Morphology: Enveloped, single-stranded positive-sense RNA virus. Family Coronaviridae, genus Betacoronavirus. Spike protein (S) → ACE2 receptor binding. Variants tracked by WHO (Omicron sub-lineages KP.3, JN.1, etc. currently).
Typical drugs
- #1Nirmatrelvir / Ritonavir— **Paxlovid 300/100 mg PO BID × 5 days** for outpatient high-risk within 5 days of symptoms. Drug-interaction screen mandatory; dose-reduce for CrCl 30–60; avoid <30.
- #2Remdesivir— **Hospitalized requiring O2 → 5-day IV course.** Outpatient 3-day IV course alternative when Paxlovid contraindicated.
- #3Molnupiravir— Salvage outpatient when both Paxlovid + remdesivir unavailable. Lower efficacy. Avoid in pregnancy.
Empiric therapy when resistant
Standard antivirals retain efficacy as of 2026. Treatment failure → consider Mpro resistance, dose-optimization, or remdesivir as alternative.
Resistance mechanisms
altered-target
Spike protein mutations → mAb resistance
Example: All monoclonal antibodies (sotrovimab, bamlanivimab, casirivimab/imdevimab, tixagevimab-cilgavimab Evusheld) lost efficacy against Omicron sub-variants. mAbs no longer recommended. Small-molecule antivirals (Paxlovid, remdesivir) retain activity.
altered-target
Mpro mutations → Paxlovid resistance
Example: Documented but currently rare clinically. Worth knowing for treatment failure.
Resistance notes
Monoclonal antibodies no longer effective against current Omicron lineages (consistent NIH/IDSA guidance since 2023). Small-molecule antivirals continue to work.
Pearls
Outpatient high-risk + within 5 days of symptoms → Paxlovid first (drug interaction check mandatory). Hospitalized + requiring O2 → remdesivir (5 days; up to 10 if not improving). Dexamethasone (6 mg daily × 10 d) for any hospitalized patient requiring O2 (RECOVERY trial 2020). Tocilizumab / baricitinib for severe disease with hyperinflammation (rapid escalation O2 → HFNC/NIV/MV). Long COVID (post-acute sequelae) — supportive; no specific antiviral evidence. Vaccines + boosters remain primary prevention; updated formulations annually targeting current variants. COVID rebound common after Paxlovid (~10–15%); no retreatment indicated.