Headache Medicine 2020, 11(1):3-6 ISSN 2178-7468, e-ISSN 2763-6178

ASAA

DOI: 10.48208/HeadacheMed.2020.2

Headache Medicine

Views and Reviews

Headache in patients infected with the novel coronavirus (Covid-19):

An integrative literature review

Cefaleia em pacientes infectados pelo novo coronavírus (Covid-19): uma revisão integrativa da literatura

Sarah Nilkece Mesquita Araújo Nogueira Bastos

Diego Afonso Cardoso Macedo

Simone Santos

e Silva Melo

Bárbara Louise Freire Barbosa

Larisse Giselle Barbosa Cruz

Raimundo Pereira

Silva-Néto

Doctorate in Nursing and Medical Student, Federal University of Delta of Parnaíba.

Master in Nursing and Medical Student, Federal University of

Delta of Parnaíba.

Medical Student, Federal University of Delta of Parnaíba.

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 “CO-

rona 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 “headache and co-

ronavirus”, “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 Ja-

nuary 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%.

Resumo

Introdução

A doença causada pelo novo vírus Corona foi batizada com o acrônimo COVID-19, que signica

“Doença de Corona VIrus”, enquanto “19” refere-se ao ano de 2019, quando foram identicados os

primeiros casos em Wuhan, na China.

Objetivo

Nosso objetivo é identicar a prevalência da cefaleia e conhecer suas características clínicas em paciente

com COVID-19, disponíveis na literatura.

Método

Com base em uma pesquisa bibliográca nas principais bases de dados médicos e utilizando os

descritores “headache 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” incluímos

artigos publicados entre janeiro de 2019 e abril de 2020. Foram encontrados 94 artigos, mas apenas

13 preencheram os critérios de inclusão.

Resultados

Em 13 artigos analisados nesta revisão, um total de 3.105 pacientes chineses (51,6% homens e 48,4%

mulheres) tiveram diagnóstico laboratorial de COVID-19. Em 240 (7,7%) pacientes, a cefaleia foi um

sintoma associado ao COVID-19, mas em apenas 52 (21,7%) deles havia alguma informação sobre as

características dessa cefaleia.

Conclusão

Os pacientes com COVID-19 apresentam várias manifestações clínicas, inclusive cefaleia que é inespe-

cíca e com uma prevalência de 7,7%.

Sarah Nilkece Mesquita Araújo

Nogueira Bastos.

Federal University of Delta of Parna-

íba, Avenida São Sebastião, 2819,

Fátima, Parnaíba, PI 64001-020,

Brazil. Fone: +55 8699470-0770.

sarahnilkece@hotmail.com.

Received: April 11, 2020.

Accepted: April 12, 2020.

Edited by

Mario Fernando Prieto Peres

Keywords:

Headache

Coronavirus

Covid-19

2019-nCoV

SARS-CoV-2

Palavras-chave:

Cefaleia

Coronavirus

Covid-19

2019-nCoV

SARS-CoV-2

Bastos SNMAN, Sousa DACM, Melo SSS, Barbosa BLF, Cruz LGB, Silva-Néto RP.

Headache in patients infected with the novel coronavirus (Covid-19): An integrative literature review

Introduction

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 syn-

drome coronavirus 2) and it is the same virus that causes Severe Acute

Respiratory Syndrome (SARS), identied 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 China

and the USA and occurs mainly with the contact of respiratory dro-

plets from infected patients

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

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

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

. Elderly and people

with underlying diseases are susceptible to infection and more pre-

disposed 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.

Methods

This study was an integrative and retrospective review of the articles

on headache as a symptom of COVID-19 published in the last 16

months. The research was performed in the online databases Litera-

tura Latino-Americana e do Caribe em Ciências da Saúde (LiLacs),

Scientic Electronic Library Online (SciELO), Chinese National

Knowledge Infrastructure (CNKI) and Medical Literature and Retrivial

System onLine (MEDLINE/PubMed®), from January 2019 to April

2020, given the current status of the pandemic by SARSCov-19. We

have used the descriptors “headache and coronavirus”, “headache

and 2019-nCoV”, “headache and SARS-CoV-2”, “headache and

coronavirus and 2019-nCoV” and “headache and coronavirus

and SARSCoV-2”.

Articles written in all languages were included. Editorials, comments,

letters to the editor, review articles, articles that were not fully availa-

ble 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 des-

cribe headache with associated symptom (36 articles). Only 13

articles describing case series were included and made up this

review, totaling 3,105 patients (Figure 1).

Figure 1. Flowchart of search and selection of studies

Data were analyzed based on demographic and clinical characte-

ristics and are presented as percentages. The percentage is always

related to the total number of patients whose information was avai-

lable for the specic issue.

Results

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 associa-

ted 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

currently known to infect humans and also responsible for the current

Bastos SNMAN, Sousa DACM, Melo SSS, Barbosa BLF, Cruz LGB, Silva-Néto RP.

Headache in patients infected with the novel coronavirus (Covid-19): An integrative literature review

pandemic that started in China

To the best of our knowledge, this is the rst study to assess he-

adache characteristics in patients with COVID-19. We found that

headache was an initial symptom of the disease in 3,105 pacients

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 Disor-

ders, 3rd edition (ICHD- 3)

, 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).

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 MERSCoV, 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

Headache was observed in patients of all age groups, both in

adults

7-13

, as in children

. 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

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 preva-

lence

Headache prevalence

Average Variation n %

Tian et al., 2020

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

62 41.0 19-65 M=35; F=27 21 34.0

71.4% of patients and it appeared at

the beginning of the disease

Huang et al., 2020

41 49.0 18-65 M=30; F=11 3 7. 3 NR

Liu et al., 2020

30 35.038 21-59 M=10; F=20 16 53.3

It appeared at the beginning of the

disease

Cheng et al., 2020

1,078 46.0 0.25-94 M=573; F=505 22 2.0 NR

Wang et al., 2020

31 7. 1 0.5-17 M=15; F=16 3 9.7 NR

Li et al., 2020

54 51.5 25-82 M=22; F=32 ? Rare NR

Chen et al., 2020

99 55.5313.1 21-82 M=67; F=32 8 8.0 NR

Liu et al., 2020

137 55.0316.0 20-82 M=61; F=76 13 9.5 NR

Mi et al., 2020

10 68.4318.5 34 -87 M=2; F=8 1 10.0 NR

Jin et al., 2020

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

5 50.239.8 39-66 M=2; F=3 2 40.0 NR

Zhang et al., 2020

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.

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

Bastos SNMAN, Sousa DACM, Melo SSS, Barbosa BLF, Cruz LGB, Silva-Néto RP.

Headache in patients infected with the novel coronavirus (Covid-19): An integrative literature review

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

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

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

. However, the headache

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.

Conclusion

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-forprot sectors.

Conflict of Interest: There is no conict of interest.

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