key: cord-0879512-pj4zjy1k
authors: Malik, Muhammad Irfan; Zafar, Sardar Al Fareed; Malik, Muna; Qayyum, Fabiha; Akram, Iqra; Arshad, Ammarah; Waheed, Khalid; Saleem, Jodat; Jabbar, Abdul; Tahir, Muhammad Junaid; Yousaf, Zohaib
title: The utility of remdesivir in SARS-CoV-2: A single tertiary care center experience from a developing country
date: 2022-02-08
journal: Explor Res Clin Soc Pharm
DOI: 10.1016/j.rcsop.2022.100107
sha: 7802420a36ffcb13d8ca2414e51e3c965ac59092
doc_id: 879512
cord_uid: pj4zjy1k

BACKGROUND: Remdesivir is a monophosphoramidate prodrug of an adenosine analog, and it has a broad-spectrum antiviral activity against paramyxoviruses, flaviviruses, and coronaviruses. Remdesivir is associated with decreased hospital stay and improved outcomes in coronavirus- disease 2019 (COVID-19). METHODOLOGY: Of 846 suspected COVID-19 patients admitted to the hospital, 612 SARS-CoV-2 nasopharyngeal RT-PCR positive patients were evaluated for enrollment in this prospective cohort study. 159 RT-PCR positive patients were given remdesivir. Their clinical, biochemical parameters, hospital stay, and outcomes related to morbidity and mortality were followed. RESULTS: Out of the 159 patients, 141 recovered after remdesivir use. The Chi-square test for independence examined the relation between the day of the first dose, dose of remdesivir, and clinical outcome. The standardized case fatality ratio (CFR) in the 453 hospitalized patients who did not receive remdesivir was 32.89% (N = 149) as compared to 11.32% (N = 18) in the patients who received remdesivir. These findings are in keeping with the therapeutic value of remdesivir in symptomatic SARS-CoV-2 infection of varying severity. CONCLUSION: The use of remdesivir is associated with a decrease in the severity of the SARS-CoV-2 infection. Its use is also associated with a decreased length of hospital stay and lower mortality than the patients who did not receive remdesivir.

In December 2019, the first case of severe acute respiratory coronavirus 2 (SARS-CoV-2) was reported, that later resulted in one of the largest pandemics in the recent history. 1, 2 Clinical presentation varies from asymptomatic to life-threatening pneumonia, leading to acute respiratory failure, multiorgan failure, and death. 3 The morbidity and mortality associated with this novel virus have piqued clinicians' and researchers' interest especially in the potential primary prevention and possible effective treatments. 4 Reducing the severity of the disease, inhospital stay, and improving the disease-associated morbidity and mortality are the other areas of interest for this novel virus. Since the start of the pandemic, there is a renewed focus on  COVID-19 patients who failed to respond to therapy. The failure to therapy was as defined by either clinical deterioration or worsening of the laboratory findings or worsening radiological findings post local standard of care (antibiotics, methylprednisolone, and enoxaparin sodium) as determined by the treating clinician i.e. o More than 50% radiological deterioration.

 Patients on Invasive mechanical ventilation (IMV).

 History of allergy to remdesivir or any of its components  Presences of chronic renal failure > 4 stage, GFR < 30ml/min/1.73m 2 .

 ALT/AST > 5 times than normal values. 

A loading dose of 200 mg Intravenous (IV) remdesivir was given to moderate disease severity patients of COVID-19. This was followed by the maintenance dose of 100 mg IV for a minimum of 5 days and a maximum of 10 days.

Data was collected from the hospital's electronic medical record. Each patient's data was abstracted into a case record form (CRF) and was subsequently accessed by study investigators before being exported into a study-specific excel spreadsheet. Each entry was coded using a unique patient identifier, accessible only to investigators. Links between the names, and the J o u r n a l P r e -p r o o f

A total of 159 COVID-19 patients were received remdesivir. The majority were males (60%, n=96), and the majority (48%, n=76) ranged between 46-60 years of age. The mean age was 47.54 S. D ± 12.70 The patients were categorized as having symptoms of moderate disease according to guidelines. (Table 1 ) The percentage of lungs involvement in Chest X-Ray (CXR) of the patients of COVID-19 was; 9 patients (6%) had < 25% unilateral involvement of lungs in CXR, 84 patients (53%) had <25% bilateral involvement of lungs, 35 patients (22%) had 25-50% bilateral involvement of lungs and 31 patients (19%) had > 50% bilateral involvement of lungs.

The mean (± SD) of the day at which the first dose of remdesivir was administered was 5.80 (± 2.59) for the day at which 1 st dose of remdesivir was administered. (Table 2 ). J o u r n a l P r e -p r o o f 

There was a statistically significant difference between groups as determined by one-way ANOVA (F(5,153) = 4.387, p = .001). The NORMPROB was plotted to assess whether or not J o u r n a l P r e -p r o o f Journal Pre-proof our data is approximately normally distributed. Although a maximum of the sample was distributed normally but some variance from the normal was observed as evident from the plot (Fig 1) .

The standardized case fatality ratio (CFR) was in the 453 hospitalized patients who did not receive remdesivir was 32.89% (n=149). In 159 Patients who received remdesivir, the standardized CFR dropped down to 11.32 % (N =18), proving the likely therapeutic value of remdesivir. The treatment guidelines for COVID-19 have been evolving since the start of the pandemic, and there is a global lack of conformity in the management strategies. 17 In this study, out of 612 SARS-CoV-2 nasopharyngeal RT-PCR positive patients, 159 patients were selected by convenient sampling, who fulfilled the inclusion and exclusion criteria.

Previous data show males are relatively more susceptible to SARS-CoV-2 infection. Males presented with more severe disease, and their mortality is double compared to females, which is also consistent with this study 18, 19 having high-grade fever and oxygen saturation < 93 %.

Similarly, fever was documented in 72-98% as the most frequent symptom. A decrease in oxygen saturation is a predictor of severity of COVID-19. 20, 21, 22 The most common comorbid condition was diabetes mellitus which is also well-documented. 23, 24 Remdesivir was given as an adjuvant therapy along with combination of antibiotics, methylprednisolone, and enoxaparin sodium to COVID-19 patients in this center. 159 COVID-19 patients included in the study received remdesivir as they failed to respond to the drug combination of 'antibiotics, methylprednisolone and enoxaparin sodium'. Most of the COVID-19 patients showed bilateral lung involvement in chest X-rays; these findings are consistent with the study conducted by Durrani et al. 25 for 15 days after disease onset and suggested it as a marker for disease severity. 28 We observed derangement of LFTs after remdesivir intervention, which is also documented in literature. 29 The primary outcome of this study was clinical effectiveness, reduction in disease severity, reduced duration of hospital stays of the patients, and clinical outcome of COVID-19 patients with remdesivir. It was observed in this study that after the failure of combination therapy of antibiotics, methylprednisolone and enoxaparin sodium, remdesivir played an essential role as an adjuvant by supporting the basic treatment, and disease severity of COVID-19 disease.

The main limitations of this study are: a relatively small sample size derived from convenient sampling, non-blinded design, an absence of a case-control design and a short follow up period.

Remdesivir is associated with decreasing the severity of the SARS-CoV-2 disease in COVID-19

patients. It has also decreased the patients' hospital stay and improved the clinical outcome and mortality of the patients.

fulfilled the inclusion criteria were enrolled. No side effects were observed during the clinical trial of remdesivir, but in a few patients prolonged steroid-induced lymphopenia was observed.

We observed derangement of LFTs after remdesivir intervention.

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We acknowledged all the medical, paramedical and nursing staff of department of Pulmonology, Anesthesia and Pathology for their unconditional services in the era of COVID-19 pandemic.