Medications for early treatment of COVID‐19 in Australia

Antivirals: Stopping Viral Replication

• Nirmatrelvir/Ritonavir (Paxlovid):

  • Mechanism: Inhibits SARS-CoV-2 protease, blocking viral replication. Ritonavir boosts drug levels by slowing metabolism .
  • Efficacy: Reduces hospitalization risk by 80% in high-risk patients if taken within 5 days of symptoms .
  • Challenges: Over 120 drug interactions (e.g., blood thinners, statins) require careful management .

• Molnupiravir:

  • Mechanism: Introduces errors into viral RNA, halting replication.
  • Efficacy: Lowers hospitalization risk by 50% and speeds recovery by ~3 days .
  • Contraindications: Avoided in pregnancy due to fetal toxicity risks .
• Remdesivir:

  Mechanism: Targets viral RNA polymerase.
  Efficacy: Intravenous use cuts hospitalization risk by 70% in early stages .
  Usage: Limited to clinics/hospitals due to IV administration .

Monoclonal Antibodies (mABs): Targeted Immunity

• Sotrovimab and Casirivimab/Imdevimab:
  • Mechanism: Bind to spike proteins, neutralizing the virus.
  • Efficacy: Reduce hospitalization by 70–80% but lose potency against Omicron subvariants .
  • Adaptation: New mABs like Bebtelovimab show promise against emerging strains .

Inhaled Corticosteroids: Dual Action

• Budesonide/Ciclesonide:
  • Mechanism: Suppress lung inflammation and inhibit viral replication.
  • Efficacy: Moderate reduction in hospitalizations (56% risk reduction in some studies) .

Non-Recommended Treatments: Debunking Myths

Despite global anecdotal use, hydroxychloroquine, ivermectin, and supplements (vitamin C/D, zinc) lack robust evidence. Meta-analyses confirm no significant impact on hospitalization or mortality . Australia’s guidelines explicitly discourage these due to risks like cardiac arrhythmias (hydroxychloroquine) and unproven benefits .

Challenges in Early Treatment

Timing and Access:

• Therapies must start within 5–7 days of symptoms, requiring rapid testing and prescribing .
• Rural areas face logistical hurdles in delivering mABs or IV remdesivir.

Variant Evolution:

• Omicron’s mutations reduce mAB efficacy, necessitating real-time genomic surveillance .

Patient-Specific Factors:

• Comorbidities (e.g., renal/liver disease) and polypharmacy complicate drug choices .

Data at a Glance

Table 1: Efficacy of Approved Treatments

Medication	Hospitalization Risk Reduction	Key Contraindications
Paxlovid	80%	Drug interactions, liver disease
Molnupiravir	50%	Pregnancy
Remdesivir	70%	IV access required
Sotrovimab	70–80% (pre-Omicron)	Omicron resistance

Table 2: Treatment Timelines

Therapy	Window for Initiation	Administration Route
Paxlovid	≤5 days	Oral
Molnupiravir	≤5 days	Oral
Remdesivir	≤7 days	Intravenous
mABs	≤7 days	Injection/Infusion

Future Directions

Next-Gen Antivirals: Drugs targeting conserved viral regions (e.g., helicase) to overcome variant resistance.

Combination Therapies: Pairing antivirals with mABs to enhance efficacy and reduce resistance .

Research Gaps: Safety data for pregnant women, children, and long COVID outcomes .

Conclusion: Staying Ahead of the Curve

Australia’s early treatment arsenal—Paxlovid, remdesivir, and adaptive mABs—has saved countless lives. However, success hinges on timely access, updated guidelines, and public awareness. Clinicians are urged to consult resources like the National COVID-19 Clinical Evidence Taskforce for real-time updates . As SARS-CoV-2 evolves, so must our strategies—ensuring Australia remains resilient in the face of future waves.

References
[1] National COVID-19 Clinical Evidence Taskforce, 2022
[2] Hill et al., 2022 (Ivermectin meta-analysis)