A Couple with Different Symptoms after Simultaneously 2019-nCoV Infected


 Background 2019-nCoV has posed a significant threat to human health since the epidemic began. So far, there is no definite safe and effective drug treatment. Proper management can help prevent mild patients from becoming severe. We report a couple with different symptoms after simultaneously infected by the same source of 2019-nCoV and analyze the changes in the diagnosis and treatment process. Case presentation We report a couple with different symptoms after simultaneously infected by the same source of 2019-nCoV in Shandong, China，describe their clinical course，characteristics and detection results in detail, and analyze the changes in the diagnosis and treatment process. The wife was mainly affected by respiratory system and had ever experienced high fever for several days. The husband's condition is lighter than his wife，mainly manifested as digestive tract symptoms，but it took longer than his wife for the nucleic acid of nasopharynx swab for 2019-nCoV to turn negative. Conclusions In the course of the disease both of the couple had hypokalemia which was easy to be corrected. CRP and ESR were consistent with the changes of the disease during the 2019-nCoV infection, which were good indicators to reflect the severity and development of the disease. Two months after discharge, both of them showed negative IgM antibody and positive IgG antibody.


Background
The novel coronavirus 2019 (2019-nCov), named by the world health organization (WHO), is now named SARS-CoV-2 by the international committee on the classi cation of viruses (ICTV) 1 . The appropriate treatment measures are also recommended by WHO based on the severity of the disease 2 . Progress is also being made in the management of mild to moderate patients 3 . Mild patients generally do not need hospital intervention, isolation and symptomatic treatment such as administration of antipyretics are suggested 2 . Proper management of complications will help prevent the development of mild to moderate patients from becoming severe. We report a couple with the same age of mild to moderate SARS-CoV-2 infection that occurred after contact with the same new SARS-CoV-2 patient at the same time. Their onset time was one day different, the clinical symptoms and course of disease were not the same,and some similar details in the process of the disease also need to be paid attention to.

Case Presentation
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 ve 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 criteria 5 for suspected diagnosis of 2019-nCoV in terms of epidemiological history, fever (respiratory symptoms) and chest CT ndings at that time, and they were admitted to the hospital and quarantined. It was subsequently con rmed 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 ake shadow in the right lung while blood routine and C reactive protein (CRP) was checked. Considering the possibility of pneumonia, he was given oseltamivir, levo oxacin, 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 con rmed 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 noti ed 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 levo oxacin 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 signi cant 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 crossinfection.
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, levo oxacin 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 signi cant 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 con rmed 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 1,4butanedisulfonate 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 o ce of Chinese Health and Health Commission and the o ce 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 rst 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 levo oxacin, 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, levo oxacin 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 con rmed 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 signi cantly increased, C reactive protein (CRP) and high sensitivity C reactive protein (hsCRP) were increased, and serum brinogen was slightly higher ( Table 2).
Chest CT showed no signi cant 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 in uence 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 rst week,the next week and the fourth week for reexamination.

Discussion And Conclusions
Coronaviruses infection affects the respiratory and digestive tract of human or animal 4 . This couple accord with this kind of characteristic, but the disease performance of the same pathogen varied greatly after infecting different people at the same time. At the beginning of the disease after contacting with the same source of infection at the meantime, the husband and the wife had fever successively, and the subsequent symptoms were different. The main manifestation of the wife was respiratory system involvement, while the husband mainly presented with digestive tract symptoms, and nally they were all recovered. The diagnosis of the two patients met the Chinese criteria for suspected diagnosis of covid-19 at the time 5 , including epidemiological history, fever and chest CT ndings or normal leukocyte count. They were admitted to the hospital and quarantined, and subsequently con rmed by covid-19 nucleic acid test.
The wife showed unusually high fever, with a maximum body temperature of 39.9 C. High fever not only appeared repeatedly, but was not easy to control and needed multiple medications, and accompanied with that her chest CT showed the pulmonary shadows were gradually aggravated. After body temperature dropped, chest CT also stopped progressing and gradually improved. The degree of fever was consistent with the development of pulmonary lesions. The other indicators concurrent with the progress of the disease were the increases of both CRP and ESR. The wife showed elevated bilirubin, which also occurred after taking iopinavir/ritonavir, and it has been reported that the administration of iopinavir/ritonavir is related to liver function damage 6 ,at the same time, the patient had obvious nausea and discomfort after taking iopinavir/ritonavir which gradually disappeared after the drug was discontinued, so the elevated bilirubin was likely to be associated with both iopinavir/ritonavir medication and viral infection which have been reported 18 .
The husband had high fever for one day before hospitalization, and the maximum temperature was 37.5 °C after admission. Although the cough was severe, his chest CT showed only a small and light shadow, which disappeared quickly. The disease was con ned to the tracheobronchial area and not developed in the lung. The biggest discomfort in the husband's complaint was diarrhea, 2-4 times a day. Blood tests showed increases in blood CRP and ESR, both of which were less severe than in his wife. The reason for the increase of bilirubin in husband also needs to consider the two factors of drug and virus infection. The husband's overall condition was milder than his wife's, with no major ups and downs or dramatic uctuations, but the nucleic acid test took longer to be positive than his wife's. In this sense, the patient with mild symptoms was not necessarily shorter than the patient with severe symptoms in terms of the length of time that the disease was infectious.
Both the husband and the wife showed slight elevation of transaminase, which occurred at the stage of improvement, especially after the wife's negative result of nucleic acid test. Therefore, they were likely to have nothing to do with viral infection and related to the use of antiviral drugs. Neither of the couple had signi cant leucopenia or reduced lymphocyte count.
Symptoms of covid-19 have been widely reported, and some are associated with progress of the disease, such as dyspnea, which may indicate the deterioration of the disease 7 . Clinical examination such as chest CT progression is a direct indicator of deterioration 8 . In our case, it was found that some simple tests, such as the increase or decrease of ESR or CRP, are consistent with the progress or improvement of novel coronavirus infection, as well as with the degree and duration of fever. They are good indicators to re ect the severity and development of the disease. Moreover, the detection method is simple and lowcost, which is very practical in clinical use.
Because of the detection of covid-19 virus in blood and feces, as well as the possible infectivity of patients 9,10 ,and in the February of the patient's illness, the nucleic acid test of stool and serum and the test of coronavirus antibody could not be completed due to the limited conditions. According to the instructions of the national diagnosis and treatment plan for covid-19 11 , the expert group for covid-19 infection in Qingdao adopted the strategy of recommending patients to continue to be isolated for 14 days after discharge, and gave patients timely follow-up.
Neither patient developed signi cant respiratory failure and the condition remained mild to moderate in this case. During the course of the disease, both the husband and the wife had obvious hypokalemia, and the wife had a brief premature heart beat. Hypokalemia is easy to induce arrhythmia and heart failure [12][13][14][15][16] , even related to some malignant arrhythmias 17 , especially for patients with basic heart disease.
Fortunately, the hypokalemia that developed in this couple was easy to correct and not stubborn. So hypokalemia should be pay attention to prevent when the urine volume is su cient if there is fever or diarrhea in patients who infected with the covid-19. Supportive therapy had ever played an important role in the treatment of Ebola virus infection, including oral or intravenous electrolyte replacement uids to correct metabolic abnormalities 19 ,which may still need attention in the infection of COVID-19.
Declarations YZ performed literature search, manuscript design, writing, and patients follow-up. SML conducted article design and literature retrieval, collected medical history and instructed case writing and patients followup. HPT guided case analysis and article writing. RZ collected case data; JL collected part of patients data; JYC and FW participated in case analysis. FZ was responsible for the collection of patients' laboratory nucleic acid data. JYL and SJL were responsible for observing the condition of the patients.
FHL was involved in the acquisition of patients laboratory data. All authors approved the nal manuscript.

Funding
Not applicable.
Ethics approval and consent to participate Ethical approval is not required because this is a single case report that involves only a retrospective review of medical records and does not include data that can identify the patient. Written informed consent was obtained from the patient for participation in this case report.

Consent for publication
Written informed consent for publication of the clinical details and clinical images was obtained from the patient.

Supplementary Files
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