key: cord-299472-pmqqemku authors: Yang, Naibin; Shen, Yuefei; Shi, Chunwei; Ma, Ada Hoi Yan; Zhang, Xie; Jian, Xiaomin; Wang, Liping; Shi, Jiejun; Wu, Chunyang; Li, Guoxiang; Fu, Yuan; Wang, Keyin; Lu, Mingqin; Qian, Guoqing title: In-flight Transmission Cluster of COVID-19: A Retrospective Case Series date: 2020-03-30 journal: nan DOI: 10.1101/2020.03.28.20040097 sha: doc_id: 299472 cord_uid: pmqqemku Objectives: No data were available about in-flight transmission of SARS-CoV-2. Here, we report an in-flight transmission cluster of COVID-19 and describe the clinical characteristics of these patients. Methods: After a flight, laboratory-confirmed COVID-19 was reported in 12 patients. Ten patients were admitted to the designated hospital. Data were collected from 25th January to 28th February 2020. Clinical information was retrospectively collected. Results: All patients are passengers without flight attendants. The median age was 33 years, and 70% were females. None was admitted to intensive care unit, and no patients succumbed through 28th February. The median incubation period was 3.0 days and from illness onset to hospital admission was 2 days. The most common symptom was fever. Two patients were asymptomatic and negative for chest CT scan throughout the disease course. On admission, initial RT-PCR were positive in 9 patients, however initial chest CT were positive in only half patients. The median lung total severity score of chest CT was 6. Notably, Crazy-Paving pattern, pleural effusion, and ground-glass nodules were also seen. Conclusion: It is potential for COVID-19 transmission by airplane, but the symptoms are mild. Passengers and attendants must be protected during the flight. more than 50000 cases have been reported [6] . Further rapid increases are expected to continue for some time. The COVID-19 spreads rapidly around the world, largely because of persons infected with the SARS-CoV-2 traveled on aircraft to other countries, since SARS-Cov-2 has strong affinity to human respiratory receptors [8] . No data were available about the risk of SARS-CoV-2 transmission on aircraft and clinical characteristics and outcomes of these COVID-19 patients. Here, we conducted a retrospective research to describe the clinical characteristics in an attempt to recognize the features of COVID-19 infected on aircraft. Since the early outbreak of COVID-19 in China, strict precautionary measures are implemented. Especially, Zhejiang provincial government initially launched a Category A response -a response to a major public health emergency -in the morning of 23 th January 2020. In one day, a commercial aircraft carrying 325 passengers and crew members flew to Hangzhou International Airport in Zhejiang. Most passengers were Chinese tourists and were returning home. When they were boarding, the All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint work group in Singapore airport implemented strict preflight screening to find out whether they had fever or respiratory symptoms. None of them were symptomatic. Most passengers had taken no precautionary measures against possible exposure to SARS-CoV-2, while all the flight attendants well wore masks. During the flight, a man passenger (patient 1) who traveled from Wuhan had a fever and no respiratory symptoms. Also, he did not wear a mask. After the 5-hour flight, the plane arrived in Hangzhou at 10 pm. Considering there were some Wuhan citizens on aircraft, staffs from the Hangzhou Center for Disease Control and Prevention (CDC) had been on standby at the airport and once the aircraft arrived they boarded to screen for possible fever and respiratory symptoms amongst the passengers and crew members. They had found that patient 1 still had a fever and his temperature was 38.1 . Then, his throat swab specimens were collected and sent to CDC. Five hours later, he was confirmed positive for SARS-CoV-2 and was admitted into the designated hospital. The crew members and rest of the passengers were placed under isolation and routine medical checks at hotels near airport for 14 days to observe whether illness onset will happen. As shown in figure 1, a further nine passengers were successively tested positive for SARS-CoV-2 and were also admitted. Another two passengers were also tested positively but we failed to interview them. No further patients were All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint found in the two weeks of isolation among the remaining 313 passengers and crew members. Then they were released from quarantine. We conducted a retrospective study focused on the clinical characteristics of ten patients with COVID-19 successively admitted to Xiaoshan First People's Hospital after having been on a flight. Patients were diagnosed based on National Health Commission of the People's Republic of China guidelines and the WHO interim guidance [9, 10] . For the ten patients included in our study, there was no recognized exposure history in 14 days before this fight. The incubation period was defined as the time from the flight arrival day to the onset of illness. Hospitalized days were defined as the period from admission to discharge day. The study has been reviewed and approved by the Medical Ethical Committees of Xiaoshan First people's Hospital (Approval NO: 2020-02). Written informed consent were waived because of the urgent need to collect clinical data on this emerging disease and entirely anonymized data therefore the individual identity cannot be identified. Epidemiology data were collected by interviewing each patient including exposure history, dates of illness onset, hospital admissions and All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Throat swab specimens collected from all patients were sent to CDC and tested for SARS-CoV-2 RNA by RT-PCR using the established sets of primers [11] . Outcomes were ready in three hours. Laboratory confirmation was achieved when the result of RT-PCR was positive. Laboratory tests conducted on the day of admission included blood cell count, C-reactive protein, procalcitonin, serum chemistry, D-dimer, fibrinogen in coagulation test, liver and renal function, electrolytes and lactate dehydrogenase. Each of five lung lobes were assessed for degree of involvement and classified as none (0%) with a score of 0, minimal (1-25%) with a score of 1, mild (26-50%) with a score of 2, moderate All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint (51-75%) with a score of 3, or severe (76-100%) with a score of 4. An overall lung "total severity score" was reached by summing the five lobes scores (range of possible scores, 0-20) [12] . All Patients received antiviral treatment with Arbidol (200mg twice daily, in ten patients), either in combination with Lopinavir/Ritonavir (400mg/100mg twice daily, in seven patients) or Darunavir/Cobicistat (800mg/150mg once daily in three patients). Patients were treated with corticosteroid (40-80mg) when their resting respiratory rate were more than 30 per minutes or when multiple pulmonary lobes showed more than 50% progression of disease on chest CT imaging in two days. Oxygen supports via nasal cannula were given when oxygen saturations were below 93% without oxygen support. Patients were discharged from hospital when the results of two RT-PCR tests taken 24 hours apart were negative for SARS-CoV-2 and symptoms improved obviously according to China guidelines 10 . MuLBSTA scores were assessed and recorded by attending physicians based on six indexes [13]. We summarized continuous variables as medians (interquartile ranges, IQR). For categorical variables, we present the counts and percentages in All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. By 28 th February, clinical data had been collected on all ten patients with laboratory-confirmed COVID-19. No flight attendants have been infected. In 14 days prior to the flight, no one including patient 1 had been exposed to confirmed or suspected COVID-19 patients. As shown in Table 1 , the median incubation period was 3.0 (IQR, 2-7; ranged from 1 to 14 or longer) days and from illness onset to hospital admission was 2 (IQR, 1-4; ranged from 1 to 6) days. The median age was 33 (IQR, 26 to 42; ranged from 20 to 52), and 70% were females and none was pregnant. None of them was health worker. Of the ten patients, two patients (patient 9 and 10) were asymptomatic and negative for chest CT scan throughout the disease course. In the other eight patients, the most common symptoms were fever in 7 (70%) patients. Among them, 5 (50%) patients had temperature between 37.3-39 , while 2 (20%) patients were above 39 . Other symptoms All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint included cough (3, 30%), headache (3, 30%), expectoration (2, 20%), whereas sore throat, anorexia and myalgia was seen in 1 (10%) patient. Table 2 shows the laboratory findings on admission. Elevated C-reactive protein (>4mg/L) was seen in 7 (70%) patients, while leucopenia (white blood cell count <3.5ൈ10 9 /L) and lymphopenia (lymphocyte count <1.1ൈ10 9 /L) was observed in 1 (10%) patient, respectively. Decreased platelet levels (<125ൈ10 9 /L) were detected in 2 (20%) patients. All the procalcitonin levels were within normal range at less than 0.5μg/L. No patient had an increased level of aspartate aminotransferase. Decreased level of potassium with 2.5mmol/L and increased level of D-dimer with 1.78mg/L were documented in 1 (10%) patient. Two (20%) patients had slight increased levels of fibrinogen (normal range, 2-4g/L). As shown in table 3, two of the ten patients had no pneumonia throughout the disease course. Typical CT findings of pulmonary parenchymal ground-glass opacities, especially with peripheral lung distribution, were seen in the other 8 patients. Among of them, bilateral lung involvements were seen in 7 patients while unilateral left lung involvement was seen in All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint 1 patient. The most frequently involved lobe was left lower lobe in all the above 8 (80%) patients and right lower lobe in 7 (70%) patients. Of the 7 patients with CT images of bilateral pulmonary parenchymal groundglass opacities, consolidations were also seen in 4 patients. Notably, "Crazy-Paving" pattern, pleural effusion (Figure 2) , and ground-glass nodules were also seen in some patients. The median number of lobes with lung opacities involvement was 4 (IQR, 1-5; range from 0 to 5). The median lung "total severity score" was 6 (IQR, 1-9; range from 0 to 13). On admission, initial RT-PCRs on admission were positive in 9 (90%) patients, however initial chest CT were positive in only half of the ten patients. In the patient with negative initial RT-PCT, the result was positive on the third time after a week following illness onset. All patients received antiviral treatment. All received Arbidol. Lopinavir/ Ritonavir was administered to in 7 patients alongside with Darunavir/ Cobicistat in 3 patients, and alongside with Oseltamivir in 3 patients. Four patients were given empirical antibiotic treatment, 3 patients were given systematic corticosteroid treatment, and 3 patients were given All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint oxygen support via nasal cannula. Five patients were treated with traditional Chinese Medicine (TCM). Interferon alpha inhalation and Chloroquine were not administered to our patients. As shown in table 4, none of the patient was ever admitted to intensive care unit (ICU). Moreover, 9 (90%) patients were discharged, and one patient was still isolated in our hospital. The median hospitalized days were 20 (IQR, 13-22; ranged from 13 to 22) of the 9 discharged patients. The median MuLBSTA score was 4.5(IQR, 0-5; range from 0 to 5). To estimate the risk of aircraft transmission, we calculated the numbers of persons diagnosed with COVID-19 divided by the total number of persons on this flight, the result is 3.69% (12/325). Here, we report clinical data from ten passengers with laboratory-confirmed COVID-19 after having been on a flight. As far as we know, this is the first reported case series of in-flight transmission of COVID-19. The clinical characteristics of these patients with All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint SARS-CoV-2 transmission on aircraft were similar to those without in-flight history, as previously reported [4, 7, 14] . Notably, the symptoms of COVID-19 patients infected in this flight were relatively mild, outcomes were inclined to be better, and the risk to passengers was higher compared with transmission of SARS on aircraft [15-17]. The imaging manifestations of these patients with COVID-19 transmission on aircraft were similar to those without in-flight history, as previously reported [12] . Pleural effusion was rarely seen amongst COVID-19 patients [18, 19] . In this case, for the first time we report small volumes of pleural effusion in both lungs in a non-severe patient of COVID-19. Moreover, 9 patients were tested RT-PCR positive at admission while only 5 patients were chest CT scan positive at admission, indicating that RT-PCR has a higher sensitivity than chest CT scans in diagnosing COVID-19 in our study. Patients in our cohort received antiviral treatment, but the types of medicine prescribed varied between patients based on their conditions. All of them received Arbidol. Use of Lopinavir combined with Ritonavia were considered to be beneficial because they had the potential to treat SARS [20] . All the rate of antibiotics, corticosteroid, and TCM use were less than half. TCM was considered to play a crucial role of treating All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Some patients were treated with oxygen support of nasal cannula when oxygen saturations were below 93% without oxygen support and recovered. Currently, there is no widely recognized effective drug treatment exists. As, to date, no results of randomized controlled studies on these drugs in COVID-19 patients have been conducted, it was unclear whether their improvement were due to these individual drugs or some combination of them. All ten patients had no risk factors known to be associated with a worse outcome such as comorbidity or advanced age (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. We believe that a most likely time for transmission of COVID-19 in the ten passengers was during or immediately before the flight. The clustering of illness onset around 3 days in these patients is consistent with the expected incubation period of COVID-19. There was no recognized exposure history within 14 days before this fight, although it is still possible that the passengers were infected before the flight because the incubation period could be longer up to 24 days [4] . Transmission on an aircraft of SARS-CoV-2 might occur when COVID-19 patients fly, especially during the symptomatic phase of illness. Therefore, we believe that the most plausible index case resulting transmission of SARS-CoV-2 in the other nine passengers was patient 1, the 45-year-old man from Wuhan, who had onset of fever during this flight. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. None of the nine flight attendants were symptomatic or tested to be infected although they interacted with the ill passengers during this flight, perhaps largely because of their use of masks. Therefore, we strongly suggest that mask-wearing and hand hygiene should be the imperative All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. were two asymptomatic patients reported in our study. We agreed that more asymptomatic carriers might be found out if all the other passengers and crew members were tested with RT-PCR assay for SARS-CoV-2 before they were released from quarantine. It was reported that presymptomatic and symptomatic patients are equally effective in All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. The authors of this study declare that they have no conflict of interest. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. [15]Olsen SJ, Chang HL, Cheung TY; Tang AF ; Fisk TL; Ooi SP All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. P a t i e n t 1 P a t i e n t 2 P a t i e n t 3 P a t i e n t 4 P a t i e n t 5 P a t i e n t 6 P a t i e n t 7 P a t i e n t 8 P a t i e n t 9 P a t i e n t 1 0 n ( % ) o r m e d i a n ( I Q R ) C h e s t C T a n d R T -P C R Q u a n t i t a t i v e R T -P C R : p o s i t O 8 ( 8 0 ) I n i t i a l c h e s t C T i m a g i n g : All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 30, 2020. . https://doi.org/10.1101/2020.03.28.20040097 doi: medRxiv preprint A Novel Coronavirus from Patients with Pneumonia in China COVID-19) outbreak A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China. The Lancet Infectious Clinical Characteristics of Coronavirus Disease 2019 in China. The New England journal of medicine