Case 1
A 55-year-old man, with a 10-year history of hypertension (treated with nicardipin 20 mg twice daily, bisoprolol 5 mg twice daily and aldactazine 1 tablet once daily) and a 5-year history of pigeon breeding, was seen in the Department of Internal Medicine on September 20, 2019, for dry cough, 2 weeks after returning from Guangzhou (Guangdong province, China). The patient did not complain of any loss of smell or taste. He had good mental orientation. Axillary temperature was 37 °C. Chest auscultation noted normal heart sounds and normal vesicular breath sounds without rales or sibilance. There was no abdominal tenderness nor enlarged liver or spleen. There was no low limb oedema. There was no loss of peripheral motor or sensor function and no other abnormal neurological signs. Laboratory results showed normal complete blood count (CBC) and procalcitonin (< 0.1 ng/ml); an elevated serum creatinine (1.8 mg/dl, hence a glomerular filtration rate, GFR, of 50.6 ml/(min*1.73m²)) and electrolytes disturbances (low sodium at 130 mmol/l, low potassium at 3.4 mmol/l and low calcium 1.04 mmol/l) (Table 1). A diagnosis of non-specific interstitial pneumonia was evoked based on a CXR showing bi-basal and posterior densification (25–30% of total chest height), blurring heart borders and diaphragm, associated with trabecular bands and ground-glass zones on the mid third of the lungs (Fig. 1a, b). He was sent back home with oral azithromycin (500 mg daily for five days), paracetamol (1000 mg up to 3 times a day if necessary) and an antitussive drug.
Table 1
Summary of laboratory tests for the 55-year-old male patient
Laboratory tests | Normal values | Sept. 20 | Oct. 10 | Oct. 14 | Oct. 17 | Oct. 23 | Oct. 28 |
Arterial Blood gas | | | | | | | |
pH | 7.35–7.45 | – | 7.55 | 7.52 | 7.55 | 7.31 | 6.97 |
PaO2 (mmHg) | 75–100 | – | 33 | 48 | 49 | 60 | 60 |
PCO2 (mmHg) | 35–45 | – | 29.7 | 36.5 | 31.6 | 43 | 74 |
SaO2 (%) | 94–100 | – | 74 | 88 | 89 | 92 | 73 |
Lactates (mmol/L) | < 2.00 | – | 1.89 | 4.00 | 3.27 | 3.1 | 12.2 |
Bicarbonates (mmol/L) | 22.0–26.0 | – | 25.1 | 28.8 | 27.0 | 21 | 16.5 |
PaO2/FiO2 (mmHg) | 400–500 | – | 157 | 229 | 233 | 60 | 60 |
Complete blood count | | | | | | | |
White blood cells (x10³/µL) | 4.00–10.00 | 8.00 | 11.60 | – | – | – | 7.60 |
Neutrophiles (x10³/µL) | 1.50–7.00 | 5.46 | 9.07 | – | – | – | 5.40 |
Lymphocytes (x10³/µL) | 1.50–4.50 | 1.63 | 1.38 | – | – | – | 1.43 |
Monocytes (x10³/µL) | 0.20–1.00 | 0.74 | 1.11 | – | – | – | 0.74 |
Eosinophiles (x10³/µL) | 0.10–0.50 | 0.16 | 0.02 | – | – | – | 0.03 |
Red blood cells (x106/µL) | 4.20–5.70 | 5.28 | 4.90 | – | – | – | 5.41 |
Hemoglobin (g/L) | 13.0–18.0 | 16.0 | 15.3 | 17.0 | – | – | 16.5 |
Hematocrit (%) | 40.0–52.0 | 45.1 | 42.3 | 50.0 | – | – | 48 |
Platelets (x10³/µL) | 150–450 | 244 | 213 | – | – | – | 156 |
Electrolytes | | | | | | | |
Sodium (mmol/L) | 135–155 | 130 | 129 | 135 | 132 | – | 133 |
Potassium (mmol/L) | 3.5–5.1 | 3.4 | 3.4 | 3.2 | 3.4 | – | 3.7 |
Chloride (mmol/L) | 96–115 | 99 | 99 | 102 | 99 | – | 115 |
Calcium (mmol/L) | 1.10–1.40 | 1.04 | 1.12 | 1.21 | 1.25 | – | 1.33 |
Magnesium (mg/dL) | 1.60–2.50 | – | – | 1.8 | – | – | 1.7 |
C-Reactive protein (mg/L) | < 3.0 | – | 54.9 | – | 98 | 43 | 102 |
Procalcitonin (ng/mL) | < 0.10 | < 0.10 | < 0.10 | – | – | 0.69 | < 0.1 |
Creatinine (mg/dL) | 0.6–1.40 | 1.80 | 2.04 | – | – | 1.80 | 3.8 |
Blood Urea Nitrogen | 8.0–23.0 | – | 40.0 | – | – | 107 | 150 |
Blood Glucose (mg/dl) | 60–110 | 82 | 127 | – | – | 82 | – |
Hb1Ac (%) | 4–5.70 | 3.29 | – | – | – | – | – |
Troponin (ng/ml) | | 0.02 | – | – | – | – | – |
Pro-BNP (pg/ml) | | – | 183.4 | – | – | 101.5 | – |
D-dimer (µg/L) | < 500 | – | 790 | – | – | – | – |
Thick blood film | Negative | – | Negative | – | – | Negative | – |
Hemocultures | Negative | – | Negative | – | – | Negative | – |
Ziehl-Neelsen stain of sputum | Negative | – | Negative | – | – | – | – |
Serologies | | | | | | | |
HIV | Negative | – | Negative | – | – | – | – |
Viral hepatitis B | Negative | – | Negative | – | – | – | – |
Viral hepatitis C | Negative | – | Negative | – | – | – | – |
Syphilis | Negative | – | Negative | – | – | – | – |
Despite treatment, coughing was exacerbated, and fever and dyspnoea occurred two weeks later. On October 10, 2019, he was admitted in the Emergency ward. The clinical evaluation noticed polypnea (30 breaths/min), tachycardia (100 beats/min) and fever (38 °C). Oxygen saturation (SaO2) measured with a pulse oximeter was 54% [normal range: 95–100%]. The patient presented a respiratory distress (nose flaring, chest retractions and cyanosis) and had fine crackles at both lung bases. Cardiovascular examination was normal. Laboratory results showed a moderate inflammatory syndrome with hyperleukocytosis (11,600 leucocytes/µl [4,000–10,000/µl] of which 9,071 neutrophils [1,500-7,000/µl] and 1,380 lymphocytes [1,500-4,500/µl]) and increased C-reactive protein (CRP, 54.9 mg/l [0–3 mg/l]). Procalcitonin levels were normal [below 0.1 ng/ml]. An arterial blood gas (ABG) analysis revealed the presence of severe hypoxemia (PaO2 33 mmHg [75–100 mmHg], SaO2 74%) and respiratory alkalosis (pH 7.55 [7.35–7.45], PaCO2 29.7 mmHg [35–45 mmHg], PaO2/FiO2 ratio 157 mmHg [400–500 mmHg], bicarbonate 25.1 mmol/l [22–26 mmol/l], and lactates 1.89 mmol/l [< 2 mmol/l]). Bacteriological investigations were all negative. Tuberculosis was unlikely given a Ziehl-Neelsen stain of sputum which was negative for three samples collected at different times. HIV serological tests were negative (Table 1). A second CXR showed persistence of the aforementioned findings, except for the trabeculae hidden by the alveolar densification that had progressed up to the level of the main bronchi, overhung by a well delimited ground glass zone without encroachment upon the apices (Fig. 1c).
The patient was hospitalized in the ICU for acute respiratory distress syndrome (ARDS) secondary to viral pneumonia with probable bacterial superinfection. He received oxygen by mask (5 litres/min) and intravenous antibiotics (combination of amoxicillin and clavulanic acid 1/0.25 g thrice daily). Despite this treatment, continuous fever (average temperature: 38.5 °C) and hypoxemia persisted, and lactates increased to 4 mmol/l. So, two days later, amoxicillin and clavulanic acid were replaced by levofloxacin (500 mg) and ceftriaxone (1 g), both twice daily, in addition to intravenous dexamethasone (16 mg thrice daily).
Four days later, no improvement was observed. The oxygen flow was increased to 10 litres/min and dexamethasone replaced by methylprednisolone (125 mg twice daily for 5 days). During the following week, there was a slight improvement of the dyspnoea and fever, but on October 23, 2019, fever reappeared, and the respiratory distress worsened. A new CXR showed a reduction of the alveolar consolidation to the advantage of an interstitial syndrome (reticulations, ground-glass, and nodules ≤ 6 mm) extending to lung tops (Fig. 1d). Meanwhile, the CRP was 49 mg/l and procalcitonin 0.62 ng/ml. A diagnosis of respiratory zoonosis was considered, given the history of pigeon breeding. Intravenous methylprednisolone (125 mg twice daily) was reintroduced and Duovent® (combined ipratropium and fenoterol) was administered in nebulization, without any improvement. SaO2 (measured with a pulse oximeter) remained at 40%, PaO2/FiO2 ratio decreased to less than 70 mmHg, and the patient became confused, with loss of notion of space and time, probably because of the hypoxia.
On October 25, 2019, the patient underwent orotracheal intubation for mechanical ventilation. This improved the SaO2 to 90–94% but on October 28, 2019, the patient developed a shock, with increased lactacidemia (12.2 mmol/l), followed within a few hours by cardiac arrest irresponsive to resuscitation.
Case 2
A 25-year-old woman, with no history of recent travel, was admitted at the Emergency ward on December 18, 2019, for a one-week progressive dyspnoea, preceded by dry cough and fever. She had no particular medical history and was a nurse in a hospital where Chinese employees from a multinational mining company are treated, of whom some had recently travelled from China (the place they came from in China could not be determined) and three of them had presented flu-like symptoms within 2 weeks. On admission, she could not complete sentences due to dyspnoea. At ambient air, she presented a SaO2 of 82% and signs of respiratory distress without cyanosis. Her pulmonary and cardiac auscultation was normal.
The CXR showed reticular lines and peribronchovascular haziness in the infrahilar and retrocardiac regions, bilaterally. This suggested a mild interstitial pneumonia (Fig. 2a, b). Laboratory results showed a slight inflammation with CRP at 14.5 mg/l, lymphopenia (700 lymphocytes/µl) and normal procalcitonin (< 0.1 ng/ml). The ABG showed a hypoxemia (PaO2 60 mmHg) and a respiratory alkalosis (pH 7.51, PaCO2 35 mmHg, PaO2/FiO2 286 mmHg, bicarbonate 27.1 mmol/l, and lactates 1.50 mmol/l). Creatinine, blood urea nitrogen and blood electrolytes were normal. HIV serology was negative.
A diagnosis of moderate ARDS secondary to a viral pneumonia was retained and the patient was admitted in the ICU, receiving oxygen (4 litres/min), azithromycin (500 mg once daily for 5 days) and Duovent® in nebulization. Three days later, she was eupnoeic with normal SaO2 at ambient air. She was discharged from hospital five days after admission.