Headache Medicine 2020, 11(2):35-38 ISSN 2178-7468, e-ISSN 2763-6178
35
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DOI: 10.48208/HeadacheMed.2020.11
Headache Medicine
© Copyright 2020
Views and Reviews
Headache in patients with coronavirus disease (Covid-19):
An integrative literature review
Sarah Nilkece Mesquita Araújo Nogueira Bastos
1
Diego Afonso Cardoso Macedo de Sousa
2
Simone Santos e Silva Melo
2
Bárbara Louise Freire Barbosa
3
Larisse Giselle Barbosa Cruz
3
Raimundo Pereira Silva-Néto
4
1
Doctorate in Nursing and Medical Student, Federal University of Delta of Parnaíba
2
Master in Nursing and Medical Student, Federal University of Delta of Parnaíba
3
Medical Student, Federal University of Delta of Parnaíba
4
Doctorate in Neurology and Adjunct Professor of Neurology, Federal University of Delta of Parnaíba, Piauí, Brazil
Abstract
Introduction
The disease caused by the new coronavirus was named by the acronym COVID-19 which
means “COrona VIrus Disease”, while “19” refers to the year 2019, when the rst cases in
Wuhan, China, were identied.
Objective
Our objective was to identify the prevalence of headache and to know its clinical characteristics
in COVID-19 patients, available in the literature.
Methods
Based on a literature search in the major medical databases and using the descriptors “heada-
che and coronavirus”, “headache and 2019-nCoV”, “headache and SARS-CoV-2”, “headache
and coronavirus and 2019-nCoV” and “headache and coronavirus and SARS-CoV-2” we
include articles published between January 2019 and April 2020. We found 94 articles, but
only 13 met the inclusion criteria.
Results
In 13 articles analyzed in this review, a total of 3,105 Chinese patients (51.6% men and
48.4% women) had laboratory diagnoses of COVID-19. In 240 (7.7%) patients, headache
was an associated symptom of COVID-19, but in only 52 (21.7%) of them there was some
information about the characteristics of this headache.
Conclusions
COVID-19 patients have several clinical manifestations, including headache that is nonspecic
with a prevalence of 7.7%.
Sarah Nilkece Mesquita Araújo
Nogueira Bastos
Federal University of Delta of
Parnaíba, Avenida São Sebastião,
2819, Fátima, Parnaíba, PI
64001-020, Brazil. Fone: +55
8699470-0770.
sarahnilkece@hotmail.com
Received: April 24, 2020.
Accepted: April 27, 2020.
Edited by
Marcelo Moraes Valença
Mario Fernando Prieto Peres
Keywords:
Headache
Coronavirus
SARS virus
36
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Bastos SNMAN, Sousa DACM, Melo SSS, Barbosa BLF, Cruz LGB, Silva-Néto RP
Headache in patients with coronavirus disease (Covid-19): An integrative literature review
Introduction
T
he disease caused by the novel coronavirus (2019-nCoV) was
named by the acronym COVID-19 which means “COrona VIrus
Disease”, while “19” refers to the year 2019, when the rst cases in
Wuhan, China, were identied. The virus that causes this disease,
a beta coronavirus, is called SARS-CoV-2 (severe acute respiratory
syndrome coronavirus 2) and it is the same virus that causes Severe
Acute Respiratory Syndrome (SARS), identied in 2002, and Middle
East Respiratory Syndrome (MERS), identied in 2012. Transmission
of 2019-nCoV from humans to humans has been conrmed in Chi-
na and the USA and occurs mainly with the contact of respiratory
droplets from infected patients
1
.
In December 2019, in China, a novel coronavirus was identied
as the cause of a severe acute respiratory syndrome and received
worldwide attention. It is a new emerging zoonotic agent that results
in a severe syndrome that, in some patients, leads to the need for
intensive respiratory treatment with specialized management in
intensive care units
2
.
In January 2020, the World Health Organization (WHO) declared
the outbreak in China as a public health emergency of international
interest. In March 2020, with the spread of the virus in different
countries, the infection caused by SARS-CoV-2 was considered a
pandemic and called COVID-19. In early April, WHO recorded
more than 1 million cases of patients infected with SARS-CoV-2
worldwide and more than 65,000 deaths caused by the pandemic
worldwide. In Brazil, at the time of writing this manuscript, there are
more than 18,000 cases of infection and more than 1,000 deaths
3
.
According to a Chinese study, the main clinical symptoms of patients
with COVID-19 are fever (88.7%), cough (67.8%), fatigue (38.1%),
sputum production (33.4%), dyspnoea (18.6%), sore throat (13.9%)
and headache (13.6%). Gastrointestinal symptoms, such as diarrhea
(3.8%) and vomiting (5.0%) are less frequent
4
. Elderly and people
with underlying diseases are susceptible to infection and more
predisposed to severe outcomes, which may be associated with
acute respiratory distress syndrome (ARDS) and the cytokine storm
5,6
.
Although headache is one of the clinical manifestations of CO-
VID-19, this symptom is still poorly characterized. In this context, our
objective was to identify the prevalence of headache and to know
its clinical characteristics in a patient with COVID-19, available in
the literature.
Met hods
This study was an integrative and retrospective review of the articles This study was an integrative and retrospective review of the articles
on headache as a symptom of COVID-19 published in the last 16 on headache as a symptom of COVID-19 published in the last 16
months. The research was performed in the online databases months. The research was performed in the online databases Litera-Litera-
tura Latino-Americana e do Caribe em Ciências da Saúdetura Latino-Americana e do Caribe em Ciências da Saúde (LiLacs), Scientic (LiLacs), Scientic
Electronic Library Online (SciELO), Chinese National KnowledgeElectronic Library Online (SciELO), Chinese National Knowledge
Infrastructure (CNKI) and Medical Literature and Retrivial System on-Infrastructure (CNKI) and Medical Literature and Retrivial System on-
Line (MEDLINE/PubMed®), from January 2019 to April 2020, given Line (MEDLINE/PubMed®), from January 2019 to April 2020, given
the current status of the pandemic by SARS-Cov-19. We have used the current status of the pandemic by SARS-Cov-19. We have used
the descriptors “headache and coronavirus”, “headache and 2019-the descriptors “headache and coronavirus”, “headache and 2019-
nCoV”, “headache and SARS-CoV-2”, “headache and coronavirus nCoV”, “headache and SARS-CoV-2”, “headache and coronavirus
and 2019-nCoV” and “headache and coronavirus and SARS-CoV-2”.and 2019-nCoV” and “headache and coronavirus and SARS-CoV-2”.
Articles written in all languages were included. Editorials, comments,
letters to the editor, review articles, articles that were not fully avail-
able or those that did not have accurate information were excluded.
To ensure the validity of these articles, the selected studies were
analyzed in detail, by all authors, for the presence of headache in
patients with COVID-19.
In our search, we found a total of 94 articles, but with the elimination
of repeated articles, only 49 remained. After reading the abstracts,
we excluded articles that did not describe headache with associated
symptom (36 articles). Only 13 articles describing case series were
included and made up this review, totaling 3,105 patients (Figure).
Figure. Flowchart of search and selection of studies
Data were analyzed based on demographic and clinical character-
istics and are presented as percentages. The percentage is always
related to the total number of patients whose information was avail-
able for the specic issue.
Result s
In 13 articles analyzed in this review, a total of 3,105 Chinese pa-
tients (51.6% men and 48.4% women) had laboratory diagnoses
of COVID-19. In 7.7% (240/3,105) patients, headache was an
associated symptom of COVID-19, but in only 21.7% (52/240) of
them there was some information about the characteristics of this
headache, as shown in Table 1.
Discussion
Coronaviruses are a large class of viruses that exist widely in nature
and the newly discovered 2019-nCoV is the seventh coronavirus
37
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Bastos SNMAN, Sousa DACM, Melo SSS, Barbosa BLF, Cruz LGB, Silva-Néto RP
Headache in patients with coronavirus disease (Covid-19): An integrative literature review
currently known to infect humans and also responsible for the current
pandemic that started in China
20
.
To the best of our knowledge, this is the rst study to assess headache
characteristics in patients with COVID-19. We found that headache
was an initial symptom of the disease in 3,105 pacient with this
disease. Its prevalence has been reported in most studies, but its
semiological characteristics have rarely been addressed.
According to the International Classication of Headache Disorders,
3rd edition (ICHD-3)
21
, headache attributed to systemic viral infection
is characterized by its temporal relation to onset of viral infection and
signicant improvement or resolution in parallel with the improvement
or resolution of systemic viral infection. Headache is usually diffuse
and of moderate to severe intensity (Table 2).
Table 2. Diagnostic criteria of ICHD-3 for headache attributed to systemic
viral infection
A. Headache of any duration fullling criterion C
B. Both of the following:
1. systemic viral infection has been diagnosed
2. no evidence of meningitic or encephalitic involvement
C. Evidence of causation demonstrated by at least two of the following:
1. headache has developed in temporal relation to onset of the systemic viral infection
2.
headache has signicantly worsened in parallel with worsening of the systemic
viral infection
3.
headache has signicantly improved or resolved in parallel with improvement in
or resolution of the systemic viral infection
4. headache has either or both of the following characteristics:
a. diffuse pain
b. moderate or severe intensity
D. Not better accounted for by another ICHD-3 diagnosis
Possibly, the neuroinvasive predisposition characteristic of corono-
viruses is an explanation for patients with COVID-19 to develop
headache. Genomic analysis shows that SARS-CoV-2 shares a
highly homologous sequence with SARS-CoV-1 and MERS-CoV, in
addition to a similarity of receptors in human cells. This can affect
the respiratory tract and also the central nervous system, especially
the thalamus and brain stem
20
.
Headache was observed in patients of all age groups, both in
adults
7-13
, as in children
6
. It is important to note that headache is a
characteristic symptom of pneumonia caused by coronavirus and
not exclusive to COVID-19, and does not behave as a differential
symptom between these viral infections
13
.
In the studied cases of COVID-19, headache was usually associated
with other typical symptoms of the disease, such as gastrointestinal
symptoms. When the patient experienced nausea, vomiting and
diarrhea, headache was more frequent, probably due to the higher
fever and hydroelectrolytic imbalance
17
.
We found in the 13 studies a prevalence of headache equal to 7.7%
(240 out of 3,105 patients), ranging from 2.0% to 53.3%. A factor
that may determine a higher prevalence of headache in COVID-19
patients is pneumonia, considered a predictive factor for severe
subtypes of the disease. We observed that in patients with changes
in pulmonary radiological images there was a higher prevalence of
headache when compared to patients with normal exams
19
.
The symptoms of COVID-19 are nonspecic, making the initial clinical
presentation indistinguishable from other viral respiratory diseases.
Initially, there is a predominance of systemic manifestations, such
as fever, fatigue, myalgia and asthenia
10
. However, the headache
Table 1. Clinical characteristics of headache in 3,105 patients with coronavirus disease 2019 (Covid-19) in the period from January 2019 to April 2020
in China
Published studies Number of patients
Age (years)
Sex
Headache prevalence
Clinical characteristics
Average Variation n %
Tian et al., 2020
7
262 47. 5 1–94 M=127; F=135 17 6.5
Mild to moderate intensity in 93.5% of
patients and it appeared at the beginning
of the disease
Xu et.al., 2020
8
62 41.0 19-65 M=35; F=27 21 34.0
It lasted ≥10 days in 71.4% of patients and
it appeared at the beginning of the disease
Huang et. al., 2020
9
41 49.0 18-65 M=30; F=11 3 7.3 NR
Liu et.al., 2020
10
30 35.0±8 21-59 M=10; F=20 16 53.3 It appeared at the beginning of the disease
Cheng et.al., 2020
11
1,078 46.0 0.25-94 M=573; F=505 22 2.0 NR
Wang et.al., 2020
12
31 7. 1 0.5-17 M=15; F=16 3 9.7 NR
Li et.al., 2020
13
54 51.5 25-82 M=22; F=32 ? Rare NR
Chen et al., 2020
14
99 55.5±13.1 21-82 M=67; F=32 8 8.0 NR
Liu et al., 2020
15
137 55.0±16.0 20-82 M=61; F=76 13 9.5 NR
Mi et al., 2020
16
10 68.4±18.5 34-87 M=2; F=8 1 10.0 NR
Jin et al., 2020
17
651 NR NR M=331; F=320 67 10.3
It was more frequent in patients with
gastrointestinal symptoms (21.6% versus
8.8%)
Ding et al., 2020
18
5 50.2±9.8 39-66 M=2; F=3 2 40.0 NR
Zhang et al., 2020
19
645 NR NR M=328; F=317 67 10.4
It was more frequent in patients with abnormal
pulmonary imaging ndings (11.3% versus
2.8%)
Legend: M – male; F – female; NR – not reported.
38
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Bastos SNMAN, Sousa DACM, Melo SSS, Barbosa BLF, Cruz LGB, Silva-Néto RP
Headache in patients with coronavirus disease (Covid-19): An integrative literature review
that can also appear at the beginning of the disease should not be
neglected, but contribute to the diagnosis, especially in those patients
with a positive epidemiological history.
This review had some limitations. All patients were from China,
so some articles found were written in Chinese and needed to
be translated
10 -13
. In addition, as it is pandemic, new studies were
published almost daily and described the headache incompletely.
However, we believe that these ndings are consistent with the
clinical manifestations of this disease.
Concl usion
COVID-19 patients have several clinical manifestations, including
headache that is nonspecic with a prevalence of 7.7%.
Funding:
This research received no specic grant from any funding
agency in the public, commercial, or not-for-prot sectors.
Conflict of Interest:
There is no conict of interest.
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