Acute respiratory failure in a patient with diffuse ground-glass opacities during the COVID-19 pandemic

History of present illness

A 78-year-old woman arrived in the emergency department (ED) due to a dry cough, worsening dyspnea, and fever. Before that ED visit, the general practitioner placed her on oral azithromycin 500 mg once daily, oral acetylcysteine 600 mg once daily, and paracetamol as needed. However, she had no improvement in the symptoms after 3 days of treatment.

Past medical history

The patient had been a heavy smoker from the age of 18 to 60 years (42 pack-years). She had a history of arterial hypertension and gastroesophageal reflux disease. About 6 months before the current presentation, she was hospitalized for obstructive jaundice from gallstones, and her gallbladder was removed. On that occasion, atrial fibrillation was found and she underwent pharmacological cardioversion with amiodarone. She received an intravenous loading dose of 300 mg diluted in 250 mL of 5% glucose over 60 minutes, followed by 450 mg in 250 mL of 5% glucose at 21 mL/hr for 8 hours, when restoration of sinus rhythm was documented. The patient then continued maintenance treatment with oral amiodarone.

Her home medication list included pantoprazole 20 mg/day, ramipril 5 mg/day, amiodarone 200 mg/day Monday through Friday, and rivaroxaban 20 mg once daily.

No vaccine for the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) was available at the time of clinical presentation.

Physical examination and early clinical findings

On presentation in ED, the patient was dyspneic, tachycardic, and feverish with a body temperature of 37.9°C (100.2°F). Peripheral oxygen saturation at the pulse oximeter (SpO ₂ ) was 86% while the patient was breathing room air. Respiratory rate was about 30 breaths per minute, and blood pressure was 135/85 mm Hg. On auscultation, the breath sounds were slightly reduced and expiratory wheezing was heard in the middle and lower lung fields. Supplemental oxygen was promptly administered. However, a 50% fraction of inspired oxygen (FiO ₂ ) via Venturi mask was required to obtain sufficient oxygen levels (SpO ₂ 92%). Arterial blood gas analysis (ABGA) with such oxygen supplement showed respiratory alkalosis with pH 7.48, partial pressure of oxygen (pO ₂ ) 68 mm Hg, and partial pressure of carbon dioxide (pCO ₂ ) 31 mmHg.

Blood tests showed leukocytosis (white blood cell count 11.820/mm ³ ), raised D-dimer (1560 μg/L FEU; normal value for patients > 50 years: age × 10 μg/L FEU), and a marked increase in C-reactive protein (CRP: 226 mg/L; normal values < 5 mg/L), whereas procalcitonin (PCT) was slightly raised (0.45 ng/mL; normal values < 0.1 ng/mL). No anemia or alteration of electrolytes or liver and kidney function was found.

Bedside ultrasound showed interstitial syndrome with several abnormal vertical artifacts (B-lines) bilaterally ( Fig. 21.1 ).

The chest radiograph demonstrated a diffuse reduction of lung transparency and multiple patchy ground-glass opacities ( Fig. 21.2 ).

Reverse transcriptase–polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab was negative.

Clinical course

The patient started helmet CPAP treatment with positive end-expiratory pressure (PEEP) of 7.5 cmH ₂ O and FiO ₂ of 50%; then she was admitted to the pulmonology department. She obtained an improvement in oxygen parameters (SpO ₂ 97%, pO ₂ 88 mmHg), and the respiratory rate decreased to approximately 22 breaths/minute. Therefore, the use of CPAP was confirmed. Empiric administration of intravenous corticosteroids and antibiotics was initiated (dexamethasone 6 mg/day, ceftriaxone 2 mg/day), and the current anticoagulant (rivaroxaban) was continued.

Due to the evidence of breath sounds suggesting bronchospasm and the significant exposure to smoke, inhaled bronchodilators were added, assuming the patient had unrecognized COPD. In particular, the doctors chose the combination of a long-acting β ₂ -agonist (LABA) and a long-acting muscarinic agent (LAMA).

The computed tomography pulmonary angiography (CTPA) was negative for pulmonary embolism but showed diffuse ground-glass opacities in all pulmonary lobes, with a slight prevalence in the subpleural regions compared to the central ones. There were also focal lucencies due to preexisting emphysema, and no pleural effusion nor mediastinal lymphadenopathies were observed ( Fig. 21.3 ).

For the first 72 hours of hospitalization, the patient maintained SpO ₂ between 97% and 99% when using CPAP. During the short meal breaks, she was using a Venturi mask with the same FiO ₂ of 50%, and the SpO ₂ diminished to about 91%.

As a precaution, the patient was kept in airborne infection isolation. However, three molecular tests on nasopharyngeal swabs for SARS-CoV-2, repeated for 3 consecutive days, were all negative. Throat swabs for the H1N1 virus and Mycoplasma pneumoniae were negative as well as urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila . The search for IgM antibodies anti– Chlamydia pneumoniae in serum was negative, too.

The patient underwent bronchoscopy using precautions intended for people infected with coronavirus, although there was still no positivity for COVID-19. The procedure was performed under the supervision of an anesthetist, using intravenous propofol and midazolam as sedation. To reduce the impact of bronchoscopy on the patient’s clinical conditions, doctors performed just a small bronchial lavage by instilling a limited amount of saline solution (20 mL in this case), which allowed the collection of an adequate lower respiratory specimen for analysis.

RT–PCR for SARS-CoV-2 in bronchial lavage fluid turned positive and the patient continued her hospitalization in the ward dedicated to COVID-19 patients. Instead, bacterial cultures were negative.

After the bronchoscopy, the patient had a worsening gas exchange. SpO ₂ dropped to 94% during CPAP with PEEP of 7.5 cmH ₂ O and FiO ₂ of 50%, while ABGA showed mild hypercapnia and respiratory acidosis: pH 7.33, pO ₂ 70 mmHg, and pCO ₂ 49 mmHg.

In the following days, the patient showed a progressive clinical improvement with the resolution of wheezing, improvement of oxygenation parameters, and reduction of inflammation indices. Arterial pH and pCO ₂ values normalized. Doctors reduced the use of noninvasive respiratory support and FiO ₂ . When ABGA with FiO ₂ 40% via Venturi mask revealed a PaO ₂ :FiO ₂ > 200 (pO ₂ 86 mmHg), they stopped the mechanical ventilation. After 10 days, the systemic corticosteroid was tapered and shifted to oral administration. However, it took > 2 weeks for SpO ₂ to be stably sufficient without supplemental oxygen.

Several electrocardiograms showed that the patient maintained sinus, slightly tachycardic rhythm.

Recommended therapy and further indications at discharge

The patient was discharged home after a total of 18 days of hospitalization, with the diagnosis of acute respiratory failure due to COVID-19 pneumonia and possible acute exacerbation of COPD.

Amiodarone was reintroduced in therapy (200 mg/day from Monday to Friday). A low dose of oral prednisone was recommended with further tapering (12.5 mg/day for 3 days, then 6.25 mg/day for an additional 3 days).

Pulmonary function tests after 3 months and chest high-resolution (HR) CT after 6 months were scheduled.

Follow-up and outcomes

Three months after the acute episode, the patient regained clinical conditions and quality of life similar to those she had before admission. Pulmonary function tests revealed a moderate airway obstruction, without significant reversibility at the bronchodilation test (postbronchodilator FEV ₁ /VC 64%, FEV ₁ 72% of predicted). Diffusing capacity of the lungs for carbon monoxide (DLCO) was reduced to 74% of predicted. Thus, the diagnosis of COPD was confirmed and the use of inhaled LABA/LAMA was continued.

A chest HRCT scan performed 6 months after discharge showed residual peripheral opacities referable to scarring fibrotic outcomes, in addition to the previously noted pulmonary emphysema. The ground-glass areas had disappeared from all lobes ( Fig. 21.4 ).