Case Report
Case 1
A 61-year-old Japanese man was admitted to our hospital on February 23,
2020, with fever, general malaise, and diarrhea. He had a history of
recent travel from Japan to Europe on February 9, and returned to Japan
on February 15. On February 16, (day 1 of illness) he reported general
malaise and a fever of less than 38°C. Because of continued fever and
malaise and the onset of diarrhea, he visited our hospital on February
23 (day 8 of illness). Upon admission, his body temperature was 39.7°C,
dyspnea was not observed, and his oxygen saturation was 99% on ambient
air. Laboratory test results showed lymphocytopenia (592/µL) and
elevated C-reactive protein (CRP 3.98 mg/dL) and ferritin (937 ng/mL)
levels (Fig. 1). Chest radiography and chest computed tomography (CT)
revealed multiple bilateral ground-glass opacities(GGO) in his lungs
(Fig. 2). The day after admission (day 9 of illness), his nasal swab
sample was positive for COVID-19 by a real-time reverse transcriptase
(RT) polymerase chain reaction (PCR) assay for severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2).
Figure 1 shows the patient’s clinical course. He was immediately
admitted to the isolation ward. Regardless of immediate administration
of empiric antibiotic therapy (ceftriaxone [2 g daily]) and
antipyretic medication, his hyperpyrexia did not improve and his
hypoxemia gradually worsened. On February 26 (day 11 of illness), oxygen
administration was initiated because of the respiratory failure, and
antiviral therapy with lopinavir/ritonavir (400 mg/100 mg twice daily)
was started. However, his respiratory failure got worsened. On February
29 (day 14 of illness), favipiravir (1800 mg twice daily on day 1; 800
mg twice daily, days 2-14) was added to the lopinavir/ritonavir therapy.
Two days after the addition of favipiravir (day 16 of illness), his
hyperpnea, pyrexia, appetite, and general malaise were clearly improved.
On March 6 (day 20 of illness), the patient no longer required oxygen.
The patient’s course as reflected by the laboratory data showed that
while the CRP and ferritin levels gradually increased after admission,
those levels gradually decreased and the patient’s lymphocytopenia
gradually improved after the initiation of lopinavir/ritonavir and the
addition of favipiravir. Representative cytokine levels were examined on
March 4 (day 18 of illness); Interleukin (IL)-5 (4 pg/ml), IL-6 (10
pg/ml), Tumor Necrosing Factor α (TNF-α) (4.6 pg/ml) and Interferon γ
(IFN-γ) (7.8 pg/ml) (Table 1). After twice confirmation of negative for
RT-PCR for SARS-CoV-2, he was discharged on March 18 (day 32 of
illness). The post-treatment chest CT revealed that GGO in bilateral
lungs were increased, however intra- and interlobular septal thickening
regeion, bronchioectasis within GGO were emarged on 17 Mar (Fig. 2).
Obvious toxicity related to the combination therapy was never observed.
Case 2
A 50-year-old Japanese man was admitted to our hospital on February 26,
2020, with fever, nausea, and cough. His travel history was similar to
that of Case 1. He reported that he first developed a fever of 38.5°C on
February 16 (day 1 of illness). His initial laboratory test results
showed an elevated CRP (4.44 mg/dL) level. Chest radiography revealed
very small ground-glass opacities in the lower right lung and a linear
shadow in the lower left lung. Chest CT revealed that the small amount
of ground-glass opacities with linear shadows were located dorsally and
bilaterally in the lower lobes of the lungs (Fig. 1). COVID-19 was
confirmed from a nasal swab specimen assayed for SARS-CoV-2 by real-time
RT-PCR.
Figure 2 shows the patient’s clinical course. Empiric antibiotic therapy
(ceftriaxone [2 g daily]) was first administered. On February 28
(day 13 of illness), lopinavir/ritonavir (400 mg/100 mg twice daily) was
started. On February 29 (day 14 of illness), favipiravir (1800 mg twice
daily on day 1; 800 mg twice daily, days 2-7) was added. Throughout the
patient’s hospitalization, he remained afebrile and asymptomatic. Twice
RT-PCR assay for SARS-CoV-2 was negative and he was discharged from the
hospital on March 7 (day 22 of illness). The patient’s course as
reflected by the laboratory data showed that his CRP levels gradually
decreased after admission. However, his ferritin level worsened once,
and gradually improved after starting lopinavir/ritonavir and adding
favipiravir. Post-treatment chest CT revealed while a part of GGO
regions were improved improvement, the linear shadow in GGO were
thickened March 17 (Fig. 2). Obvious toxicity related to the combination
antiviral therapy was never observed.
Case 3
A 54-year-old Japanese man was admitted to our hospital on April 10,
2020, with fever, dyspnea and diarrhea. He had been Tokyo from March 30
to 31 to help his son with house-moving. He reported that he first
developed a fever of 39°C on April 4 (day 1 of illness). His initial
laboratory test results showed an elevated CRP (3.85 mg/dL) level. Chest
CT revealed diffuse ground-glass opacities in bilateral lungs (Fig. 1).
COVID-19 was confirmed from a nasal swab specimen assayed for SARS-CoV-2
by real-time RT-PCR.
Figure 2 shows the patient’s clinical course. Although
lopinavir/ritonavir (400 mg/100 mg twice daily) and meropenem (1 g
thrice daily ) was started on April 11 (day 8 of illness), he got to
worse as a respiratory failure on the next day. On April 13 (day 10 of
illness), favipiravir (1800 mg twice daily on day 1; 800 mg twice daily,
days 2-14) was added. Four days after the addition of favipiravir (day
16 of illness), his hyperpnea, pyrexia, appetite, and general malaise
were improved. On April 22 (day 19 of illness), the patient no longer
required oxygen. The patient’s course as reflected by the laboratory
data showed that while the CRP, ferritin and β2 microglobulin levels
gradually increased after admission, those levels gradually decreased
and the patient’s lymphocytopenia gradually improved after the addition
of favipiravir. Representative cytokine levels were examined on April
10, 13 and May 7 (day 7, 10 and 30 of illness, respectively). IL-6,
TNF-α and Tumor Growth Factor β1(TGFβ1) level were abnormally elevated
(Table 1). After twice confirmation of negative for RT-PCR for
SARS-CoV-2, he was discharged on May 11 (day 34 of illness). The
post-treatment chest CT revealed that bilateral intra- and interlobular
septal thickening regeion were emarged on 11 May (Fig. 2). Obvious
toxicity related to the combination therapy was never observed.