Abstract
Up till now, no evidence based studies have recommended specific therapeutic modality to treat corona virus disease-19 (COVID-19). Many regimens were tested since the outbreak has started. Among commonly tested drugs are hydroxychloroquine, an antimalarial agent, which was proposed based on its anti-inflammatory as well as antiviral effects and remdesivir, an antiviral that showed indigo and invitro activity against the formerly known corona-viruses The Food & Drug Administration (FDA) approved using remdesivir in the treatment of severe cases of COVID-19. Objectives: To evaluate the effectiveness of remdesivir versus hydroxychloroquine against SARS-CoV-2 in terms of infectivity period in hospitalized COVID-19 patients. Methods: Fifty patients that were clinically diagnosed with Covid-19 admitted to Tanta University Isolation Hospital from June - September, 2020 were included in this study and divided into 2 groups. Group I had hydroxychloroquine as the main therapeutic agent in their treatment regimen, while group II had the antiviral remdesivir instead. Laboratory testing involved nasopharyngeal swabbing which was transported immediately to Tanta University Hospital laboratory for Real-time PCR. Results: There was a significant better outcome and shorter infectivity period in group 2 who received the antiviral remdesivir. Conclusions: Remdesivir showed significant better outcome in COVID19 hospitalized patients, as it reduced period needed for clinical improvement while administration of hydroxychloroquine was not associated with better outcome or increased risk to the patients.
Introduction
The global outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was declared by the World Health Organization (WHO) as a pandemic in 2020 when about 120,000 announced infections and about 4000 deaths were reported in more than 100 countries [1, 2]. In Egypt, the officially reported COVID-19 confirmed cases were 94,316 with 4,834 deaths on August 2020 [3]. The information on the patient features of COVID19 infection and the risk factors of disease severity in Egypt is scarce [4]. Clinical presentation varies widely among infected individuals. However, most infected subjects may remain asymptomatic or develop mild to moderate illness that recover without need for hospitalization or specific treatment. However, about 10-15% of infected adults develop severe pneumonia that requires supplementary O2 therapy while 5% may progress to critical forms showing acute respiratory distress syndrome (ARDS) necessitating artificial ventilation. Moreover, disseminated intravascular coagulation (DIC) and multi-organ failure may lead to higher mortality rate in those critical cases [5]. Detection of the viral nucleic acid (RNA) in upper respiratory specimens using amplification tests such as real-time polymerase chain reaction (RT-PCR) is considered the gold standard method in the diagnosis of COVID-19 infection. In areas with widespread SARS-CoV-2 transmission especially in communities with limited laboratory resources, detection of a single target nucleic acid sequence by RT-PCR is considered sufficient for diagnosis [6].
Methods
Study population, setting, and data collection This study was done as a part of the outbreak investigation conducted at Tanta University Hospitals, Egypt and supported by the Ministry of Higher Education (MHE). Patients who were admitted to Tanta University Isolation Hospital ICU between June and September, 2020 with laboratory confirmed SARS-CoV-2 infection were included. Out of eighty-six patients with clinically diagnosed Covid-19 who were admitted to Tanta University Isolation Hospital during the period of the research, a total of thirty-six patients were excluded from this study either because lack of positive PCR confirmation or failure to complete the suggested treatment regimen as being transferred to other health facilities or death shortly after admission, Thus, fifty patients were included in this study as illustrated in the study flow chart (Figure 1). Informed consents were obtained from all participants in the study and it was approved by the ethical committee of Faculty of Medicine, Tanta University. Data from electronic medical records was obtained e.g. demographic data, clinical manifestations and PCR results on admission. Recent travelling history was obtained showing that included patients had not travelled recently to an endemic area or country at that time, such as countries of South-East Asia. However, most of patients (85%) reported recent contact with a clinically suspected COVID-19 patient who was not PCR confirmed. The most common clinical manifestations on admission were fever, shortness of breath and cough. Co-existing chronic medical conditions were common in critically ill patients such as diabetes mellitus, hypertension, respiratory asthmatic condition, current or former smokers and chronic obstructive pulmonary disease. Specimen collection and testing Clinical specimens for COVID-19 diagnostic testing were obtained according to the Centers for Disease Control and Prevention (CDC) guidelines [14, 15]. Management and laboratory investigation of cases were immediately initiated on admission. Laboratory testing involved nasopharyngeal swabbing that was transported immediately to Tanta University Hospital laboratory. Real-time PCR was done with RT-PCR Detection Kit System, primers and probes provided under supervision of MHE. The PCR conditions used were exactly as described in Corman and his colleagues [6]. A guidance developed by the Egyptian Ministry of Health (MOH) at that time suggested HCQ as a therapeutic agent for SARS-CoV-2 infected patients who were classified as moderate-to-severe cases [16] defined as O2 resting saturation > 93% on room air. The suggested HCQ regimen was (800 mg) on the first day as a loading dose, then half that dose (400 mg/day) for the next 6 days. To prevent the occurrence of secondary bacterial infection, azithromycin was used in combination with HCQ. The use of HCQ was discontinued on July 10, 2020 and the antiviral “remdesivir” was added to the MOH treatment protocol [17]. For either regimen, all patients received their first dose during the first twenty-four hours of hospital admission and patients suffering from ARDS with progressive increase in IL6 level received immune-modulatory agents e.g. IL6 inhibitor. To exclude the impact of some variants like coexisting chronic conditions and the use of immune-modulatory agents in some patients, the Sequential Organ Failure Assessment (SOFA) score was used [18]. It was also used for assessment of the final patients’ outcome. The score is a calculation of different six sub-scores for six body systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems) [19]. The Score usually ranges from 0-24. A Score >=2 or a change of 2 or more points is associated with increase in mortality rate by 20% [20]. Statistical analysis Analysis was performed with T test. Statistical Package for Social Sciences (SPSS) version 23 was used for data analysis. Data were expressed in number (No.), percentage (%), mean (x), and standard deviation (SD). P-value < 0.05 was considered statistically significant.
Results
Demographic and clinical characteristics of the patients Out of the 50 patients included in this study, half of which (25 patients) received HCQ in their treatment regimen (group I) while the other half received the antiviral Remdesivir (group II). The mean age of the patients (±SD) was 44.04 ± 16.549 for group I and 44.80 ± 15.663 for group II with 52% of them were men. The baseline characteristics of patients according to therapeutic agent used is shown in (Tables 1&2). Microbiological results All patients had SARS-CoV-2 infection that was laboratory-confirmed by RT-PCR assay using a nasopharyngeal swab at Tanta University Lab. Table 3 shows the correlation between infectivity period (duration of PCR positivity) in relation to the treatment regimen used in both groups. There was a significant difference between the two groups with better outcome and shorter infectivity period in group 2 who received the antiviral remdesivir. Figure 2a shows negative SARS-CoV-2 real-time PCR report while figure 2 b shows positive SARSCoV-2 real-time PCR report.
Discussion
Finding an appropriate antiviral therapeutic agent is essential for undertaking this COVID-19 global pandemic. Many introduced drugs have shown an in-vitro activity against the closely related beta coronaviruses. They have also shown some sort of in-vitro activity against SARS-Cove and Merson, and sometimes can be also used synergistically with certain antivirals as ribavirin [21, 22]. This cross-sectional observational study involved a moderate number of hospitalized COVID-19 patients divided into two groups. Group I received the antimalarial HCQ as the main therapeutic agent while group II received the antiviral remdesivir. We observed a significant better clinical and laboratory patients’ outcome on using the antiviral “remdesivir” in the management protocol in critical COVID-19 patients evidenced by the shorter infectivity and PCR positivity period together with faster improvement of the clinical symptoms when compared to using the HCQ protocol.
Conclusion
To conclude, it appears that remdesivir provides a general beneficial therapeutic effect to hospitalized COVID patients, as it can reduce the mean time needed to clinical recovery especially when administrated in patients with mild to moderate forms of the disease or when administrated early in the severe forms of the disease. Hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk to the patients. Further random clinical trials of HCQ in COVID patients are needed. Given the observational design of our study, we can’t rule out the beneficial or harmful aspects of using HCQ as we mainly aimed to evaluate the effectiveness of remdesivir versus HCQ as common approved therapeutic agents against SARS-CoV-2. However, our findings don’t encourage the use of HCQ as a solitary anti-COVID agent. Moreover, we recommend further research of some points to overcome the limitations of our study such as using larger sample size and a multicentral study that should help supporting and generalization of data. Credited to Maii A. Shams Eldeen Alternatives Compared | Plaquenil (hydroxychloroquine) | Sales of antibiotics and hydroxychloroquine | Hydroxychloroquine (Plaquenil) | Facts about chloroquine and hydroxychloroquine | get rx for hydroxychloroquine | hydroxychloroquine get you high | Hydroxychloroquine Uses | Side Effects of Plaquenil (Hydroxychloroquine) | Hydroxychloroquine tablets |
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