IDCases 25 (2021) e01214

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Case Report

Red face may be a speciﬁc sign of SARS-CoV-2 alpha variant
Aya Nakaya* , Eiji Ogura, Yuki Katayama, Masami Yoshii, Eiko Yoshino, Kazuya Hozumi,
Saori Tago, Yuko Teranishi, Yuki Minamibashi, Makiko Harada, Mami Yoshioka,
Yuri Kawano, Yuka Arai, Keno Yoshida, Shozo Shimizu, Kazuma Ogura,
Katsuaki Iwashita, BOH Covid 19 TeamInternal Medicine, Biwako Ohashi Hospital, 5-1-29 Mano, Otsu city, Shiga, 520-0232, JapanA R T I C L E I N F O

A B S T R A C TArticle history:
Received 29 June 2021
Received in revised form 29 June 2021
Accepted 30 June 2021

Japan is currently suffering the fourth wave of the COVID-19 pandemic, with the dominant type being
SARS-CoV-2 alpha variant. Patients with COVID-19 variant types show more aggressive symptoms. In thepresent study, three patients developed a red face during treatment. Two of them suddenly worsened
shortly after. We assumed that the red face reﬂected a cytokine storm and conjectured that it may be aspeciﬁc sign of variant type COVID-19, because we have never seen it in patients with non-variant type.
Moreover, we believe that red face may be predictive of a sudden deterioration.
© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords:
COVID-19
SARS-CoV-2 alpha variantRed facePneumonia
Cytokine stormIntroduction
We are suffering the fourth wave of the pandemic, with thedominant type being SARS-CoV-2 alpha variant [1].
Frontline workers who are treating patients with COVID-19
have noticed different symptoms in patients with variant types
more than in patients with non-variant. We have experienced
more treatment failure in patients with variant types, and we feelthe need to adjust treatment as soon as possible when we noticechanges in these patients. Therefore, it is important to identify
signs of aggravation, especially in patients with variant-type
COVID-19. However, the speciﬁc features of the variant types are
not even known.
In the present study, three patients with variant COVID-19
showed red face. Two of them experienced sudden deterioration
after this symptom appeared, while one showed no othersymptoms. We believe that red face may be a speciﬁc symptomof variant type, because we have never seen it before (Table 1).
Case 1
A 71-year-old Japanese woman was admitted to our hospital
because her husband had COVID-19 and had been hospitalized atour institution 3 days prior. She had no symptoms and had gone tothe swimming pool the day before hospitalization. Although she
had no symptoms, computerized tomography (CT) showed mildpneumonia. She was diagnosed with an intermediate disease withpneumonia, according to Japanese guidelines [2]. She had a historyof dyslipidemia and had one aggravation risk factor: age > 65-yearold. Her body temperature was 37.2  C and her saturation ofpercutaneous oxygen (SpO2) was 98 % upon arrival. She received
information from the public health center that her specimen had
revealed the COVID-19 variant type.
She was started on favipiravir (3600 mg on day 1, 1800 mg fromday 2 onwards) and dexamethasone (6 mg from day 1 to day 10).
She developed steroid-induced hyperglycemia, which was controlled using insulin. After hospitalization, she showed intermittent fever on day 4 (37.6  C), day 7 (37.3  C), and day 8 (37.9  C),
which was immediately resolved using antipyretics. On themorning of day 7, she noticed that her face had turned red. She
felt heat on both cheeks, without sweat. There was no rash on thetrunk. During the night of day 7, her SpO2 gradually decreased from97 % to 91 %, and CT showed worsening of the pneumonia.
However, she had no upper respiratory symptoms. She was startedon oxygen during the night. On the morning of day 8, her SpO2 had
not improved (92 % with 2 L of O2). She was transferred to anadvanced medical center. Her red face continued until the transfer.
Case 2* Corresponding author.
E-mail address: nakaya1016@yahoo.co.jp (A. Nakaya).

A 68-year-old Japanese woman who developed fatigue andfever (maximum: 38.8  C) was diagnosed with COVID-19. There

http://dx.doi.org/10.1016/j.idcr.2021.e01214
2214-2509/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

A. Nakaya, E. Ogura, Y. Katayama et al.

IDCases 25 (2021) e01214

Table 1
Patients’ characteristics.

AgeSex
Vital on admission

Laboratory data

Case 1Case 2

Case 3BP(mmHg)
HR(bpm)BT( C)
SpO2(%)
D-dimer(mg/mL)
ferritin(ng/mL)
CRP(mg/L)
KL-6(U/mL)

71
F
159/1039036.3970.5
1660.73136

67
F115/8490
36.4
97
0.7
79
0.29
337

78
M
148/81
83
36.7
970.9
315
3.88
556

BP(mmHg)
HR(bpm)BT( C)
SpO2(%)

favipiravir deximesathone
132/8384
37.9
93

favipiravir deximesathone
144/877337.1
90

remdesivir methylprednisolone––––

CT on admission

Treatment
Vital on sudden change

Red Face

CT on sudden change

No sudden change

Case 3

had been an outbreak at her swimming club, which was the same
club to which the patient in Case 1 belonged. She was diagnosed
with mild disease without pneumonia upon arrival. She had twoaggravation risk factors: age > 65 years and hypertension.
Her temperature was 37.1  C and SpO2 97 % upon admission.
She was started on favipiravir (3600 mg on day 1, 1800 mg fromday 2 onwards) and dexamethasone (6 mg on days 1–10). Her
temperature was normal on the next day, and her fatigue
gradually improved. On the morning of day 5, the nurse pointed
out a change in her face color. There was no rash on her trunk, anda red color was localized in her face. She did not feel heat on hercheeks, had no other symptoms, and her SpO2 level was 99 %. Her
vital signs were stable, and she did not complain of any othersymptoms, so we simply observed her. A few hours later, her SpO2
suddenly dropped from 98 % to 94 %. Although she did notcomplain of any new symptoms, we performed CT. CT revealed a
new lesion of pneumonia. She was switched from favipiravir toremdesivir (200 mg/day on day 1, 100 mg from day 2 onwards)
and from dexamethasone to methylprednisolone (1000 mg/dayon days 1–3, 125 mg/day on days 4–5). Her SpO2 dropped to 90 %at the lowest during the night, and she was started on oxygen. The
next morning, she had recovered from the hypoxia (SpO2: 98 %),and oxygen was stopped. Her red face disappeared at that time.
Her pneumonia had resolved and she was discharged 12 days
later.

A 78-year-old Japanese man who developed fatigue, cough, anddysgeusia without fever was diagnosed with COVID-19. His bodytemperature was 36.7  C and his SpO2 97 % upon arrival. His CT
showed pneumonia, and he was diagnosed with intermediate
disease with pneumonia. His medical history included hypertension, dyslipidemia, hyperuricemia, and cerebral infarction. He had
two aggravation risk factors: age > 65 years and hypertension. Hewas started on remdesivir (200 mg/day on day 1, 100 mg from day 2onwards) and methylprednisolone (1000 mg/day on days 1–3, 125
mg/day on days 4–5). The patient’s subjective symptoms
improved. On day 5, he complained that his face was red. He
felt heat on both cheeks, without sweat. His trunk did not change,
he was afebrile, and his SpO2 was 97 %. The red face continued for 2days. He showed no aggravation of the disease, and he wasdischarged 14 days after hospitalization.
Discussion
Several clinical manifestations have been reported since theCOVID-19 pandemic emerged. However, red face has not yet beenreported.
In Cases 1 and 2, a red face was observed just before the sudden
deterioration. In Case 1, the patient developed intermittent fever,2

A. Nakaya, E. Ogura, Y. Katayama et al.

IDCases 25 (2021) e01214

from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review
by the Editor-in- Chief of this journal on request.

but the red face was not associated with any fever; instead, it wasseen continuously, even when the fever was down. In Case 2, thepatient had no fever or heat on the cheeks. In all cases, the red face
was not restricted to the cheeks; it was on the whole face, was notnecessarily accompanied by heat on the cheeks, and occurred
without sweat or fever. In Cases 1 and 2, the patients developed
worsening pneumonia after they developed red face, so wereasoned that the red face may have reﬂected cytokine release.
Both showed a red face in the morning and developed pneumonia
in the afternoon, so there was a time lag.
Our patients had already started steroid therapy, so we cannot
exclude the inﬂuence of steroids. Flush has been reported as anadverse effect of steroids. The timing of steroid-related ﬂush isunclear, but most adverse effects of steroids occur soon after thedrug start. Our patients developed red face 5–7 days after steroidadministration. In Case 3, methylprednisolone was initiated, but
the patient showed red face on day 7, when the methylprednisolone had already been stopped. Therefore, the timing of red faceand steroid use did not match. We believe that the red face was not
related to the steroids, but rather that the steroids were masking
the symptoms of a cytokine storm, which is why the patient in Case
3 did not develop severe pneumonia.
We believe that this symptom is a speciﬁc sign of the COVID-19
caused by SARS-CoV-2 alpha variant and that it may be predictiveof a sudden deterioration. We hope this report will help medicalworkers struggling with COVID-19 on the frontline.

Authors contribution
AN: study design, data collections, data analysis, writing, EO:
data analysis, YK, MY, EY, KH, ST, YT, YM, MH, MY, YK, YA, KY, SS, KO,
KI: data collections.
Author statement
Aya Nakaya: Conceptualization, Writing-Original Draft, Eiji
Ogura: Supervision, Yuki Katayama: Data Curation, Masami Yoshii :Data Curation, Eiko Yoshino :Data Curation, Kazuya Hozumi :DataCuration, Saori Tago: Data Curation, Yuko Teranishi: Data Curation,Yuki Minamibashi: Data Curation, Makiko Harada: Data Curation,Mami Yoshioka: Data Curation, Yuri Kawano: Data Curation, Yuka
Arai: Data Curation, Keno Yoshida: Data Curation, Shozo Shimizu:
Data Curation, Kazuma Ogura: Data Curation, Katsuaki Iwashita:
Data Curation.
Acknowledgments
We thank Yuu Tochitani, Rika Umeda, Shizuka Morita, Yohei
Takano, Masanori Fujie, Tsutomu Ito, Yuko Hirai, Ayako Igosaki, andSatomi Ozawa for their assistance.

Declaration of Competing Interest
References
The authors report no declarations of interest.
[1] Ministry of Health, Labor and Welfare. Information on Covid-19. 2021. .
(Accessed 24 May 2021) https://www.mhlw.go.jp.
[2] Ministry of Health, Labor and Welfare and the National Institute of Infectious
Diseases. Clinical management of patients with COVID-19 (version 4.2). 2021.

Sources of funding
This study has no funding for research.
Consent
This study was approved by the institutional review board ofBiwako Ohashi Hospital. Written informed consent was obtained3