DOI: 10.1002/jmv.

25938

LETTER TO THE EDITOR

Conjunctivitis and COVID‐19: A meta‐analysis

To the Editor, The presence of COVID‐19 at conjunctival polymerase chain

The coronavirus disease 2019 (COVID‐19) pandemic started as reaction (PCR) was analyzed only by Xia and Wu; only in 4% (3/68) of
an outbreak in Wuhan and spread from there to the rest of the the cases, PCR revealed the positivity of COVID‐19 (Supporting
world. The lungs are the site primarily affected by COVID‐19 and Information Material).
the severe form of the disease is characterized by severe The overall rate of conjunctivitis was 1.1%; it was 3% and
pneumonia, acute respiratory distress syndrome (ARDS), and 0.7% in severe and nonsevere COVID‐19 patients, respectively.
hypercoagulation. 1 The meta‐analysis showed that patients with severe COVID‐19
Until now, the exact transmission route of COVID‐19 remains infection had, at admission to the hospital, increased incidence of
unclear. The respiratory tract probably is not the only transmis- conjunctivitis (odds ratio: 3.4; 95% confidence interval:1.1‐10.2;
sion route for this viral infection; some authors hypothesized that P = .030) (Figure 1). No heterogeneity between trials was
COVID‐19 droplets, or infected hands, can also contaminate the observed (I2 = 0); the publication bias was not statistically
conjunctiva, that could represent the initial site of a spread in- significant (Egger's test; P = .336).
fection.2 The conjunctivitis, also called “Pink eye,” is a frequent This meta‐analysis provides evidence that conjunctivitis could be
disease and its etiology could be bacterial or viral. This has been associated with a more severe form of COVID‐19.
previously described as associated to coronavirus infection in Previous studies reported about eye infection and con-
3
humans and animals. junctivitis in animals and humans infected by coronavirus. 3
Recent studies showed that conjunctivitis could be a mani- However, the role of conjunctiva in COVID‐19 still remains
festation of COVID‐19.4 Because the eye could be considered as unclear.8,9
5
a direct potential portal of entry for the virus, it is of interest to The results of this study could have important clinical im-
analyze the association between conjunctivitis and the severity plications. First, medical doctors have to recognize conjunctivitis
of COVID‐19; scarce and conflicting data have been reported. In as a possible sign of COVID‐19 associated to a severe form of
particular, only three studies in Chinese population described disease. Second, considering that eye could be a COVID‐19 route,
this topic,2 with different results. Xia et al 6 did not find an in- we want to underscore the necessity to use protective equipment
creased incidence of conjunctivitis in severe COVID‐19; they for healthcare personnel and for all the people that enter in
performed a prospective study in 30 COVID‐19 patients to assess contact with a suspected or diagnosed COVID patient. To confirm
the presence of the virus in the tears.6 Conversely, Guan et al, 2 the importance of eye protection, a previous study in patients
who retrospectively analyzed clinical characteristics of 1099 infected by SARS‐COV‐1 showed that unprotected eye contact
7
COVID‐19 patients, and Wu et al, who retrospectively in- was associated with transmission of the disease to healthcare
vestigated the ocular characteristics of 38 COVID‐19 patients, workers.10
reported an increased incidence of conjunctivitis in patients with This study has the following limitations. First, even if this meta‐
severe disease. analysis included 1167 COVID‐19 patients, more studies with a
Thus, to better explore this issue, this meta‐analysis aims to major number of patients are needed to have solid results. Second,
evaluate the incidence of conjunctivitis in patients affected by severe conjunctival swab to test the local involvement of COVID‐19 was not
and nonsevere COVID‐19. reported in all the studies; however, a previous study showed that
Methods are reported in Supporting Information Material. conjunctival swab test results positive for COVID‐19 only in about
We included studies in patients with COVID‐19 that assessed 5% of the patients.7 Third, the population included in this meta‐
the severe (as severe pneumonia, mortality, ARDS, use of mechanical analysis is composed only of Chinese patients who might have dif-
ventilation or intensive care unit recovery) and nonsevere forms of ferent clinical features from those of the patients of other countries.
the disease and reported the incidence of conjunctivitis. Future studies in other populations will be necessary to confirm the
Three studies,2,6,7 including 1167 patients, assessed the clinical results of this meta‐analysis.
course of patients with COVID‐19 and presence or absence of con- In conclusion, the results of this meta‐analysis show that
junctivitis. Clinical characteristics of the studies are reported in conjunctivitis may represent a sign of COVID‐19 infection
Supporting Information Material. The age of the patients enrolled associated to a more severe form of disease and suggest the use
ranged from a median of 47 to 68 years old and the male sex was of protective equipment for all people potentially exposed to
prevalent in all the studies. infected subjects.

J Med Virol. 2020;1–2. wileyonlinelibrary.com/journal/jmv © 2020 Wiley Periodicals LLC | 1

2 | LETTER TO THE EDITOR

FIGURE 1 Meta‐analysis of conjunctivitis in patients with severe vs nonsevere coronavirus disease 2019

Lorenzo Loffredo MD1 R E F E R E N CE S

Fernanda Pacella MD2
1. Violi FPD, Cangemi R, Pignatelli P, Loffredo L. Hypercoagulation and
Elena Pacella MD2 anti‐thrombotic treatment in COVID‐19: a new challenge. Thromb
Giulia Tiscione MD1 Haemost. 2020. http://dx.doi.org/10.1055/s‐0040‐1710317
Alessandra Oliva MD3 2. Guan W‐j, Ni Z‐y, Hu Y, et al. Clinical Characteristics of Coronavirus
Disease 2019 in China. New England Journal of Medicine. 2020;382(18):
Francesco Violi MD1
1708‐1720. http://dx.doi.org/10.1056/nejmoa2002032
3. Seah I, Agrawal R. Can the coronavirus disease 2019 (COVID‐19)
1
Department of Clinical, Internal Medicine, Anesthesiology affect the eyes? A review of coronaviruses and ocular implications in
and Cardiovascular Sciences, Sapienza University of Rome, Rome, humans and animals. Ocul Immunol Inflamm. 2020;28(3):391‐395.
4. Qing H, Li Z, Yang Z, et al. The possibility of COVID‐19 transmission
Italy
2
from eye to nose. Acta Ophthalmol. 2020;98.
Department of Sense Organs, Faculty of Medicine and Dentistry, 5. Belser JA, Rota PA, Tumpey TM. Ocular tropism of respiratory
Sapienza University of Rome, Rome, Italy viruses. MMBR. 2013;77(1):144‐156.
3 6. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears
Department of Public Health and Infectious Diseases, Sapienza
and conjunctival secretions of patients with SARS‐CoV‐2 infection.
University of Rome, Rome, Italy
J Med Virol. 2020;92:589‐594.
7. Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of
patients with coronavirus disease 2019 (COVID‐19) in Hubei
Correspondence
province, China. JAMA Ophthalmol. 2020.
Lorenzo Loffredo, MD, Divisione I Clinica Medica, 8. Guo D, Xia J, Shen Y, Tong J. SARS‐CoV‐2 may be related to con-
Viale del Policlinico 155, 00161 Rome, Italy. junctivitis but not necessarily spread through the conjunctiva SARS‐
Email: lorenzo.loffredo@uniroma1.it CoV‐2 and conjunctiva. J Med Virol. 2020.
9. Liu Z, Sun CB. Conjunctiva is not a preferred gateway of entry for
SARS‐CoV‐2 to infect respiratory tract. J Med Virol. 2020.
OR CID 10. Raboud J, Shigayeva A, McGeer A, et al. Risk factors for SARS
transmission from patients requiring intubation: a multicentre in-
Lorenzo Loffredo http://orcid.org/0000-0002-6542-6235
vestigation in Toronto, Canada. PLoS One. 2010;5(5):e10717.
Fernanda Pacella http://orcid.org/0000-0002-3649-5805
Elena Pacella http://orcid.org/0000-0002-5431-6399
Giulia Tiscione http://orcid.org/0000-0002-1153-9509 SUPPO RTING IN F ORMATION
Alessandra Oliva http://orcid.org/0000-0003-0832-7975 Additional supporting information may be found online in the
Francesco Violi http://orcid.org/0000-0002-6610-7068 Supporting Information section.