A 62-year-old man living in Wuhan suffered from cough, productive purulent yellow sputum, shortness of breath and chest distress, accompanied by a running nose on January 25, 2020. Neither fever, fatigue, sore throat nor myalgia was reported. He had a history of hypertension and diabetes. Oropharyngeal swab tests of SARS-CoV-2 by qualitative real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay were positive and he was confirmed as a COVID-19 patient on February 3. Chest CT scan showed multiple patchy consolidation and ground-glass opacities. He was given oxygen support and antiviral therapy (No details available). But his conditions were getting worse, then he was referred to our hospital on February 19.
On admission, physical examination revealed unstable vital signs with oxygen saturation of 66% when breathing ambient air. His respiratory rate was 30 breaths per minute, with pulse of 127 beats per minute and blood pressure of 143/89 mmHg. He had no fever. Symptoms like cough, expectoration, shortness of breath and chest distress were obvious. Arterial blood gas analysis indicated hyoxemia with arterial oxygen tension (PaO2) of 63 mmHg and carbon dioxide tension (PaCO2) of 33 mmHg. Data from laboratory tests showed that the patient had a high level of inflammation with increased white blood cells(WBC, 13.1*109/L, normal range: 3.5–9.5*109/L) and C-reactive protein(CRP,75.68 mg/L, normal range:0–4 mg/L) and procalcitonin(PCT,0.22 ng/mL, normal range: 0-0.05 ng/mL).
Considering serious respiratory symptoms, the patient received high-flow oxygen therapy (the fraction of inspired oxygen (FiO2): 100%, oxygen flow rate: 50L/min). Other supportive treatments were started in accordance with Chinese guidelines. Noticeably, Ulinastatin (3 million IU, administered intravenously once a day) was injected to block inflammatory cascade reactions.
A week later, however, the patient presented a worsening in respiratory symptoms. His oxygen saturation was around 90% under therapy of high-flow oxygen. The patient was admitted to intensive care unit (ICU) on February 27. Chest X-ray showed right lung was almost white and large haziness shadow was observed in left lung (Fig. 1A). Thus, the parameters of the high-flow oxygen were adjusted to oxygen concentration of 100% and oxygen flow rate of 50L/min. Then oxygen saturation reached up to 100%. Arterial blood gas analysis showed a ratio of PaO2 to FiO2 was 281 mmHg. Laboratory tests showed that the concentration of PCT was higher than before. Figure 2 showed the dynamics of inflammatory markers. However, one day later, on February 28, his oxygen saturation suddenly decreased to 85% and respiratory rate rose up to 44 breaths per minute. Therefore, high-flow oxygen was switched to ventilatory supportive care using positive end-expiratory pressure of 8cmH2O. Then oxygen saturation gradually reached 93%. Nevertheless, the patient became dysphoric and oxygen saturation dropped to 91% five hours later. So, oxygen support was changed back to high-flux nasal oxygen delivery. The concentration of interleukin 6(IL-6) was measured on February 29, and as expected, it was significantly higher than its upper limit (Seen in Fig. 2), which meant there existed systemic inflammatory storm caused by virus infection. To control inflammation related with IL-6, TCZ (400 mg, administered intravenously once) was initiated on the next day. There were no adverse reactions.
Since March 2, his conditions were getting better and the set parameters of oxygen support were gradually down-regulated with oxygen saturation around 98%. Oropharyngeal swab tests of SARS-CoV-2 on March 3 and March 10 were both negative. On March 4, high-flow oxygen therapy was ceased and oxygen support through nasal cannula with oxygen flow rate of 5L/min was taken instead. Chest X-ray on March 12 indicated that pulmonary edema and inflammation has been greatly ameliorated (Fig. 1B). Thus, the patient was transferred to general ward. On March 17, the patient had neither fever, chest distress or expectoration. His appetite became normal and enteral nutrition was stopped. But he still felt shortness of breath and couldn’t be capable of walking around on room air. Dry cough was prominent especially at night. His chest CT on March 17 indicated multiple patchy ground-glass shadows in both lobes, predominantly confined to the peripheral and middle zones of the lung (Fig. 3A, 3C, 3E and 3G). On March 23, after negotiating with his family members and himself, the patient received stem cell therapy in the following hospital stay. The protocol of stem cell therapy was that 40 million human umbilical cord mesenchymal stem cells (hUC-MSCs, purchased from Vcanbio Cell & Gene Engineering Corp. LTD, Tianjin, China) injected through peripheral vein 3 times every three days. The last transfusion was finished on March 29. No side effects were observed. Other supportive care remained as before. Now, as of today, March 31, he is able to breathe free without nasal cannula when engaging in daily activities. It was noticeable that he could walk 50 meters far away when breathing ambient air. His oxygen saturation was around 96% on room air. Meanwhile, he reported no dry cough and mild shortness of breath after activity. CT examination on March 30 also showed multiple absorption of infectious lesions in both lungs compared with CT on March 17 (Fig. 3B, 3D, 3F and 3H). The results of nucleic acid detection of COVID-19 on March 17,18,24 and 29 were all negative. Finally, he was successfully discharged. The oxygen support mode from the admission day to March 31 was shown in Fig. 4.