A male, 54-year-old patient with body mass index 25.7 kg/m2 was admitted to the intensive care unit (ICU) isolation ward of Liaocheng People's Hospital after 8 days of fever and 7 days of coughing.
No accurate contact history was available. The patient had been diagnosed with diabetes 2 years earlier and had been on oral metformin (DMBG). No details were available about blood glucose control.
The patient developed a fever with no apparent triggers on February 3, 2020, with a highest recorded body temperature of 38.0 C. He had no chills or shivering, and developed a cough on February 4, with yellow-colored sputum accompanied by mild chest tightness and pain, fatigue, and discomfort. The symptoms were not relieved by traditional Chinese medicine, and he was admitted to the local hospital on February 7. CT scan on admission showed inflammatory affections on both lungs. The patient was given anti-inflammatory and anti-viral treatments. On February 9 he tested positive to the pharyngeal swab COVID-19 nucleic acid test and was transferred to the airborne-isolation ward of Liaocheng Infectious Disease Hospital for further treatment and quarantine. On February 10 his highest temperature was 39.0 C and cough with sputum and chest tightness persisted; transcutaneous oxygen saturation was 93% (oxygen uptake of 2 L/min). On February 11 breathing became more difficult and chest tightness worsened. Arterial blood gas analysis (oxygen uptake of 4 L/min) reported the following: pH, 7.46; PaCO2, 26 mmHg; PaO2, 50 mmHg; blood lactate (Lac), 5.6 mmol/L; and oxygenation index (OI), 135 mmHg. The patient was then transferred to the ICU isolation ward of Liaocheng People's Hospital at 23:45 on February 11.
On February 12 (Day 1 of hospitalization to ICU isolation ward of Liaocheng People's Hospital) body temperature was 36.9 C, heart rate 81 bpm, respiratory frequency 35/min, and blood pressure 141/87 mmHg. The patient was conscious but nervous, and showed hyperventilation and lip cyanosis. The breathing sound was thick on both lungs, without obvious dry or wet rales. The heart rate was regular, the abdomen was flat and soft, without tender or rebound pain. There was no edema on either leg, and hands and feet were warm.
On February 9, a pharyngeal swab COVID-19 nucleic acid test performed at the Liaocheng Center for Disease Control (CDC) was positive.
On February 12 blood test results were as follows: white blood cells (WBC), 7.62 x 109/L; neutrophils (NE), 6.98 x 109/L; neutrophil percentage (NEU%), 91.7%; lymphocytes (LYM), 0.30 x 109/L; platelets (PLT), 282 x 109/L; C-reactive protein (CRP), 88.0 mg/L; erythrocyte sedimentation rate (ESR), 80 mm/h; procalcitonin (PCT), 0.78 ng/mL; D-dimer, 0.72 ug/mL; CD3+ T cells, 175 x 103/ml; CD4+ T cells: 79 x 103/ml; CD8+ T cells, 95 x 103/ml; CD4/CD8 ratio, 0.83; albumin, 31g/L; creatinine, 52 mumol/L. Troponin I (cTn I), brain natriuretic peptide (BNP), creatine kinase (CK) and blood urea nitrogen (BUN) were normal.
Arterial blood gas analysis gave the following values: pH, 7.43; PCO2, 32.9 mmHg; PO2, 84 mmHg, Na+, 144 mmol/L; K+, 3.56 mmol/L; Hb, 10.4 g/dL; Lac, 2.8 mmol/L; , 22.9 mmol/L (with high-flow nasal cannula (HFNC) for 2 h, flow velocity of 45 L/min, and FiO2 60%); OI, 140 mmHg.
A large area of ground-glass opacity with uneven density was seen on chest CT on February 12 in the subpleural region of both lungs, with fine grid (crazy-paving sign), predominantly in the lower lobes. Multiple patchy consolidations were apparent in the lingular segment of the left upper lobe and bilateral lower lobes, with air bronchus-charging sign and thickening of the pulmonary interstitium surrounding the lesions (Figures 1A,B).
The patient was treated with HFNC with flow velocity of 45 L/min, and the respiratory distress stopped worsening, with FiO2 falling from 60 to 50% on day 2, and to 40% on day 4. On day 5 OI increased to 328 mmHg. On day 6 oxygen inhalation through nasal catheter was used with a velocity of 3 L/min, and OI was 288 mmHg. After 36 h the heart rate increased, the cough became heavier, and OI fell to 209 mmHg. HFNC was then reapplied with a velocity of 40 L/min and FiO2 35%. On day 15 the velocity of oxygen inhalation through nasal catheter was 3L/min, falling to 1 L/min on day 17, until oxygen inhalation was terminated on day 19.
The patient was treated with plasma exchange, 12 h after hospitalization, by Fresenius (Germany) multifiltrate bedside blood purifier and Fresenius P2 plasma separator, processing 2000 ml of blood plasma in 120 min. The process was smooth and the patient did not have fever, shivers from cold, or rashes.
On February 12 Ribavirin (RBV) 500 mg was administered by intravenous drip infusion 2 times per day for 4 days; on February 12 umifenovir 0.2 g was administered orally 3 times per day for 2 days, and recombinant human interferon alpha-2b (5 million units) by aerosol inhalation 2 times per day for 7 days.
On admission (on February 12) the patient was given imipenem-cilastatin (1.0 g) by intravenous drip infusion once every 8 h for 3 days; on day 4 ceftriaxone sodium (2.0 g) was given instead by intravenous drip infusion once per day for 4 days. On day 8 the antibiotics was changed to cefoperazone-sulbactam (3.0 g) by intravenous drip infusion once every 8 h for 7 days. On day 9 linezolid (600 mg) was added by intravenous drip infusion once every 12 h for 6 days, and on day 9 the first dose of caspofungin by intravenous drip infusion was 70 mg, and later 50 mg were given once per day for 10 days. On day 15 cefoperazone-sulbactam and linezolid were discontinued and levofloxacin (500 mg) was administered by intravenous drip infusion once per day for 5 days. On day 19 caspofungin was discontinued.
Starting on day 1 thymalfasin 1.6 mg was subcutaneously injected every 12 h for 14 days, and once per day for 5 days starting on day 15. Starting on day 1 immune globulin 10.0 g was administered by intravenous drip infusion once per day for 10 days.
On day 1 methylprednisolone 40 mg was administered by intravenous drip infusion every 8 h. On day 2 it was reduced to every 12 h for 3 days, and once a day from day 5 for 2 days, until it was discontinued on day 7.
On day 2 D-dimer coagulation increased. The patient was lying in bed and catheterization of the femoral vein was applied. To avoid the formation of deep venous thrombosis, enoxaparin 5000U was added by subcutaneous injection every 12 h for 16 days. The D-dimer was high throughout the course, the highest value being 3.26 ug/ml.
Liquid volume was monitored by bedside ultrasound to prevent the increase of lung water. From day 1 furosemide 10 mg was intravenously injected every 12 h for 2 days; on day 3 it was changed to spironolactone 20 mg and hydrochlorothiazide 25 mg, both administered orally twice per day.
The patient had a history of diabetes and developed serious gastro-intestinal symptoms after admission. From day 2 dieticians performed nutritional risk screening and dietary intake assessments, and the nutritional therapy plan was made according to guidelines and clinical experience. The daily energy input was 20-25 Kcal/kg, and that of protein 1-1.5 g/kg. Nutritional support therapy not only meets the energy and protein requirements, but also guarantees blood glucose stability, liquid balance, and gastrointestinal tolerance.
Sedation, analgesia, humanistic care, early-stage physical therapy, traditional Chinese medicine therapy, and blood glucose control were administered as well.
On admission the patient had dry cough without sputum; when moving or changing body position the cough became heavier, but breathing did not become more difficult, and chest tightness was not more severe. On day 7, after oxygen inhalation through nasal catheter, the cough worsened. On day 9 there was yellow-colored sputum with blood, which later increased. On day 14 there was an obvious decrease of sputum. The daily changes of body temperature are shown in Figure 2.
Changes in absolute values of lymphocytes, CD3+ T cells, CD4+ T cells, and CD8+ T cells are shown in Figure 3, while those of IL-6 are shown in Figure 4.
Although the pharyngeal COVID-19 swab before hospitalization to Liaocheng Infectious Disease Hospital had been positive, two whole-blood COVID-19 tests on day 2 and 3 after admission to Liaocheng People's Hospital were negative, as were four pharyngeal swab COVID-19 nucleic acid tests from day 3 to 6 and the anal swab COVID-19 test on day 5. Sputum culture revealed a normal flora, and blood culture showed no bacterial growth. On day 18 the results of the COVID-19 serum antibodies IgG and IgM qualitative analyses were both positive.
Patchy ground-glass opacity was seen on CT in the subpleural region of both lungs on day 6, with multiple chords and consolidation shades in the bilateral lower lobes, but the extent decreased and the density thinned (Figures 1C,D). The same was observed, with increased extent, on day 12 (Figures 1E,F). On day 19 the lungs appeared much improved on CT (see Figures 1G,H).
After hospitalization blood pressure was stable, heartbeat and blood lactate were normal, and there was no circulatory dysfunction. Hemobilirubin was slightly elevated, aminotransferases were normal, creatinine was low, and urea nitrogen initially increased but gradually became normal. After enoxaparin was applied D-dimer remained elevated. Thromboelastograms (TEG) on day 3 and 17 showed that the clotting status was normal.
On the afternoon of day 1 a remote consultation conference was held with the COVID-19 expert team of the Shandong Province. The severity evaluation was adjusted from critical illness to severe illness, and to moderate illness on day 6. On day 20 the patient was cured and discharged. At the time of discharge, the patient was in good spirits, with stable breathing, no cough or expectoration, good nutrition and sleep, and normal fasting and postprandial blood sugar. During 30 days of follow-up, blood analysis showed all indexes returned to normal, significantly improved chest CT, and no complications.
Informed consent to publication was obtained from the patient.