As researchers try to piece together a therapeutic strategy against the ongoing COVID-19 pandemic, a recent retrospective study from Cleveland Clinic Abu Dhabi, assessed the Hydroxychloroquine's efficacy in increasing SARS-CoV-2 viral clearance, finding that it appeared to significantly slow viral clearance in mild to moderately ill COVID-19 patients. The study titled 'Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study', is published on the preprint server medRxiv.
Study: Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study. Image Credit: creativeneko / Shutterstock
Containing virus transmission with Hydroxychloroquine
The current focus of therapeutic drugs is to cut short the period of viral shedding to keep the disease from spreading and slow the progression of the pandemic. Hydroxychloroquine (HCQ) and chloroquine (CQ) have garnered intense attention as drugs that might lower viral load and reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission.
Hydroxychloroquine was initially developed as an antimalarial for malaria patients who were sensitive to chloroquine. It is also used to reduce inflammatory responses in illnesses like rheumatoid arthritis, lupus, and Porphyria cutanea tarda (PCT).
The mechanism of action of HCQ in COVID-19 is inhibition of viral entry via the prevention of endosomal acidification and glycosylation of host cell receptors for the virus. In vitro studies showed its effectiveness in blocking infection with SARS-CoV-2.
However, its use in the treatment of COVID-19 remains highly controversial, with conflicting data from different studies. Several studies concluded that the use of HCQ seemed to have no significant effect on reducing symptoms or viral load.
A couple of French studies appeared to support the use of HCQ with azithromycin, other studies found it could result in potentially severe cardiac dysrhythmia and warned against its indiscriminate use, particularly in mild to moderately ill patients. However, HCQ continued to be prescribed for off-label use in the absence of other proven therapies.
The current study aimed to examine the effectiveness of this therapy when used early in the course of illness, to increase the rate of clearance of the virus in confirmed hospitalized cases of COVID-19.
How was the study done?
The study was undertaken with 34 consecutive confirmed COVID-19 patients admitted to the hospital between March 1, 2020, and March 25, 2020. of which 19 reported symptoms and 14 had pneumonia. Symptomatic patients reported mild to moderate symptoms, including cough (in 50% of cases), fever, and pneumonia. The median age of the subjects was 37 years, and almost 75% were male.
About half the patients presented with cough and a quarter had a fever. Over 40% had pneumonia requiring oxygen by nasal cannula. No patient required intensive care, mechanical ventilation, or high-flow oxygen. There were no deaths. Therefore all patients in this study had mild or moderate illness.
HCQ was administered to 21 patients, from a median of 0 (range: 0-2) days from admission. The dose was 800 mg for one day, followed by 400 mg daily for ten days. Doctors measured the negative nasopharyngeal swab conversion time – from the first confirmed positive result to the second of two negative reverse transcriptase-polymerase chain reaction (RT-PCR) tests 24 hours apart.
The non-HCQ group had a higher rate of coexisting medical conditions but were otherwise comparable in all relevant characteristics to the HCQ group.
What did the study show?
Results showed that the drug was well tolerated, with no side effects observed.
Patients who received HCQ took longer to test negative than those who did not. With HCQ, the average time to negativity test was around 17 days, while it was only 10 days in patients who were not administered the antimalarial.
There was no other association except with HCQ, such as the presence of symptoms at presentation, the presence of pneumonia, or the requirement for oxygen therapy.
The findings also showed that only 48% of HCQ patients had a negative test on da 14, compared to 91% of the non-HCQ group. Thirdly, there was no significant effect of HCQ on the inflammatory markers or rate of drop in lymphocyte count.
How is the poor performance of HCQ explained?
Researchers postulated that HCQ's effect on the immune system might be responsible for the slower viral clearance observed in the COVID-19 patients. An earlier trial of HCQ in HIV patients also showed that it increased the viral load and reduced the CD4 count.
The dose at which HCQ could be expected to inhibit viral activity, based on the in vitro studies, would be well over 70,000 mg, that is, 356 tablets of HCQ at 200 mg each. Thus, the standard dosing regimen is not sufficient to produce a clinical antiviral effect.
Also, administering HCQ did not seem to affect inflammatory markers or lymphocyte counts. The study attributed this to the low inflammatory reaction associated with mild illness severity of the patients. An earlier study using much higher doses of HCQ also showed no impact on lymphocyte numbers, though the inflammatory marker CRP did show a decline.
The study is limited by its population, which included only mild to moderate cases, and by the small size of the sample, as well as its retrospective design. The results are not applicable to severe illness. Nonetheless, it suggests that HCQ may not be capable of living up to the hype in COVID-19.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.