Background: Hyposmia is frequently reported as an initial symptom in coronavirus disease 2019 (COVID-19). Objective: As hyposmia accompanies cognitive impairment in several neurological disorders, we aimed to study whether hyposmia represents a clinical biomarker for both neurological involvement and cognitive impairment in mild CO-VID-19. We aimed to study whether olfactory dysfunction (OD) represents a clinical biomarker for both neurological involvement and cognitive impairment in mild COVID-19. Methods: Formal olfactory testing using the Sniffin’Sticks® Screening test, neuropsychological assessment using the Montreal Cognitive Assessment (MoCA), and detailed neurological examination were performed in 7 COVID-19 patients with mild disease course and no history of olfactory or cognitive impairment, and 7 controls matched for age, sex, and education. Controls were initially admitted to a dedicated COVID-19 screening ward but tested negative by real-time PCR. Results: The number of correctly identified odors was significantly lower in COVID-19 than in controls (6 ± 3, vs. 10 ± 1 p = 0.028, r = 0.58). Total MoCA score was significantly lower in COVID-19 patients than in controls (20 ± 5 vs. 26 ± 3, p = 0.042, r = 0.54). Cognitive performance indicated by MoCA was associated with number of correctly identified odors in COVID-19 patients and controls (COVID-19: p = 0.018, 95% CI = 9–19; controls: p = 0.18, r = 0.63, 95% CI = 13–18.5 r = 0.64). Discussion/Conclusion: OD is associated with cognitive impairment in controls and mild COVID-19. OD may represent a potentially useful clinical biomarker for subtle and even subclinical neurological involvement in severe acute respiratory distress syndrome coronavirus-2 infection.

1.
Moein
ST
,
Hashemian
SMR
,
Mansourafshar
B
,
Khorram-Tousi
A
,
Tabarsi
P
,
Doty
RL
.
Smell dysfunction: a biomarker for COVID-19
.
Internat Forum Allergy Rhinol
.
2020
;
10
:
944
50
.
2.
Lechien
JR
,
Chiesa-Estomba
CM
,
De Siati
DR
,
Horoi
M
,
Le Bon
SD
,
Rodriguez
A
, et al.
Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study
.
Eur Arch Otorhinolaryngol
.
2020 Aug
;
277
(
8
):
2251
61
. .
3.
Churnin
I
,
Qazi
J
,
Fermin
CR
,
Wilson
JH
,
Payne
SC
,
Mattos
JL
.
Association between olfactory and gustatory dysfunction and cognition in older adults
.
Am J Rhinol Allergy
.
2019 Mar
;
33
(
2
):
170
7
. .
4.
Dintica
CS
,
Marseglia
A
,
Rizzuto
D
,
Wang
R
,
Seubert
J
,
Arfanakis
K
, et al.
Impaired olfaction is associated with cognitive decline and neurodegeneration in the brain
.
Neurology
.
2019
;
92
(
7
):
e700
9
. .
5.
Saini
D
,
Mukherjee
A
,
Roy
A
,
Biswas
A
.
A comparative study of the behavioral profile of the behavioral variant of frontotemporal dementia and Parkinson’s disease dementia
.
Dement Geriatr Cogn Dis Extra
.
2020 Sep-Dec
;
10
(
3
):
182
94
. .
6.
Domellof
ME
,
Lundin
KF
,
Edstrom
M
,
Forsgren
L
.
Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson’s disease
.
Parkinsonism Relat Disord
.
2017 May
;
38
:
41
7
.
7.
Marin
C
,
Vilas
D
,
Langdon
C
,
Alobid
I
,
López-Chacón
M
,
Haehner
A
, et al.
Olfactory dysfunction in neurodegenerative diseases
.
Curr Allergy Asthma Rep
.
2018 Jun 15
;
18
(
8
):
42
. .
8.
Shin
T
,
Kim
J
,
Ahn
M
,
Moon
C
.
Olfactory dysfunction in CNS neuroimmunological disorders: a review
.
Mol Neurobiol
.
2019 May
;
56
(
5
):
3714
21
. .
9.
Bagheri
SHR
,
Asghari
AM
,
Farhadi
M
,
Shamshiri
AR
,
Kabir
A
,
Kamrava
SK
, et al.
Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak
.
medRxiv
.
2020
.
10.
Yan
CH
,
Faraji
F
,
Prajapati
DP
,
Boone
CE
,
DeConde
AS
.
Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms
.
Int Forum Allergy Rhinol
.
2020
;
10
(
7
):
806
13
. .
11.
Helms
J
,
Kremer
S
,
Merdji
H
,
Clere-Jehl
R
,
Schenck
M
,
Kummerlen
C
, et al.
Neurologic features in severe SARS-CoV-2 infection
.
N Engl J Med
.
2020
;
382
(
23
):
2268
70
. .
12.
Mao
L
,
Jin
H
,
Wang
M
,
Hu
Y
,
Chen
S
,
He
Q
, et al.
Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China
.
JAMA Neurol
.
2020
;
77
:
683
90
.
13.
Lechien
JR
,
Chiesa-Estomba
CM
,
Place
S
,
Van Laethem
Y
,
Cabaraux
P
,
Mat
Q
, et al.
Clinical and epidemiological characteristics of 1420 European patients with mild-to-moderate coronavirus disease 2019
.
J Intern Med
.
2020 Sep
;
288
(
3
):
335
44
. .
14.
Divani
AA
,
Andalib
S
,
Biller
J
,
Di Napoli
M
,
Moghimi
N
,
Rubinos
CA
, et al.
Central nervous system manifestations associated with COVID-19
.
Curr Neurol Neurosci Rep
.
2020 October 30
;
20
(
12
):
60
. .
15.
Moriguchi
T
,
Harii
N
,
Goto
J
,
Harada
D
,
Sugawara
H
,
Takamino
J
, et al.
A first case of meningitis/encephalitis associated with SARS-Coronavirus-2
.
Int J Infect Dis
.
2020 Apr 3
;
94
:
55
8
. .
16.
Chen
T
,
Wu
D
,
Chen
H
,
Yan
W
,
Yang
D
,
Chen
G
, et al.
Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study
.
Bmj
.
2020 Mar 26
;
368
:
m1091
. .
17.
Hadziefendic
S
,
Haxhiu
MA
.
CNS innervation of vagal preganglionic neurons controlling peripheral airways: a transneuronal labeling study using pseudorabies virus
.
J Auton Nerv Syst
.
1999 May 28
;
76
(
2–3
):
135
45
. .
18.
Matsuda
K
,
Park
CH
,
Sunden
Y
,
Kimura
T
,
Ochiai
K
,
Kida
H
, et al.
The vagus nerve is one route of transneural invasion for intranasally inoculated influenza a virus in mice
.
Vet Pathol
.
2004 Mar
;
41
(
2
):
101
7
. .
19.
Li
YC
,
Bai
WZ
,
Hashikawa
T
.
The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients
.
J Med Virol
.
2020 Feb 27
;
92
:
55
5
.
20.
Hummel
T
,
Sekinger
B
,
Wolf
SR
,
Pauli
E
,
Kobal
G
.
‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold
.
Chem Senses
.
1997 Feb
;
22
(
1
):
39
52
. .
21.
Tan
JP
,
Li
N
,
Gao
J
,
Wang
LN
,
Zhao
YM
,
Yu
BC
, et al.
Optimal cutoff scores for dementia and mild cognitive impairment of the Montreal Cognitive Assessment among elderly and oldest-old Chinese population
.
J Alzheimers Dis
.
2015
;
43
(
4
):
1403
12
. .
22.
Zhou
Y
,
Ortiz
F
,
Nuñez
C
,
Elashoff
D
,
Woo
E
,
Apostolova
LG
, et al.
Use of the MoCA in detecting early Alzheimer’s disease in a spanish-speaking population with varied levels of education
.
Dement Geriatr Cogn Dis Extra
.
2015
;
5
(
1
):
85
95
. .
23.
Atalar
,
Erdal
Y
,
Tekin
B
,
Yıldız
M
,
Akdoğan
Ö
,
Emre
U
.
Olfactory dysfunction in multiple sclerosis
.
Mult Scler Relat Disord
.
2018 Apr
;
21
:
92
6
. .
24.
Pirker
A
,
Schmied
C
,
Dal-Bianco
P
.
T-cells show increased production of cytokines and activation markers in Alzheimer’s disease
.
Brain Disord. Ther
.
2013
;
3
(
1
):
4
.
25.
Sochocka
M
,
Zwolińska
K
,
Leszek
J
.
The infectious etiology of Alzheimer’s disease
.
Curr Neuropharmacol
.
2017
;
15
(
7
):
996
1009
. .
26.
Chen
N
,
Zhou
M
,
Dong
X
,
Qu
J
,
Gong
F
,
Han
Y
, et al.
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
.
Lancet
.
2020 Feb 15
;
395
(
10223
):
507
13
. .
27.
Welge-Lüssen
A
.
Re-establishment of olfactory and taste functions
.
GMS Curr Top Otorhinolaryngol Head Neck Surg
.
2005
;
4
:
Doc06
..
28.
Soler
ZM
,
Patel
ZM
,
Turner
JH
,
Holbrook
EH
.
A primer on viral-associated olfactory loss in the era of COVID-19
.
Int Forum Allergy Rhinol
.
2020 Apr 9
;
10
:
814
20
.
29.
Sungnak
W
,
Huang
N
,
Bécavin
C
,
Berg
M
,
Queen
R
,
Litvinukova
M
, et al.
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
.
Nat Med
.
2020 April 23
;
26
:
681
7
.
30.
Butowt
R
,
Bilinska
K
.
SARS-CoV-2: olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection
.
ACS Chem Neurosci
.
2020 Apr 13
;
11
:
1200
3
.
31.
Chen
R
,
Wang
K
,
Yu
J
,
Chen
Z
,
Wen
C
,
Xu
Z
.
The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain
.
bioRxiv
.
2020
.
32.
Sarma
D
,
Bilello
LA
.
A case report of acute transverse myelitis following novel coronavirus infection
.
Clin Pract Cases Emerg Med
.
2020 Aug
;
4
(
3
):
321
3
. .
33.
Pezzini
A
,
Padovani
A
.
Lifting the mask on neurological manifestations of COVID-19
.
Nat Rev Neurol
.
2020 November1
;
16
(
11
):
636
44
. .
34.
Wang
Y
,
Li
X
,
Wei
B
,
Tung
TH
,
Tao
P
,
Chien
CW
.
Association between chronic obstructive pulmonary disease and dementia: systematic review and meta-analysis of cohort studies
.
Dement Geriatr Cogn Dis Extra
.
2019 May-Aug
;
9
(
2
):
250
9
. .
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