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Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?

ABSTRACT: Chloroquine and hydroxychloroquine belong to the aminoquinoline drugs. Studies revealed that chloroquine and hydroxychloroquine shows antagonism activity against COVID-19 under laboratory conditions. ARDS and ALI are conditions that occur in patients with COVID-19 as the main pathological complications of cytokine storm. Inflammasomes play a key role in the pathogenesis of many diseases associated with destructive inflammation. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The possible role of NLRP3 inflammasome inhibitors in the treatment of COVID-19 has been considered. We surveyed the potential inhibitory effect of chloroquine and hydroxychloroquine on inflammasome. Studies indicate that one of the possible anti-inflammatory mechanisms of chloroquine and hydroxychloroquine is inhibition of the activity of NLRP3 inflammasome.

SUBMITTER: Bahadoram M

PROVIDER: S-EPMC7792551 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?

Bahadoram Mohammad M Keikhaei Bijan B Saeedi-Boroujeni Ali A Mahmoudian-Sani Mohammad-Reza MR

Naunyn-Schmiedeberg's archives of pharmacology 20210108 5

Chloroquine and hydroxychloroquine belong to the aminoquinoline drugs. Studies revealed that chloroquine and hydroxychloroquine shows antagonism activity against COVID-19 under laboratory conditions. ARDS and ALI are conditions that occur in patients with COVID-19 as the main pathological complications of cytokine storm. Inflammasomes play a key role in the pathogenesis of many diseases associated with destructive inflammation. NLRP3 inflammasome has been shown to play a key role in the pathogen ...[more]

PMID: 33416933

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Project description:IntroductionGiven the current lack of an approved and effective treatment or vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), repositioning old drugs for use as an antiviral treatment is an interesting strategy because knowledge about these drugs' safety profile, posology, and drug interactions is already known. Chloroquine and hydroxychloroquine, widely used as antimalarial and autoimmune disease drugs, have recently been reported as a potential broad-spectrum antiviral drug.BackgroundThe in vitro antiviral activity of chloroquine has been identified since the late 1960s. However, antiviral mechanisms of chloroquine remain speculative. Several clinical trials have been conducted to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19-associated pneumonia. The quality of the studies and the outcomes are evaluated in this systematic review and meta-analysis.Review resultsLiterature review revealed 23 clinical studies. Only 9 of 23 studies were randomized controlled trials. Of nine randomized controlled trials, only study by Skipper et al. was deemed to be at low risk of bias. All studies evaluated variedwith different outcomes. Mechanical ventilation and virological clearance were the only common outcomes evaluated in more than two studies. Virological clearance odds ratio (OR) was 1.25 (95% confidence interval [CI] of 0.57-2.73; Chi2 = 0.83; I2 = 0%). GRADE quality of evidence was downgraded by three levels to very low due to concerns about the risk of bias, inconsistency, and imprecision. For mechanical ventilation, OR was 1.09 (95% CI 0.80-1.50; Chi2 = 0; I2 = 0). GRADE quality of evidence was downgraded by two levels to low due to concerns about the risk of bias and imprecision. There was no statistically significant difference between the groups for these two outcomes.ConclusionAs per the available evidence, based on our review, we conclude that hydroxychloroquine/chloroquine has not shown to be beneficial when used for the treatment of patients with COVID-19 pneumonia.How to cite this articleShetty RM, Namachivayam A. Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19. Indian J Crit Care Med 2021;25(4):441-452.

Project description:Despite several studies designed to evaluate the efficacy of chloroquine and hydroxychloroquine in the treatment of coronavirus disease 2019 (COVID-19), there is still doubt about the effects of these drugs, especially in patients with severe forms of the disease. This randomized, open-label, controlled, phase III trial assessed the efficacy of chloroquine or hydroxychloroquine for five days in combination with standard care compared to standard care alone in patients hospitalized with severe COVID-19. Chloroquine 450 mg BID on day 1 and 450 mg once daily from days 2 to 5 or hydroxychloroquine 400 mg BID on day 1 and 400 mg once daily from days 2 to 5 were administered in the intervention group. Patients were enrolled from April 16 to August 06, 2020, in 6 hospitals in southern Brazil. The primary outcome was the clinical status measured on day 14 after randomization with a 9-point ordinal scale. The main secondary outcomes were all-cause mortality; invasive mechanical ventilation use; the incidence of acute renal dysfunction in 28 days; and the clinical status of patients on days 5, 7, 10 and 28. All patients with a positive RT-PCR result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were analyzed (modified intention to treat (mITT) population). Arrythmias and cardiovascular complications were assessed as safety outcomes. A total of 105 patients were enrolled and followed for 28 days. The trial was stopped before reaching the planned sample size due to harmful effects. Patients in the intervention group had a worse clinical outcome on the 14th day (odds ratio (OR) 2.45 [1.17 to 4.93], p = 0.016) and on the 28th day (OR 2.47 [1.15 to 5.30], p = 0.020). Moreover, the intervention group had higher incidences of invasive mechanical ventilation use (risk ratio (RR) 2.15 [1.05 to 4.40], p = 0.030) and severe renal dysfunction (KDIGO stage 3) (RR 2.24 [1.01 to 4.99], p = 0.042) until the 28th day of follow-up. No significant arrythmia was noted. In patients with severe COVID-19, the use of chloroquine/hydroxychloroquine added to standard treatment resulted in a significant worsening of clinical status, an increased risk of renal dysfunction and an increased need for invasive mechanical ventilation.Trial Registration: ClinicalTrials.gov, NCT04420247. Registered 09 June 2020-Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT04420247 .

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Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?

Publications

Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?

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