Four cases from a family cluster were diagnosed as COVID-19 after 14-day of quarantine period.

To the Editor,

Since December 2019, coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2), has spread to a lot of countries worldwide. , On 30 January 2020, the World Health Organization (WHO) had declared that the outbreak of COVID‐19 is a Public Health Emergency of International Concern. On 11 March 2020, the spread of COVID‐19 was declared a pandemic by the WHO. Nowadays, more and more COVID‐19 cases are reported by a lot of countries/regions. To control the spread of SARS‐CoV‐2, quarantining suspected cases and close contacts is the most important urgency we have to do. The quarantine period is determined according to the incubation period. To date, it is accepted that the longest incubation period of COVID‐19 is of 14 days. , So suspected cases, close contacts have to be quarantined for 14 days to exclude them from SARS‐CoV‐2 infection. Here, we reported that four cases from a family cluster were diagnosed as SARS‐CoV‐2 infection after they had undergone 14 days of quarantine period (Figure 1). The present study was approved by the Ethical Committee of the Third Affiliated Hospital of Guangzhou Medical University. We obtained written consent from the patients to publish the piece.

Figure 1

Relationship of the family members and chronology of symptoms onset and positive results of them

Case 1: A patient with severe symptoms and radiological images of COVID‐19 and positive quantitative reverse transcriptase‐polymerase chain reaction results for SARS‐CoV‐2. The time period from infection to symptoms onset was estimated to be 26 days.

A 68‐year‐old man, the husband of patient 2, had a history of hypertension, no history of diabetes, chronic obstructive pulmonary disease, and coronary heart disease. On 22 January 2020, he left Wuhan, Hubei Province to Guangzhou, Guangdong Province, China with his family members (Patients 2‐6) by high‐speed rail. Then, all members of the family were quarantined at home for 14 days. On 7 February, the quarantine period ended. Then, all of them lived in their community of Guangzhou and occasionally went shopping near home. Furthermore, there were no reported COVID‐19 cases in their community of Guangzhou. On 17 February, he had a fever (37.5°C), fatigue, and poor appetite. On 20 February, he had polypnea and was referred to Guangzhou Eighth People's Hospital as he was suspected of COVID‐19. Blood routine tests on admission showed that white blood cell counts were normal and lymphocyte counts were decreased (Table 1). The chest radiograph showed massive bilateral consolidation opacities (Figure 2A). Nasopharyngeal swabs were obtained twice and both were positive for SARS‐Cov‐2 detected by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Then, he was isolated and treated in Guangzhou Eighth People's Hospital.

Table 1

Laboratory results of the patients infected with SARS‐CoV‐2

	Patient 1	Patient 2	Patient 4
WBC count, ×109/L	5.96 (3.5‐9.5)	8.06 (3.5‐9.5)	5.92 (3.5‐9.5)
NEUT, ×109/L	5.13 (1.8‐6.3)	6.98 (1.8‐6.3)	3.32 (1.8‐6.3)
NEUT, %	86.1 (40‐75)	86.7 (37‐80)	56.0 (40‐75)
LYM, ×109/L	0.64 (1.1‐3.2)	0.68 (1.1‐3.2)	2.13 (1.1‐3.2)
LYM, %	10.7 (20‐50)	8.4 (20‐50)	36 (20‐50)
PLT count, ×109/L	216 (125‐350)	323 (125‐350)	260 (125‐350)
RBC count, ×109/L	3.83 (4.3‐5.8)	3.63 (3.8‐5.1)	4.35 (4.3‐5.8)
Hb, g/L	118 (130‐175)	114 (115‐150)	144 (130‐175)
CRP, mg/L	108.16 (<10)	150.12 (0‐10)	<10 (<10)

Abbreviations: CRP, C‐response protein; Hb, hemoglobin; LYM, lymphocyte; NEUT, neutrophil; PLT, platelet; RBC, red blood cell; SARS‐CoV‐2, severe acute respiratory syndrome‐coronavirus 2; WBC, white blood cell.

Figure 2

Chest computed tomography (CT) images or chest radiographs of the patients. A, Chest radiographs of patient 1, both images showed massive bilateral consolidation and lesion in the right lung showed absorption while in the left lung showed progressive 5 days after symptoms onset. B, CT scans of the chest of patient 2, showed bilateral multiple lobular and subsegmental areas of ground‐glass opacity and consolidation 10 days after symptoms onset. C, CT scans of the chest of patient 3, showed right lobular and subsegmental areas of ground‐glass opacity one day after symptoms onset. D, CT scans of the chest of patient 5, showed bilateral multiple lobular and subsegmental areas of nodules

Case 2: A patient with severe symptoms and radiological images of COVID‐19 and positive qRT‐PCR results for SARS‐CoV‐2. The time period from infection to symptoms onset was estimated to be 20 days.

Patient 2, a 65‐year‐old woman, the wife of patient 1, had a history of hypertension and diabetes, no chronic obstructive pulmonary disease and coronary heart disease. On 11 February, she had a fever (38°C), cough, and sore throat. On 14 February, she had abdominal distension and vomited. On 17 February, she saw a doctor in a hospital near home and was diagnosed with abdominal pain. Then she was administrated with symptomatic therapy for 3 days. On 20 February, because her husband (patient 1) was diagnosed as COVID‐19, she was immediately referred to the Third Affiliated Hospital of Guangzhou Medical University. Blood routine tests on admission showed that white blood cell counts were normal and lymphocyte counts were decreased (Table 1). Computed tomography (CT) scans of the chest showed bilateral multiple lobular and subsegmental areas of ground‐glass opacity and consolidation (Figure 2B). Nasopharyngeal swabs were obtained twice and both were positive for SARS‐CoV‐2 detected by qRT‐PCR. Because her SpO2 level was relatively lowered, then, she was transferred to the First Affiliated Hospital of Guangzhou Medical University for isolation and treatment.

Case 3: A patient with typical symptoms and radiological images of COVID‐19 and positive qRT‐PCR results for SARS‐CoV‐2. The time period from infection to symptoms onset was estimated to be 30 days.

Patient 3, a 7‐year‐old boy, the grandson of patients 1 and 2, had a low fever (37.3°C) on 21 Februry 2020. Then he was referred to the Third Affiliated Hospital of Guangzhou Medical University. CT scans of the chest showed right lobular and subsegmental areas of ground‐glass opacity (Figure 2C). Furthermore, nasopharyngeal swabs were obtained twice and both were positive for SARS‐CoV‐2 detected by qRT‐PCR. Then he was transferred to Guangzhou Women and Children's Medical Center for isolation and treatment.

Case 4: An asymptomatic case with positive qRT‐PCR results for SARS‐CoV‐2.

Patient 4, a 37‐year‐old man, the son‐in‐law of patients 1 and 2, had no symptoms. On 20 February, 2020, he was referred to Guangzhou Eighth People's Hospital because his parents‐in‐law were diagnosed with COIVD‐19. Blood routine tests on admission showed that white blood cell counts were normal and lymphocyte counts were not decreased (Table 1). Furthermore, CT scans of the chest were normal. However, nasopharyngeal swabs were obtained twice and both were positive for SARS‐CoV‐2 detected by qRT‐PCR.

Case 5: A patient with abnormal radiological images but no typical radiological images of COVID‐19 and with negative qRT‐PCR results for SARS‐CoV‐2.

Patient 5, a 13‐year‐old girl, the granddaughter of patients 1 and 2, had no symptoms. She was referred to the Third Affiliated Hospital of Guangzhou Medical University because her grandparents were diagnosed as COVID‐19. CT scans of the chest showed multiple lobular and subsegmental areas of nodules (Figure 2D). However, nasopharyngeal swabs were obtained three times and both were negative for SARS‐CoV‐2 detected by qRT‐PCR.

Case 6: A case without any symptoms and radiological images of COVID‐19 and with negative qRT‐PCR results for SARS‐CoV‐2.

Patient 6, a 39‐year‐old woman, the daughter of patients 1 and 2, had no symptoms of COVID‐19. She was referred to the Third Affiliated Hospital of Guangzhou Medical University because her parents were diagnosed as COVID‐19. Blood routine tests on admission showed that white blood cell counts were normal and lymphocyte counts were not decreased. CT scans of the chest were normal. Furthermore, nasopharyngeal swabs were obtained four times and both were negative for SARS‐CoV‐2 detected by qRT‐PCR. Sputum samples were collected and sequenced by using next‐generation sequencing and not found a viral gene of SARS‐CoV‐2.

DISCUSSION

In the present report, all members of the family cluster had undergone 14 days of the quarantine period. Furthermore, there were no reported COVID‐19 cases in the community of Guangzhou they lived in. Two members (patients 5 and 6) of the family cluster were not diagnosed with SARS‐CoV‐2 infection, because samples of them were collected more than twice and both were negative for SARS‐CoV‐2 tested by qRT‐PCR. However, the other four members (patients 1‐4) from the family cluster were diagnosed as SARS‐CoV‐2 infection after 14 days of the quarantine period. The time period from infection to symptoms onset of them was estimated to be 25.33 ± 5.03 days (95% confidence interval, 15.47‐35.19).

There are no effective antiviral drugs to treat COVID‐19 and no vaccine to prevent the spread of SARS‐CoV‐2 globally. To control the pandemic of SARS‐CoV‐2, the most important and effective method is to quarantine suspected cases, close contacts. , The quarantine period is determined according to the incubation period. Nowadays, the incubation period is evaluated to be 5 days (mean, 5 days; range, 2‐14 days), 6.4 days (mean, 6.4 days; range, 2.1‐11.1 days), 7 days (mean, 7 days; range, 2‐14 days), respectively. As a result, those suspected cases, close contacts have to be quarantined for 14 days to exclude them from COVID‐19. However, Lauer et al recently reported that 1% (101 out of every 10 000 cases) of suspected cases or close contacts would develop symptoms of COVID‐19 after 14 days of the quarantine period. In our study, four cases of the family cluster were diagnosed as COVID‐19 after they had undergone 14 days of the quarantine period. Furthermore, the time period from infection to symptoms onset of them was estimated to be 25.33 ± 5.03 days. Taken together, we believe that the incubation period of some COVID‐19 cases could be longer than 14 days.

In sum, perhaps the incubation period of some COVID‐19 cases could be long out of our imagination. As a result, the quarantine period of some suspected cases or close contacts could be prolonged to more than 14 days to miss the diagnosis of COVID‐19. This could make it difficult to control the spread of SARS‐CoV‐2. Because only four cases were enrolled to estimate the incubation period in the present study, more cases should be enrolled to further evaluate the incubation period of COVID‐19 in the future. COVID‐19 is a newly emerged disease, so we should pay more attention to observe the characteristics of it, and think the unthinkable, and prepare enough to face it.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.

AUTHOR CONTRIBUTIONS

DC, YL, and XD enrolled cases. XO, HH, and YL collected data. XP and CL designed the study. XP wrote the manuscript. CL reviewed the manuscript.