key: cord-337809-bxvgr6qg
authors: Xiong, Yong; Song, Shihui; Ye, Guangming; Wang, Xinghuan
title: Family cluster of three recovered cases of pneumonia due to severe acute respiratory syndrome coronavirus 2 infection
date: 2020-05-04
journal: BMJ Case Rep
DOI: 10.1136/bcr-2020-235302
sha: 
doc_id: 337809
cord_uid: bxvgr6qg

The coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in late 2019 and has affected more than 1 270 000 people worldwide. The numbers of reported cases continue to rise and threaten global health. Transmissions among family members are frequently observed, although the route of transmission is partially known. Here we report three cases of SARS-CoV-2 infection within one family. Sequencing of the S gene of the viral genome showed 100% identity among samples, suggesting that the same strain caused the infection. Following treatment with oseltamivir and short-term methylprednisolone combined with symptomatic management, all three patients recovered within 3 weeks, as evidenced by the disappearance of their symptoms, clearance of pulmonary infiltrates and consecutive negative molecular diagnostic test findings. Our observations suggest the importance of preventing family transmission and the efficacy of current integrated treatment for mild/moderate pneumonia in COVID-19 cases.

The coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in late 2019 and has affected more than 1 270 000 people worldwide. The numbers of reported cases continue to rise and threaten global health. Transmissions among family members are frequently observed, although the route of transmission is partially known. Here we report three cases of SARS-CoV-2 infection within one family. Sequencing of the S gene of the viral genome showed 100% identity among samples, suggesting that the same strain caused the infection. Following treatment with oseltamivir and short-term methylprednisolone combined with symptomatic management, all three patients recovered within 3 weeks, as evidenced by the disappearance of their symptoms, clearance of pulmonary infiltrates and consecutive negative molecular diagnostic test findings. Our observations suggest the importance of preventing family transmission and the efficacy of current integrated treatment for mild/ moderate pneumonia in COVID-19 cases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the ongoing outbreak of pneumonia in Wuhan, China. Since the first cluster of atypical pneumonia cases was reported on 31 December 2019, 1 the disease has spread with surprising speed. While much attention has been focused on viral transmission dynamics and the spectrum of clinical illness, these aspects are not yet completely understood. [2] [3] [4] [5] [6] [7] [8] This report describes the epidemiological and clinical features of coronavirus disease (COVID-19) among three members of a family following SARS-CoV-2 infection. Owing to the unavailability of effective vaccines for the prevention of SARS-CoV-2, most preventive measures aim to reduce the risk of infection. 9 Despite several recommended drugs, including the combination of lopinavir/ritonavir, nelfinavir and interferon-beta-1b, effective treatment options are scarce. 2 Hence, prevention of infection is of utmost importance. We provide evidence to support the increasing concerns regarding person-to-person transmission of SARS-CoV-2.

On 10 and 11 January 2020, a family of three, comprising the father (65 years), the mother (61 years) and the son (38 years), were admitted to the Department of Infectious Disease at the Zhongnan Hospital of Wuhan University with symptoms of cough and fever. On 21 December 2019, the mother had started coughing with expectoration. Five days later, the father also developed a cough; he developed fever 7 days prior to admission. He had a history of hypertension and coronary heart disease, for which he had received a stent. Both had symptoms of restricted breathing. On 3 January 2020 (12 days after the mother's illness), the son developed a cough. Prior to admission, all three patients experienced fatigue and intermittent fever (37.9℃-39.1℃) for at least 1 day (figure 1). They had no shortness of breath or chest pain.

Physical examination revealed some degree of tonsil enlargement in the father and the son. Lung auscultation revealed rhonchi in the father and the mother. Other examination findings were generally unremarkable. None of the patients had visited the Huanan Seafood Wholesale Market in Wuhan or the surrounding area in the previous 2 weeks. They denied any contact with diagnosed patients with similar symptoms.

On admission, haemograms revealed lymphocyte counts reduced by nearly 50% in the mother and near-to-low-normal in the father and the son. Other parameters such as white cell count, neutrophil and blood platelet counts were near-to-low-normal, suggesting not only lymphopaenia but also a haematological regeneration abnormality following infection. Moreover, all of these parameters doubled on discharge of the patients from the hospital. None of the patients had abnormal haemoglobin values. Oxygen saturation values were normal. Additional laboratory investigations in these three patients showed no abnormalities except for increased C reactive protein levels (table 1) .

Pneumonia was diagnosed based on chest CT scans. The mother's lung showed a peripheral lesion with increased intensity and bilateral patchy shadows in the outer zone of the lungs. Numerous patchy or segmental ground-glass opacities were observed in both lungs of the father and the son. 10 The lung opacities started to clear after 10 days of hospitalisation (figure 2).

Rapid nucleic acid amplification tests for respiratory syncytial virus, adenovirus, influenza virus A new disease figure 1 Body temperature (blue) and heart rate (red) values after hospitalisation. The temperature of all three patients decreased within 3-5 days. The mother experienced only occasional febrile episodes, while the son had moderate-to-high fever for 4 days after admission. (table 2) .

The treatment during hospitalisation was largely supportive. The patients intermittently received supplemental oxygen through a nasal cannula at a rate of 2 L per minute. Owing to the difficulties in early diagnosis, all three patients were initially treated for suspected influenza with 75 mg oseltamivir phosphate capsules two times per day for the first 5 days of hospitalisation. The patients received 80 mg of methylprednisolone sodium succinate per day for the first 3 days, followed by 40 mg per day during the following 3 days, and 20 mg per day for another 3 days before being discontinued. The father received methylprednisolone at a dose of 40 mg per day for 5 days and 20 mg per day for another 5 days.

Considering the possibility of bacterial coinfection, the mother and the father were administered amoxicillin sodiumflucloxacillin sodium (6 g, intravenous infusion every 12 hours) for 2 weeks. The son received ceftriaxone-tazobactam (2 g, intravenous infusion, every 12 hours) for 3 days, followed by biapenem (0.3 g, intravenous infusion every 8 hours) for another 9 days.

Additionally, the mother and the son were administered levofloxacin (0.4 g, intravenous infusion, daily) starting on admission day 6 until day 14. The father received moxifloxacin (0.4 g, intravenous infusion, daily) for 2 weeks starting on admission day 1.

The fever disappeared in all three patients approximately 5-7 days following admission and their clinical conditions further improved thereafter. After approximately 3 weeks of hospitalisation, lung inflammation had largely resolved, as indicated by CT scans, and two consecutive throat swab samples tested negative for SARS-CoV-2 with the RT-PCR test performed for each new disease figure 2 Chest CT scans of the three patients. The mother's lung shows a peripheral lesion with increased intensity and bilateral patchy shadows in the outer zones. Multiple patchy or segmental ground-glass opacities were observed in both lungs of the father and the son. Due to the initial shortage of testing kits for SARS-CoV-2, the cases were not diagnosed until 20 January 2020. Throat swabs obtained from all three patients on admission day 9 tested positive. Subsequently, throat swabs obtained from them on admission days 18 and 20 tested negative for SARS-CoV-2 (figure 1).

The genetic sequences of the viral S gene from samples collected from each family member were identical (data not shown) to each other and also were 100% identical to the reported viral strain (WHU01) currently spreading in Wuhan.

Our results not only support human-to-human transmission but also suggest that close contact within families is a high-risk factor. Effective intervention measures for the prevention of family transmission need to be adopted.

► Severe acute respiratory syndrome coronavirus 2 transmission among family members was confirmed. ► The patients recovered after treatment with oseltamivir and methylprednisolone. ► Prevention of family transmission is important. ► The current integrated treatment for mild/moderate pneumonia is effective in COVID-19.

World Health Organization. Pneumonia of unknown cause China

Potential of large "first generation" human-to-human transmission of 2019-nCoV

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

Importation and human-to-human transmission of a novel coronavirus in Vietnam

Transmission of 2019-nCoV infection from an asymptomatic contact in Germany

Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia

A novel coronavirus from patients with pneumonia in China

Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Acknowledgements We thank all the doctors and nurses who cared for these three patients.

The case report was written by YX and SS and edited by GY and XW.funding This study was funded by the Medical Science Advancement Program (Clinical Medicine) of Wuhan University (grant number TFLC2018002).

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