On February 4, 2020, an elderly couple who were both 62 years old presented to the fever clinic of Qingdao municipal hospital in Qingdao, Shandong province,China༌with masks on their faces. The husband coughed for five days and had fever four days ago. The wife had a fever for three days. They told their history of epidemiology, on January 26, the husband drove back to his hometown Weifang with his wife, where they had a close contact with their relative in driving and eating together. After being told by telephone that the relative had just been diagnosed with novel coronavirus infection, as well as the state's report on the 2019-nCoV, attention to isolation, etc., they immediately went to the fever clinic of the hospital considering the possibility of novel coronavirus infection.
The diagnosis of the two patients met the Chinese criteria5 for suspected diagnosis of 2019-nCoV in terms of epidemiological history, fever (respiratory symptoms) and chest CT findings at that time, and they were admitted to the hospital and quarantined. It was subsequently confirmed by 2019-nCoV nucleic acid test.
The husband
The husband developed fever at night on January 31, with the highest body temperature of 38.6。C, accompanied by chills, cough, abdominal discomfort, nausea, diarrhea 2–3 times a day, the stools were watery and mushy,no vomiting, no phlegm at the beginning, and white phlegm appeared after 2 days. On February 2, he went to a nearby hospital for treatment. Chest computed tomography(CT)showed that there was a very small light flake shadow in the right lung༌while blood routine and C reactive protein (CRP) was checked. Considering the possibility of pneumonia, he was given oseltamivir, levofloxacin, Ibuprofen Tablets and traditional Chinese medicine orally. The next day his temperature dropped.
He had previously diagnosed unstable angina pectoris, which was easy to attack in winter when he was tired, and had no symptoms for nearly half a year. The patient had no special hobbies and never smoke. The physical examination revealed a body temperature of 36.2 °C, blood pressure of 134/88 mmHg, pulse of 105 beats per minute, respiratory rate of 20 breaths per minute. The patient was then given blood routine and CRP test (Fig. 1), which showed normal counts of leukocytes and lymphocytes, and chest CT examination (Table 1), which still showed small and light shadow of the right lung. After a multidisciplinary consultation in the hospital, including respiratory department, laboratory, imaging department, ICU, and hospital sensory department, it was concluded that the patient was a suspected case of 2019-nCoV according to the history of close contact with the confirmed patient and chest imaging changes. The decision was made to isolate the couple in a single room in the fever observation ward for clinical observation, and the CDC was informed to take oropharyngeal and nasopharyngeal swabs and sputum for nucleic acid testing. Medical and cleaning personnel were notified to follow the procedures of patient contact, blood collection and ward rounds in accordance with the standard of complete protection 5.
On February 5 (the second day of admission,day 6 of illness), the husband had no obvious fever, relieved cough, a small amount of mucous sputum, no aggravation of abdominal discomfort and diarrhea, the heart rate dropped to 81 beats/min, blood oxygen saturation could reach 99% while the patient was breathing ambient air, and other vital signs were stable. Administration of levofloxacin to patients; The CDC reported the positive nucleic acid test for 2019-nCov at 10 p.m.
From days 3 through 5 of hospitalization, the patient still had cough and diarrhea, and his vital signs were stable. The chest CT examination showed no significant change in the pulmonary condition. There was no obvious abnormality in blood routine examination, CRP and biochemical combination ( Table 1). Ribavirin, oseltamivir, montmorillonite powder, live bacillus subtilis, compound methoxyphenamine capsules, a recombinant human interferon a1b atomization inhalation therapy and traditional Chinese medicine therapy were used successively. The couple were separated in isolated rooms to avoid cross-infection.
On the hospital day 6 no special changes in the patient's symptoms and signs. Biochemical tests showed that bilirubin increased, blood potassium decreased, leukocyte increased, CRP increased ( Table 1). The patient was given oral and intravenous potassium supplementation, levofloxacin was stopped, ceftazidime was used for anti infection treatment, and magnesium isoglycyrrhizinate injection and oral ursodeoxycholic acid were used for liver protection.
On the hospital day 7 and 8, bilirubin was still elevated by biochemical test, serum potassium was improved, blood routine was normal, CRP was lower than before, and the patient's symptoms and signs were stable. The chest CT scan showed no significant change compared with that of 2020-02-07. The multidisciplinary consultation suggested that ribavirin should be discontinued, iopinavir/ritonavir should be added, and traditional Chinese medicine decoction should be continued. Stop using other drugs and give the liver protection treatment such as ademetionine 1,4 - butanedisulfonate for injection.
On the 8 day of hospitalization, according to the guidelines of the Municipal Health Commission, the couple were transferred to the Chest Hospital where the confirmed patients were treated centrally by the special medical staff composed of respiratory department, ICU and department of infection control who were drawn from major hospitals. This management approach to acute respiratory infections was successfully implemented during severe acute respiratory syndrome( SARS) in 2003 in Qingdao.
The patient was transferred to the special ward of Chest Hospital on the hospital day 9 (February 12). From the 9th to the 12th day of hospitalization, the patient had no fever, cough was relieved, a small amount of white sputum, diarrhea was improved, and physical signs were normal. The test showed that the total bilirubin was higher, the lung texture of chest CT was clear, and there was no obvious sign of pneumonia. Abdominal CT showed no abnormal changes in liver and gallbladder. Under the basic principles of blood glucose monitoring, oxygen inhalation, continuous electrocardiographic monitoring, attention to rest and nutritional support, the patients were given iopinavir/ritonavir orally, a recombinant human interferon a1b atomization inhalation therapy and traditional Chinese medicine. On the hospital day 12, due to the increase of bilirubin, iopinavir/ritonavir was stopped and ademetionine 1,4 - butanedisulfonate for injection was used.
On hospital day 13, the patient presented with itchy skin around the waist and umbilicus, mild cough, and no abdominal discomfort or diarrhea. The patient reported that he had skin eczema in the past, and the present symptoms were the same as those of the previous eczema.
There was no change in skin pruritus on the hospital day 14. Bilirubin was normal in the reexamination, and symatine (adenosine butylmethionine) was discontinued.
The nucleic acid was still positive in the review on hospital day 15, abidor orally was started.
On days 16 through 24 of hospitalization (days 20 through 28 of illness), the patient’s all symptoms have resolved with the exception of the skin pruritus around the waist and umbilicus. The nucleic acid for 2019-nCov was still positive after reexamination on hospital day 17. On hospital day 19, the patient was given loratadine anti-allergy treatment.
On hospital day 20 the result of nucleic acid retest was still positive. The skin itchy on hospital day 21 was better. The nucleic acid test was sent again on hospital day 22(illness day 26), and the test report showed negative on day 23 of hospitalization, and it was submitted for test again, it was reported negative on hospital day 24. According to 2019-nCov pneumonia diagnosis and treatment plan of the office of Chinese Health and Health Commission and the office of the State Administration of Traditional Chinese Medicine, the results of two consecutive nucleic acid tests were negative more than one day apart. The patient was discharged on February 28 (hospital day 25,illness day 29).
The wife
The wife first developed fever of 39.4。C on February 1,accompanied by chills, neither cough nor chest tightness, etc. On February 2, she was treated in a nearby hospital with oral drugs oseltamivir༌levofloxacin, and traditional Chinese medicine༌and her temperature dropped the next day. She went to the fever clinic of our hospital with her husband at 21:00 p.m. on February 4, and was admitted to the isolation ward of the fever clinic with her husband as a suspected case.
The wife had a history of hypertension for 20 years. Her blood pressure was well controlled by taking nifedipine controlled release tablets every day. She was a nonsmoker and had no other hobbies. The physical examination of admission revealed her temperature of 36.7℃, blood pressure of 147/103 mmHg, pulse of 92 beats per minute, respiratory rate of 20 beats per minute. She also received blood tests, CRP ( Table 2 ), chest CT and nasopharynx nucleic acid tests,and no obvious pneumonia on chest CT ( Fig. 2 ). Her 2019-nCov nucleic acid test report showed positive on February 5 (hospital day 2).
On February 6, the wife was febrile again with a maximum body temperature of 39.6。C. Ribavirin, oseltamivir, lopinavir/ritonavir, levofloxacin and traditional Chinese medicine were taken orally, and interferon a-2b atomization therapy was used; ibuprofen and arginine aspirin were given to reduce fever. She continued to take nifedipine controlled release tablets every day to control her blood pressure.
Febrile again on February 7, the body temperature of wife reached 39.9。C, the chest CT showed the progress of pulmonary lesions (see Table 2), the ECG showed frequent ventricular premature beats, and the blood electrolyte test showed that the low potassium was 2.9 mmol/l; paracetamol was given orally, indomethacin was used by anal medicine to reduce fever, thymosin alpha-1 for injection, recombinant human interferon a1b atomization inhalation, metoprolol orally and intravenous rehydration and potassium supplement, and Chinese medicine was given orally and intravenously.
On February 8, the patient's highest body temperature was 38.3℃, and the serum creatinine was detected to be 86.38ummol/L. One acetaminophen tablet was given to reduce the fever, and intravenous medication of traditional Chinese medicine was continued.
On February 9, the maximum body temperature was 37.5℃, and on February 10, it dropped below 37℃; Then intravenous administration of traditional Chinese Medicine was stopped.
There was no fever on February 11,and the symptoms and signs were stable. Chest CT reexamination showed that the lung lesions were larger than before.
In February 12, the patient had occasional mild cough, no fever or other obvious discomfort after transferred to the chest hospital according to the arrangements of the Qingdao Municipal Health Commission about the confirmed patients treated centrally.
Her condition was stable on 13 and 14 February. On February 13, the test showed that total bilirubin and erythrocyte sedimentation rate (ESR) were significantly increased, C reactive protein (CRP) and high sensitivity C reactive protein (hsCRP) were increased, and serum fibrinogen was slightly higher ( Table 2). Chest CT showed no significant change from February 11 (Fig. 2). Under the same basic principles as her husband,such as monitoring blood glucose, inhaling oxygen, continuous ecg monitoring, paying attention to rest and increasing nutrition, she continued to be given oral lopinavir/ritonavir and a recombinant human interferon a1b atomization inhalation therapy. Antihypertensive drug nifedipine controlled release tablets was given, and traditional Chinese medicine was continued.
After taking lopinavir/ritonavir on February 15, she felt obvious nausea, bitter mouth, no vomiting, and relieved by herself, no abdominal pain, no influence on appetite, no abnormal urine and feces, no fever, etc.
On February 16, the blood tests showed that the total bilirubin, ESR and CRP were all improved,and the chest CT reexamination showed that the lesions were absorbed compared with before. The reaction after taking lopinavir/ritonavir was the same as that of the previous day. The maximum postprandial blood sugar was 13.4 mmol/l, and no drug treatment was given.
On February 17 and 18, the symptoms were stable, and there was still nausea after taking lopinavir/ritonavir. The nucleic acid was still positive after review on February 18.
On the 19th, lopinavir/ritonavir was discontinued and abidol was initiated.
From February 21 to 24, the patient's all symptoms have resolved. The nucleic acid tests for 2019-nCov submitted on February 21 and 22 were all negative. On February 24 (hospital day 20,illness day 24), chest CT showed that the focus was obviously absorbed and improved. The blood tests showed that the total bilirubin and CRP was normal. Both alanine aminotransferase and aspartate aminotransferase were slightly higher. The wife discharged.
After discharge, the couple was quarantined for 14 days without any special discomfort. They were asked to return to the hospital in the first week,the next week and the fourth week for reexamination.