208.1 🎓 醫孞生版

208.1.0.1 📌 䞀頁重點

  • Virus: ssRNA β-coronavirus (similar SARS-CoV-1 2003, MERS-CoV 2012)
  • Receptor: ACE2 + TMPRSS2 (lung epithelium, GI, heart, kidney, brain)
  • Spike protein primary antigen + vaccine target
  • 2019 Wuhan → global pandemic 2020
  • WHO PHEIC ended May 2023, but virus endemic, ongoing variants + waves
  • Major Variants (2024-2025):
    • Pre-Omicron: Alpha, Beta, Gamma, Delta (more severe)
    • Omicron lineage dominant since 2022
    • BA.5 → XBB.1.5 → JN.1 → KP.3 / KP.2 / LB.1 / XEC ongoing evolution
  • Clinical (acute):
    • Mild URI / common cold-like (most cases)
    • Fever, cough, headache, myalgia, fatigue, loss of taste/smell (less Omicron era)
    • Sore throat, congestion
    • GI symptoms
    • Severe: pneumonia → ARDS, multi-organ failure
    • Thromboembolism (DVT, PE, stroke) increased
    • Cytokine storm + macrophage activation syndrome
    • MIS-C/MIS-A (multisystem inflammatory syndrome) — pediatric + adult post-COVID
  • Risk for severe:
    • ≥ 65 yr (especially ≥ 75)
    • Comorbidities (DM, CKD, obesity, immunocompromise, cardiopulmonary, malignancy)
    • Pregnancy
    • Unvaccinated / non-boosted
  • Long COVID (PASC, Post-Acute Sequelae of COVID-19):
    • 1-3% prevalence (varies)
    • Fatigue, brain fog, dyspnea, palpitations, POTS, anxiety/depression
    • Multi-organ involvement
    • Mechanism: incomplete clearance + immune dysregulation + microvascular damage + autoimmune
  • Diagnosis:
    • PCR (RT-PCR) = gold standard
    • Rapid antigen — POC, 15 min, less sensitive
    • Multiplex respiratory PCR
    • Antibody (post-infection or post-vaccine; not for acute)
  • Treatment (outpatient high-risk + < 5 days symptom):
    • Nirmatrelvir-ritonavir (Paxlovid) 300/100 mg PO bid × 5d — preferred
    • Remdesivir (Veklury) 200 mg IV → 100 mg × 2 (3-day course outpatient) or 5-10d hospitalized
    • Molnupiravir alternative (less effective, EUA, not for pregnancy)
    • Pemivibart (Pemgarda) — mAb for immunocompromise pre-exposure prophylaxis 2024
  • Hospitalized:
    • Remdesivir 5-10d
    • Dexamethasone 6 mg PO/IV × 10d (RECOVERY trial — severe + oxygen-requiring)
    • Tocilizumab / baricitinib (IL-6 / JAK1/2 inhibitor) for severe cytokine storm
    • Anticoagulation prophylaxis routinely
    • Therapeutic anticoagulation in select severe (ATTACC, REMAP-CAP)
  • Vaccines (2024-2025):
    • Updated annual monovalent mRNA (Pfizer-BioNTech, Moderna) — formulated against KP.2/XBB-era variants
    • Novavax (protein subunit) — alternative
    • Universal ≥ 6 mo annual
    • High-risk: more frequent boosters considered
  • Public Health:
    • Endemic + ongoing waves
    • Surveillance for variants
    • 通報 Taiwan + most countries

208.1.0.2 1⃣ Virology

  • ssRNA, ~ 30 kb (largest RNA virus)
  • β-coronavirus
  • Surface proteins: Spike (S), Envelope (E), Membrane (M), Nucleocapsid (N)
  • S protein = vaccine + mAb target
  • ACE2 + TMPRSS2 receptors
208.1.0.2.1 Variants
  • Antigenic drift continuous
  • Notable lineages:
    • Wuhan-Hu-1 (original)
    • Alpha (B.1.1.7, UK 2020-2021)
    • Beta (B.1.351, South Africa 2020-2021)
    • Gamma (P.1, Brazil 2020-2021)
    • Delta (B.1.617.2) — 2021, more severe
    • Omicron (B.1.1.529) — 2022 onwards, more transmissible, less severe but immune evasion
      • BA.1, BA.2, BA.4, BA.5, BQ.1, XBB, XBB.1.5, JN.1 (2023-2024), KP.3, KP.2, LB.1, XEC (2024-2025)
208.1.0.2.2 2024-2025 Variants
  • KP.3 dominant globally 2024
  • JN.1 wide spread early 2024
  • XEC rising end 2024
  • LB.1 + others sporadic
  • All Omicron sub-lineages — share immune evasion features
208.1.0.2.3 Pathogenesis
  • ACE2 binding → cell entry
  • Cytokine release syndrome in severe
  • Microvascular thrombosis + endothelial damage
  • Multi-organ tropism (lung, heart, kidney, GI, brain)

208.1.0.3 2⃣ Epidemiology

208.1.0.3.1 Pandemic Course
  • 2019 Dec: first cases Wuhan
  • 2020 March: WHO pandemic
  • Multiple waves with variants
  • 2022: Omicron — transmissibility surge, lower severity per infection
  • 2023: WHO PHEIC ended May
  • 2023-2025: endemic + ongoing waves
  • 7M+ confirmed COVID-19 deaths globally (excess mortality estimates higher 20M+)
208.1.0.3.2 Transmission
  • Respiratory droplets + aerosols + contact
  • Highly transmissible (R0 increased with each variant)
  • Asymptomatic + presymptomatic transmission
208.1.0.3.3 Current Status
  • Endemic
  • Annual seasonal waves
  • Variant emergence ongoing
  • Surveillance critical
  • Lower mortality per case in highly vaccinated populations

208.1.0.4 3⃣ Clinical (Acute)

208.1.0.4.1 Mild Course (Most Cases)
  • Fever, cough, headache, myalgia, fatigue
  • Sore throat, congestion
  • Loss of taste/smell (less common in Omicron era)
  • Diarrhea, nausea
  • 5-10 days self-limited
208.1.0.4.2 Severe Course
208.1.0.4.2.1 Pneumonia → ARDS
  • Bilateral ground-glass opacities + consolidation
  • Crazy paving pattern
  • ARDS in severe (P/F ratio < 300, < 200, < 100)
  • Mechanical ventilation
  • ECMO refractory
208.1.0.4.2.2 Multi-Organ Involvement
  • Thromboembolism: DVT, PE, stroke, MI (5-10× increased)
  • Cytokine storm + MAS-like: IL-6 elevated, hyperferritinemia, hyperinflammation
  • Acute Kidney Injury (AKI): direct viral + ATN + cytokine
  • Acute Heart Injury: myocarditis, MI, arrhythmia
  • Hepatic injury: transaminitis, less commonly liver failure
  • Encephalopathy + Stroke + GBS + neuropathy
208.1.0.4.2.3 MIS-C / MIS-A
  • Multisystem inflammatory syndrome in children (MIS-C) or adults (MIS-A)
  • 2-6 wk post-acute COVID
  • Persistent fever + multi-organ + cardiac (myocarditis) + GI + 玅疹 + LAP similar to Kawasaki
  • Children: 8-18 yr peak
  • Adults: severe rare presentation
  • Treatment: IVIG + steroid + biologic (anakinra, tocilizumab) for refractory
208.1.0.4.3 Diagnosis Acute
  • PCR (RT-PCR) of NP / saliva — gold standard, > 95% sens
  • Rapid antigen test — POC, 70-85% sens (acute infection); useful for outpatient triage
  • Multiplex respiratory panel (COVID + flu + RSV + others)
  • Imaging: CXR / CT — ground-glass opacities, consolidation
  • Labs: lymphopenia, elevated D-dimer, CRP, ferritin, troponin (severe)

208.1.0.5 4⃣ Risk Stratification

208.1.0.5.1 High Risk for Severe Disease
  • Age ≥ 65 (especially ≥ 75)
  • Diabetes mellitus
  • CKD
  • Cardiovascular disease
  • Chronic lung disease (COPD, asthma severe)
  • Obesity (BMI ≥ 30, especially ≥ 40)
  • Immunocompromise (HIV, transplant, anti-CD20 like rituximab, corticosteroids, chemo)
  • Hematologic malignancy
  • Active cancer
  • Pregnancy (especially 3rd trimester)
  • Vaccination status (unvaccinated / non-boosted higher risk)
  • Smoking
  • Native American populations

208.1.0.6 5⃣ Treatment

208.1.0.6.1 Outpatient High-Risk + Early (< 5 Days Symptom)
208.1.0.6.1.1 Nirmatrelvir-Ritonavir (Paxlovid)
  • 300/100 mg PO bid × 5d
  • First-line outpatient treatment
  • Reduces hospitalization 80%+ in high-risk
  • Drug interactions (critical):
    • Tacrolimus, cyclosporine (transplant) — major adjustment / hold
    • Statins (simvastatin, lovastatin) — hold
    • Amiodarone — caution
    • Apixaban, rivaroxaban — caution
    • Lurasidone, midazolam, sildenafil for PAH — contraindicated
    • Many others — review with pharmacist / Liverpool COVID interaction tool
  • Renal adjustment: CrCl 30-60 dose-adjusted; < 30 contraindicated
  • Pregnancy: limited data, case-by-case; benefit > risk often
208.1.0.6.1.2 Remdesivir
  • 3-day course (outpatient): 200 mg IV day 1 → 100 mg IV × 2 days
  • Alternative when Paxlovid contraindicated
  • Hospitalized: 5-10d
208.1.0.6.1.3 Molnupiravir
  • 800 mg PO bid × 5d
  • Less effective than Paxlovid
  • Pregnancy contraindicated (mutagenic)
  • Reserved when others unavailable
208.1.0.6.1.4 Pemivibart (Pemgarda, 2024 FDA)
  • Pre-exposure prophylaxis for immunocompromise
  • mAb (replaced tixagevimab-cilgavimab which lost activity to variants)
  • Single IV infusion q3 mo
  • For severely immunocompromise patients
208.1.0.6.2 Hospitalized
208.1.0.6.2.1 Remdesivir
  • 5-10d depending severity
208.1.0.6.2.2 Dexamethasone
  • 6 mg PO/IV qd × 10d
  • For oxygen-requiring patients (RECOVERY trial 2020)
  • Mortality reduction in severe
208.1.0.6.2.3 Tocilizumab (Anti-IL-6 mAb)
  • For severe + rapid progression / cytokine elevation
  • Single IV dose
208.1.0.6.2.4 Baricitinib (JAK1/2 inhibitor)
  • For severe + oxygen-requiring
  • Alternative to tocilizumab
  • Reduces mortality (COV-BARRIER trial)
208.1.0.6.2.5 Anticoagulation
  • Prophylactic VTE doses routinely for hospitalized
  • Therapeutic anticoagulation in severe non-ICU (ATTACC, REMAP-CAP) — but not for ICU patients (paradox in trial data)
208.1.0.6.2.6 Convalescent Plasma
  • Effectiveness limited; rarely used now
  • Some role in immunocompromise + early disease
208.1.0.6.2.7 ECMO
  • Refractory ARDS
  • Center-specific capability
208.1.0.6.3 Long COVID Treatment
  • Multidisciplinary management (cardiology, pulm, neuro, psychiatry, rehab)
  • Symptom-specific:
    • Fatigue: graded exercise (controversial), CBT, pacing
    • POTS: salt + fluid, midodrine, ivabradine
    • Dyspnea: pulm rehab
    • Brain fog: cognitive rehab
    • Pain: gabapentinoid, TCA
    • Anxiety/Depression: SSRI, CBT
  • Active research; many proposed therapies (mast cell stabilizers, antihistamines, low-dose naltrexone, antivirals retrial)
  • No definitive cure yet

208.1.0.7 6⃣ Vaccines

208.1.0.7.1 Annual Monovalent mRNA
  • 2024-2025 formulation: KP.2-targeted (Moderna, Pfizer-BioNTech)
  • Single dose annually for most
  • Multiple doses for immunocompromise (some 2-3× year)
  • Universal ≥ 6 mo
  • High-risk and immunocompromise: more frequent doses considered
208.1.0.7.2 mRNA Vaccines
  • Pfizer-BioNTech (Comirnaty): mRNA encoding S protein
  • Moderna (Spikevax): mRNA encoding S protein
  • mRESVIA (Moderna): combination RSV
  • High initial efficacy, waning over months
  • Boosters maintain protection against severe disease
208.1.0.7.3 Other Vaccines
  • Novavax (Nuvaxovid): protein subunit + adjuvant — alternative to mRNA
  • Janssen (J&J) — discontinued in many areas (rare TTS thrombotic events)
  • AstraZeneca (Vaxzevria) — replaced
208.1.0.7.4 Universal Recommendation
  • All ≥ 6 mo annually
  • Pregnant: vaccinate regardless of trimester
  • Immunocompromise: additional doses
  • Co-administration with flu + RSV + pneumococcal OK
  • Healthcare workers + high-risk priority
208.1.0.7.5 Adverse Events
  • Mild: site reaction, fatigue, fever, headache
  • Rare:
    • Myocarditis / pericarditis (mRNA, young males, post-2nd dose) — usually mild self-limited
    • TTS (J&J, AstraZeneca) — rare thrombotic + thrombocytopenia
    • Anaphylaxis (rare, < 1/100K)
  • Overall safety profile excellent
208.1.0.7.6 Why Continue Vaccinating (Endemic Era)
  • Reduces severe disease + hospitalization + death
  • Reduces transmission (modest)
  • Protects vulnerable
  • Long COVID risk reduction with vaccination
  • Variant-targeted boosters maintain efficacy