Management of severe COVID-19 in an elderly patient requiring supplemental oxygen

Presentation, history and investigations
A 73-year-old male presented to the Accident & Emergency Department on 8 March 2022 (day 1) with fever (38°C), sore throat, cough, sputum and shortness of breath (SOB). Upon arrival, his blood pressure was 159/59 mm Hg, heart rate was 90 beats/minute, and oxygen saturation was 85 percent on room air, which improved to 96 percent with 3 L/min of supplemental oxygen. He was a hepatitis B virus carrier not receiving antivirals and had diabetes mellitus, which was well controlled with diet. He was not vaccinated against SARS-CoV-2 and had no prior exposure to COVID-19 oral antivirals.

Investigations showed positive SARS-CoV-2 on polymerase chain reaction (PCR) test (cycle threshold [Ct] value, 22.6). Blood tests included haemoglobin (Hb, 13.6 g/dL), white blood cells (WBC, 7.6 x 10⁹/L: lymphocytes, 0.5 x 10⁹/L; neutrophils, 6.7 x 10⁹/L), platelet (315 x 10⁹/L), creatinine (55 μmol/L; estimated glomerular filtration rate [eGFR], approximately 80 mL/min/1.73 m²), alanine transaminase (ALT, 23 IU/L), alkaline phosphatase (59 U/L), lactate dehydrogenase (LDH, 449 IU/L), C-reactive protein (CRP, 136 mg/L), D-dimer (503 ng/mL) and procalcitonin (0.05 ng/mL).

Treatment
Upon admission, remdesivir treatment as initiated with a 200 mg intravenous (IV) loading dose, followed by 100 mg Q24H on the subsequent 4 days. Prophylactic anticoagulation was given with subcutaneous enoxaparin 40 mg Q24H until 20 March 2022. The patient also received IV amoxicillin/clavulanate 1.2 g Q8H from admission until 18 March 2022, followed by ceftazidime 1 g Q12H until 23 March 2022, and dexamethasone 6 mg STAT on admission and then Q24H until 20 March 2022. In addition, continuous rehabilitation was provided during hospitalization.

Early clinical improvements were observed, which led to gradual weaning off supplemental oxygen from day 3 and full discontinuation of supplemental oxygen by day 6. The patient never required mechanical ventilation. During his hospital stay, the laboratory values continued to improve. By 17 March 2022, CRP was 3 mg/L and LDH was 384 IU/L. He was discharged from hospital on 23 March 2022, but was readmitted on 29 March 2022 for SOB. The patient is currently stable but has mild SOB on exertion.

Discussion
In Hong Kong, remdesivir in combination with dexamethasone is recommended for hospitalized COVID-19 patients with moderate symptoms who require supplemental oxygen, or moderate-to-severe symptoms who require oxygen through a high-flow device or noninvasive ventilation.¹

The optimal timing for remdesivir initiation is on admission to hospital, simultaneously with dexamethasone. A retrospective cohort study in Hong Kong among 10,445 hospitalized patients with moderate COVID-19 evaluated the clinical benefits of remdesivir initiation prior to or simultaneously with dexamethasone (exposure group) vs late introduction or no remdesivir use (nonexposure group). The exposure group had significantly shorter time to clinical improvement (median, 12 days vs 13 days; hazard ratio [HR], 1.23; 95 percent confidence interval [CI], 1.02–1.49; p=0.032) and positive immunoglobulin G (IgG) antibody (median, 5 days vs 6 days; HR, 1.22; 95 percent CI, 1.02–1.46; p=0.029), shorter hospital length of stay by 2.65 days (95 percent CI, 1.01–4.29; p=0.002) among survivors, and lower risk of in-hospital death (HR, 0.59; 95 percent CI, 0.36–0.98; p=0.042) vs the nonexposure group.² Similarly, a prospective controlled study in Italy (n=151) reported beneficial results with simultaneous use of remdesivir and dexamethasone vs dexamethasone alone, in terms of 30-day mortality, length of stay, viral clearance, improvement of respiratory function and inflammatory markers.³

Our patient had three risk factors – advanced age, unvaccinated status and underlying diabetes – for progression to severe COVID-19. The ACTT-1 and WHO Solidarity trials included patients with similar characteristics and demonstrated that, compared with placebo or standard of care, remdesivir was associated with faster clinical recovery (median recovery time, 10 days vs 15 days; rate ratio, 1.29; 95 percent CI, 1.12–1.49; p<0.001) in patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection, and reduced in-hospital mortality (rate ratio, 0.87; 95 percent CI, 0.76–0.99; p=0.03) in nonventilated patients on lowor high-flow oxygen initially.^4,5 Additionally, use of remdesivir was found to reduce progression to mechanical ventilation among hospitalized patients with COVID-19 who were on supplemental oxygen initially in the WHO Solidarity and CATCO trials.^5,6 Notably, patients in need of supplemental oxygen, such as our patient, reaped greater clinical benefits.^5,6

The importance of early initiation of remdesivir among hospitalized patients with moderate COVID-19 is further supported by real-world evidence. A population-based observational study in Hong Kong (n=10,419) showed that initiation of remdesivir within 2 days of hospital admission was associated with significantly shorter time to clinical improvement, achieving low viral load and positive IgG antibody, and a lower risk of in-hospital death vs no remdesivir.⁷ (Figure)

A similar US study (n=570) also showed that remdesivir significantly decreased the time to clinical recovery among hospitalized COVID-19 patients (median, 5 days vs 7 days; adjusted HR, 1.47; 95 percent CI, 1.22–1.79) vs matched controls.⁸ A systematic review and meta-analysis of 11 studies (n=166,399) demonstrated the real-world effectiveness of remdesivir in reducing mortality in hospitalized COVID-19 patients.⁹

Furthermore, a single-centre, prospective study in Hong Kong (n=208) found that early remdesivir monotherapy (within 7 days of symptom onset) accelerated the decline in upper respiratory tract viral load in COVID-19 patients who developed pneumonitis.¹⁰

Cautious use of remdesivir is recommended in patients with underlying renal impairment or abnormal baseline liver function. Assessment of liver function and eGFR is recommended before initiation of remdesivir, particularly among hospitalized patients, and consider repeating these tests during the treatment course as clinically indicated. Discontinuation of remdesivir may be considered if ALT level exceeds 10 times the upper limit of normal.^11,12 Since remdesivir may be associated with arrhythmia (eg, bradycardia), heart rate should be monitored following infusion and throughout the treatment course,^13,14 especially among patients with concomitant use of negative chronotropic agents or with underlying heart conduction issues.

For patients with severe renal impairment, therapeutic benefits of remdesivir may outweigh risks in certain situations (eg, severe COVID-19 requiring supplemental oxygen). Safety analyses of clinical trial data showed no further worsening of kidney function or adverse liver outcomes when remdesivir is administered in patients with impaired renal function.^15-17

Although initial symptoms of COVID-19 may be mild or unnoticeable in the elderly, the disease can progress rapidly to the inflammatory phase. Close patient monitoring and optimal timing of remdesivir initiation are crucial for achieving favourable clinical outcomes.