Infectious Disease · PANCE / PANRE

COVID-19

Respiratory illness caused by SARS-CoV-2 — managed with antivirals (nirmatrelvir-ritonavir, remdesivir) and supportive care; vaccination remains the cornerstone of prevention.

Also known as: COVID-19, SARS-CoV-2, coronavirus, novel coronavirus

Overview

Acute respiratory illness caused by SARS-CoV-2, an enveloped positive-sense RNA betacoronavirus. Spectrum ranges from asymptomatic infection to severe pneumonia, ARDS, multi-organ failure, and post-acute sequelae (long COVID).

Epidemiology

Worldwide pandemic since 2020; >7 million confirmed deaths and likely far more excess deaths. Endemic transmission continues with periodic surges driven by new variants. Highest morbidity in older adults, immunocompromised, and those with cardiopulmonary, metabolic, and obesity-related comorbidities.

Try two board-style COVID-19 questions

Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.

Question 1Infectious DiseaseMedium
A 68-year-old woman presents to clinic with 2 days of cough, sore throat, and low-grade fever. She has hypertension and type 2 diabetes. Home medications are lisinopril, metformin, and atorvastatin. She has no known drug allergies. Vital signs: temperature 38.1 C, HR 92/min, BP 138/82 mm Hg, oxygen saturation 96% on room air. Lungs are clear. A rapid SARS-CoV-2 antigen test is positive. eGFR is 78 mL/min/1.73 m2. She is at high risk for progression to severe disease. Which of the following is the most appropriate outpatient treatment?
  • AMolnupiravir
  • BDexamethasone
  • CNirmatrelvir-ritonavir
  • DRemdesivir
Reveal answer & full explanation
Correct answer: C — Nirmatrelvir-ritonavir
  • AMolnupiravir
  • BDexamethasone
  • CNirmatrelvir-ritonavir
  • DRemdesivir

Why nirmatrelvir-ritonavir is correct

  • This patient has mild-to-moderate COVID-19 in a high-risk outpatient (age >65, diabetes) within 5 days of symptom onset — the ideal candidate for nirmatrelvir-ritonavir (Paxlovid)
  • Nirmatrelvir is a SARS-CoV-2 main protease (Mpro/3CLpro) inhibitor; ritonavir is a CYP3A4 inhibitor that boosts nirmatrelvir levels
  • In the EPIC-HR trial, Paxlovid reduced hospitalization or death by ~89% when started within 5 days of symptoms
  • Dose is 300 mg/100 mg twice daily for 5 days; requires eGFR >=30 (dose-reduce if 30-60) and careful drug-interaction review (notably statins, which should be held)

Why the others are wrong

  • Remdesivir — effective but requires 3 days of IV infusions, which is far less convenient for outpatient use and is reserved for patients who cannot take Paxlovid
  • Molnupiravir — second-line oral antiviral with lower efficacy (~30% reduction); used only when Paxlovid and remdesivir are unavailable or contraindicated
  • Dexamethasone — beneficial only in hospitalized patients requiring supplemental oxygen; can worsen outcomes in mild outpatient COVID-19

Additional high-yield points

  • Atorvastatin should be held during the Paxlovid course
Question 2Infectious DiseaseMedium
A 68-year-old man with type 2 diabetes presents with 9 days of low-grade fever, dry cough, and progressively worsening shortness of breath. He also reports fatigue and loss of taste over the past week. On exam he is comfortable at rest but has an oxygen saturation of 86% on room air, with scattered bilateral crackles. Chest CT shows bilateral peripheral, lower-lobe ground-glass opacities. CBC shows lymphopenia, and procalcitonin is low. Which of the following is the most likely diagnosis?
  • AInfluenza pneumonia
  • BCOVID-19 pneumonia
  • CBacterial pneumonia
  • DAtypical pneumonia
Reveal answer & full explanation
Correct answer: B — COVID-19 pneumonia
  • AInfluenza pneumonia
  • BCOVID-19 pneumonia
  • CBacterial pneumonia
  • DAtypical pneumonia

Why COVID-19 pneumonia is correct

  • Subacute course over ~1 week with dry cough, fever, and loss of taste (ageusia) is classic for SARS-CoV-2.
  • Silent hypoxia (SpO2 86% while comfortable, disproportionate to a relatively unremarkable exam) is a hallmark clue.
  • Bilateral peripheral, lower-lobe ground-glass opacities on CT, lymphopenia, and a low procalcitonin all point to a viral pneumonitis rather than a bacterial process. Confirm with SARS-CoV-2 RT-PCR or antigen testing.

Why the others are wrong

  • Influenza pneumonia: typically more abrupt onset with prominent myalgia; it does not characteristically cause loss of taste or the peripheral lower-lobe ground-glass pattern seen here.
  • Bacterial pneumonia: expected to show higher fevers, focal lobar consolidation, productive purulent sputum, and leukocytosis with an elevated procalcitonin, not bilateral ground-glass with lymphopenia and a low procalcitonin.
  • Atypical pneumonia: Mycoplasma, Chlamydia, and Legionella can cause diffuse infiltrates, but the combination of ageusia, peripheral lower-lobe ground-glass opacities, and silent hypoxia is far more characteristic of COVID-19.
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Risk factors

  • Age ≥65, residence in long-term care
  • Cardiopulmonary disease (CAD, HF, COPD, asthma, OSA)
  • Diabetes, obesity (BMI ≥30), CKD, liver disease
  • Immunocompromise (transplant, chemotherapy, advanced HIV, biologics)
  • Pregnancy (especially third trimester)
  • Smoking, lower-income, racial/ethnic minorities (structural inequities)
  • Incomplete vaccination

Pathophysiology

SARS-CoV-2 spike protein binds ACE2 receptor (abundant on respiratory epithelium, vascular endothelium, GI tract) with TMPRSS2-mediated entry. Initial replication in upper airway; in severe disease, lower respiratory tract involvement with dysregulated immune response, endothelial dysfunction, thrombotic microangiopathy, and ARDS. Cytokine release ('cytokine storm') drives multi-organ injury. Post-acute syndromes likely reflect persistent inflammation, microvascular damage, autonomic dysfunction.

Clinical presentation

Symptoms

  • Variable — fever, cough, dyspnea, fatigue, myalgia, headache, sore throat, rhinorrhea, congestion
  • GI: nausea, vomiting, diarrhea, anorexia
  • Anosmia/ageusia (more common with earlier variants)
  • Severe disease (typically week 2): worsening dyspnea, hypoxia, respiratory failure, ARDS
  • Pediatric: usually mild; MIS-C (multisystem inflammatory syndrome) ~4-6 weeks post-infection — fever, rash, conjunctivitis, GI symptoms, shock (Kawasaki-like)
  • Long COVID: persistent fatigue, dyspnea, cognitive impairment ('brain fog'), POTS, post-exertional malaise, anosmia >12 weeks

Signs / physical exam

  • Fever, tachypnea, hypoxia (sometimes 'silent hypoxia' — low SpO2 without distress)
  • Bilateral crackles, sometimes wheezing
  • Often unremarkable exam in mild disease

Classic findings

Patient with new dyspnea, hypoxia disproportionate to chest exam, and bilateral peripheral/lower-lobe ground-glass opacities on CT — consider COVID-19. Silent hypoxia (SpO2 <90% with patient comfortable) is a clue.

Differential diagnosis

  • Influenza — Abrupt onset, myalgia prominent; rapid antigen/PCR; treat with oseltamivir within 48 h
  • RSV — Wheezing in young children, bronchiolitis; PCR
  • Bacterial pneumonia — Higher fevers, focal consolidation, productive purulent sputum, leukocytosis with left shift; sputum culture and procalcitonin
  • Pulmonary embolism — Pleuritic pain, sudden dyspnea, RV strain on echo; D-dimer/CTPA
  • Heart failure — Orthopnea, JVD, elevated BNP, cardiomegaly on CXR
  • Other respiratory viruses (rhinovirus, parainfluenza) — Multiplex PCR
  • Atypical pneumonia (Mycoplasma, Chlamydia, Legionella) — Diffuse infiltrates, hyponatremia for Legionella; macrolide/doxycycline-responsive

Diagnostic workup

Diagnostic criteria

Positive SARS-CoV-2 RT-PCR or antigen test in symptomatic patient or exposed contact.

Labs

  • SARS-CoV-2 RT-PCR (gold standard) or rapid antigen test (good for symptomatic, less sensitive in pre-symptomatic phase)
  • CBC (lymphopenia common), CMP, LDH, ferritin, D-dimer, CRP, procalcitonin (low in pure viral; may help guide antibiotic decisions), troponin if cardiac symptoms
  • ABG if hypoxic; consider blood cultures if concern for bacterial superinfection
  • Coagulation studies in severe disease (DVT/PE risk increased)

Imaging

  • Chest X-ray — bilateral patchy or peripheral infiltrates
  • CT chest (if needed) — peripheral ground-glass opacities, often bilateral and lower lobe; 'crazy paving' in severe disease
  • Echocardiography if myocarditis suspected or hemodynamic compromise

Diagnostic algorithm

Disease SeverityDefinitionFirst-line Therapy
Mild (outpatient, high-risk)Sx without hypoxia, risk factorsPaxlovid PO x 5 d; remdesivir if contraindicated
Moderate-severe (hospitalized)SpO2 <94% on RA, needs O2Remdesivir + dexamethasone
Severe (high O2/HFNC/NIV)Needs HFNC/NIVAbove + tocilizumab or baricitinib
Critical (mechanical vent/ICU)Vent or vasopressorsDexamethasone + tocilizumab/baricitinib; lung-protective vent
MIS-C (pediatric)Post-COVID hyperinflammationIVIG + steroids; cardiology consult
NIH-aligned COVID-19 therapy by disease severity.

Treatment

First-line

  • Outpatient, high-risk for progression (within 5-7 days of symptom onset):
  • • Nirmatrelvir-ritonavir (Paxlovid) 300/100 mg PO BID × 5 days — first-line; many drug interactions via CYP3A4; renal dose adjust
  • • Remdesivir 200 mg IV day 1, then 100 mg IV daily × 2 more days (outpatient infusion) — alternative when Paxlovid contraindicated
  • • Molnupiravir 800 mg PO BID × 5 days — third-line; modest efficacy; contraindicated in pregnancy
  • Hospitalized, requiring supplemental oxygen:
  • • Remdesivir × 5 days
  • • Dexamethasone 6 mg PO/IV daily × up to 10 days (RECOVERY trial — mortality benefit if oxygen required)
  • • Add immunomodulator if progressing (high oxygen need or ICU): tocilizumab (anti-IL-6) or baricitinib (JAK inhibitor)
  • Anticoagulation: prophylactic dose enoxaparin for hospitalized non-ICU patients; therapeutic dose in select non-ICU patients per ACTIV-4a; prophylactic dose in ICU
  • Lung-protective ventilation (TV 6 mL/kg IBW), prone positioning for ARDS

Second-line / adjunct

  • Convalescent plasma generally not recommended (limited efficacy in most settings)
  • Monoclonal antibodies — variable activity by variant; many de-authorized due to emerging resistance
  • Tixagevimab-cilgavimab (Evusheld) — pre-exposure prophylaxis (de-authorized 2023 due to variant resistance)
  • Updated mRNA vaccines (Pfizer-BioNTech, Moderna) and protein-subunit vaccine (Novavax) — primary prevention; recommendations updated periodically
  • Long COVID: symptom-targeted multidisciplinary care; pulmonary rehab, cognitive rehab, autonomic management

Complications

  • ARDS, secondary bacterial pneumonia
  • Thromboembolism (DVT, PE, stroke, MI)
  • Myocarditis, arrhythmias, heart failure
  • AKI, hepatic dysfunction
  • Encephalopathy, Guillain-Barre, stroke
  • Multisystem inflammatory syndrome in children (MIS-C) and rarely adults (MIS-A)
  • Post-acute sequelae (long COVID): persistent dyspnea, fatigue, cognitive impairment, POTS
  • Death (varies by age, comorbidity, vaccination, and variant)

PANCE pearls

  • Paxlovid is first-line outpatient antiviral for high-risk patients — must be started within 5 days of symptom onset (remdesivir window extends to 7 days); review drug interactions before prescribing.
  • Dexamethasone benefits ONLY patients requiring supplemental oxygen — DO NOT give to mild outpatient disease (RECOVERY trial showed harm signal in non-oxygen-requiring patients).
  • Silent hypoxia — patients can have SpO2 in the 80s with surprisingly minimal distress; pulse oximetry essential in outpatient triage.
  • Vaccination markedly reduces severe disease and death; bivalent/updated boosters target circulating variants.
  • Long COVID management requires multidisciplinary, symptom-driven approach; rule out reversible cardiopulmonary disease (PE, myocarditis).

References

  • NIH 2024 — COVID-19 Treatment Guidelines (covid19treatmentguidelines.nih.gov)
  • RECOVERY 2021 — Dexamethasone in Hospitalized Patients with Covid-19 (NEJM)
  • EPIC-HR — Hammond et al., Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19 (NEJM 2022)
  • ACTIV-4a — Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19 (NEJM 2021)

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Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.