key: cord-0759035-b4j2bun3
authors: Enomoto, Takatoshi; Shiroyama, Takayuki; Hirata, Haruhiko; Amiya, Saori; Adachi, Yuichi; Niitsu, Takayuki; Noda, Yoshimi; Hara, Reina; Fukushima, Kiyoharu; Suga, Yasuhiko; Miyake, Kotaro; Koyama, Shohei; Iwahori, Kota; Nagatomo, Izumi; Tokuhira, Natsuko; Uchiyama, Akinori; Takeda, Yoshito; Kumanogoh, Atsushi
title: COVID‐19 in a human T‐cell lymphotropic virus type‐1 carrier
date: 2022-02-15
journal: Clin Case Rep
DOI: 10.1002/ccr3.5463
sha: 773f714cd98ad88a78d718f76244beac992e9b12
doc_id: 759035
cord_uid: b4j2bun3

This is the first report of COVID‐19 in a human T‐cell lymphotropic virus type‐1 (HTLV‐1) carrier. HTLV‐1 infection can cause immune dysfunction even in asymptomatic carriers. This case highlights the need for guidance on management of COVID‐19‐HTLV‐1 coinfection, specifically on the appropriate use of corticosteroid treatment while considering secondary infection.

COVID-19 in individuals with human T-cell lymphotropic virus 1 type-1 (HTLV-1) infection, and a need for guidance on management of patients with HTLV-1 and COVID-19 coinfection. 2 Herein, we report a fatal case of COVID-19 in a previously undiagnosed HTLV-1 carrier.

A 73-year-old man with a 20-pack year smoking history presented to the hospital with a 6-day history of fever. His medical history included diabetes, dyslipidemia, and surgery for gallbladder and colon cancer.

On physical examination, his vital signs were as following: blood pressure 124/78 mmHg, respiratory rate 23 breaths per minute, peripheral oxygen saturation (SpO 2 ) 94% (in room air), and the body temperature 37.0°C. Chest computed tomography (CT) showed bilateral subpleural ground-glass opacities. A nasopharyngeal specimen tested positive for SARS-CoV-2 infection using real-time reverse transcriptase-polymerase chain reaction. Laboratory tests showed an elevated C-reactive protein (CRP) (4.27 mg/dl; upper limit of normal, 0.3 mg/ dl), while other laboratory test results were normal. He was initiated a compassionate administration of favipiravir (1,800 mg twice daily, followed by 800 mg twice daily) and ciclesonide inhalation. He was transferred to our hospital on Day 8 after symptom onset due to progressive respiratory failure. His vital signs were pulse rate 67 beats per minute, blood pressure 145/73 mm Hg, respiratory rate 29 breaths per min, SpO 2 96% (on 5 L/ min oxygen), and the body temperature 36.9°C. He was admitted to the intensive care unit (ICU) and mechanically ventilated on the same day due to further worsening of respiratory failure.

The patient's clinical course is summarized in Figure 1 . Chest X-ray ( Figure 2A ) and CT on admission showed marked radiographic worsening with bilateral subpleural ground-glass opacities. His laboratory test results showed lymphopenia (840 cells/µl) and slightly elevated CRP and ferritin levels, but his D-dimer level was normal. Screening tests for infectious diseases revealed HTLV antibodies on chemiluminescent immunoassay. The results of a line immunoassay and PCR for the HTLV-1 provirus were positive, confirming this diagnosis of asymptomatic HTLV-1 infection. He was treated with dexamethasone (6 mg daily), remdesivir (200 mg daily followed by 100 mg daily), and intravenous meropenem (1 g three times a day). His respiratory condition and radiographic imaging F I G U R E 1 Clinical course of the patient. mPSL, methylprednisolone; MRSA, methicillin-resistant Staphylococcus aureus; ARDS, acute respiratory distress syndrome were improved ( Figure 2B ), and he was extubated after two weeks of mechanical ventilation.

However, he developed recurrent respiratory failure with radiographic worsening and was reintubated on Day 24 after symptom onset. He was treated with intravenous piperacillin/tazobactam (4.5 g four times a day) for suspected bacterial pneumonia. The dexamethasone was switched to prednisolone (10 mg daily), followed by tapering and discontinuation; however, his condition did not improve significantly. He developed a septic shock and severe ARDS due to a catheter-related Staphylococcus epidermidis bloodstream infection 41 days after symptom onset. Laboratory tests showed an elevated β-D glucan level (19.7 pg/ml; upper limit of normal, 11 pg/ml). He also developed mouth ulcers, and human herpesvirus 1 was detected in a nasopharyngeal swab by metagenomic next-generation sequencing. Therefore, we started intravenous administration of piperacillin/tazobactam (4.5 g four times a day), vancomycin (targeting trough concentrations of 15 to 20 mg/L), sulfamethoxazoletrimethoprim (3 g three times a day for 21 days), and acyclovir (500 mg three times a day for 10 days). We also restarted corticosteroids to treat ARDS, septic shock, and possible recurrence of COVID-19-related inflammation. Although his clinical condition was gradually improved, laboratory tests showed a sudden elevation of his β-D glucan level (347.2 pg/ ml) on Day 59 after symptom onset. Candida glabrata was cultured from gastric juice and stool specimens. Although blood cultures were negative, he was diagnosed with invasive candidiasis which we attributed to the use of corticosteroids, broad-spectrum antibiotics, and vascular devices, as well as to a prolonged ICU stay. He was treated with intravenous micafungin (150 mg daily) and amphotericin B (300 mg daily), and his β-D glucan levels were transiently decreased; however, his clinical condition and chest infiltrations gradually worsened ( Figure 2C ).

He eventually died 93 days after symptom onset due to uncontrollable infections.

We describe a fatal case of COVID-19 in an HTLV-1 carrier. Despite receiving intensive care, including invasive ventilatory support, antibiotics, antifungals, antivirals, and corticosteroids, the patient died of multiple secondary infections. Although previous studies have found that the risk factors for false-positive HTLV-1 results include cross-reactivity of severe acute respiratory syndrome coronavirus 1 infection, 3,4 the patient was confirmed to have HTLV-1 infection by both antibody and PCR tests. To the best of our knowledge, this is the first case report of COVID-19 in an HTLV-1 carrier.

Although HTLV-1 can cause several fatal diseases such as adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis, the majority of infected individuals remain asymptomatic throughout their lives. 5 Importantly, HTLV-1 infection can cause immune dysfunction even in asymptomatic carriers. 5, 6 Infection of CD4+ T cells by HTLV-1 might reduce CD4+ T-cell function, and expression of HTLV-1 regulatory proteins inhibits pathogen sensing. 5,7 COVID-19 can cause a decrease in CD4+ T and CD8+ T cells 8 and be a risk factor for fungal infections and reactivation of herpesvirus infection, including cytomegalovirus infection. 9, 10 In our patient, possible immune dysfunction by HTLV-1 and SARS-CoV-2 coinfection could be a factor in multiple secondary infections. There is only one previous case report of COVID-19 in a patient with HTLV-1 infection, in which the patient with ATL recovered without developing secondary infections. 11 However, the reasons for our patient developing a more severe disease than that developed by the patient with ATL are unclear because of the differences in patient backgrounds. The patient with ATL developed COVID-19 while undergoing chemotherapy and was also treated with corticosteroids. Therefore, further accumulation of cases is required to better understand the clinical features of COVID-19 in patients with HTLV-1 infection.

In the present case, the patient had a relatively good response to the initial steroid treatment and relapsed after its discontinuation, which motivated us to continue steroids while tapering. However, long-term corticosteroid therapy in patients with severe COVID-19 may increase the risk of invasive fungal infection. 12, 13 Therefore, it is needed to optimize corticosteroid treatment for COVID-19, especially in immunocompromised patients such as HTLV-1 carriers.

In conclusion, this report describes a fatal case of COVID-19 in an HTLV-1 carrier. This case highlights the need for the accumulation of similar cases and guidance on how to prevent and manage secondary infection in patients with COVID-19-HTLV-1 coinfection. Clinicians should bear in mind that long-term steroid use may contribute to an increased risk of secondary infection in such patients.

Analysis of epidemiological and clinical features in older patients with coronavirus disease 2019 (COVID-19) outside Wuhan

Human T leukaemia type 1 and COVID-19

False positive antibody results against human T-cell lymphotropic virus in patients with severe acute respiratory syndrome

A retrospective analysis of false-positive infectious screening results in blood donors

Modulation of innate immune responses during human T-cell leukemia virus (HTLV-1) pathogenesis

Human T-lymphotropic virus 1: recent knowledge about an ancient infection

Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state

Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou City

Co-infections in people with COVID-19: a systematic review and meta-analysis

Herpes simplex virus and cytomegalovirus reactivations among severe COVID-19 patients

COVID-19 pneumonia in a patient with adult T-cell leukemia-lymphoma

COVID-19-associated candidiasis (CAC): an underestimated complication in the absence of immunological predispositions?

Occurrence of invasive pulmonary fungal infections in patients with severe COVID-19 admitted to the ICU

We would like to thank all the colleagues and staff who were involved in the treatment of the patient presented in this case.

All authors declare that they have no competing interests.

TE involved in study design, data collection, and manuscript preparation. TS involved in study design and manuscript preparation. HH, SA, YA, TN, YN, NT, and AU collected the data. All authors participated in revising the manuscript critically and approved the final manuscript.

Patient gave written informed consent to publish this case report and related evidence.

Local ethical guidelines state no need of ethical approval for a case report.

Data sharing was not applicable to this article as no datasets were generated or analyzed during the current study.

Takatoshi Enomoto https://orcid. org/0000-0002-1771-6684 Takayuki Shiroyama https://orcid. org/0000-0002-2816-9428