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.
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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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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
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
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)
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).
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.