Antimicrobials

Specific therapies

This position is endorsed by the Australian guidelines for the clinical care of people with COVID-19, and the Australasian Society for Infectious Diseases (ASID) Interim guidelines for the clinical management of COVID-19 in adults.

Antimicrobials

Lopinavir-ritonavir: This combined antiretroviral agent was proposed as a potential treatment for SARS in 2003, based on apparent reductions in mortality in preliminary research in Hong Kong. Given the hypothesised role of lopinavir-ritonavir, five of the first 18 patients diagnosed with COVID-19 in Singapore were administered this agent. Three improved, while two experienced progressive respiratory failure. Four of those receiving antivirals developed gastrointestinal side effects, and three developed liver function test derangement.

On 18 March a randomised, controlled, open-label trial of lopinavir-ritonavir in 199 hospitalised adults with COVID-19 in China was published. No benefit was observed in those treated with the antiviral compared with controls. Nearly 14% of those receiving lopinavir-ritonavir were unable to complete 14 days of treatments due to adverse events. The authors recommended further research in patients with severe illness, or potentially with combination therapies.

Remdesivir: The first patient diagnosed with COVID-19 in the United States received this investigational nucleotide prodrug in January 2020, with the drug supplied on a compassionate basis. Developed as a potential therapy for Ebola, there is in vitro evidence that remdesivir can inhibit replication of coronaviruses, including MERS-CoV and SARS-CoV-2. Based on in vitro and limited animal evidence of antiviral efficacy, several local guidelines recommended consideration of remdesivir for the treatment of COVID-19. Four clinical trials to assess the efficacy of remdesivir against COVID-19 have commenced in the United States, and two are registered in China.

Chloroquine/Hydroxychloroquine: Chloroquine and hydroxychloroquine are antimalarial agents which also have immunomodulatory properties which lead to established indications for use in the treatment of rheumatological conditions including systemic lupus erythematosus and rheumatoid arthritis. Adverse effects of chloroquine and hydroxychloroquine can include retinal toxicity, QTc prolongation and other cardiological and dermatological effects. 

In early February 2020, chloroquine was reported to inhibit SARS-CoV-2 replication in vitro. By mid-February, treatment of COVID-19 with chloroquine was being hailed as a ‘breakthrough’ with a published letter stating that the results of treatment in over 100 patients in China had demonstrated that chloroquine was ‘superior to control treatment’; no data were provided.

Similar to the situation with the antiviral agents discussed above, several institutional and local guidelines, and notable public figures, have supported the potential use of chloroquine or hydroxychloroquine for the treatment of COVID-19. In addition, there are reports of prophylactic use by Australian clinicians, for which there is no clinical evidence of efficacy. In light of reports of significant limitations of supply of hydroxychloroquine for patients with rheumatological conditions, the Pharmaceutical Society of Australia and ASID have called for immediate cessation of prescribing and dispensing of hydroxychloroquine for indications relating to COVID-19.

Further, sufficiently powered, well designed and conducted multicentre clinical trials are clearly needed to address questions of both therapeutic, and prophylactic efficacy. A recent systematic review identified 23 separate ongoing clinical trials of chloroquine and hydroxychloroquine, all in China .