key: cord-0904283-95c72rl8
authors: Mori, Nobuaki; Katayama, Mitsuya; Nukaga, Shigenari
title: Triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia
date: 2020-10-05
journal: J Microbiol Immunol Infect
DOI: 10.1016/j.jmii.2020.09.003
sha: 8c6d68e98d086edf14b662bc4002afe4bec3d39b
doc_id: 904283
cord_uid: 95c72rl8

No specific therapy is available for COVID-19. We report the effectiveness and adverse effects of triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia. The patient’s clinical condition improved within 5 days in response to therapy.

showed that patients with COVID-19 who were given hydroxychloroquine had greater SARS-CoV-2 clearance and a shorter time to fever normalization than the control group 2 . However, an observational study showed hydroxychloroquine administration was not associated with lower the risk of intubation or death 3. Addition of azithromycin to hydroxychloroquine has been found to be associated with faster virologic clearance compared with hydroxychloroquine monotherapy 4 . Ciclesonide, an inhaled corticosteroid used to treat asthma, has been demonstrated to inhibit replication of the SARS-CoV-2 5 . However, the clinical effectiveness of combination therapy with these three agents for COVID-19 pneumonia is unknown.

J o u r n a l P r e -p r o o f Therefore, we report the effectiveness and safety of triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia in adult patients.

This case-series study was conducted at the National Hospital Organization Tokyo Medical Center located in Tokyo, Japan, from March to April 2020.

Patients aged 18 years or older were eligible if they had a positive reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 in nasopharyngeal swab specimens and had pneumonia confirmed by chest imaging. The following data were collected from medical charts for all patients: age, sex, underlying diseases, smoking history, symptoms, use of angiotensin converting-enzyme inhibitor or angiotensin II receptor blocker medication, body temperature, oxygen saturation in ambient air on admission, days of administrating triple therapy from symptom onset, time to fever and respiratory symptom normalization, adverse events, and outcome.

Five patients with COVID-2019 pneumonia were administered triple therapy during the study period. The basic and clinical patient characteristics are shown in Hydroxychloroquine blocks viral entry into cells by inhibiting glycosylation of host receptors, proteolytic processing, endosomal acidification, and attenuation of cytokine production and inhibition of autophagy and lysosomal activity in host cells 6 . Although azithromycin belongs to a class of antibiotics used to treat several bacterial infections, its use as potential antiviral has come to light in the recent years through studies on its immunomodulatory and anti-inflammatory effects 7, 8 . Adding azithromycin to the J o u r n a l P r e -p r o o f treatment regimen may also be effective to treat underlying potential secondary infections. Ciclesonide has an anti-inflammatory effect on respiratory epithelium 5 .

Although there is no clear evidence, we expected an additive or synergistic effect of using ciclesonide which has anti-inflammatory effect on respiratory epithelium for COVID-19 pneumonia, in addition to the viral clearance effect of the combination of hydroxychloroquine and azithromycin. In our report, response within 5 days from administering triple therapy lead to favorable outcome. However, the difference in host factors influencing the response to triple therapy is unknown. The Infectious Diseases

Society of America COVID-19 guideline warns about the potential for QT prolongation with the combination of hydroxychloroquine and azithromycin 7 . Although combination therapies with different mechanisms of action generally have an additive or synergistic effect, it is also necessary to consider the risk of synergistic adverse effects. Therefore, if there is no response to therapy within 5 days, it should be discontinued because of the

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Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base Comment. The Lancet Respiratory

Observational study of hydroxychloroquine in hospitalized patients with Covid-19

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15

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The immunomodulatory