April 15, 2020

Delayed initiation of remdesivir beneficial for COVID‐19, neutrophil-to-lymphocyte ratio predicts mortality in hospitalised patients with COVID-19, and arbidol monotherapy for COVID-19

By Denise Baez

NEW YORK -- April 15, 2020 -- In today’s DG Alert, we cover late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor for mortality in hospitalised patients with coronavirus disease 2019 (COVID-19), and the efficacy of arbidol monotherapy versus lopinavir/ritonavir for COVID-19.

A case report published in Pharmacotherapy describes the successful treatment of a patient with COVID-19 with remdesivir antiviral therapy 13 days after symptom onset. 

A male aged 40 years was admitted to Mercy Health Saint Mary’s Hospital, Grand Rapids, Michigan, 3 days after the onset of COVID-19 symptoms (cough, fever, shortness of breath). The patient was obese, had hypercholesterolemia, and had a history of anxiety, depression, and vaping with nicotine. 

The patient’s condition progressed and he was mechanically ventilated. A request for compassionate use remdesivir was submitted on the same day he tested positive for SARS-CoV-2 on positive real-time reverse transcriptase polymerase chain reaction (RT-PCR).

Supportive measures, including a 5‐day course of hydroxychloroquine, cefepime 2 g every 8 hours, and azithromycin 500 mg every 24 hours were maintained until remdesivir was delivered on day 9 of hospitalisation (13 days after symptom onset). A 200 mg IV loading dose was administered to the patient, followed by 100 mg IV maintenance dose every 24 hours for the next 9 days. 

During the following 48 hours, the patient continued to progress and was able to tolerate aggressive mechanical ventilation weaning. On day 16 of illness (hospital day 12), he was extubated without incident. Oxygen saturations remained stable requiring 2 to 3 litres of oxygen by nasal cannula and his oxygenation saturation was maintained on room air by day 17 of illness (hospital day 13).The patient continues to be in stable condition on room air and is progressing towards discharge. 

“Late initiation of remdesivir may be effective in treating SARS‐CoV‐2, unlike antivirals utilised for different disease states, such as oseltamivir, which are most effective when started as soon as possible following symptom onset,” wrote Julie J. Belfer, Mercy Health Saint Mary’s, and colleagues. “Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS‐CoV‐2 as well as to meet manufacturing demands.”

Another study, published in the Journal of Infection, provides evidence that NLR is an independent risk factor for in-hospital mortality in patients with COVID-19, especially for male patients. 

Yuwei Liu, MD, Zhongnan Hospital of Wuhan University, Wuhan, China, and colleagues retrospectively analysed 245 patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1, 2020, to February 29, 2020. 

In-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.01-1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14-224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02-1.19; P = 0.016).

“Assessment of NLR may help identify high-risk individuals with COVID-19,” the authors concluded. 

Lastly, another study also published in the Journal of Infection showed that arbidol monotherapy is superior to lopinavir/ritonavir in the treatment of COVID-19.

Zhen Zhu, MD, Third People’s Hospital of Changzhou, Changzhou, China, and colleagues analysed data from 34 patients with laboratory-confirmed COVID-19 who received lopinavir/ritonavir 400 mg/100 mg and 16 patients with COVID-19 who received arbidol monotherapy (0.2 g tid). The cycle threshold values of open reading frame 1ab and nucleocapsid genes by RT-PCR assay were monitored during antiviral therapy. 

None of the patients developed severe pneumonia or acute respiratory distress syndrome. On day 14 after the admission, no viral load was detected in the arbidol group compared with 15 (44.1%) patients in the lopinavir/ritonavir group. In addition, patients in the arbidol group had a shorter duration of positive RNA test compared with those in the lopinavir/ritonavir group (P< 0.01). 

“Our data suggest that arbidol monotherapy is more effective than lopinavir/ritonavir in treating COVID-19,” the authors concluded.

SOURCE: Pharmacotherapy, Journal of Infection
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