key: cord-296492-knofua00
authors: Qiu, L.; Chen, S.; Wang, C.; Liu, C.; Wang, H.; Zhao, X.; Fang, Z.; Chang, S.; Zhao, G.; Zhang, G.
title: Clinical characteristics and epidemiology survey of lung transplantation recipients accepting surgeries during the COVID-19 pandemic:from area near Hubei Province
date: 2020-07-07
journal: nan
DOI: 10.1101/2020.07.06.20147264
sha: 
doc_id: 296492
cord_uid: knofua00

Lung transplantation recipients (LTx) were susceptible to severe acute respiratory syndrome-corona virus-2 (SARS-Cov-2) and suffered a higher mortality risk than healthy subjects. Here we aim to analyze whether it was appropriate or and valuable to maintain lung transplant programs in medical institutions accepting coronavirus disease 2019 (COVID-19) patients. In this study, the clinical characteristics, laboratory testing and epidemiology survey results of 10 LTx recipients undergoing allograft lung transplantation surgeries in the First Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic were collected. A web-based epidemiology questionnaire was used to collect the information of LTx recipients after discharge. Up to now, none of the LTx recipients or their family members get infected with SARS-CoV-2 during the novel coronavirus pandemic. In conclusion, under the premise of taking appropriate preventive measures during hospitalization and after discharge, the lung transplant program can be maintained in the medical institution that accepts patients with COVID-19.

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in Wuhan, Hubei, China in December 2019, large amounts of people have been infected and killed due to the rapid spread of such virus in China and around the world [1, 2] . SARS-CoV-2 was previously called 2019-nCoV, until February 11, 2020, the International Committee on Taxonomy of Viruses renamed this virus [3] . At the same time, World Health Organization(WHO)renamed the disease caused by SARS-CoV-2 as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 targets angiotensin-converting enzyme 2 (ACE2) as a receptor and enters the host cell through it, resulting in a novel CoV-related pneumonia [4] . According to real-time statistics released by Johns Hopkins University, until May 5th, 2020, there were more than 3.87 million confirmed cases of COVID-19 globally, and the death toll exceeded 250 thousand, which reached to 250687 cases.

Organ transplantation recipients are a special group of population with immunity greatly suppressed due to the immunosuppressants. Compared to healthy individuals, they are more susceptible to SARS-CoV-2 and at even higher risk of severe illness from COVID-19 according to "list of susceptible people" published by Public Health England [5] . It is worth noting that current epidemiological evidence indicates that most of the patients with COVID-19 are not severe cases and enable to recover after appropriate treatment. However, the mortality rate of COVID-19 patients with comorbidities (especially with lung diseases) was much higher than those without . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint diseases [6, 7] .

During the pandemic of COVID-19, large amounts of transplantation surgeries were delayed or canceled, especially in the seriously affected areas. Our medical institution is located in Henan Province in the central of China and adjacent to Wuhan, Hubei Province. During the COVID-19 pandemic, our area was severely affected. At this critical time, whether the lung transplant program needs to be maintained, and the clinical characteristics and SARS-CoV-2 infection conditions of these lung transplantation (LTx) recipients remain unclear. In this work, we collected characteristics of these LTx recipients and designed an epidemiology questionnaire to obtain the information of SARS-CoV-2 infection condition and after-discharge preventive measures of LTx recipients who underwent surgeries in the hospital accepting COVID-19 patients during the COVID-19 pandemic.

This is a retrospective and single-center study, all data sources coming from the First Affiliated Hospital of Zhengzhou University of China.

All patients receiving allograft lung transplantation surgeries in the First Affiliated Hospital of Zhengzhou University were included, from the inception of the . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint COVID-19 pandemic (January 2020) to the day when the Secondary Prevention Level of Public Health Emergencies in Henan Province was removed (May 5 th , 2020).

A web-based epidemiology questionnaire was used to collect the information of LTx recipients after discharge, which was designed by clinicians and public health experts and collected by 2 independent investigators.

The continuous variable of a normal distribution is expressed as mean value (standard deviation), and the continuous variable that is not normally distributed is expressed as median (interquartile space). Categorical variables were described through count and frequency. All statistical analyses were conducted on version 26.0 of SPSS software.

A total of 10 LTx recipients consisting of 1 female and 9 males were identified in this study, whose characteristics were showed in Table 1 . The median age is 60 (50~64) and the youngest case is only 15 years old. The main cause of lung transplantation in this study was idiopathic interstitial pneumonia (IIP) accounting for 60% and one rare cause was cystic fibrosis with only one case. All patients suffered dyspnea on admission. From the time of admission to accept lung transplantation surgery, 6 patients received ordinary nasal catheter oxygen therapy, 1 patient received high-flow . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint nasal catheter oxygen therapy (HFNC) with 60L/min, and 3 patients underwent endotracheal intubation combined with an invasive ventilator for assisted breathing.

In general, patients with lung fibrosis suffered severer dyspnea than those who suffered bronchiectasis. As for surgical approaches, single lung transplantation surgery was the main surgical method used in this study. Only one 15-year patient received bilateral lung transplantation surgery, who was diagnosed as cystic fibrosis.

Meanwhile, part of the LTx recipients suffered comorbidities, including 1 case with viral hepatitis of type B and 1 case with diabetes, hyperlipidemia and subclinical hyperthyroidism.

Laboratory results of the 10 LTx recipients before lung transplantation surgery were summarized in Table 2 , including blood routine, biochemistry, myocardial enzyme, blood gas analysis, and tacrolimus metabolic type. In all identified patients, the average white blood cell (WBC) count was 9.5±3.9×109 cells/liter and 3 (30%) cases had an abnormal WBC count. The average neutrophil percentage was 70.4%±15.2%

with 3 cases abnormal. The average lymphocyte percentage was 19.2%±11.2% and 4 (40%) LTx recipients had lymphopenia, among them 2 cases had a lymphocyte percentage lower than 10%. Besides, 1 patient had both liver and kidney function insufficiency and 3 patients suffered heart function insufficiency before accepting lung transplantation surgery and taking tacrolimus. Blood gas analysis results indicated all the 10 patients appeared respiratory failure, including 2 cases of type . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint respiratory failure and 8 cases of type respiratory failure. Due to the personal financial situation and medical insurance, tacrolimus metabolic type tests were only conducted on 5 LTx recipients. The results showed that 1 subject had a normal metabolism and 4 subjects had a slow metabolism.

A total of 6 LTx recipients were followed up and all of them lived in Henan Province after discharge. The epidemiological survey results of SARS-CoV-2 prevention in these LTx recipients after discharge were presented in Table 3 . Good hand hygiene habitats were kept in all followed-up LTx recipients, and all of the LTx recipients (100%) consciously often or occasionally used the seven-step hand-washing method to wash hands. It should be noted that all included LTx recipients owned personal hand towels. Indoor ventilation measures were daily carried out in all LTx recipients' homes. Masks were essential especially the medical/surgical masks (83%) if these LTx recipients went out. 50% of the LTx recipients tended to choose two types of masks, while the other 50% wore only one type of mask. Indoor disinfection behaviors were conducted in 5 LTx recipients' homes (83%), including floors, the surface of furniture and toilets. Due to the demand for postoperative recovery and the prevention of pathogenic bacteria and viruses, separate bedroom (100%), personal bedsheets/ quilts (100%) and drinking glasses (100%) were prepared for all these LTx recipients. At the end of follow-up, none of these LTx recipients and their family members were infected with SARS-CoV-2 during the coronavirus pandemic.

. CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint

This is the largest report of LTx patients accepting allograft lung transplantation surgery in severe epidemic areas during the COVID-19 pandemic. In our study, part of LTx recipients had hyperlipidemia, diabetes, subclinical hyperthyroidism, viral hepatitis type B comorbidities. Besides, 4 LTx recipients (40%) had lymphopenia, 3

LTx recipients (30%) had impaired heart function and 1 LTx recipient had both of the impaired alanine aminotransferase (ALT) and aspartate transaminase (AST).

Previous studies have indicated that human beings are susceptible to SARS-Cov-2 [8, 9] .

The immunity of LTx recipients is greatly suppressed because of immunosuppressive agents, making them more susceptible to SARS-COV-2 infection [5] . Early COVID-19 patients' reports indicated that lymphopenia and impaired ALT were associated with severe complicated disease and even resulted in death [10] . Recent SARS-CoV-2 patients' reports also showed that age ≥ 65 years, dyspnea, coronary heart disease, cerebrovascular disease and AST level > 40 U/L were independent risk factors associated with fatal outcome of infective subjects [11] . All included subjects in our study were susceptible people of SARS-CoV-2, and they would suffer a higher mortality rate if they were infected.

By the end of the follow-up, no LTx recipients included in our reports have been infected by SARS-CoV-2. We surveyed SARS-CoV-2 preventive measures taken by . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint these LTx recipients after discharge, based on a web comprehensive questionnaire.

Results revealed that the seven-step hand-washing method was done (100%) by all the LTx recipients and masks were protective items that must be carried when they went out (100%). Separate bedrooms (100%), personal bedsheets/ quilts (100%) and drinking glass (100%) were also prepared for them by their family members. The rate of indoor disinfection behavior reached 83%. Consistent with previous reports [12, 13] , the key reasons for the zero SARS-CoV-2 infective rate of LTx recipients in our study may be due to the good performance of hand hygiene, wearing masks and indoor disinfection, and even isolation from family members. According to the guideline published by the World Health Organization (WHO), using masks can reduce potential exposure risk from an infected patient during the pre-symptomatic or an asymptomatic phase [14] . Some clinical trials have shown that masks and hand hygiene could effectively protect the coronavirus transmission in the community [15] . Besides, masks seemed to be more effective than hand hygiene alone, and the two together are more protective [16] .

In our reports, 83% of the LTx recipients tended to use medical masks/ surgical masks or N95 masks rather than ordinary masks. However, the WHO stated that medical masks were necessary only when people were involved in taking care of people with suspected or confirmed COVID-19 [17] . Since SARS-CoV-2 outbroke in December 2019, it had caused considerable psychological stress on both public and doctors and led to the increasing mental health problems [18] [19] [20] [21] . The abovementioned behavior . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint precisely reflected the panic of the epidemic among the public. Interestingly, whether it was necessary to wear higher-level protective masks for people who received lung transplantation surgery during the COVID-19 pandemic was unknown. However, the use of medical masks, good hand hygiene behaviors and frequent disinfection of indoor furniture surfaces can help to release the LTx recipients' anxieties during this severe period.

It should be noted that anxieties in part of LTx recipients were observed during our follow-up, which mostly came from the exposure to multiple co-occurring risk factors (e.g., spouse's or children's job loss, credit-card repayment, marital conflict). It can be seen that, in addition to the impact of the disease on public health, this large-scale public health crisis has caused incalculable damage to the global and national economy because of the nationwide shutdown and home confinement directives that prohibit national and regional economic activities [22, 23] . We then separate this investigation in the future.

Since Henan Province is close to Hubei Province, therefore, our area was severely affected during the COVID-19 pandemic. Our hospital was the main medical institution to treat COVID-19 patients in Henan Province. To ensure the maintenance of the transplant programs, patients were admitted to the hospital only when no imaging findings of SARS-CoV-2 infection on chest CT or tested negative for SARS-CoV-2. Besides, our medical institution set an independent ward for . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. 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 July 7, 2020. . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. . CC-BY-NC 4.0 International license It is made available under a 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 July 7, 2020. Data are expressed as mean ± SD and n/N(%)

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint Table 3 . Epidemiology survey on SARS-CoV-2 prevention after discharge.

Returning home 5(83%)

Before eating food 5(83%)

After toilets 6(100%)

After coughing or sneezing 4(67%)

Seven-step hand-washing method 6(100%)

Often 2(33%)

Occasionally 4(67%)

Soaps 4(67%)

Hand sanitizer 3(50%) Dry hand paper 3(50%)

Personal hand towel 5(83%)

Frequency/Daily 

Personal drinking glass 6(100%)

Personal tableware 4(67%)

Personal bedsheets/quilts 6(100%)

Data are expressed as n (%) and n/N (%).

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint

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The copyright holder for this preprint this version posted July 7, 2020. . https://doi.org/10.1101/2020.07.06.20147264 doi: medRxiv preprint