Epidemiology
The familial clustering cases consists of 6 SARS-CoV-2-infected family members: case 1 (index), case 2 (wife of case 1), case 3 (daughter of cases 1 and 2), case 4 (sister-in-law of index), case 5 (mother-in-law of index), and case 6 (father-in-law of index). Of this familial cluster, 5 were laboratory-confirmed COVID-19 cases and one was asymptomatic carrier.
Case 1 had been working in Wuxi city, Jiangsu province of China. During January 26 and January 31, 2020, he contacted with one of his relatives, a confirmed COVID-19 patient from Xianning city, Hubei, China. On January 31, 2020, he went back to Zhoushan and lived with six family members from January 31 to February 3, 2020. Then, case 1 left Zhoushan to Wuxi on February 3, 2020. On February 6, case 1 got pneumonia and was tested positive for SARS-COV-2 genomic RNA in Wuxi. Putuo CDC was then informed by Wuxi CDC to quarantine his family members. After being quarantined in Zhoushan on February 8, 2020, the 5 family members were examined for the presence of SARS-COV-2 by qRT-PCR. Apart from case 2, cases 3, 4, 5, and 6 were tested positive for SARS-COV-2 and then transferred to the designated hospitals at that night. On the next day, chest CT showed pulmonary inflammation and ground-glass opacity in cases 4, 5, and 6, rather than in case 3. Case 2 was negative for SARS-COV-2 genomic RNA but positive for IgG and IgM. She was then subjected to take chest CT scanning for further diagnosis. Due to the sign of pulmonary infection, she was admitted to Putuo hospital as well. According to epidemiological investigation by Zhoushan CDC, cases 2, 3, 4, 5, and 6 lived together all the time and never left Zhoushan at the last 2–3 weeks before onset of illness. During this period, they had not contacted with other COVID-19 patients, patients with respiratory symptoms, and any wild animal. The chronology of family relationship, exposure history, symptom onset, and identification of SARS-CoV-2 genomic RNA and antibodies findings are presented in Fig. 1.
Clinical, and radiographic findings
Case 1, a 41-year-old man, was diagnosed as COVID-19 of the common-type. He got pneumonia and then hospitalized on February 6, 2020. Case 2, a 41-year-old woman, presented positive pneumonia CT image at admission and was ever febrile during hospital stay (February 9 to February 28, 2020). She was also diagnosed as common-type COVID-19. Case 3, a 7-year-old girl, was asymptomatic carrier. She was positive for SARS-CoV-2 genomic RNA on February 9, 2020, but free of any clinical manifestation. CT images and laboratory parameters of this girl were normal as well. Case 4 was a 42-year-old woman who was diagnosed as common-type COVID-19. She developed fever, cough, and diarrhea at admission. On March 17, 2020, she was discharged from hospital and tested positive for IgM and IgG antibodies to SARS-CoV-2. Case 5, a 64-year-old woman, developed common-type COVID-19. Expectoration was the only symptom. Routine blood test showed lower saturation of haemoglobin oxygen saturation. On February 17, 2020, illness of case 5 progressed but did not meet the criteria of severe-type COVID-19. Case 6, a 66-year-old man, had the most serious COVID-19 and the longest duration of hospitalization of this familiar cluster. He was mild at the early stage of hospital stay (February 10–16, 2020), but progressed rapidly to be severe COVID-19. He suffered apparent clinical symptoms since illness onset, including fever, productive cough, diarrhea, and dyspnoea. Except case 3, the asymptomatic carrier, all cases had abnormal chest CT images, indicating pneumonia was present at admission (Table 1).
Table 1
Epidemiological, clinical features, pathogen and serological results of the family cluster infected with SARS-CoV-2
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 |
Age (years) | 41 | 41 | 7 | 42 | 64 | 66 |
Gender | Male | Female | Female | Female | Female | Male |
Travel history | | | | | | |
Wuxi | + | – | – | – | – | – |
Zhoushan | + | + | + | + | + | + |
Contact history | | | | | | |
Confirmed patients | + | + | + | + | + | + |
Wild animal | – | – | – | – | – | – |
Domestic animals | – | – | – | – | – | – |
Interval between exposure and symptom onset (days) | 11 | 11 | – | 9 | 9 | 9 |
Interval between symptom onset and hospitalization (days) | 0 | 1 | – | 0 | 0 | 0 |
Main symptoms | | | | | | |
Fever | – | + | – | + | – | + |
Cough | – | – | – | +(dry) | +(productive) | +(productive) |
Short of breath | – | – | – | – | – | + |
Diarrhoea | – | – | – | + | – | – |
Pathogen and Serological tests at admission | | | | | | |
qRT-PCR-CT values | | | | | | |
Throat swab | NA | 0.00 | 22.00 | 0.00 | NA | 0.00 |
Sputum specimen | NA | 0.00 | NA | 0.00 | NA | 30.63 |
Fecal specimen | NA | 0.00 | 36.61 | 0.00 | NA | 0.00 |
OD/CO of anti-IgM | NA | 0.29 | NA | 16.11 | NA | 32.26 |
OD/CO of anti-IgG | NA | 0.25 | NA | 19.15 | NA | 25.62 |
Chest radiography findings | Present | Present | Absent | Present | Present | Present |
Clinical classification of COVID-19 | common | common | asymptomatic carrier | common | common | severe |
CT, cycling threshold; OD/CO, optical density/cut-off value; COVID-19, novel coronavirus disease in 2019; NA, not available; +, positive; |
–, negative. |
Dynamics in pathogenic and serological findings
Pathogenic and serological tests were regularly conducted during hospital stay and follow-up period. However, cases 1 and 5 refused to be followed-up. Thus the continuous data of the two patients were lacking. For case 3, viral load of SARS-CoV-2 in fecal samples, reflected by the CT values of qRT-PCR, declined gradually during hospital stay and follow-up period. On March 17, 2020, the OD/CO value of IgM and IgG antibodies to SARS-COV-2 in case 3 were 1.05 and 3.96, respectively. Case 4 was positive for IgM and IgG antibodies to SARS-COV-2 and negative for SARS-COV-2 genomic RNA at her last follow-up on March 17, 2020. Case 6 remained positive for SARS-CoV-2 genomic RNA in his sputum specimens, rather than in throat swabs and fecal specimens, during February 17 and April 8, 2020, thereafter he was tested negative for 3 consecutive times at 1 day interval.
Interestingly, case 2 was admitted to hospital due to her positive CT image. She was negative for SARS-CoV-2 viral RNA in throat swabs, sputum samples, and fecal samples. Meanwhile, the titers of serum IgM and IgG antibodies to SARS-CoV-2 kept increasing during hospital stay and follow-up period from February 9 to March 24. The OD/CO ratio of IgM increased from 1.02 to 8.06 and the ratio of IgG increased from 1.50 to 4.62. The titers of IgM and IgG antibodies increased again after decreased on March 8, 2020 (Fig. 2). Thus, case 2 might recovered from COVID-19 before centralized isolation in hospital and then be exposed to SARS-CoV-2 again, possibly from her affected family members.