A 62-year-old man with a 10-day history of COVID-19 was admitted to the ICU and intubated 16 hours ago for worsening hypoxemic respiratory failure. He is on volume-controlled mechanical ventilation (PEEP 10 cm H₂O) and receiving norepinephrine via a central line. He has been on dexamethasone 6 mg IV daily for the past 3 days but continues to have worsening oxygenation. His most recent C-reactive protein is 120 mg/L. He has no history of gastrointestinal perforation or other active infections. Given his critical COVID-19 requiring intubation within the last 24 hours, elevated inflammatory markers, and ongoing corticosteroid therapy, what is the most appropriate next step in pharmacologic management?

A 62-year-old, 75-kg man with diffuse large B-cell lymphoma is in the intensive care unit on day 5 after receiving chimeric antigen receptor (CAR) T-cell therapy. He develops a fever of 39.5°C, hypotension requiring norepinephrine at 0.1 mcg/kg/min via a central line, and progressive hypoxemia requiring mechanical ventilation. His C-reactive protein is 180 mg/L. He is receiving broad-spectrum antibiotics and supportive care. Which of the following is the most appropriate initial pharmacologic intervention for presumed Grade 4 cytokine release syndrome (CRS)?

A 45-year-old man (70 kg) with relapsed B-cell lymphoma is in the ICU on day 5 after receiving CAR-T cell therapy. He develops a fever of 39.5°C (103.1°F), hypotension requiring a norepinephrine infusion via his central venous catheter, and hypoxia requiring 4 L/min of oxygen by nasal cannula. Which of the following is the most appropriate initial pharmacologic intervention?

A 62-year-old man weighing 75 kg is admitted to the intensive care unit with rapidly progressive COVID-19. Eighteen hours ago he was intubated and is now on mechanical ventilation with a PEEP of 10 cm H₂O and requires a continuous norepinephrine infusion for vasopressor support. His C-reactive protein is 120 mg/L (normal <5 mg/L), and he is receiving dexamethasone 6 mg IV daily. During evening rounds, the team considers additional immunomodulatory therapy due to worsening respiratory status and marked inflammation. Which of the following is the most appropriate adjunctive therapy to initiate at this time?

A 45-year-old man (weight 80 kg) is admitted to the ICU for progressive critical COVID-19. He was hospitalized at an outside facility for 2 days before intubation and transfer. Upon ICU arrival 12 hours ago, his C-reactive protein (CRP) was 85 mg/L (normal 0–10 mg/L), and he was started on dexamethasone 6 mg IV daily. He remains on assist-control ventilation and norepinephrine 0.05 mcg/kg/min via central line. His current vital signs are BP 105/60 mmHg, HR 98 bpm, RR 18 breaths/min (ventilator-supported), SpO₂ 92% on FiO₂ 0.7. He has no history of immunosuppression or GI perforation. Which is the most appropriate next intervention?

A 65-year-old man (weight 75 kg), unvaccinated against SARS-CoV-2, is admitted to the ICU on day 2 of hospitalization for severe COVID-19 pneumonia. He has been febrile for 8 days, is on assist-control mechanical ventilation, receiving norepinephrine 0.05 mcg/kg/min via a central line, and has been on dexamethasone 6 mg IV daily since admission. His CRP is 120 mg/L (normal < 5 mg/L), WBC 18.5×10^9/L, creatinine 0.9 mg/dL, and AST/ALT are within normal limits. According to current IDSA guidelines, which of the following is the most appropriate next pharmacologic step?

A 28-year-old woman weighing 70 kg is in the intensive care unit on day 5 after receiving a CAR-T cell infusion for relapsed B-cell acute lymphoblastic leukemia. She develops a persistent fever of 39.5 °C, hypotension requiring a continuous norepinephrine infusion, and new-onset hypoxia with an oxygen saturation of 88% on 6 L/min via nasal cannula. A central venous catheter is in place for infusions and monitoring. Laboratory results show a C-reactive protein of 180 mg/L and ferritin of 2,500 ng/mL. Based on this presentation, which intervention is the most appropriate first-line pharmacologic treatment for this patient’s condition?

A 62-year-old man with severe COVID-19–associated ARDS is receiving assist-control ventilation, dexamethasone 6 mg daily, and received tocilizumab 8 mg/kg 24 hours ago. His temperature is 37.2 °C, WBC count is 8,500 /mm³, CRP has fallen from 120 to 30 mg/L, and lactate is 1.8 mmol/L. Given the effects of tocilizumab on inflammatory markers, which monitoring strategy is most critical to detect new infections?

A 62-year-old, 80 kg man is admitted to the ICU with critical COVID-19 pneumonia requiring mechanical ventilation for the past 12 hours. He is receiving dexamethasone 6 mg IV daily and is on vasopressor support. His C-reactive protein is 120 mg/L. According to current Infectious Diseases Society of America (IDSA) guidelines, which of the following immunotherapeutic agents is the recommended first-line biologic to add to his regimen?

A 62-year-old, 80-kg man presented to the hospital 7 days after onset of fever, cough, and dyspnea and was admitted to the ICU 2 days ago with COVID-19 pneumonia. He requires high-flow nasal cannula at an FiO2 of 0.8 to maintain SpO2 >92% and is receiving dexamethasone 6 mg IV daily. His inflammatory markers are elevated: CRP 110 mg/L (normal <5), ferritin 1200 ng/mL (30–400), and D-dimer 1500 ng/mL (<500). He has no history of gastrointestinal perforation or active infection other than COVID-19. The team is considering additional immunomodulatory therapy due to progressive respiratory failure and marked inflammation. Which of the following is the most appropriate next step in pharmacologic management?