In late December 2019, an outbreak of an emerging disease (COVID-19) due to a novel coronavirus (named SARS-CoV-2 latter) started in Wuhan, China and rapidly spread in China and outside. The epidemic of COVID-19 was declared as pandemic by WHO on March 12th, 2020. According to a recent Chinese stud, about 80% of patients present with mild disease and the overall case-fatality rate is about 2.3% but reaches 8.0% in patients aged 70 to 79 years and 14.8% in those aged ≥80 years. There is an urgent need for an effective treatment to treat symptomatic patients and to decrease virus carriage to reduce transmission from person to person. Till now there are no drugs or other treatments approved by US FDA to prevent or to treat COVID-19. Current clinical management includes infection prevention and control measures and supportive care, including supplemental oxygen and mechanical ventilatory support when indicated.
Among possible candidate drugs to treat COVID-19, repositioning of old drugs for antiviral treatment is an interesting strategy as detailed knowledge of their pharmacokinetic profile, side effects, drug interaction and posology are well known. According to a recent paper, chloroquine (an old antimalarial drug) and remdesivir (a new antiviral drug) have inhibitory effect on growth of SARS- CoV-2 invitro. In an early clinical trial conducted in COVID-19 Chinese patients, chloroquine had shown significant effect in terms of clinical outcome and viral clearance when compared to control group. For this, the U.S. Food and Drug Administration (FDA) has been working to investigate the use of chloroquine in COVID-19 s. Hydroxy chloroquine, which is an analogue of chloroquine has similar therapeutic effects and fewer adverse effects.
Here are reports of two clinical trials of hydroxychloroquine (HCQ) for treatment of COVID-19.
1) Chen et al conducted a clinical trial to access efficacy of hydroxychloroquine in patients with COVID-19 in Renmin Hospital of Wuhan University.
- From February 4 to February 28, 2020, 142 patients with confirmed COVID-19 cases were admitted to Renmin Hospital of Wuhan University. Among those 62 patients who met trial criteria were randomly assigned into two groups.
- Both groups received the standard treatment (oxygen therapy, antiviral agents, antibacterial agents, and immunoglobulin, with or without corticosteroids). Patients in the HCQ treatment group received additional oral HCQ (hydroxychloroquine sulfate tablets, Shanghai Pharma) 400 mg/d (200 mg/bid) between days 1 and 5. Patients in the control group receives the standard treatment only.
- Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ.
- 17 patients in the control group and 22 patients in the HCQ treatment group had a fever in day 0. Compared with the control group [3.2 (1.3) days], the body temperature recovery time was significantly shortened in the HCQ treatment group [2.2 (0.4) days]. 15 patients in the control group and 22 patients in the HCQ treatment group had a cough in day 0, The cough remission time was significantly reduced in the HCQ treatment group. Among 62 patients, 4 patients progressed to severe illness, all of which occurred in the control group not receiving HCQ treatment. There were two patients with mild adverse reactions in the HCQ treatment group, one patient developed a rash, and one patient experienced a headache. When chest CT of patients was analyzed for pneumonia, patients in HCQ treatment group (80.6%, 25 of 31) show more improvement than control group (54.8%, 17 of 31).
- They had also conducted a follow-up survey in which they found that none of 80 SLE (Systemic Lupus Erythematous) patients who took long-term oral HCQ had been confirmed to have SARS-CoV-2 infection or appeared to have related symptoms. In addition, among the 178 patients diagnosed with COVID-19 pneumonia in the same hospital, none were receiving HCQ treatment before admission.
2) Gautret et al conducted a clinical trial for assessing the effect of hydroxychloroquine on SARS-CoV-2-infected patients in coordination with The Méditerranée Infection University Hospital Institute in Marseille, France.
- Hospitalized patients with confirmed COVID-19 were included in this study if they fulfilled two primary criteria: i) age >12 years; ii) PCR documented SARS-CoV-2 carriage in nasopharyngeal sample at admission whatever their clinical status. Patients having known allergy to hydroxychloroquine or chloroquine and breastfeeding and pregnant patients were excluded.
- A total of 26 patients received hydroxychloroquine and 16 were control patients. Six hydroxychloroquine-treated patients were lost in follow-up during the survey because of early cessation of treatment due to various reasons. None of the control patients was lost in follow-up.
- Patients were seen at baseline for enrolment, initial data collection and treatment at day 0, and for daily follow-up for 14 days. Each day, patients received a standardized clinical examination and nasopharyngeal sample was collected whenever possible.
- All patients were given oral hydroxychloroquine sulfate 200 mg, three times per day for ten days. Depending on their clinical presentation, azithromycin was added to the treatment.
- The primary endpoint was virological clearance at day-6 post-inclusion. Secondary outcomes were virological clearance overtime during the study period, clinical follow-up (body temperature, respiratory rate, long of stay at hospital and mortality), and occurrence of side-effects.
- Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
Though the sample size or case number is small in both clinical trials, the potential of HCQ in treatment of COVID-19 has been partially confirmed. Large scale clinical and basic research is needed to clarify its specific mechanism and to continuously optimize the treatment plan.
Beside its potential in treatment of COVID-19, its potential detrimental effects of should also be considered. Retinopathy is one of the major adverse reactions of long-term therapy with HCQ. In patients with rheumatoid diseases treated with HCQ may occasionally experience arrhythmias. Other rare adverse reactions include gastrointestinal reactions, cramps, liver dysfunction, itching, headache, dizziness, insomnia, peripheral neuropathy.
References
- https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3.
- https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549/.
- https://www.ncbi.nlm.nih.gov/pubmed/32081636.
Disclaimer: This is only for education purpose. Please, consult your physician for your health specific condition.
