On March 21st, 2022, the patient, a 78-year-old man, who had four negative nucleic acid tests and a fifth positive, was transferred to our hospital. He has been isolated in the designed hotel since March 17th, 2022, due to close contact with his daughter, a laboratory-confirmed COVID-19 patient. His daughter had worked with other laboratory-confirmed COVID-19 patients, who had close contact with the COVID-19 cases from other provinces.
This patient described that he only had a mild cough and denied other symptoms, including fever, chills, sore throat, runny nose, chest pain, shortness of breath, muscle soreness, and fatigue. Chest computed tomography (CT) in the local hospital didn't show typical signs of COVID-19, like glass opacity, bilateral multifocal ground, peripheral distribution, and multilobe involvement.
This patient had a 20-year history of primary hypertension and paroxysmal atrial fibrillation. His daily medication included one 40 mg telmisartan, one 5 mg amlodipine, and one 2.5 mg warfarin, all taken orally. He had a history of tuberculous pleurisy, which had already been cured for many years (details unknown). He also had a history of gallstone surgery about 26 years ago (details unknown). He had received inactivated COVID-19 vaccine (Sinovac Coronavac) two times (August 19th, 2021 and September 9th, 2021).
This patient and his wife did not have a significant personal history. They had one son and one daughter, and the family medical history was unremarkable for any significant disorders.
Upon admission, the detected temperature, pulse, respiratory rate, blood pressure, and oxygen saturation of the patient were within normal range. The auscultation of the heart revealed an irregular heartbeat and the varied intensity of the first heart sound. At the same time, there were no apparent abnormalities observed in the examination of the lungs, abdomen, and limbs. The baseline laboratory findings of this patient showed no obvious abnormalities (Table 1). Moreover, he tested negative for both anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies.
This patient had multiple positive reverse-transcription polymerase chain reaction (RT-PCR) results of SARS-CoV-2 nucleic acid during hospitalization [a cycle threshold (Ct) value <40 was defined as SARS-CoV-2 viral positive; Ct value of ORF1ab/N gene: March 21st, 10.22/7.46; March 22nd, 29.20/33.72; March 26th, 21.31/23.53; March 27th, 20.79/22.73]. The genome sequencing test confirmed the infection of the SARS-CoV-2 Omicron BA.2 variant.
Based on the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia" (9th Trial Version) and the discussion of our COVID-19 expert group, this patient was diagnosed with a confirmed case of COVID-19. Then this patient received traditional Chinses medicine for 15 days (starting on March 23rd) and appropriate treatment for primary hypertension and paroxysmal atrial fibrillation.
On March 25th, 2022, this patient developed a low-grade fever, with a maximum body temperature of 37.9 C. Chest CT revealed few pulmonary ground-glass opacities (Figure 1A). Later, on March 27th, this patient's body temperature rose to 38.5 C, and he presented with shortness of breath. The oxygenation index greatly decreased, with a minimum number of 115 mmHg. Re-examination of chest CT showed the pulmonary lesions increased significantly (Figure 1B). According to the Berlin definition, this patient was diagnosed with moderate ARDS. Meanwhile, the interleukin (IL)-6 dramatically rose to 1,137 pg/mL, and other inflammatory parameters:including white blood cell, percentage of neutrophils and C-reactive protein:were all increased than at admission. The number of lymphocytes decreased gradually, with the lowest value of 0.36 x 109/L. The coagulation parameters:including platelet, D-dimer, activated partial thromboplastin time, prothrombin time, and thrombin time:didn't change a lot over time. And the laboratory parameters of heart, liver, and kidney function didn't show signs of organ failure. Table 1 presents detailed results of laboratory parameters.
Considering this patient's condition deteriorated rapidly, he was soon transferred into the intensive care unit. Our COVID-19 expert group conducted an urgent consultation, and a series of interventions were taken: (1) this patient had rapidly escalating oxygen requirements, therefore the high flow nasal cannula (HFNC) oxygen therapy (flow rate 50 L/min, oxygen concentration 50%) was administered. However, after several hours, his oxygenation index tended to decrease (oxygenation index = 115 mmHg), therefore we switched it to non-invasive ventilation (spontaneous/timed model, inspiratory positive airway pressure 10 cm H2O, expiratory positive airway pressure 6 cm H2O, fraction of inspired O2 40%); (2) this patient had a persistent fever, increased inflammatory parameters and radiographically observed pulmonary lesions, therefore co-infected with bacterial should be considered. This patient received piperacillin-tazobactam intravenously (4.5 g thrice daily); (3) methylprednisolone (40 mg once daily) was used to suppress cytokine storm for 3 days; (4) thymalfasin (1.6 mg once daily) and immunoglobulin (20 g once daily) were used to modulate immunity for 3 days; and (5) anti-hypertension (adalat, 30 mg once daily), anticoagulation (edoxaban, 60 mg once daily), stabilizing ventricular rate (digoxin, 0.125 mg once daily), and nutritional supplementation were used and adjusted according to the actual situations.
After treatment, this patient's temperature fell to normal on March 28th, 2022. Although his temperature fluctuated in the following days, values were lower than 38.5 C. We observed a trend toward a reduced respiratory rate, and this patient had an improved symptom of shortness of breath. The oxygen index increased to 200-300 mmHg, and this patient was weaned from non-invasive ventilation on March 31st, 2022. Follow-up chest CT on March 30th and April 3rd showed the pulmonary lesions were further reduced (Figures 1C,D). Until April 3rd, this patient recovered well with no complications. Figure 2 presents the timeline of essential clinical parameters and management of this patient. On April 7th, this patient achieved two negative results of nucleic acid tests (Ct value of ORF1ab/N gene: April 6, 39.45/39.48; April 7, 35.36/39.68), and his oxygen index was 348 mmHg without fever and shortness of breath. Then, he was monitored for disease progress and continued the treatment program of the underlying diseases.