key: cord-258029-gyvg7ffa authors: Moolasart, Visal; Wongsawat, Jurai; Phokhom, Priyanut; Thienthong, Varaporn title: Favipiravir-based regimen for coronavirus disease 2019 pneumonia for a 47-day-old male newborn date: 2020-10-15 journal: SAGE Open Med Case Rep DOI: 10.1177/2050313x20964046 sha: doc_id: 258029 cord_uid: gyvg7ffa Coronavirus disease 2019 pneumonia in the newborn is a difficult-to-treat condition. Early clinical signs of pneumonia are nonspecific and present as respiratory distress of varying severity, and tachypnea is a predominant clinical sign. A 47-day-old, asymptomatic male newborn of coronavirus disease 2019 infected mother tested positive for coronavirus disease 2019 by reverse transcription polymerase chain reaction. During hospitalization, he developed progressive tachypnea, tachycardia, and chest radiography abnormalities, and was diagnosed as coronavirus disease 2019 pneumonia. He was treated with favipiravir, hydroxychloroquine, and lopinavir/ritonavir. A favipiravir-based regimen may be the drug of choice for coronavirus disease 2019 pneumonia in the newborn. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus causing coronavirus disease 2019 (COVID- 19) , which emerged in Wuhan, Hubei Province, China, in mid-December 2019 to become pandemic disease. 1, 2 Adults may have asymptomatic to lifethreatening disease, and older adults have greater risk of severe disease. 3, 4 Infection in infants aged under 1 year was recently reported, 5 and those without underlying diseases had mild COVID-19. 6 In Hubei, pediatric cases were treated with antiviral therapy (interferon, arbidol, oseltamivir, lopinavir/ritonavir (LPV/r), or empirical antibiotics), and a few critical cases also received invasive mechanical ventilation, systemic corticosteroids, and intravenous immunoglobulin. 7 No deaths were reported. 7 To date, no recommendations from randomized controlled trials (RCTs) have been published for any specific anti-SARS-CoV-2 treatment for patients with COVID-19. Favipiravir is a broad-spectrum oral antiviral agent with in vitro anti-SARS-CoV-2 activity. Data on its effectiveness and optimal dosage for COVID-19 are limited, especially in the newborn. 8 A 47-day-old, male newborn was asymptomatic but had household contact with his COVID-19 infected mother. He was hospitalized due to the household contact and tested positive for COVID-19 infection. He was transferred to the Bamrasnaradura Infectious Diseases Institute (BIDI) for isolation in negative pressure. He was the first child of consanguineous parents and was born by cesarean section with a birth weight of 2895 g. His mother had malaise, nausea, and vomiting. The newborn had no previous hospitalizations. On admission, the newborn was alert, afebrile, and not tachypneic. His vital signs were a body temperature of 36.8°C, blood pressure of 120/70 mm Hg, pulse rate of 148 beats/min, a respiratory rate of 28 to 38 breaths/min, and a peripheral oxygen saturation of 99% on room air. The patient's complete blood count results were a white blood cell count of 12,000/mL (lymphocytes 70%, neutrophil 25%), the neutrophil to lymphocyte ratio (NLR) of 0.36, hemoglobin of 10.7 g/dL, and platelet count of 326,000/mL. On the day of admission, reverse transcription polymerase chain reaction (RT-PCR) for COVID-19 was positive, while a nasopharyngeal and throat swabs for influenza type A and B by rapid test, respiratory syncytial virus by RT-PCR, and hemoculture were all negative. Chest radiography showed no abnormalities ( Figure 1 ). Azithromycin was given as empirical treatment. On day 6 of admission, he was tachypneic (a respiratory rate of 40 breaths/min) and tachycardic, and his chest radiography showed abnormalities ( Figure 2 ). According to the Thailand Ministry of Health guidelines for COVID-19, 9 a cocktail regimen of favipiravir (day 1: 30 mg/kg/dose BID, days 2-10: 10 mg/kg/dose BID), hydroxychloroquine (day 1: 10 mg/kg/dose BID, days 2-10: 6.5 mg/kg/dose BID), and LPV/r (days 1-10: 300/75 mg/m 2 / dose BID) were given for a total of 10 days. On day 8 of admission, his clinical condition began to improve. On day 14, his chest radiography showed decreased haziness (Figure 3 ). On day 20 of admission, he was discharged from hospital in good general condition. He and his parents were quarantined and monitored for 14 days. Serial RT-PCR for COVID-19 was taken every 72 h. The results were positive on days 1, 4, and 7, and then negative on day 10 of quarantine and monitoring. This study was reviewed and approved by the Institutional Review Board of the BIDI, Ministry of Public Health, Nonthaburi, Thailand. The reference approval letter codes are S019h/63_Exempt. Initial clinical studies revealed the promising therapeutic potential of several drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, a repurposed antimalarial drug that interferes with the virus endosomal entry pathway. 8 LPV/r is a pneumonia-associated adjuvant drug, which was used in the clinical treatment of patients with COVID-19, 10 and hydroxychloroquine showed good clinical outcomes among patients with COVID-19, which is thought to be due to the excellent efficiency of virus clearance after administration of this combination therapy. 11 The mechanism of actions of favipiravir is thought to relate to the selective inhibition of viral RNA-dependent RNA polymerase. 12 In February 2020, favipiravir was studied in China as an experimental treatment for COVID-19. 13, 14 A previous study showed it had a favorable safety profile regarding total and serious adverse events. However, safety concerns remain, including hyperuricemia, teratogenicity, and QTc prolongation. Favipiravir may be safe and tolerable for short-term use, but more evidence is needed to assess the effects of long-term treatment. 15 Chloroquine or hydroxychloroquine was reported to have potential broad-spectrum antiviral activity by increasing the endosomal pH required for virus/cell fusion and interfering with the glycosylation of cellular receptors of SARS-CoV. 5, 16 In early in vitro studies, chloroquine was found to block COVID-19 infection at low-micromolar concentrations, with a half-maximal effective concentration (EC50) of 1.13 µM and a half-cytotoxic concentration (CC50) greater than 100 µM. 17 Different radiographic patterns are seen as COVID-19 progresses. Typically, after the first to second week of the onset, lesions progress to bilateral diffuse pattern with consolidations. By contrast, both ground-glass opacification and consolidation were present relatively early in SARS. 18 Patients with COVID-19 developed dyspnea within a median (interquartile range (IQR)) of 5 days (1-10) after the onset of illness, while others did not develop any respiratory distress. 19 Pediatric patients with COVID-19 had a mild inflammatory infiltration, 20 which indicates that they are more likely to recover than adults after symptomatic treatment. A favipiravir-based regimen may be the drug of choice for COVID-19 pneumonia in the newborn, safe and tolerable in short-term use, but more evidence is needed to assess the effects of long-term treatment. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This study was reviewed and approved by the Institutional Review Board of the Bamrasnaradura Infectious Diseases Institute, Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi 11000, Thailand. The reference approval letter codes are S019h/63_Exempt. The author(s) received no financial support for the research, authorship, and/or publication of this article. The patient's mother provided written permission for publication of this case report and associated images. Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article (Thai language version). Visal Moolasart https://orcid.org/0000-0002-1151-4790 FeRences 1 and World Health Organization. Novel coronavirus (2019-nCoV) situation reports Epidemiological characteristics and prevention and control measures of corona virus disease 2019 in children Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model Coronavirus disease (COVID-19) and neonate: what neonatologist need to know Clinical characteristics of children with coronavirus disease 2019 in Hubei, China A review of SARS-CoV-2 and the ongoing clinical trials Thailand ministry of public health. Thailand guideline for COVID-19 Clinical efficacy of lopinavir/ ritonavir in the treatment of Coronavirus disease 2019 Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial The ambiguous basepairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5′-triphosphate towards influenza a virus polymerase Therapeutic options for the 2019 novel coronavirus (2019-nCoV) BRIEF-Corrected-Zhejiang Hisun Pharma gets approval for clinical trial to test flu drug Favipiravir for pneumonia caused by new coronavirus. Reuters Healthcare. Epub ahead of print 17 A review of the safety of favipiravir-a potential treatment in the COVID-19 pandemic? Effects of chloroquine on viral infections: an old drug against today's diseases Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Radiographic and clinical features of children with 2019 novel coronavirus (COVID-19) pneumonia