s
,
h
ig
h
e
r
h
o
s
p
ital
r
ea
d
m
is
s
io
n
r
ates,
an
d
m
o
r
tality
th
r
o
u
g
h
s
u
p
p
r
ess
in
g
th
e
im
m
u
n
e
r
esp
o
n
s
es
[
2
5
]
as
s
h
o
wn
i
n
Fig
u
r
e
3
.
T
h
is
n
u
t
r
itio
n
al
s
tr
ess
,
alo
n
g
with
v
ir
al
in
f
ec
tio
n
,
s
ig
n
if
ica
n
tly
in
cr
ea
s
es
o
x
id
ativ
e
s
tr
ess
an
d
th
e
f
o
r
m
atio
n
of
f
r
ee
r
ad
icals
lea
d
in
g
to
ce
ll
d
ea
th
.
Var
io
u
s
m
icr
o
n
u
tr
ie
n
ts
’
s
y
n
er
g
is
tic
r
o
les
in
im
m
u
n
ity
ar
e
well
estab
lis
h
ed
an
d
r
ec
en
tly
r
ev
iewe
d
.
Dif
f
er
en
t
m
ac
r
o
-
an
d
m
icr
o
n
u
t
r
ien
ts
in
f
l
u
en
ce
th
e
ab
ilit
y
of
t
h
e
im
m
u
n
e
s
y
s
tem
to
re
s
p
o
n
d
to
in
f
ec
t
io
n
s
.
Fo
r
e
x
am
p
le,
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
2
,
J
u
n
e
20
25
:
8
8
6
-
8
9
7
890
th
e
im
m
u
n
o
r
e
g
u
lato
r
y
a
n
d
a
n
t
i
-
in
f
lam
m
ato
r
y
p
r
o
p
e
r
ties
of
v
itam
in
D
r
e
g
u
late
t
h
e
g
r
o
wth
an
d
d
if
f
er
e
n
tiatio
n
of
m
u
ltip
le
ce
ll
ty
p
es
in
v
o
l
v
ed
in
an
in
n
ate
a
n
d
ad
a
p
tiv
e
im
m
u
n
e
s
y
s
tem
(
m
ac
r
o
p
h
ag
es,
d
en
d
r
itic
ce
lls
,
T
ce
lls
an
d
B
ce
lls
)
[
2
6
]
.
Similar
ly
,
v
itam
in
C
im
p
r
o
v
es
im
m
u
n
e
d
ef
e
n
s
e
th
r
o
u
g
h
s
u
p
p
o
r
tin
g
th
e
ce
ll
u
lar
f
u
n
ctio
n
s
of
b
o
th
t
h
e
in
n
ate
an
d
a
d
ap
tiv
e
im
m
u
n
e
s
y
s
tem
s
.
Vitam
in
C
is
in
v
o
lv
ed
in
ap
o
p
to
s
is
an
d
clea
r
a
n
ce
of
s
p
en
t
n
e
u
tr
o
p
h
ils
f
r
o
m
in
f
ec
tio
n
s
ites
by
m
ac
r
o
p
h
ag
es,
th
er
e
b
y
d
ec
r
ea
s
in
g
n
e
cr
o
s
is
/NE
T
o
s
is
an
d
p
o
ten
tial
tis
s
u
e
d
am
ag
e
[
2
7
]
.
L
ac
k
of
o
th
e
r
m
icr
o
n
u
t
r
ien
ts
s
u
ch
as
zin
c
d
ef
icien
c
y
a
d
v
er
s
el
y
af
f
ec
t
T
ly
m
p
h
o
cy
te
m
at
u
r
at
io
n
,
d
i
f
f
er
en
tiatio
n
,
cy
to
k
in
e
p
r
o
d
u
ctio
n
,
B
ce
ll
a
ctiv
atio
n
,
an
d
p
lasma
ce
ll
d
if
f
er
en
tiatio
n
,
a
n
d
alter
th
e
ac
tiv
ities
of
m
o
n
o
cy
tes,
n
eu
tr
o
p
h
ils
,
an
d
n
atu
r
al
k
iller
ce
lls
.
T
h
er
ap
eu
tic
e
f
f
ec
ts
of
zi
n
c
s
u
p
p
lem
e
n
tatio
n
h
av
e
b
ee
n
r
ep
o
r
ted
f
o
r
v
ir
al
d
is
ea
s
es
in
clu
d
in
g
r
esp
ir
ato
r
y
tr
ac
t
in
f
ec
tio
n
s
,
th
e
c
o
m
m
o
n
co
ld
,
an
d
p
n
e
u
m
o
n
ia
[
2
8
]
.
Similar
ly
,
th
e
estab
lis
h
m
en
t
an
d
p
r
o
g
r
ess
io
n
of
v
ir
al
in
f
ec
tio
n
s
ar
e
in
f
lu
en
c
ed
by
th
e
r
e
d
o
x
s
tate
of
th
e
h
o
s
t
ce
ll,
an
d
s
elen
iu
m
r
eg
u
lates
th
e
ce
llu
lar
r
e
d
o
x
b
a
lan
ce
an
d
r
esu
lts
in
b
o
t
h
b
e
n
ef
icial
an
d
d
etr
im
en
tal
e
f
f
ec
ts
on
ce
llu
lar
im
m
u
n
ity
in
th
e
o
ld
er
p
o
p
u
latio
n
[
2
9
]
.
B
o
th
m
ac
r
o
-
an
d
m
icr
o
n
u
tr
ien
t
s
h
av
e
to
m
ed
iate
im
m
u
n
o
l
o
g
i
ca
l
ef
f
ec
ts
on
t
h
e
h
o
s
t
im
m
u
n
e
r
esp
o
n
s
e
th
r
o
u
g
h
ch
a
n
g
es
in
gut
m
icr
o
b
es.
In
p
a
r
ticu
lar
,
f
ib
er
a
n
d
f
er
m
en
ted
f
o
o
d
s
p
lay
cr
u
cial
r
o
les
in
m
ain
tain
in
g
h
ea
lth
y
gut
m
icr
o
b
io
ta
an
d
in
s
u
p
p
o
r
tin
g
th
e
im
m
u
n
e
s
y
s
tem
'
s
n
o
r
m
al
f
u
n
ctio
n
i
n
g
.
E
q
u
a
lly
,
p
r
o
b
io
tics
h
av
e
b
ee
n
p
r
o
p
o
s
ed
to
m
ed
iate
ac
u
te
u
p
p
er
r
esp
ir
ato
r
y
tr
ac
t
i
n
f
e
ctio
n
s
by
r
eg
u
latin
g
th
e
im
m
u
n
e
r
esp
o
n
s
es
[
3
0
]
.
E
s
s
en
tial
am
in
o
ac
id
s
an
d
p
o
ly
u
n
s
atu
r
ated
f
atty
ac
id
s
h
el
p
to
r
ed
u
ce
in
f
lam
m
atio
n
a
n
d
en
h
an
ce
im
m
u
n
e
p
r
o
tectio
n
f
o
r
v
ir
al
in
f
ec
tio
n
s
.
Ad
d
itio
n
ally
,
v
itam
in
s
an
d
tr
a
ce
elem
en
ts
,
in
clu
d
in
g
v
itam
in
s
A,
B
6
,
B
1
2
,
C,
D,
E,
zin
c,
ir
o
n
,
s
elen
iu
m
,
m
ag
n
e
s
iu
m
,
co
p
p
er
,
a
n
d
o
m
eg
a
-
3
f
at
ty
ac
id
s
,
p
lay
ess
en
tial
an
d
b
e
n
ef
icial
r
o
les
in
th
e
im
p
r
o
v
em
e
n
t
of
im
m
u
n
e
r
esp
o
n
s
es
[
3
1
]
.
Vitam
in
A
h
as
b
ee
n
p
r
o
v
en
to
be
ess
en
tial
f
o
r
th
e
r
eg
u
latio
n
of
in
n
ate
an
d
ce
ll
-
m
ed
iate
d
im
m
u
n
ity
by
g
r
o
wth
an
d
d
if
f
er
en
tiatio
n
of
B
ce
lls
,
n
atu
r
al
k
iller
ce
lls
,
m
ac
r
o
p
h
ag
es,
a
n
d
n
eu
tr
o
p
h
ils
[
3
2
]
.
V
i
t
a
m
i
n
B
-
6
d
e
f
i
c
i
e
n
c
y
in
t
h
e
o
l
d
e
r
p
o
p
u
l
a
t
i
o
n
h
a
s
b
e
e
n
f
o
u
n
d
to
i
m
p
a
i
r
i
n
t
e
r
l
e
u
k
i
n
-
2
p
r
o
d
u
c
t
i
o
n
a
n
d
p
e
r
i
p
h
e
r
a
l
b
l
o
o
d
l
y
m
p
h
o
c
y
t
e
p
r
o
l
i
f
e
r
a
t
i
o
n
to
b
o
t
h
T
-
a
n
d
B
-
c
e
l
l
m
i
t
o
g
e
n
s
,
w
h
i
l
e
v
i
t
a
m
i
n
C
i
n
t
a
k
e
a
p
p
e
a
r
s
to
p
r
e
v
e
n
t
r
e
s
p
i
r
a
t
o
r
y
a
n
d
s
y
s
t
e
m
ic
i
n
f
e
c
t
i
o
n
s
by
s
t
r
e
n
g
t
h
e
n
i
n
g
t
h
e
i
m
m
u
n
e
s
y
s
t
em
.
In
a
d
d
i
t
i
o
n
,
z
i
n
c
d
e
f
i
c
i
e
n
c
y
in
el
d
e
r
l
y
p
e
o
p
l
e
d
u
e
to
l
o
w
d
i
et
a
r
y
z
i
n
c
i
n
t
a
k
e
a
n
d
i
n
t
e
s
ti
n
a
l
m
al
a
b
s
o
r
p
ti
o
n
a
p
p
e
a
r
s
to
i
m
p
a
i
r
t
h
e
i
m
m
u
n
e
r
e
s
p
o
n
s
e
,
l
e
a
d
i
n
g
to
d
e
g
e
n
e
r
a
t
i
v
e
d
i
s
e
a
s
es
.
It
h
as
b
e
e
n
s
h
o
w
n
t
h
a
t
l
o
w
s
el
e
n
i
u
m
s
t
a
tu
s
i
n
c
r
e
a
s
e
s
t
h
e
r
is
k
of
m
o
r
t
a
l
i
t
y
by
n
e
g
a
t
i
v
e
l
y
a
f
f
ec
t
i
n
g
t
h
e
i
m
m
u
n
e
s
y
s
t
e
m
[
3
3
]
.
Fig
u
r
e
3
.
Dete
r
m
i
n
an
ts
o
f
r
is
k
o
f
in
f
ec
tio
n
(
C
OVI
D
-
1
9
)
in
t
h
e
o
ld
er
p
o
p
u
latio
n
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
S
yn
d
emic
s
o
f c
o
r
o
n
a
viu
r
s
d
is
ea
s
e
a
n
d
a
g
in
g
:
th
e
in
terp
la
y
a
mo
n
g
n
u
tr
itio
n
,
th
e
immu
n
e
…
(
S
eh
a
r
I
q
b
a
l
)
891
3
.
4
.
M
icro
nu
t
rient
s
a
nd
CO
VID
-
19
Dif
f
er
en
t
s
tu
d
ies
d
is
cu
s
s
ed
p
o
ten
tial
tr
ea
tm
en
t
s
tr
ateg
ies,
in
clu
d
in
g
th
e
in
ter
r
elat
io
n
s
h
ip
of
C
OVI
D
-
19
an
d
im
m
u
n
e
-
b
u
ild
in
g
n
u
tr
itio
n
,
to
o
v
er
co
m
e
th
e
g
lo
b
al
th
r
ea
ts
of
th
is
p
an
d
em
ic
[
1
7
]
.
Vitam
in
s
,
tr
ac
e
elem
en
ts
an
d
n
u
tr
ac
eu
tic
als
in
v
ir
al
in
f
ec
tio
n
s
m
ig
h
t
p
l
ay
ess
en
tial
r
o
les
in
th
e
n
u
tr
iti
o
n
al
m
an
a
g
em
en
t
of
C
OVI
D
-
19+
eld
er
ly
p
atie
n
ts
.
Fu
r
th
er
m
o
r
e,
s
ev
er
al
s
tu
d
ies
h
av
e
d
em
o
n
s
tr
ated
th
e
a
s
s
o
ciatio
n
s
b
etwe
e
n
m
icr
o
n
u
tr
ie
n
ts
an
d
C
OVI
D
1
9
;
th
ese
as
s
h
o
wn
in
T
ab
le
1
(
s
e
e
in
Ap
p
en
d
i
x
)
.
T
h
e
s
tu
d
ies
f
o
u
n
d
lo
w
zin
c
le
v
els
[
1
6
]
,
[
3
4
]
–
[
3
8
]
an
d
s
elen
iu
m
[
3
9
]
in
C
OVI
D
in
f
ec
ted
p
atien
t
s
.
In
c
o
n
tr
ast,
th
e
tr
ea
tm
en
t
of
C
OVI
D
-
19
in
f
ec
ted
p
eo
p
le
with
v
ar
io
u
s
or
m
u
ltip
l
e
m
icr
o
n
u
tr
ien
t
s
u
p
p
lem
en
ts
a
p
p
ea
r
s
to
h
av
e
b
e
n
ef
icial
ef
f
ec
ts
an
d
to
r
ed
u
ce
th
e
r
is
k
of
ad
v
er
s
e
d
is
ea
s
e
o
u
tc
o
m
es
[
4
0
]
,
[
4
1
]
.
T
h
e
th
e
r
ap
e
u
tic
ef
f
ec
ts
of
zin
c
s
u
p
p
lem
en
ts
on
C
OVI
D
-
19
in
f
ec
tio
n
s
can
be
ex
p
lain
e
d
as
due
to
m
o
d
u
latio
n
of
an
tiv
i
r
al
an
d
an
tib
ac
ter
ial
im
m
u
n
it
y
an
d
by
r
e
d
u
cin
g
in
f
lam
m
atio
n
an
d
v
e
n
tilato
r
-
in
d
u
ce
d
lu
n
g
in
j
u
r
y
[
4
2
]
.
L
ik
ewi
s
e,
d
iar
r
h
ea
is
a
f
r
e
q
u
en
tly
o
b
s
er
v
ed
s
y
m
p
to
m
in
p
atien
ts
with
C
OVI
D
-
19
[
4
3
]
,
an
d
th
e
k
n
o
w
n
b
e
n
ef
icial
ef
f
ec
t
of
zin
c
s
u
p
p
lem
en
ts
to
tr
ea
t
a
cu
te
an
d
p
er
s
is
ten
t
d
iar
r
h
ea
m
ig
h
t
h
elp
to
r
ed
u
ce
th
e
d
is
ea
s
e
m
o
r
b
id
ities
[
4
4
]
.
A
r
ec
en
t
s
tu
d
y
f
o
u
n
d
t
h
at
s
elen
iu
m
d
ef
icien
cy
h
as
b
ee
n
ass
o
ciate
d
with
C
OVI
D
-
19
-
r
elate
d
m
o
r
tality
due
to
r
ed
u
ce
d
p
r
o
d
u
ctio
n
of
s
elen
o
p
r
o
tein
-
P
an
d
g
lu
tath
io
n
e
p
er
o
x
id
ase
ac
tiv
ity
[
4
5
]
.
T
h
e
in
itiatio
n
of
ad
e
q
u
ate
s
u
p
p
lem
en
tatio
n
in
h
ig
h
-
r
i
s
k
ar
ea
s
an
d
/o
r
s
o
o
n
af
ter
th
e
tim
e
of
s
u
s
p
ec
ted
in
f
ec
tio
n
with
C
OVI
D
-
19
m
ig
h
t
h
elp
to
r
ed
u
ce
th
e
ad
v
er
s
e
d
is
ea
s
e
co
n
s
eq
u
en
ce
s
[
4
6
]
.
In
ad
d
itio
n
,
im
m
ed
iate
in
ter
v
en
tio
n
with
v
itam
in
B3
m
ig
h
t
be
b
e
n
ef
icial
d
u
r
in
g
C
OVI
D
-
19
due
to
its
lu
n
g
-
p
r
o
tectiv
e
ef
f
ec
ts
[
1
4
]
.
3
.
5
.
Ass
o
cia
t
io
n
bet
wee
n
v
it
a
m
in
D
a
nd
CO
VID
-
19
T
h
er
e
is
a
d
ir
ec
t
lin
k
b
etwe
en
v
itam
in
D
s
u
p
p
lem
e
n
ts
an
d
s
e
v
er
e
clin
ical
o
u
tc
o
m
es
of
p
atien
ts
in
f
ec
ted
with
C
OVI
D
-
19.
Stu
d
ies
f
o
u
n
d
th
at
v
itam
in
D
d
e
f
icien
cy
c
an
ag
g
r
a
v
ate
ac
u
te
r
esp
ir
ato
r
y
d
is
tr
ess
s
y
n
d
r
o
m
e
(
AR
DS)
in
p
atien
ts
with
co
r
o
n
av
ir
u
s
SAR
S
-
C
o
V
-
2
in
f
ec
tio
n
s
[
4
7
]
.
T
h
u
s
,
a
d
o
s
e
of
1
0
,
0
0
0
I
U/d
of
v
itam
in
D3
th
r
o
u
g
h
im
p
r
o
v
in
g
2
5
(
OH)
D
co
n
ce
n
tr
atio
n
s
h
as
b
ee
n
s
u
g
g
ested
f
o
r
p
eo
p
le
at
r
is
k
of
s
ev
er
e
C
OVI
D
-
19
o
u
tco
m
es
[
4
8
]
.
T
h
e
m
o
s
t
r
ec
en
t
d
ata
co
n
f
ir
m
th
e
p
o
s
i
tiv
e
ass
o
ciatio
n
b
etwe
en
v
it
am
in
D
s
tatu
s
or
s
u
p
p
lem
en
tatio
n
a
n
d
its
ef
f
ec
t
on
C
OVI
D
-
19
as
s
h
o
wn
in
T
ab
le
2
(
s
ee
in
Ap
p
e
n
d
ix
)
.
A
s
tu
d
y
by
L
i
n
g
an
d
co
lleag
u
es
f
o
u
n
d
th
at
ch
o
leca
lcif
er
o
l
b
o
o
s
ter
th
er
a
p
y
,
r
eg
a
r
d
less
of
b
aselin
e
s
er
u
m
2
5
(
OH)
D
lev
els,
ap
p
ea
r
s
to
r
ed
u
ce
th
e
r
is
k
of
m
o
r
tality
an
d
ad
v
e
r
s
e
C
OVI
D
-
19
o
u
tc
o
m
es
in
ac
u
te
C
OVI
D
-
19
in
f
ec
ted
p
eo
p
le
[
4
9
]
.
Similar
ly
,
an
o
th
er
s
tu
d
y
s
h
o
wed
th
at
ad
m
in
is
tr
atio
n
of
a
h
ig
h
d
o
s
e
of
ca
lcif
ed
io
l
or
25
-
h
y
d
r
o
x
y
v
itam
in
D
s
ig
n
if
ican
tly
r
e
d
u
ce
d
th
e
n
ee
d
f
o
r
I
C
U
tr
ea
tm
en
t
in
C
OVI
D
in
f
ec
ted
p
atien
ts
[
5
0
]
.
Ad
d
itio
n
ally
,
s
ev
e
r
al
o
n
g
o
in
g
tr
ials
h
av
e
b
ee
n
d
esig
n
ed
to
ev
alu
ate
th
e
d
eter
m
in
ed
ef
f
ec
ts
o
f
v
itam
in
D
s
u
p
p
lem
en
tatio
n
o
n
C
OVI
D
-
1
9
d
is
ea
s
e
p
r
o
g
r
ess
io
n
a
n
d
m
o
r
tality
r
is
k
s
.
O
th
er
s
tu
d
ies
f
o
u
n
d
th
at
lo
w
v
itam
in
D
s
tatu
s
in
C
OVI
D
-
19
in
f
ec
ted
p
eo
p
le
led
to
ad
v
er
s
e
d
is
ea
s
e
o
u
tco
m
es.
Als
o
,
lo
w
v
itam
in
D
s
tatu
s
wa
s
r
ep
o
r
ted
in
C
OVI
D
p
atien
ts
lead
in
g
to
ad
v
er
s
e
h
ea
lth
o
u
tco
m
es a
n
d
h
ig
h
m
o
r
tality
r
is
k
s
[
5
1
]
–
[
5
9
]
.
3
.
6
.
Nut
rit
io
na
l
re
c
o
mm
enda
t
io
ns
f
o
r
o
lder
po
pu
la
t
io
n
a
nd
CO
VID
-
19
-
infe
ct
ed
pa
t
ient
s
Giv
en
th
e
i
n
ter
r
elatio
n
s
h
ip
of
m
aln
u
tr
itio
n
an
d
im
m
u
n
e
r
esp
o
n
s
e,
r
esto
r
atio
n
of
d
ef
icien
t
m
icr
o
n
u
tr
ie
n
ts
is
r
ec
o
m
m
e
n
d
ed
to
e
n
h
an
ce
im
m
u
n
ity
,
th
er
eb
y
in
c
r
ea
s
in
g
r
esis
tan
ce
to
i
n
f
ec
tio
n
a
n
d
f
aster
r
ec
o
v
er
y
in
d
if
f
e
r
en
t
life
s
tag
es,
in
clu
d
in
g
ag
in
g
.
Fo
r
in
s
ta
n
ce
,
v
itam
in
D
s
u
p
p
lem
e
n
tatio
n
h
as
s
h
o
wn
s
tr
o
n
g
b
en
ef
icial
ef
f
ec
ts
on
ce
ll
-
m
ed
iated
im
m
u
n
ity
in
th
e
o
ld
er
p
o
p
u
latio
n
.
A
d
aily
d
o
s
e
of
m
u
ltiv
itam
in
or
tr
ac
e
m
in
er
al
s
u
p
p
lem
e
n
ts
s
u
ch
as
elem
en
tal
zin
c
(
1
2
0
m
g
/
d
ay
)
,
s
elen
iu
m
(
1
0
0
m
g
/d
ay
)
,
an
d
a
d
a
ily
d
o
s
e
of
v
itam
in
E
s
u
p
p
lem
en
ts
(
2
0
0
m
g
/d
a
y
)
ar
e
r
ec
o
m
m
en
d
e
d
to
r
ev
er
s
e
a
g
e
-
r
elate
d
im
m
u
n
e
d
y
s
f
u
n
ctio
n
[
6
0
]
.
Similar
ly
,
a
v
itam
in
C
in
tak
e
of
1
0
0
-
2
0
0
m
g
/d
ay
is
s
u
g
g
ested
to
o
p
tim
ize
ce
ll
an
d
tis
s
u
e
lev
els
an
d
to
am
elio
r
ate
th
e
s
ev
er
ity
of
co
m
m
o
n
c
o
ld
in
f
ec
tio
n
s
[
2
7
]
.
T
h
e
W
o
r
ld
Hea
lth
Or
g
an
izat
io
n
(
W
HO)
r
ec
o
m
m
en
d
ed
r
e
g
u
lar
n
u
t
r
itio
n
al
ass
ess
m
en
ts
,
ad
eq
u
ate
p
r
o
tein
in
tak
e,
d
ietar
y
co
u
n
s
elin
g
,
an
d
o
r
al
s
u
p
p
lem
en
ts
,
in
cl
u
d
in
g
ad
e
q
u
ate
am
o
u
n
ts
of
v
it
am
in
s
an
d
m
in
er
als,
to
m
ee
t
th
e
o
ld
er
p
o
p
u
latio
n
’
s
n
u
tr
itio
n
al
r
e
q
u
ir
em
e
n
ts
.
W
HO
an
d
th
e
f
o
o
d
an
d
ag
r
ic
u
ltu
r
e
o
r
g
an
izatio
n
(
FAO)
p
r
o
v
id
e
d
th
e
r
ec
o
m
m
en
d
e
d
n
u
tr
ien
t
in
tak
es
(
R
NI
s
)
f
o
r
v
itam
in
s
an
d
m
in
e
r
als
in
th
e
o
ld
er
p
o
p
u
latio
n
a
s
h
o
wn
in
T
ab
le
3
.
A
d
d
itio
n
ally
,
ca
r
b
o
h
y
d
r
ate,
p
r
o
tein
,
an
d
en
er
g
y
r
eq
u
ir
em
e
n
ts
ar
e
r
ec
o
m
m
en
d
e
d
to
p
r
ev
e
n
t
weig
h
t
lo
s
s
,
r
ed
u
ce
th
e
r
is
k
of
C
OVI
D
-
19
co
m
p
licatio
n
s
,
an
d
p
r
o
m
o
te
d
is
ea
s
e
r
ec
o
v
er
y
.
W
HO
an
d
FAO
em
p
h
asize
a
well
-
b
alan
ce
d
d
iet
in
clu
d
in
g
f
r
esh
an
d
u
n
p
r
o
ce
s
s
ed
f
o
o
d
,
p
le
n
ty
of
wate
r
to
k
ee
p
h
y
d
r
ated
,
a
m
o
d
er
ate
n
u
m
b
e
r
of
o
ils
an
d
f
at,
an
d
less
s
alt
an
d
s
u
g
ar
in
tak
e
to
b
o
o
s
t
im
m
u
n
e
s
y
s
tem
s
an
d
to
lo
wer
th
e
r
is
k
s
of
ch
r
o
n
ic
illn
ess
es
an
d
in
f
ec
tio
u
s
d
is
ea
s
es.
T
h
e
E
u
r
o
p
e
a
n
S
o
c
i
e
t
y
f
o
r
C
li
n
i
c
al
Nu
t
r
i
t
i
o
n
a
n
d
M
e
t
a
b
o
li
s
m
(
E
S
PE
N
)
h
a
s
p
r
o
v
i
d
e
d
a
c
o
n
c
i
s
e
g
u
i
d
e
f
o
r
t
h
e
n
u
t
r
it
i
o
n
a
l
m
a
n
a
g
e
m
e
n
t
of
C
O
V
I
D
-
19
i
n
f
e
c
t
e
d
p
e
o
p
l
e
,
w
h
i
c
h
i
n
c
l
u
d
e
s
m
a
l
n
u
t
r
i
t
i
o
n
a
s
s
e
s
s
m
e
n
t
,
o
p
t
i
m
iz
a
t
i
o
n
of
n
u
t
r
i
t
i
o
n
a
l
s
t
at
u
s
,
m
i
c
r
o
n
u
t
r
i
e
n
t
s
u
p
p
l
e
m
e
n
t
s
,
r
e
g
u
l
a
r
p
h
y
s
i
c
al
ac
t
i
v
i
t
y
,
o
r
a
l
n
u
t
r
i
ti
o
n
s
u
p
p
l
e
m
e
n
t
s
-
if
r
e
q
u
i
r
e
d
to
m
e
e
t
p
a
ti
e
n
t
s
’
n
e
e
d
s
,
an
d
e
n
t
er
a
l
n
u
t
r
i
ti
o
n
f
o
r
t
h
e
p
a
ti
e
n
ts
w
h
o
s
e
n
u
t
r
i
t
i
o
n
a
l
r
e
q
u
i
r
e
m
e
n
t
s
c
a
n
n
o
t
be
m
et
o
r
a
l
l
y
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
2
,
J
u
n
e
20
25
:
8
8
6
-
8
9
7
892
T
ab
le
3
.
R
ec
o
m
m
e
n
d
ed
N
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tr
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R
NI
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R
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M
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l
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>
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r
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r
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d
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g
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r
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r
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r
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g
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l
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g
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4
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g
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S
e
l
e
n
i
u
m
3
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g
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g
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d
a
y
M
a
g
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e
si
u
m
2
2
4
m
g
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d
a
y
1
9
0
m
g
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d
a
y
Zi
n
c
(
M
o
d
e
r
a
t
e
b
i
o
a
v
a
i
l
a
b
i
l
i
t
y
)
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m
g
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a
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9
m
g
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a
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A
d
o
p
t
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d
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r
o
m WH
O
a
n
d
F
A
O
g
u
i
d
e
l
i
n
e
s
[
6
1
]
ᵃ
Est
i
ma
t
e
d
m
e
a
n
r
e
q
u
i
r
e
m
e
n
t
:
ᵇ
Th
e
o
r
e
t
i
c
a
l
c
a
l
c
i
u
m
a
l
l
o
w
a
n
c
e
b
a
s
e
d
o
n
a
n
a
n
i
mal
p
r
o
t
e
i
n
i
n
t
a
k
e
o
f
2
0
–
4
0
g
:
ᶜ
n
i
a
c
i
n
e
q
u
i
v
a
l
e
n
t
s.
4.
CO
NCLU
SI
O
N
T
he
o
ld
er
p
o
p
u
latio
n
with
t
h
e
u
n
d
er
ly
i
n
g
co
n
d
itio
n
of
m
aln
u
tr
itio
n
ap
p
ea
r
ed
to
be
at
a
h
ig
h
er
r
is
k
of
v
ir
al
in
f
ec
tio
n
d
u
e
to
an
i
n
ter
p
lay
am
o
n
g
v
a
r
io
u
s
b
io
s
o
cia
l
ev
en
ts
,
in
clu
d
in
g
m
aln
u
tr
iti
o
n
an
d
an
ag
e
th
at
co
m
p
r
o
m
is
es
im
m
u
n
e
r
esp
o
n
s
es
to
m
ak
e
p
ar
ticu
lar
p
o
p
u
l
atio
n
s
v
u
ln
er
ab
le
to
be
in
f
ec
t
ed
an
d
af
f
ec
ted
by
C
OVI
D
-
19.
Mo
s
t
of
th
e
s
tu
d
i
es
in
clu
d
ed
in
t
h
is
r
ev
iew
co
n
f
ir
m
ed
a
p
o
s
itiv
e
ass
o
ciatio
n
b
etwe
en
v
itam
in
D
s
tatu
s
or
s
u
p
p
lem
en
tatio
n
an
d
its
ef
f
ec
t
on
C
OVI
D
-
19,
wh
ile
o
th
er
s
tu
d
ies
r
e
p
o
r
ted
a
lo
w
zin
c
an
d
s
elen
iu
m
s
tatu
s
in
C
O
VI
D
-
19
-
in
f
ec
ted
p
eo
p
le.
Fu
r
th
e
r
s
tu
d
ies
f
o
cu
s
in
g
on
a
d
eq
u
ate
n
u
tr
itio
n
m
a
n
ag
em
en
t
of
eld
e
r
ly
p
atien
ts
to
r
ed
u
ce
a
d
v
er
s
e
d
i
s
ea
s
e
o
u
tco
m
es
ar
e
n
ee
d
e
d
.
Fu
r
th
er
m
o
r
e
,
im
m
ed
iate
m
ea
s
u
r
es,
in
clu
d
in
g
t
h
e
p
lan
n
in
g
an
d
im
p
lem
e
n
tatio
n
of
n
u
tr
itio
n
al
s
tr
ateg
ies
to
r
e
d
u
ce
ag
e
-
r
elate
d
m
aln
u
tr
itio
n
,
will
h
elp
to
m
in
im
ize
th
e
r
is
k
of
C
OVI
D
-
19
-
m
ed
iat
ed
ad
v
er
s
e
h
ea
lth
ef
f
ec
ts
,
in
f
u
tu
r
e
.
Hen
ce
,
s
im
ilar
cr
itical
s
itu
atio
n
will
r
eq
u
ir
e
a
co
m
p
r
eh
en
s
iv
e
a
p
p
r
o
ac
h
f
o
r
co
n
s
id
er
in
g
all
r
elev
an
t
asp
ec
t
s
to
ad
d
r
ess
th
e
g
lo
b
al
h
ea
lth
c
h
allen
g
es
im
p
o
s
ed
by
an
y
p
an
d
em
ic,
esp
ec
ially
f
o
r
th
e
eld
e
r
ly
.
AP
P
E
NDI
X
T
ab
le
1
.
C
h
ar
ac
ter
is
tics
o
f
s
tu
d
ies s
h
o
win
g
th
e
ass
o
ciatio
n
b
etwe
en
m
icr
o
n
u
t
r
ien
ts
an
d
C
OVI
D
-
19
M
icr
onut
r
ient
Ref
.
S
tudy
de
s
ign
S
tudy
a
im
s
Numbe
r
of
pa
r
ti
c
ipants
I
nter
ve
n
ti
on
R
e
s
ult
s
C
onc
lus
ion
Z
inc
[
34]
A
c
r
os
s
s
e
c
ti
ona
l
s
tudy
T
he
s
tudy
a
im
e
d
to
e
va
luate
z
inc
s
tatus
in
C
OV
I
D
pa
ti
e
nts
a
s
c
ompar
e
d
to
the
c
ontr
ol
gr
oup
T
otal
(
n=
171)
N/A
Z
inc
c
onc
e
ntr
a
ti
ons
in
C
OV
I
D
pa
ti
e
nts
(
mea
n±SD
)
Z
n=
717.
4±246.
2
μg/
L
Z
inc
c
onc
e
ntr
a
ti
ons
in
he
a
lt
hy
s
ubjec
ts
(
mea
n±
S
D)
Z
n=
975.
7±294.
0
μg/
L
Z
inc
c
onc
e
ntr
a
ti
ons
in
C
OV
I
D
pa
ti
e
nts
we
r
e
low
c
ompar
e
d
to
he
a
lt
hy
s
ubjec
ts
.
Z
in
c
a
nd
a
s
c
o
r
bi
c
a
c
i
d
[
3
5]
A
r
a
n
do
mi
z
e
d
c
l
i
ni
c
a
l
t
r
i
a
l
T
h
e
s
t
u
d
y
a
i
m
e
d
t
o
e
x
a
m
in
e
w
h
e
t
h
e
r
h
i
g
h
-
do
s
e
z
i
nc
a
n
d/
or
h
i
g
h
-
do
s
e
a
s
c
o
r
bi
c
a
c
i
d
r
e
d
u
c
e
th
e
s
e
v
e
r
it
y
or
du
r
a
t
i
on
o
f
di
s
e
a
s
e
s
y
mp
t
om
s
c
o
m
p
a
r
e
d
w
i
th
u
s
u
a
l
c
a
r
e
a
m
o
ng
a
m
b
ul
a
t
or
y
p
a
t
i
e
nt
s
w
i
t
h
S
A
R
S
-
C
oV
-
2
i
n
f
e
c
t
io
n
T
o
t
a
l
(
n
=
2
14
)
A
l
l
o
c
a
t
e
d
t
o
a
nd
r
e
c
e
i
ve
d
s
t
a
n
d
a
r
d
o
f
c
a
r
e
(
n
=
50
)
A
l
l
o
c
a
t
e
d
t
o
a
nd
r
e
c
e
i
ve
d
a
s
c
o
r
bi
c
a
c
id
o
n
l
y
(
n
=
48
)
A
l
l
o
c
a
t
e
d
t
o
a
nd
r
e
c
e
i
ve
d
z
i
nc
o
n
l
y
(
n
=
58
)
A
l
l
o
c
a
t
e
d
t
o
a
nd
r
e
c
e
i
ve
d
a
s
c
o
r
bi
c
a
c
id
a
n
d
z
i
n
c
(
n
=
58
)
P
a
t
i
e
n
t
s
w
e
r
e
r
a
n
do
mi
z
e
d
i
n
a
1
:
1
:1
:
1
a
l
lo
c
a
ti
o
n
r
a
t
io
t
o
r
e
c
e
i
v
e
e
i
t
h
e
r
1
0
d
a
y
s
o
f
i
)
z
i
n
c
gl
u
c
on
a
t
e
(
5
0
m
g
)
,
i
i
)
a
s
c
or
bi
c
a
c
i
d
(
8
,
0
00
m
g)
,
i
i
i)
b
o
th
z
i
n
c
a
n
d
a
s
c
o
r
bi
c
a
c
i
d
,
i
v
)
s
t
a
n
d
a
r
d
o
f
c
a
r
e
.
T
i
m
e
t
o
50
%
r
e
d
u
c
t
io
n
i
n
s
y
mp
t
om
s
(
m
e
a
n
±
S
D
)
U
s
u
a
l
c
a
r
e
w
i
th
ou
t
s
u
p
p
l
e
m
e
nt
a
t
io
n
=
(
6
.
7
±4
.
4
d
a
y
s
)
A
s
c
o
r
bi
c
a
c
i
d
gr
ou
p
m
e
a
n
=
(
5
.
5
±
3
.
7
d
a
y
s
)
Z
in
c
g
l
u
c
o
n
a
t
e
gr
o
up
=
(
5.
9
±4
.
9
d
a
y
s
)
R
e
c
e
i
v
e
d
b
o
th
z
i
n
c
a
n
d
a
s
c
o
r
bi
c
a
c
i
d
=
(
5
.
5
±3
.
4
d
a
y
s
)
T
h
e
s
t
u
d
y
f
o
un
d
t
h
a
t
tr
e
a
t
m
e
nt
w
it
h
h
i
g
h
-
do
s
e
z
i
n
c
g
l
u
c
on
a
t
e
,
a
s
c
o
r
bi
c
a
c
i
d
,
o
r
a
c
o
m
bi
n
a
ti
o
n
of
t
h
e
2
s
u
p
pl
e
m
e
n
t
s
di
d
n
o
t
s
i
g
ni
f
i
c
a
n
tl
y
d
e
c
r
e
a
s
e
t
h
e
d
u
r
a
t
i
on
o
f
s
y
m
p
to
m
s
c
o
m
p
a
r
e
d
w
it
h
s
t
a
n
d
a
r
d
of
c
a
r
e
.
Z
inc
[
36]
An
obs
e
r
va
t
ional
c
ohor
t
s
tudy
T
h
e
s
t
u
d
y
i
n
v
e
s
ti
g
a
te
d
th
e
a
s
s
o
c
i
a
t
io
n
b
e
t
w
e
e
n
s
e
r
u
m
z
i
nc
c
o
n
t
e
nt
a
n
d
C
OV
I
D
-
19
d
i
s
e
a
s
e
p
r
o
gr
e
s
s
i
o
n
T
otal
(
n=
249)
N/A
S
e
r
um
z
inc
c
ontent
a
t
a
dmi
s
s
ion
(
<
50
µ
g
/dL
)
a
nd
r
is
k
of
in
-
hos
pit
a
l
de
a
th
OR
3.
2
(
95%
C
I
,
1.
01
-
10.
12)
T
he
s
tudy
f
indi
n
gs
s
howe
d
that
low
s
e
r
um
z
inc
leve
ls
a
r
e
a
s
s
oc
iate
d
with
a
dve
r
s
e
C
OV
I
D
-
19
outcome
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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t J Pu
b
lic
Hea
lth
Sci
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SS
N:
2252
-
8
8
0
6
S
yn
d
emic
s
o
f c
o
r
o
n
a
viu
r
s
d
is
ea
s
e
a
n
d
a
g
in
g
:
th
e
in
terp
la
y
a
mo
n
g
n
u
tr
itio
n
,
th
e
immu
n
e
…
(
S
eh
a
r
I
q
b
a
l
)
893
T
ab
le
1
.
C
h
ar
ac
ter
is
tics
o
f
s
tu
d
ies s
h
o
win
g
th
e
ass
o
ciatio
n
b
etwe
en
m
icr
o
n
u
t
r
ien
ts
an
d
C
OVI
D
-
19
(
C
o
n
tin
u
e
d
)
M
icr
onut
r
ient
Ref
.
S
tudy
de
s
ign
S
tudy
a
im
s
Numbe
r
of
pa
r
ti
c
ipants
I
nter
ve
n
ti
on
R
e
s
ult
s
C
onc
lus
ion
Z
inc
[
37]
A
pr
os
pe
c
t
ive
s
tudy
T
he
s
tudy
a
im
e
d
to
e
va
luate
the
r
e
lations
hip
be
twe
e
n
s
e
r
um
z
inc
in
C
OV
I
D
-
19
pa
ti
e
nts
a
nd
it
s
c
or
r
e
latio
n
with
dis
e
a
s
e
s
e
ve
r
it
y
C
OV
I
D
-
19
pa
ti
e
nts
(
n=
47)
He
a
lt
hy
c
ontr
ols
(
n=
45
)
N/A
Z
in
c
s
t
a
tu
s
i
n
C
O
VI
D
p
a
t
i
e
n
t
s
m
e
d
ia
n
(
i
nt
e
r
q
u
a
r
t
il
e
r
a
n
g
e
)
7
4
.
5
(
53
.
4
–
94
.
6
)
μg
/
dl
Z
in
c
s
t
a
tu
s
i
n
c
o
nt
r
ol
g
r
ou
p
m
e
d
ia
n
(
i
nt
e
r
q
u
a
r
t
il
e
r
a
n
g
e
)
1
0
5
(
9
5
.
65
–
12
0
.
9
0)
μ
g
/
dl
T
he
s
tudy
r
e
por
ted
tha
t
a
s
igni
f
ica
nt
number
o
f
C
OV
I
D
-
19
pa
ti
e
nts
we
r
e
z
inc
de
f
icie
nt
a
nd
z
inc
de
f
icie
nc
y
wa
s
a
s
s
oc
iate
d
with
a
pr
olonge
d
hos
pit
a
l
s
tay
a
nd
incr
e
a
s
e
d
mor
tali
ty
Z
inc
[
38]
A
r
e
tr
os
pe
c
ti
ve
obs
e
r
va
t
ional
s
tudy
T
his
c
ompar
a
ti
ve
s
tudy
e
xa
mi
ne
d
the
outcome
s
a
mong
hos
pit
a
li
z
e
d
C
OV
I
D
-
19
pa
ti
e
nts
who
r
e
c
e
ived
hydr
oxyc
hlor
o
qui
ne
a
nd
a
z
it
hr
om
yc
in
plus
z
inc
s
ulphate
ve
r
s
us
hydr
oxyc
hlor
o
qui
ne
a
nd
a
z
it
hr
om
yc
in
a
lone
P
a
ti
e
nts
takin
g
z
inc
s
ulphate
in
a
ddit
ion
t
o
hydr
oxyc
hlor
o
q
uine
a
nd
a
z
it
hr
om
yc
in
(
n=
411)
P
a
ti
e
nts
takin
g
hydr
oxyc
hlor
o
q
ui
ne
a
nd
a
z
it
hr
om
yc
in
a
lone
(
n=
521)
T
r
e
a
tm
e
nt
gr
oup:
pa
ti
e
nts
we
r
e
taking
z
inc
s
ulphate
(
220
mg
c
a
ps
ule
c
ontaining
50
mg
e
leme
ntal
z
inc
twice
da
il
y
f
or
5
da
ys
)
a
long
with
hydr
oxyc
hlor
o
qui
ne
(
400
mg
load
f
oll
owe
d
by
200
mg
twice
da
il
y
f
or
5
da
ys
)
a
nd
a
z
it
hr
om
yc
in
(
500
mg
onc
e
da
il
y)
C
ontr
ol
g
r
oup:
pa
ti
e
nts
w
e
r
e
taking
hydr
oxyc
hlor
o
qui
ne
(
400
mg
load
f
oll
owe
d
by
200
mg
twice
da
il
y
f
or
f
ive
da
ys
)
a
nd
a
z
it
hr
om
yc
in
(
500
mg
onc
e
da
il
y)
a
lone
Z
inc
s
ulphate
s
uppleme
ntatio
n
a
nd
f
r
e
que
nc
y
to
dis
c
ha
r
ge
f
r
o
m
hos
pit
a
l
OR
1.
53
(
95%
C
I
,
1.
12
–
2.
09)
Z
inc
s
ulphate
s
uppleme
n
tatio
n
a
nd
r
e
duc
ti
on
in
mor
tali
ty
or
tr
a
ns
f
e
r
to
hos
pice
a
mong
pa
ti
e
nts
who
did
not
r
e
quir
e
I
C
U
leve
l
c
a
r
e
OR
0.
449
(
95%
C
I
,
0.
271
–
0.
744)
T
he
s
tudy
f
indi
n
gs
s
howe
d
that
z
inc
s
ulphate
a
ppe
a
r
s
to
play
a
pos
it
ive
r
ole
in
ther
a
pe
uti
c
mana
ge
ment
f
or
C
OV
I
D
-
19
S
e
lenium
[
39]
A
c
r
os
s
-
s
e
c
ti
ona
l
s
tudy
T
he
s
tudy
a
im
e
d
to
a
na
lyze
the
blood
s
e
r
um
s
e
lenium
leve
ls
in
C
OV
I
D
-
19
pa
ti
e
nts
c
ompar
e
d
to
he
a
lt
hy
c
ontr
ols
to
unde
r
s
tand
the
c
or
r
e
latio
n
be
twe
e
n
s
e
lenium
leve
ls
a
nd
C
OV
I
D
-
19
vir
a
l
in
f
e
c
ti
on
T
otal
(
n=
60)
C
OV
I
D
pa
t
ien
t
(
n=
30)
He
a
lt
hy
c
ontr
ols
(
n=
30
)
N/A
S
e
lenium
le
ve
ls
of
C
OV
I
D
pa
ti
e
nts
(
mea
n±SD
)
S
e
=
69.
2
+
8.
7
ng/m
L
S
e
lenium
le
ve
ls
of
c
ontr
ol
gr
oup
(
mea
n±SD
)
S
e
=
79.
1
+
10.
9
ng/m
L
T
he
s
tudy
f
ound
a
low
s
e
lenium
s
tatus
in
pa
ti
e
nts
with
C
OV
I
D
-
19
a
s
c
ompar
e
d
to
he
a
lt
hy
c
ontr
o
ls
Vitamin
C
[
40]
A
r
a
ndomi
z
e
d
c
ontr
oll
e
d
tr
ial
T
h
e
s
t
u
d
y
a
i
m
e
d
t
o
a
s
s
e
s
s
t
h
e
e
f
f
i
c
a
c
y
o
f
a
dd
i
ng
h
ig
h
-
d
o
s
e
i
nt
r
a
v
e
n
ou
s
v
i
t
a
m
i
n
C
(
H
DI
V
C
)
t
o
th
e
r
e
g
im
e
n
s
f
or
p
a
t
i
e
n
t
s
w
i
t
h
s
e
v
e
r
e
C
O
V
I
D
-
19
d
i
s
e
a
s
e
T
otal
(
n=
60)
S
uppleme
n
tatio
n
gr
oup
(
n=
30
)
C
ontr
ol
gr
ou
p
(
n=
30)
T
he
tr
e
a
tm
e
nt
gr
oup
we
r
e
r
e
c
e
ivi
ng
1.
5
g
vit
a
mi
n
C
(
I
V)
e
ve
r
y
6
h
f
or
5
da
ys
C
ontr
ol
g
r
oup
include
d
pa
ti
e
n
ts
who
did
not
r
e
c
e
ive
vit
a
mi
n
C
Hos
pit
a
l
length
of
s
tay
(
da
ys
)
,
media
n
(
I
QR
)
T
r
e
a
tm
e
nt
gr
oup=
8.
50
(
7.
0
–
12.
0)
da
ys
C
ontr
ol
g
r
oup
=
6.
50
(
4.
0
–
12.
0)
da
ys
T
he
s
tudy
did
not
f
ind
s
igni
f
ica
ntl
y
be
tt
e
r
outcome
s
in
the
gr
oup
who
we
r
e
tr
e
a
ted
with
HD
I
VC
in
a
ddit
ion
to
the
main
tr
e
a
tm
e
nt
r
e
gim
e
n
a
t
dis
c
ha
r
ge
Vitamin
D,
magne
s
ium
,
a
nd
vit
a
mi
n
B
12
[
41]
A
c
ohor
t
obs
e
r
va
t
ional
s
tudy
T
his
s
tudy
a
im
e
d
to
de
ter
mi
ne
c
li
nica
l
outcome
s
of
older
pa
ti
e
nts
with
c
or
ona
vi
r
us
(
C
OV
I
D
-
19)
w
ho
r
e
c
e
ived
a
c
ombi
na
ti
o
n
of
vit
a
mi
n
D,
magne
s
ium
,
a
nd
vit
a
mi
n
B
12
(
DM
B
)
c
ompa
r
e
d
with
thos
e
who
did
not
r
e
c
e
ive
the
s
uppleme
nts
T
otal
hos
pit
a
li
z
e
d
pa
ti
e
nts
>
50
y
of
a
ge
(
n=
43)
R
e
c
e
ived
s
uppleme
nts
(
n=
17)
Not
r
e
c
e
ived
s
uppleme
nts
(
n=
26)
T
he
s
uppleme
ntatio
n
(
DM
B
)
gr
oup
we
r
e
tr
e
a
ted
with
a
c
ombi
na
ti
o
n
of
1000
I
U/d
or
a
l
vit
a
mi
n
D3,
150
mg/
d
or
a
l
magne
s
ium
,
a
nd
500
mcg/d
or
a
l
vit
a
mi
n
B
12
DM
B
e
xpos
u
r
e
a
nd
oxyge
n
ther
a
py
OR
0.
13
(
95%
C
I
,
0.
03
–
0.
59)
DM
B
e
xpos
ur
e
a
nd
int
e
ns
ive
c
a
r
e
s
uppor
t
OR
0.
20
(
95%
C
I
,
0.
04
–
0.
93)
A
vit
a
mi
n
D/magne
s
ium
/vi
t
a
mi
n
B
12
c
ombi
na
ti
o
n
in
older
C
OV
I
D
-
19
pa
ti
e
nts
wa
s
a
s
s
oc
iate
d
with
a
s
igni
f
ica
nt
r
e
duc
ti
on
in
int
e
ns
ive
c
a
r
e
s
uppor
t,
r
e
qui
r
ing
oxyge
n
s
uppor
t,
or
both
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
14
,
No
.
2
,
J
u
n
e
20
25
:
8
8
6
-
8
9
7
894
T
ab
le
2
.
C
h
ar
ac
ter
is
tics
o
f
th
e
s
tu
d
ies s
h
o
win
g
an
ass
o
ciatio
n
b
etwe
en
Vitam
in
D
an
d
C
OVI
D
-
19
Ref
.
S
tudy
de
s
ign
S
tudy
a
im
Numbe
r
of
pa
r
ti
c
ipants
I
nter
ve
n
ti
on
R
e
s
ult
s
C
onc
lus
ion
[
49]
A
c
r
os
s
-
s
e
c
ti
ona
l
mul
ti
c
e
nte
r
obs
e
r
va
ti
ona
l
s
tudy
T
he
s
tudy
a
im
e
d
to
e
va
luate
the
a
s
s
oc
iation
be
twe
e
n
s
e
r
um
25
-
hydr
oxy
vit
a
m
in
D
[
25(
OH
)
D]
leve
ls
,
vit
a
mi
n
D
s
tatus
,
or
c
holec
a
lcif
e
r
o
l
ther
a
py,
a
nd
it
s
e
f
f
e
c
t
on
pr
e
dicto
r
s
of
C
OV
I
D
-
19
m
or
tal
it
y
T
otal
(
n=
986)
T
r
e
a
tm
e
nt
gr
oup
(
n=
151)
T
r
e
a
tm
e
nt
with
c
holec
a
lcif
e
r
o
l
us
ing
high
-
dos
e
boos
ter
ther
a
py
(
a
ppr
ox
im
a
tely
≥280,
000
I
U
up
to
7
we
e
ks
)
B
oos
ter
c
holec
a
lcif
e
r
ol
the
r
a
py
a
nd
r
e
duc
e
r
is
k
of
C
OV
I
D
-
19
mor
talit
y
OR
0.
13
(
95%
C
I
,
0.
05
–
0.
35)
T
h
e
s
t
u
d
y
f
o
u
nd
t
h
a
t
c
h
o
l
e
c
a
l
c
if
e
r
o
l
b
oo
s
t
e
r
t
h
e
r
a
p
y
,
r
e
g
a
r
dl
e
s
s
o
f
b
a
s
e
l
i
n
e
s
e
r
um
2
5
(
O
H
)
D
l
e
v
e
l
s
,
a
p
p
e
a
r
s
t
o
r
e
d
u
c
e
th
e
r
i
s
k
of
mo
r
t
a
l
it
y
in
a
c
u
t
e
C
OV
I
D
-
19
p
a
t
i
e
n
t
s
[
51]
A
pr
os
pe
c
ti
ve
mul
ti
c
e
nte
r
obs
e
r
va
ti
ona
l
s
tudy
T
he
s
tudy
inves
ti
ga
ted
the
a
s
s
oc
iation
of
vit
a
mi
n
D
s
tatus
a
nd
a
dve
r
s
e
C
OV
I
D
outcome
s
T
otal
(
n=
109)
N/A
Vitamin
D
s
tatus
in
C
OV
I
D
pa
ti
e
nts
dur
ing
hos
pi
taliza
ti
on
Vitamin
D
(
<
30
nmo
l/
L
)
=
38%
Vitamin
D
(
30
–
50
nm
ol/
L
)
=
27
%
Vitamin
D
(
>
50
nmo
l/
L
)
=
35
%
9.
2%
of
pa
ti
e
nts
r
e
c
e
ived
vit
a
mi
n
D
s
uppleme
ntatio
n
dur
ing
hos
pit
a
li
z
a
ti
o
n,
but
the
ini
ti
a
ti
on
of
s
uppleme
ntation
wa
s
not
r
e
late
d
to
dis
e
a
s
e
s
e
ve
r
it
y.
How
e
ve
r
,
D
-
Dime
r
leve
ls
we
r
e
moder
a
tely
a
s
s
oc
iate
d
with
25(
OH
)
D
leve
ls
a
t
dis
e
a
s
e
ons
e
t
(
r
=
0.
437,
p<
0.
05)
Vitami
n
D
de
f
icie
nc
y
wa
s
f
r
e
que
nt
a
mong
C
OV
I
D
-
19
pa
ti
e
nts
dur
ing
hos
pit
a
l
iza
ti
on,
but
the
s
tudy
did
no
t
f
ind
a
ny
a
s
s
oc
iation
o
f
vit
a
mi
n
D
s
tatus
with
a
dve
r
s
e
dis
e
a
s
e
outcome
s
[
50]
A
r
a
ndomi
z
e
d
double
-
mas
ke
d
c
li
nica
l
tr
ial
T
he
s
tudy
e
va
luate
d
the
e
f
f
e
c
t
of
c
a
lcif
e
diol
tr
e
a
t
ment
on
I
C
U
a
dmi
s
s
ion
a
nd
mor
tali
ty
r
a
te
a
mong
S
pa
nis
h
pa
ti
e
nts
hos
pit
a
li
z
e
d
f
or
C
OV
I
D
-
19
T
otal
(
n=
76)
T
r
e
a
ted
with
c
holec
a
lcif
e
r
o
l
(
n=
50)
No
tr
e
a
tm
e
nt
(
n=
26)
T
r
e
a
t
m
e
n
t
g
r
o
u
p
p
a
t
i
e
n
t
s
w
e
r
e
g
i
v
e
n
o
r
a
l
c
a
l
c
i
f
e
d
i
o
l
(
0
.
5
3
2
m
g
)
a
t
t
h
e
d
a
y
o
f
ad
m
i
s
s
i
o
n
,
t
h
e
n
o
r
a
l
c
a
l
c
i
f
e
d
i
o
l
(
0
.
2
6
6
m
g
)
o
n
d
a
y
3
a
n
d
7
,
a
n
d
t
h
e
n
w
e
e
k
l
y
u
n
t
i
l
d
i
s
c
h
a
r
g
e
o
r
I
C
U
a
d
m
i
s
s
i
o
n
R
is
k
E
s
ti
mate
Odds
R
a
ti
o
f
or
I
C
U
a
dmi
s
s
ion
in
pa
ti
e
nts
with
c
a
lci
f
e
diol
tr
e
a
tm
e
nt
vs
without
c
a
lcif
e
diol
tr
e
a
tm
e
nt
OR
0.
03
(
95%
C
I
,
0.
003
–
0.
25)
T
he
s
tudy
f
ound
t
ha
t
a
dmi
nis
ter
i
ng
a
high
dos
e
of
c
a
lcif
e
diol
o
r
25
-
hyd
r
oxyv
it
a
mi
n
D,
s
igni
f
ica
ntl
y
r
e
duc
e
d
the
ne
e
d
f
or
I
C
U
tr
e
a
tm
e
nt
in
C
OV
I
D
-
19
pa
ti
e
nts
.
[
52]
A
r
e
tr
os
pe
c
ti
ve
obs
e
r
va
ti
ona
l
s
tudy
T
he
s
tudy
a
im
e
d
to
e
va
luate
the
r
o
le
of
s
e
r
um
25(
OH
)
vit
a
mi
n
D
s
tatus
on
C
OV
I
D
dis
e
a
s
e
s
e
ve
r
it
y
a
nd
r
e
late
d
mor
tali
ty
T
otal
(
n
=
149)
N/A
Vitamin
D
de
f
icie
nc
y
a
nd
r
is
k
o
f
in
-
hos
pit
a
l
mor
ta
li
ty
OR
0.
92
(
95%
C
I
,
0.
87
–
0.
98)
T
he
s
tudy
f
ound
t
ha
t
low
s
e
r
um
25(
OH
)
vit
a
mi
n
D
wa
s
a
s
s
oc
iate
d
with
mor
tali
ty
in
C
OV
I
D
-
19
pa
ti
e
nts
[
53]
A
r
e
tr
os
pe
c
ti
ve
obs
e
r
va
ti
ona
l
tr
ial
T
he
s
tudy
de
ter
mi
ne
d
the
a
s
s
oc
iation
be
twe
e
n
s
e
r
um
25
-
hydr
oxy
vit
a
m
in
D
25(
OH
)
D
leve
l
on
a
dmi
s
s
ion
a
nd
r
a
diol
og
ic
s
tage
a
nd
a
dve
r
s
e
C
OV
I
D
-
19
outcome
s
T
otal
(
n
=
186)
N/A
Vitamin
D
de
f
icie
nc
y
(
<
20
ng/m
L
)
a
nd
r
is
k
of
mor
ta
li
ty
OR
3.
87
(
95%
C
I
,
1.
30
–
11.
55)
T
he
s
tudy
f
ound
t
ha
t
low
25(
OH
)
D
leve
ls
in
C
OV
I
D
pa
ti
e
nts
on
hos
pit
a
l
a
dmi
s
s
ion
a
r
e
a
s
s
oc
iate
d
with
C
OV
I
D
-
19
d
is
e
a
s
e
s
tage
a
nd
mor
talit
y
[
54]
A
pr
os
pe
c
ti
ve
obs
e
r
va
ti
ona
l
s
tudy
T
he
s
tudy
a
im
e
d
to
inves
ti
ga
te
that
the
a
s
s
oc
iation
be
twe
e
n
25
-
hyd
r
oxyv
it
a
mi
n
D
25(
OH
)
D
leve
ls
a
nd
a
dve
r
s
e
outcome
s
of
C
OV
I
D
-
19
pne
umoni
a
T
otal
(
n=
30)
N/A
28
-
d
a
y
I
C
U
m
or
t
a
l
i
ty
i
n
lo
w
v
it
a
mi
n
D
g
r
ou
p
(
<
1
5
.
2
ng
/
mL
)
n
=
5
28
-
Da
y
I
C
U
mor
talit
y
in
high
vit
D
gr
oup
(
>
15.
2
ng/
mL
)
n=
0
S
ur
vi
va
l
a
na
lys
is
s
howe
d
that
the
low
vit
a
mi
n
D
gr
oup
ha
d
a
higher
28
-
da
y
mor
tali
ty
r
is
k
(
lo
g
-
r
a
n
k
tes
t,
p=
0.
01)
T
he
s
tudy
f
indi
ngs
s
howe
d
that
a
ll
C
OV
I
D
-
19
pa
ti
e
nts
who
died
withi
n
28
da
ys
in
I
C
U
be
longed
to
the
lo
w
v
it
a
mi
n
D
gr
oup
[
55]
An
obs
e
r
va
ti
ona
l
s
tudy
T
h
e
s
t
u
dy
a
im
e
d
t
o
i
n
v
e
s
ti
g
a
te
2
5
OH
-
v
i
t
a
m
i
n
D
s
e
r
u
m
c
o
n
c
e
nt
r
a
t
i
on
s
w
i
t
h
c
l
i
ni
c
a
l
p
a
r
a
m
e
t
e
r
s
o
f
l
u
n
g
i
n
vo
l
v
e
m
e
nt
i
n
e
l
d
e
r
l
y
p
a
t
ie
n
t
s
h
o
s
p
it
a
l
i
z
e
d
f
o
r
S
A
R
S
-
C
o
V
-
2
i
nf
e
c
ti
o
n
T
otal
(
n=
65)
N/A
A
s
igni
f
ica
ntl
y
lowe
r
vit
a
mi
n
D
s
e
r
um
leve
ls
we
r
e
f
ound
in
the
e
lde
r
ly
C
OV
I
D
-
19
pa
ti
e
nts
who
died
du
r
ing
hos
pit
a
li
z
a
ti
on
c
om
pa
r
e
d
to
thos
e
who
s
ur
vived
(
media
n
=
3.
0
vs
.
8.
4
ng/m
L
,
p=
0.
046)
T
h
i
s
s
t
u
d
y’
s
f
i
nd
in
g
s
s
h
o
w
e
d
th
a
t
25
O
H
-
v
i
t
a
m
i
n
D
s
e
r
um
d
e
f
i
c
i
e
n
c
y
i
s
a
s
s
o
c
i
a
t
e
d
w
i
t
h
m
or
e
s
e
ve
r
e
l
u
ng
i
n
v
ol
v
e
m
e
n
t
,
l
on
g
e
r
d
i
s
e
a
s
e
d
u
r
a
t
i
on
,
a
n
d
r
i
s
k
of
d
e
a
t
h
in
e
l
d
e
r
ly
C
O
V
I
D
-
19
p
a
ti
e
n
t
s
[
56]
A
mul
ti
c
e
nter
,
double
-
b
li
nd,
r
a
ndomi
z
e
d,
plac
e
bo
-
c
ont
r
oll
e
d
tr
ial
T
he
s
tudy
a
im
e
d
to
inves
ti
ga
te
the
e
f
f
e
c
t
of
a
s
ingl
e
high
dos
e
of
vit
a
mi
n
D3
on
hos
pit
a
l
length
of
s
tay
in
pa
ti
e
nts
with
C
OV
I
D
-
19
T
otal
(
n=
240)
T
r
e
a
tm
e
nt
gr
oup
(
n=
120)
P
lac
e
bo
(
n=
120
)
T
r
e
a
tm
e
nt
gr
oup
r
e
c
e
ived
a
s
ingl
e
or
a
l
dos
e
of
200000
I
U
o
f
vit
a
mi
n
D3
T
i
m
e
t
o
h
o
s
p
i
t
a
l
s
t
a
y
m
e
d
i
a
n
(
i
n
t
e
r
q
u
a
r
t
i
l
e
r
a
n
g
e
)
V
i
t
a
m
i
n
D
3
g
r
o
u
p
=
7
.
0
(
4
.
0
-
1
0
.
0
)
d
a
y
s
P
l
a
c
e
b
o
g
r
o
u
p
=
7
.
0
(
5
.
0
-
1
3
.
0
)
d
a
y
s
V
i
t
a
m
i
n
D
3
g
r
o
u
p
v
s
p
l
a
c
e
b
o
g
r
o
u
p
[
b
e
t
w
e
e
n
-
g
r
o
u
p
d
i
f
f
e
r
e
n
c
e
(
9
5
%
C
I
)
%
]
R
i
s
k
o
f
m
o
r
t
a
l
i
t
y
2
.
5
(
9
5
%
C
I
,
-
4
.
1
–
9
.
2
)
]
A
d
m
i
s
s
i
o
n
t
o
t
h
e
i
n
t
e
n
s
i
v
e
c
a
r
e
u
n
i
t
[
-
5
.
2
(
9
5
%
C
I
,
-
1
5
.
1
–
4
.
7
)
%
]
N
e
e
d
f
o
r
m
e
c
h
a
n
i
c
a
l
v
e
n
t
i
l
a
t
i
o
n
.
[
-
6
.
8
(
95
%
C
I
,
-
15
.
1
–
1
.
2)
%
]
T
he
s
tudy
f
ound
that
a
s
ingl
e
high
dos
e
o
f
vit
a
mi
n
D3,
c
ompar
e
d
with
plac
e
bo,
did
not
s
igni
f
ica
ntl
y
r
e
duc
e
hos
pit
a
l
length
of
s
tay
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
S
yn
d
emic
s
o
f c
o
r
o
n
a
viu
r
s
d
is
ea
s
e
a
n
d
a
g
in
g
:
th
e
in
terp
la
y
a
mo
n
g
n
u
tr
itio
n
,
th
e
immu
n
e
…
(
S
eh
a
r
I
q
b
a
l
)
895
T
ab
le
2
.
C
h
ar
ac
ter
is
tics
o
f
th
e
s
tu
d
ies s
h
o
win
g
an
ass
o
ciatio
n
b
etwe
en
Vitam
in
D
an
d
C
OVI
D
-
19
(
C
o
n
tin
u
ed
)
R
e
f
.
S
tudy
de
s
ign
S
tudy
a
im
Numbe
r
of
pa
r
ti
c
ipants
I
nter
ve
n
ti
on
R
e
s
ult
s
C
onc
lus
ion
[
57]
A
r
e
tr
os
pe
c
ti
ve
,
obs
e
r
va
ti
ona
l
s
tudy
T
he
s
tudy
a
im
e
d
to
e
xa
mi
ne
vit
a
mi
n
D
leve
ls
in
pa
ti
e
nts
with
a
c
ute
r
e
s
pi
r
a
tor
y
f
a
il
ur
e
due
to
C
OV
I
D
-
19
a
nd
to
a
s
s
e
s
s
a
ny
c
or
r
e
lation
of
vit
a
mi
n
D
s
tatus
with
dis
e
a
s
e
s
e
ve
r
it
y
a
nd
pr
ognos
is
T
otal
(
n=
42)
N/A
A
s
ur
vival
a
na
l
ys
is
highl
i
ghted
that,
a
f
ter
10
da
ys
of
hos
pit
a
li
z
a
ti
on,
s
e
ve
r
e
C
OV
I
D
pa
ti
e
nts
with
vit
a
mi
n
D
de
f
icie
nc
y
ha
d
a
50%
mor
ta
li
ty
r
is
k,
while
C
OV
I
D
pa
ti
e
nts
with
vit
a
mi
n
D
(
≥
10
ng/m
L
)
ha
d
a
5%
mo
r
talit
y
r
is
k
(
p=
0.
019)
T
he
s
tudy
f
ound
that
pa
ti
e
nts
with
s
e
ve
r
e
vit
a
mi
n
D
de
f
icie
nc
y
ha
d
a
s
igni
f
ica
ntl
y
higher
mo
r
talit
y
r
is
k
[
58]
A
pr
os
pe
c
ti
ve
,
obs
e
r
va
ti
ona
l
s
tudy
T
he
s
tudy
inves
ti
ga
ted
the
a
s
s
oc
iation
be
twe
e
n
vit
a
mi
n
D
de
f
icie
nc
y
a
nd
S
AR
S
-
C
oV
-
2
inf
e
c
ti
o
n
r
a
te
a
nd
mor
tali
ty
r
is
k
T
otal
(
n=
66,
945)
N/A
An
inver
s
e
c
or
r
e
latio
n
wa
s
obs
e
r
ve
d
be
twe
e
n
the
mea
n
leve
l
of
25(
OH
)
D
a
nd
S
AR
S
-
C
oV
-
2
inf
e
c
ti
on
r
a
te
(
r
=
−
0.
43,
p=
0.
02)
a
nd
mor
tali
ty
r
a
te
(
r
=
−
0.
42,
p=
0.
02)
T
he
s
tudy
f
indi
ngs
s
howe
d
a
n
a
s
s
oc
iation
of
vit
a
mi
n
D
s
tatus
with
S
AR
S
-
C
oV
-
2
inf
e
c
ti
on
a
n
d
r
e
late
d
mor
tali
ty
[
59]
A
pr
os
pe
c
ti
ve
,
obs
e
r
va
ti
ona
l
s
tu
dy
T
he
s
tudy
a
im
e
d
to
e
xa
mi
ne
the
pr
e
va
lenc
e
of
vit
a
mi
n
D
de
f
icie
nc
y
in
hos
pit
a
li
z
e
d
C
OV
I
D
pa
ti
e
nts
a
nd
s
tudi
e
d
the
a
s
s
oc
iation
of
ba
s
e
li
ne
(
25
-
OH
)
D
leve
ls
wi
th
the
s
e
ve
r
it
y
of
C
OV
I
D
-
19
inf
e
c
ti
on
T
otal
(
n=
410)
T
r
e
a
ted
with
c
holec
a
lcif
e
r
o
l
(
n=
128)
C
holec
a
lcif
e
r
o
l
(
media
n
d
os
e
of
60,
000
I
U)
25
-
OH
D
(
ng/m
L
)
s
tatus
a
nd
dis
e
a
s
e
s
e
ve
r
it
y
in
the
older
populatio
n
OR
1.
00
(
95%
C
I
,
0.
99
–
1.
002)
T
he
s
tudy
r
e
por
ted
a
high
pr
e
va
lenc
e
of
vit
a
mi
n
D
de
f
icie
nc
y
in
C
OV
I
D
-
19
pa
ti
e
nts
.
How
e
ve
r
,
ther
e
wa
s
no
a
s
s
oc
iatio
n
be
twe
e
n
ba
s
e
li
ne
s
e
r
um
(
25
-
OH
)
D
leve
l
a
nd
s
e
ve
r
e
dis
e
a
s
e
outcome
s
of
C
OV
I
D
-
19
RE
F
E
R
E
NC
E
S
[
1
]
J.
S
.
K
a
h
n
a
n
d
K
.
M
c
I
n
t
o
s
h
,
“
H
i
s
t
o
r
y
a
n
d
r
e
c
e
n
t
a
d
v
a
n
c
e
s
i
n
c
o
r
o
n
a
v
i
r
u
s
d
i
sco
v
e
r
y
,
”
P
e
d
i
a
t
r
i
c
I
n
f
e
c
t
i
o
u
s
D
i
s
e
a
s
e
J
o
u
rn
a
l
,
v
o
l
.
2
4
,
n
o
.
1
1
S
U
P
P
L.
,
p
p
.
2
2
3
–
2
2
7
,
2
0
0
5
,
d
o
i
:
1
0
.
1
0
9
7
/
0
1
.
i
n
f
.
0
0
0
0
1
8
8
1
6
6
.
1
7
3
2
4
.
6
0
.
[
2
]
F
.
K
o
d
a
ma,
D
.
A
.
N
a
c
e
,
a
n
d
R
.
L.
P
.
J
u
mp
,
“
R
e
s
p
i
r
a
t
o
r
y
s
y
n
c
y
t
i
a
l
v
i
r
u
s
a
n
d
o
t
h
e
r
n
o
n
i
n
f
l
u
e
n
z
a
r
e
sp
i
r
a
t
o
r
y
v
i
r
u
ses
i
n
o
l
d
e
r
a
d
u
l
t
s,
”
I
n
f
e
c
t
i
o
u
s D
i
se
a
se
C
l
i
n
i
c
s
N
o
r
t
h
A
m
e
ri
c
a
,
v
o
l
.
3
1
,
n
o
.
Ja
n
u
a
r
y
,
p
p
.
7
6
7
–
7
9
0
,
2
0
1
7
.
[
3
]
A
.
F
e
r
n
á
n
d
e
z
-
Q
u
i
n
t
e
l
a
e
t
a
l
.
,
“
K
e
y
a
s
p
e
c
t
s
i
n
n
u
t
r
i
t
i
o
n
a
l
m
a
n
a
g
e
me
n
t
o
f
C
O
V
I
D
-
19
p
a
t
i
e
n
t
s,
”
J
o
u
r
n
a
l
C
l
i
n
i
c
a
l
Me
d
i
c
i
n
e
,
v
o
l
.
9
,
n
o
.
8
,
p
.
2
5
8
9
,
2
0
2
0
,
d
o
i
:
1
0
.
3
3
9
0
/
j
c
m
9
0
8
2
5
8
9
.
[
4
]
I
.
A
l
i
,
“
C
O
V
I
D
-
1
9
:
A
r
e
w
e
r
e
a
d
y
f
o
r
t
h
e
sec
o
n
d
w
a
v
e
?
,
”
D
i
s
a
s
t
e
r
Me
d
i
c
i
n
e
Pu
b
l
i
c
H
e
a
l
t
h
Pre
p
a
re
d
n
e
ss
,
v
o
l
.
2
0
2
0
,
p
p
.
1
–
3
,
2
0
2
0
,
d
o
i
:
1
0
.
1
0
1
7
/
d
m
p
.
2
0
2
0
.
1
4
9
.
[
5
]
EC
D
C
,
“
Th
e
e
u
r
o
p
e
a
n
r
e
sp
i
r
a
t
o
r
y
v
i
r
u
s
s
u
r
v
e
i
l
l
a
n
c
e
su
m
mary
(
E
R
V
I
S
S
)
,
”
Th
e
E
u
r
o
p
e
a
n
R
e
sp
i
r
a
t
o
r
y
V
i
r
u
s
S
u
r
v
e
i
l
l
a
n
c
e
S
u
mm
a
r
y
(
ER
V
I
S
S
)
.
A
c
c
e
sse
d
:
N
o
v
.
1
2
,
2
0
2
4
.
[
O
n
l
i
n
e
]
.
A
v
a
i
l
a
b
l
e
:
h
t
t
p
s
:
/
/
w
w
w
.
e
c
d
c
.
e
u
r
o
p
a
.
e
u
/
e
n
/
p
u
b
l
i
c
a
t
i
o
n
s
-
d
a
t
a
/
e
u
r
o
p
e
a
n
-
r
e
s
p
i
r
a
t
o
r
y
-
v
i
r
u
s
-
su
r
v
e
i
l
l
a
n
c
e
-
s
u
mm
a
r
y
-
e
r
v
i
ss
.
[
6
]
M
.
L
o
c
k
a
n
d
P
.
K
a
u
f
e
r
t
,
“
M
e
n
o
p
a
u
se
,
l
o
c
a
l
b
i
o
l
o
g
i
e
s,
a
n
d
c
u
l
t
u
r
e
s o
f
a
g
i
n
g
,
”
Am
e
ri
c
a
n
J
o
u
rn
a
l
o
f
H
u
m
a
n
B
i
o
l
o
g
y
,
v
o
l
.
1
3
,
n
o
.
4
,
p
p
.
4
9
4
–
5
0
4
,
2
0
0
1
,
d
o
i
:
1
0
.
1
0
0
2
/
a
j
h
b
.
1
0
8
1
.
[
7
]
M
.
S
i
n
g
e
r
,
N
.
B
u
l
l
e
d
,
a
n
d
T
.
Le
a
t
h
e
r
man
,
“
A
r
e
t
h
e
r
e
g
l
o
b
a
l
s
y
n
d
e
mi
c
s?,
”
Me
d
i
c
a
l
A
n
t
h
r
o
p
o
l
o
g
y
:
C
ro
ss
C
u
l
t
u
ra
l
S
t
u
d
i
e
s
i
n
H
e
a
l
t
h
a
n
d
I
l
l
n
e
ss
,
v
o
l
.
4
1
,
n
o
.
1
,
p
p
.
4
–
1
8
,
2
0
2
2
,
d
o
i
:
1
0
.
1
0
8
0
/
0
1
4
5
9
7
4
0
.
2
0
2
1
.
2
0
0
7
9
0
7
.
[
8
]
E.
P
e
p
r
a
h
,
E.
C
a
l
e
r
,
A
.
S
n
y
d
e
r
,
a
n
d
F
.
K
e
t
e
m
a
,
“
D
e
c
o
n
st
r
u
c
t
i
n
g
s
y
n
d
e
mi
c
s
:
T
h
e
ma
n
y
l
a
y
e
r
s
o
f
c
l
u
s
t
e
r
i
n
g
m
u
l
t
i
-
c
o
m
o
r
b
i
d
i
t
i
e
s
i
n
p
e
o
p
l
e
l
i
v
i
n
g
w
i
t
h
H
I
V
,
”
I
n
t
e
r
n
a
t
i
o
n
a
l
J
o
u
r
n
a
l
E
n
v
i
r
o
n
m
e
n
t
a
l
Re
se
a
r
c
h
Pu
b
l
i
c
H
e
a
l
t
h
,
v
o
l
.
1
7
,
n
o
.
1
3
,
p
p
.
1
–
7
,
2
0
2
0
,
d
o
i
:
1
0
.
3
3
9
0
/
i
j
e
r
p
h
1
7
1
3
4
7
0
4
[
9
]
M
.
V
i
sw
a
n
a
t
h
a
n
e
t
a
l
.
,
“
A
ssessi
n
g
t
h
e
r
i
sk
o
f
b
i
a
s
o
f
i
n
d
i
v
i
d
u
a
l
st
u
d
i
e
s
i
n
s
y
st
e
mat
i
c
r
e
v
i
e
w
s
o
f
h
e
a
l
t
h
c
a
r
e
i
n
t
e
r
v
e
n
t
i
o
n
s,
”
i
n
Ag
e
n
c
y
f
o
r
H
e
a
l
t
h
c
a
r
e
R
e
se
a
rc
h
a
n
d
Q
u
a
l
i
t
y
Me
t
h
o
d
s
G
u
i
d
e
f
o
r
C
o
m
p
a
r
a
t
i
v
e
E
f
f
e
c
t
i
v
e
n
e
ss
Re
v
i
e
w
s
,
v
o
l
.
1
2
,
2
0
1
2
,
p
.
1
.
[
1
0
]
R
.
P
o
r
c
h
e
d
d
u
,
C
.
S
e
r
r
a
,
D
.
K
e
l
v
i
n
,
N
.
K
e
l
v
i
n
,
a
n
d
S
.
R
u
b
i
n
o
,
“
S
i
mi
l
a
r
i
t
y
i
n
c
a
se
f
a
t
a
l
i
t
y
r
a
t
e
s (
C
F
R
)
o
f
C
O
V
I
D
-
1
9
/
S
A
R
S
-
C
O
V
-
2
i
n
I
t
a
l
y
a
n
d
C
h
i
n
a
,
”
J
o
u
r
n
a
l
I
n
f
e
c
t
i
o
n
D
e
v
e
l
o
p
o
i
n
g
C
o
u
n
t
ri
e
s
,
v
o
l
.
1
4
,
n
o
.
2
,
p
p
.
1
2
5
–
1
2
8
,
2
0
2
0
,
d
o
i
:
1
0
.
3
8
5
5
/
j
i
d
c
.
1
2
6
0
0
.
[
1
1
]
B
.
T
.
R
o
u
se
a
n
d
S
.
S
e
h
r
a
w
a
t
,
“
I
mm
u
n
i
t
y
a
n
d
i
mm
u
n
o
p
a
t
h
o
l
o
g
y
t
o
v
i
r
u
ses:
W
h
a
t
d
e
c
i
d
e
s
t
h
e
o
u
t
c
o
me
?
,
”
N
a
t
u
re
Re
v
i
e
w
I
m
m
u
n
o
l
o
g
y
,
v
o
l
.
1
0
,
n
o
.
7
,
p
p
.
5
1
4
–
5
2
6
,
2
0
1
0
,
d
o
i
:
1
0
.
1
0
3
8
/
n
r
i
2
8
0
2
.
[
1
2
]
C
.
V
e
l
l
a
s
,
P
.
D
e
l
o
b
e
l
,
P
.
D
e
S
o
u
t
o
B
a
r
r
e
t
o
,
a
n
d
J.
I
z
o
p
e
t
,
“
C
O
V
I
D
-
1
9
,
v
i
r
o
l
o
g
y
a
n
d
g
e
r
o
sc
i
e
n
c
e
:
a
p
e
r
sp
e
c
t
i
v
e
,
”
J
o
u
r
n
a
l
o
f
N
u
t
ri
t
i
o
n
,
H
e
a
l
t
h
a
n
d
Ag
i
n
g
,
v
o
l
.
2
4
,
n
o
.
7
,
p
p
.
6
8
5
–
6
9
1
,
2
0
2
0
,
d
o
i
:
1
0
.
1
0
0
7
/
s
1
2
6
0
3
-
0
2
0
-
1
4
1
6
-
2
.
[
1
3
]
J.
N
i
k
o
l
i
c
h
-
Z
u
g
i
c
h
,
K
.
S
.
K
n
o
x
,
C
.
T.
R
i
o
s,
B
.
N
a
t
t
,
D
e
e
p
t
a
B
h
a
t
t
a
c
h
a
r
y
a
,
a
n
d
M
.
J
.
F
a
i
n
,
“
S
A
R
S
-
C
o
V
-
2
a
n
d
C
O
V
I
D
-
1
9
i
n
o
l
d
e
r
a
d
u
l
t
s:
w
h
a
t
w
e
m
a
y
e
x
p
e
c
t
r
e
g
a
r
d
i
n
g
p
a
t
h
o
g
e
n
e
s
i
s,
i
mm
u
n
e
r
e
sp
o
n
ses
,
a
n
d
o
u
t
c
o
m
e
s,
”
G
e
r
o
sc
i
e
n
c
e
,
v
o
l
.
4
2
,
n
o
.
5
,
p
p
.
5
0
5
–
5
1
4
,
2
0
2
0
,
d
o
i
:
1
0
.
1
0
0
7
/
s1
1
3
5
7
-
0
2
0
-
0
0
2
3
2
-
x
.
[
1
4
]
M
.
A
.
C
h
o
w
d
h
u
r
y
,
N
.
H
o
ssa
i
n
,
M
.
A
.
K
a
sh
e
m,
M
.
A
.
S
h
a
h
i
d
,
a
n
d
A
.
A
l
a
m,
“
I
mm
u
n
e
r
e
s
p
o
n
s
e
i
n
C
O
V
I
D
-
1
9
:
A
r
e
v
i
e
w
,
”
J
o
u
r
n
a
l
I
n
f
e
c
t
i
o
n
Pu
b
l
i
c
H
e
a
l
t
h
,
p
p
.
1
–
1
1
,
2
0
2
0
,
d
o
i
:
1
0
.
1
0
1
6
/
j
.
j
i
p
h
.
2
0
2
0
.
0
7
.
0
0
1
.
[
1
5
]
I
.
Li
d
o
r
i
k
i
,
M
.
F
r
o
u
n
t
z
a
s
,
a
n
d
D
.
S
c
h
i
z
a
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