Effect of Hydroxychloroquine on Clinical Improvement and Mortality Among Patients with COVID-19 Admitted to Four General Hospitals in Saudi Arabia

Background: The use of hydroxychloroquine in coronavirus disease (COVID-19) pandemic raised significant concerns as regards safety and efficacy in hospitalized patients. The objective was to examine the effect of hydroxychloroquine on clinical improvement and mortality among hospitalized patients with COVID-19. Methods: A prospective cohort study was conducted at four general hospitals in the Western region, Saudi Arabia. Patients who had absolute or relative contraindication for using hydroxychloroquine were excluded. Patients concomitantly receiving other medications including azithromycin, antivirals, and supportive treatment were not excluded. Results: A total 267 patients were included in the current analysis; 185 (69.3%) on hydroxychloroquine and 82 (30.7%) on non-hydroxychloroquine treatments. The average age was 46.0±13.3 years and 78.3% of the patients were males. Approximately 95.9% of the patients were symptomatic with mild (50.6%), moderate (32.6%), severe (8.2%), or ARDS symptoms (4.5%). Compared with no hydroxychloroquine, those on hydroxychloroquine had significantly longer length of stay (11.5±7.1 versus 7.8±4.3 days, p<0.001), more ICU admission (22.7% versus 9.8%, p=0.012), and more intubation (12.4% versus 3.7%, p=0.026). Improvement of symptoms (84.3% versus Freely Available Online www.openaccesspub.org IJCV CC-license DOI: 10.14302/issn.2692-1537.ijcv-20-3652 Vol-2 Issue 2 Pg. no.– 14 Introduction Since its first appearance in Wuhan (China) in late 2019, more than 30 million patients globally were infected with severe acute respiratory syndrome coronavirus number 2 (SARS-CoV-2) with more than 950 thousands related deaths by mid-September 2020 [1, 2]. Although the mortality observed in the current coronavirus disease (COVID-19) pandemic (4.1% of closed cases) is much lower than other coronaviruses such as SARS-CoV (10%) and the Middle East Respiratory Syndrome-CoV (MERS-CoV, 35%)[3], the rapid and universal spread of COVID-19 caused unprecedented global public health emergency and major healthcare crises [4, 5]. With the lack of recognized therapeutic medications or effective vaccine, the management of COVID-19 was largely dependent on off-label use of available medications [6, 7]. Several medications have been tried during the pandemic including anti-viral drugs, antimalarial drugs, and immunomodulatory agents (such as tocilizumab and interferons) [6, 7]. Chloroquine and hydroxychloroquine have been used for decades in the prevention and treatment of malaria and then the treatment of some autoimmune diseases [8]. Their earlier use in the COVID pandemic was based on pre-pandemic reports that showed their ability to inhibit viral replication of several viruses including SARS and human immunodeficiency virus (HIV) [8, 9]. Additionally, in vitro reports published early in the pandemic showing the ability of hydroxychloroquine to inhibit SARS-CoV-2 replication [10]. The use of hydroxychloroquine in the COVID pandemic raised significant concerns as regards safety and efficacy, specially among cardiac patients [11]. Accumulating evidence and scientific debates forced several international organizations such as the World Health Organization (WHO) and the US Food and Drug Administration (FDA) to limit or halt the use of hydroxychloroquine in the management of patients with COVID-19 [11, 12]. The objective of the current study was to examine the effect of hydroxychloroquine on clinical improvement and mortality among patients with COVID-19 admitted earlier in the pandemic to general hospitals in Saudi Arabia.


Introduction
Since its first appearance in Wuhan (China) in late 2019, more than 30 million patients globally were infected with severe acute respiratory syndrome coronavirus number 2 (SARS-CoV-2) with more than 950 thousands related deaths by mid-September 2020 [1,2]. Although the mortality observed in the current coronavirus disease (COVID-19) pandemic (4.1% of closed cases) is much lower than other coronaviruses such as SARS-CoV (10%) and the Middle East Respiratory Syndrome-CoV (MERS-CoV, 35%) [3], the rapid and universal spread of COVID-19 caused unprecedented global public health emergency and major healthcare crises [4,5].
With the lack of recognized therapeutic medications or effective vaccine, the management of COVID-19 was largely dependent on off-label use of available medications [6,7]. Several medications have been tried during the pandemic including anti-viral drugs, antimalarial drugs, and immunomodulatory agents (such as tocilizumab and interferons) [6,7].
Chloroquine and hydroxychloroquine have been used for decades in the prevention and treatment of malaria and then the treatment of some autoimmune diseases [8]. Their earlier use in the COVID pandemic was based on pre-pandemic reports that showed their ability to inhibit viral replication of several viruses including SARS and human immunodeficiency virus (HIV) [8,9]. Additionally, in vitro reports published early in the pandemic showing the ability of hydroxychloroquine to inhibit SARS-CoV-2 replication [10]. The use of hydroxychloroquine in the COVID pandemic raised significant concerns as regards safety and efficacy, specially among cardiac patients [11].
Accumulating evidence and scientific debates forced several international organizations such as the World Health Organization (WHO) and the US Food and Drug Administration (FDA) to limit or halt the use of hydroxychloroquine in the management of patients with COVID-19 [11,12]. The objective of the current study was to examine the effect of hydroxychloroquine on clinical improvement and mortality among patients with COVID-19 admitted earlier in the pandemic to general hospitals in Saudi Arabia.   in patients receiving hydroxychloroquine [16][17][18].

Setting
However, the results of these studies were conflicting as regards the ability of hydroxychloroquine to limit the radiologic progression [17][18][19]. Variability may be related to the difference in disease severity and time of re-assessment of chest imaging in different study designs.
Hydroxychloroquine in the current study was associated with longer length of stay in both univariate and multivariate analysis. Similarly, hydroxychloroquine with or without azithromycin was associated with longer length of stay in both univariate and multivariate analysis in a retrospective cohort design [20]. However, most of the previous studies either did not focus on the length of stay as an outcome or could not find benefit of hydroxychloroquine on the length of stay [21,22]. It should be mentioned that the length of stay may be easily affected by the hospital capacity and discharge polices [20].
The patients in the current study who were However, the observational design allowed for evaluation of actual treatment practices while adjusting for group differences at admission in multivariate analysis.
The concomitant use of other types of treatments represented an important confounding factor for the current outcomes. However, it is probably unethical to deprive patients from other potential treatments at the time of pandemic with limited therapeutic information.
Additionally, this has been adjusted for in multivariate analysis. In

Acknowledgments:
Thanks for all staff at four hospitals who assisted in data collection and other study logistics

Funding
None received

Disclosures
The authors report no conflicts of interest in this