General Medication Considerations
Currently there are no approved treatments specifically for COVID-19, although several clinical trials of investigational therapies are underway.
Hydroxychloroquine/Chloroquine
Mechanism
- Antimalarial medication with several proposed antiviral properties (Wang, et al., Cell Res., 2020; Colson, et al., Int J Antimicrob Agents, 2020)
- Alkylization of the phagosome, inhibiting pH-dependent steps viral replication including infusion and uncoating
- Glycosylation of cellular receptors of SARS-CoV-2
Evidence
- In-vitro studies demonstrate potent inhibition of SARS and SARS-CoV-2 (Yao, et al., Clin Infect Dis, 2020; Devaux, et al., Int J Antimicrob Agents, 2020)
- Human clinical trials (alone or in combination with azithromycin) have been promising, although are limited by poor trial design and incomplete reporting of prespecified outcomes (Gautret, et al., Int J Antimicrob Agents, 2020; Chen, et al., medRxiv, 2020)
Recommendations
- UPHS guidelines recommend consideration of hydroxychloroquine in hospitalized patients with risk factors for progression to severe disease, and critically-ill patients, including those requiring mechanical ventilation
Remdesivir
Mechanism
- Nucleoside analogue that interferes with RNA polymerase, inhibiting viral transcription (Agostini, mBio, 2020)
Evidence
- In vitro evidence of activity against Ebola virus, Marburg, SARS-CoV and MERS-CoV, RSV, Nipah virus and Hendra virus
- Un-controlled compassionate-use demonstrated clinical improvement in 36 of 53 patients (68%) (Grein, et al., NEJM 2020)
- Overall mortality 13% over a median follow-up of 18 days (0.56 per 100 hospitalization days [95% CI, 0.14 to 0.97]), compared to 22% in a recent study of lopinavir-ritonavir, despite the remdesivir trial including a sicker population (6 of 34 patients [18%] on mechanical ventilation in remdesivir trial vs. 1 of 199 [0.5%] in the lopinavir-ritonavir trial)
- Several ongoing clinical trials (ClinicalTrials.gov)
Recommendations
- UPHS guidelines recommend consideration of clinical trial enrollment and are actively seeking/screening patients with positive SARS-CoV-2 molecular testing
IL-6 inhibitors/Immunomodulators
Mechanism
- The primary immunomodulatory approach to treating COVID-19 has employed humanized monoclonal antibodies to IL-6 to treat complications related to cytokine release syndrome
Evidence
- Tocilizumab currently indicated for treatment of cytokine release syndrome in the setting of chimeric antigen T-cell receptor therapy for leukemia/lymphoma (Grupp, et al., NEJM, 2013; Frey and Porter, Biol Blood Marrow Transplant, 2019)
- In a retrospective study of 21 Chinese patients (17 severe, 4 critical) treated with tocilizumab 400mg x1 in addition to “standard of care” (including methylprednisolone and lopinavir), 19/21 were discharged including 2 critically-ill patients (Xu et al., ChinaXiv 2020)
- In a retrospective study of 21 Italian patients treated with siltuximab, CRP levels improved among 16 patients with available data, 7/21 patients improved clinically, 9/21 stabilized, and 5/21 worsened (with 1 death and 1 stroke) (Gritti, et al., medRxiv, 2020)
- Multiple randomized controlled trials of tocilizumab, sarilumab, and siltuximab are currently enrolling/in progress (ClinicalTrials.gov)
Convalescent Serum/Plasma
Form of passive immunotherapy which involves the administration of serum/plasma (obtained via apheresis) containing neutralizing antibodies from patients who have recovered from infection
Mechanism
- May accelerate viral clearance and limit entry into host target cells
Evidence
- Administration of convalescent sera has been attempted in non-randomized trials during outbreaks of other infectious diseases, including H1N1 influenza, SARS, MERS, and Ebola with varying but promising efficacy (Cheng, et al., Eur J Clin Microbiol Infect Dis , 2005; Casadevall, et al., J Clin Invest, 2020; Leider, et al., Transfusion, 2020)
- Small case series from China of 5 patients with COVID-19 who received convalescent plasma demonstrated improvement in body temperature, SOFA score, viral loads, and need for mechanical ventilation (Shen, et al., JAMA 2020)
Antibiotics
- Rates of bacterial co-infection among patients with COVID-19 remain poorly defined, although one study identified 16% of participants (11/68) with secondary infection (Ruan, et al., Intensive Care Med, 2020)
Recommendations
- If concern exists for bacterial co-infection, evaluation may include sputum culture, MRSA culture, blood and/or urine cultures, procalcitonin, and evaluation with diagnostic imaging
- Consider empiric treatment for bacterial pneumonia (particularly ventilator associated pneumonia) with antibiotics based on local treatment guidelines and risk factors for drug-resistant organisms (MRSA, pseudomonas)
Post-Exposure Prophylaxis
Clinical trials are ongoing to investigate the role of antiviral medications in prevention of disease following exposure (eg. hydroxychloroquine post-exposure prophylaxis trial)