A prospective observational study was conducted from January 2021-October 2021 in the Isolation and Infectious Treatment Centre, which is one of the largest tertiary care centers in Pakistan designated for the treatment of Covid-19 patients. The institutional ethical research committee reviewed and approved the study (ethics approval number A/28/EC/20/2020. Written informed consent was obtained from each patient or their legal representative. The research was carried out in accordance with the declaration of Helsinki .
Patients were eligible for inclusion if they met the following inclusion criteria: age > 18 years, have a positive SARS COV-2 RT-PCR assay in the respiratory tract sample, have an acute onset of mild to severe acute respiratory distress syndrome (ARDS) identified as RR > 20, SpO2 < 94% on room air and pulmonary infiltrates < 50% on X-ray or CT scan, and patients with respiratory compromise sufficiently severe to include Non-Invasive Ventilation NIV (continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BIPAP)), high flow nasal cannula (HFNC), at the time of admission according to WHO interim Guidelines . Patients were excluded from the study with alanine aminotransferase (ALT) > 5 times the upper limit, creatinine clearance < 50ml/min, scheduled corticosteroid therapy during the previous week, known corticosteroid contraindications, pregnancy or breastfeeding, patients needing mechanical ventilation, and ICU admission at the time of enrollment, or doses of remdesivir and dexamethasone discontinued during the study based on clinical conditions.
Treatment included intravenous Remdesivir 200 mg loading dose followed by 100 mg for the next 4 days along with standard care therapy. All patients received corticosteroid therapy at the time of admission. Patients were hospitalized for at least 5 days (duration of treatment). PCR of every patient was performed before discharge and after the 5th dose of remdesivir and patients were assessed for clinical improvement before discharge. Patients were discharged on stable clinical conditions with swab-negative results after two repeated PCRs within 24 hours. All participants were managed according to the general standard of care practices according to WHO guidelines. Oxygen flow rates were given by oxygen delivery devices (e.g., a nasal cannula for rates up to 5 L/min; face mask for flow rates 6–10 L/min; and face mask with reservoir bag for flow rates 10–15 L/min) to attain a target of > 90% SpO2 in moderately severe patients with respiratory distress. Non-invasive positive pressure ventilation in the form of CPAP and BIPAP is the cornerstone of respiratory support reserved for severe COVID-19 disease adults with emergency indications of occluded breathing, and serious respiratory distress [18–19]. Within 1 hour of initial assessment, empiric antimicrobials were started in severe COVID-19 patients based on clinical judgment, and blood cultures were obtained. Antimicrobial therapy was started per NICE recommendations . To prevent venous thromboembolism in COVID-19 patients, pharmacological prophylaxis with low molecular weight heparin was given according to the guidelines (local or international) .
The following demographics were collected at the time of admission; blood pressure (BP), heart rate (HR), comorbidities, and body temperature were recorded. Serum electrolytes, D-dimers, Ferritin, glomerular filtration rate (GFR), serum creatinine, ALT, alkaline phosphatase (ALP), globulin, total protein, bilirubin T, albumin, leukocytes, neutrophils, hemoglobin, lymphocyte, platelets values were recorded at the baseline. Arterial blood gases (ABGS), CRP levels, and data on patients’ oxygen-support requirements were recorded at the time of admission and after completion of remdesivir and corticosteroid therapy in remdesivir treated and control group patients respectively.
The response to treatment was specified as 1; swab PCR before discharge 2; length of hospitalization, 3; requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or requiring invasive mechanical ventilation and 5; change in CRP levels from baseline.
A favorable response was defined as: discharged within 7 days of treatment on room air with more than 50% patients with swab negative PCR; reduction in CRP levels after 5th dose of remdesivir treatment in remdesivir treated group and standard care treatment in the control group; reduction in liters of oxygen demand and shift from BIPAP, CPAP, HFNC to low-flow oxygen delivery after remdesivir and corticosteroid therapy completion among remdesivir treated and control group patients respectively.
Categorical variables are presented as percentages, while numerical variables as means with standard deviations for normally distributed variables and medians with interquartile ranges for non-normally distributed variables. Kolmogorov-Smirnov test was used to check numerical variables for normalcy. Student t-test was used to test between-group differences among categorical variables such as gender, PCR negativity, and change in oxygen status. For independent variables which were not normally distributed Mann Whitney U test was employed, while the Wilcoxon Signed Rank Test was used for pre and post-treatment differences comparison to test between-group differences in numerical variables that were not normally distributed. The adjusted odds ratios were calculated using a multivariate stepwise regression model which included factors with a significant association to the outcome. Statistical significance was defined as a p-value of less than 0.001. SPSS v25.0 (IBM, Armonk, NY, USA) was used to analyze the data.