key: cord-0780612-rzhrgp5q
authors: Hou, Jiabao; Wan, Xing; Shen, Qianni; Zhu, Jie; Leng, Yan; Zhao, Bo; Xia, Zhongyuan; He, Yuhong; Wu, Yang
title: COVID-19 infection, a potential threat to surgical patients and staff? A retrospective cohort study
date: 2020-09-03
journal: Int J Surg
DOI: 10.1016/j.ijsu.2020.08.037
sha: 28c203fdd22c8180c328f0c98849c8881186eba2
doc_id: 780612
cord_uid: rzhrgp5q

BACKGROUND: This study aimed to describe the epidemiologic and clinical characteristics of coronavirus disease 2019 (COVID-19) in surgical patients and medical staff. METHODS: A single-center case series of 1586 consecutive surgical patients was selected at our hospital from January 13 to March 12, 2020. The epidemiological and clinical characteristics of COVID-19 were analyzed and followed up to May 20, 2020. The transmission of COVID-19 between the surgical patients and medical staff was also recorded. RESULTS: Seventeen (1.07%) surgical patients were diagnosed with COVID-19, with a high incidence in the thoracic department (9.37%), and the median age was 58 years (IQR, 53-73). The median time from hospital admission to COVID-19 diagnosis was 9.0 days (7.0-12.0) and was 6.0 days (4.0-7.0) from the day of surgery to COVID-19 diagnosis. Eleven (64.70%) patients suffered from pulmonary infection before surgery. When COVID-19 was diagnosed, common symptoms were fever (82.35%) and cough (94.12%), and most (82.35%) neutrophil/lymphocyte ratios were high (>3.5). Chest computed tomography (CT) (82.35%) showed bilateral dense shadows. Surgical patients with COVID-19 stayed in the hospital for approximately 35.0 days (25.5-43.0), with a mortality rate of 11.76%. Sixteen medical staff were infected with COVID-19 in the early stage. CONCLUSIONS: In this series of 1586 surgical patients, the COVID-19 infection rate was 1.07%, with an especially high incidence among patients with thoracic diseases. Middle-aged and elderly patients with preoperative pulmonary infection were more susceptible to COVID-19 infection after surgery. Medical staff were infected with COVID-19 and should take protective measures to protect themselves.

The current outbreak of coronavirus disease 2019 is the third epidemic caused by coronavirus in the 21st century. Currently, the number of cases is far beyond 80 000 in China and will likely increase by the time of publication. 1 COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its main manifestations are fever, dry cough, fatigue, respiratory distress, which can be transmitted by droplet, contact and aerosol transmission. [2] [3] [4] The high infection rate of the virus and the ability of the host to shed the infection with unexpectedly widespread transmission in communities and hospitals has led to high severity and mortality ratios. 5, 6 However, most studies have focused on the epidemiological and clinical characteristics of normal patients infected with COVID-19, and a few have reported medical staff were infected, 3, 6, 7 which means that nosocomial infection may be a very serious problem in the early stage of the COVID-19 epidemic.

However, the epidemiological risk of perioperative infection with COVID-19 pneumonia and the clinical manifestations of COVID-19 in surgical patients are still unknown. 8 Moreover, studies on how to protect clinical medical staff from COVID-19 infection are urgently needed.

Answers to these questions are essential for formulating the principles and guidelines of perioperative treatment for surgical patients and protection for medical staff during the epidemic of COVID-19 pneumonia. 8 In this study, we report the epidemiological and clinical characteristics, treatment, and outcomes of surgical patients with confirmed COVID-19 pneumonia infection and the infection transmission from surgical patients to medical staff.

This retrospective clinical study was registered with No. ChiCTR2000031245 and approved by the Medical Ethical Committee of our hospital (No. WDRY-2020-K024), and written informed consent was obtained from each enrolled patient, and the work has been reported in line with the STROCSS criteria. 9 A retrospective review of COVID-19 infection in surgical patients admitted to our hospital and staff was performed , and the latest follow-up was May 20, 2020 . The inclusion criteria were consecutive surgical patients receiving surgeries from January 13 to March 12, 2020, and surgeries performed out of the above periods were excluded.

The diagnosis of COVID-19 pneumonia was based on the New Coronavirus Pneumonia Prevention and Control Program (5th edition) published by the National Health Commission of China. 10 Patients with COVID-19 pneumonia were considered positive for SARS-CoV-2 with the use of the Chinese Center for Disease Control and Prevention (CDC) recommended kit (BioGerm, Shanghai, China), following WHO guidelines for qRT-PCR, 5 or by chest computed tomographic (CT) scans. 10 In the early stage of this epidemic (before January 23th, 2020), the nucleic acid tests were performed only on the suspected surgical patients with fever more than 37.3 ℃ and/or pulmonary infection (Chest CT/X-R ray showing) when entering the operating room, and medical staff only used the surgical mask to protect themselves. However, massive testing of nucleic acid test was performed for surgical patients, and medical staff used personal protective equipment (PPE) including protective suits surgical masks, N95 respirators and face shields after January 23th in our hospital.

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Epidemiological and clinical records, laboratory findings, chest CT scans, treatments and outcome data were obtained with customized data collection forms from electronic medical records. Information recorded included demographic data, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, chest CT scans, and treatment measures (i.e., antiviral therapy, corticosteroid therapy and respiratory support). The date of COVID-19 pneumonia onset was defined as chest CT scans and throat swab samples that were positive for 2019 novel coronavirus (2019-nCoV) nucleic acid. Medical staff, diagnosed with COVID-19, had a history of expose to the COVID-19 surgical patients, signs and symptoms with the evidence of chest CT or positive COVID-19 nucleic acid.

All statistical analyses were performed using SPSS (version 22.0, IBM, Armonk, NY, USA).

Categorical variables were described as percentages, and continuous variables were described using median and interquartile range (IQR) values. The Mann-Whitney test was used for analyzing continuous variables in table 3. Fisher's exact test was used for the proportions of categorical variables in table 3. For unadjusted comparisons, a 2-sided α of less than .05 was considered statistically significant.

The study population included 1586 hospitalized surgical patients (598 males, 988 females, median 47 years and IQR Most of the surgical patients with COVID-19 received general anesthesia (7 [23.53%]), with 1 patient receiving regional block and 1 patient receiving epidural anesthesia. The COVID-19 surgical patients were mainly distributed in the thoracic (9.37%), gastrointestinal (2.80%), and neurosurgery (1.85%) departments ( Table 1 ).

The median time from hospital admission to onset of COVID-19 diagnosis was 9.0 days (7.0-12.0), and the median time from the day of surgery to onset of COVID-19 diagnosis was 6.0 days (4.0-7.0) ( 

Before surgery, 6 patients presented with cough (31.29%), and 1 patient presented with fever (5.88%). After surgery, 10 patients presented with cough (58.82%), and 6 patients presented with fever (35.29%). After being diagnosed with COVID-19 pneumonia, 14 patients presented with fever (84.35%), and 16 patients presented with cough (94.12%) ( Table 3 ). The symptoms of dyspnea, chest tightness, malaise, dizziness and diarrhea did not change during this period (Table   3 ).

Data from laboratory tests showed that neutrophil counts were increased and lymphocyte counts were decreased after surgery and COVID-19 pneumonia diagnosis ( (Table 3) , and 14 (85.7%) patients' NLRs were higher than 3.5 when COVID-19 pneumonia was diagnosed (Table 2) . Additionally, 13 (76.47%) patients had elevated concentrations of C-reactive protein (>10 mg/L), and 11 (64.71%) patients had elevated concentrations of procalcitonin (>0.1 ng/ml) when COVID-19 was diagnosed ( Table 2 ). COVID-19 had no effect on the eGFR, ALT/AST ratio, or monocyte and platelet counts in surgical patients (Table 3 ). Blood cellular immune function showed that the median counts of CD3+, CD4+, CD16+ and CD56+ cells were decreased compared with the normal ranges, but the CD4+/CD8+ ratio was in the normal range when COVID-19 pneumonia was diagnosed (eTable 1 in the Supplement).

Before surgery, 11 patients (64.71%) were diagnosed with pulmonary infection by chest CT scan, and only 4 patients (23.53%) showed typical multiple patchy ground-glass shadows in the lungs (Table 3) . After surgery, the number of patients with typical multiple patchy ground-glass shadows in the lungs increased to 10 (58.82%) ( Table 3) . However, 14 (82.35%) of them showed J o u r n a l P r e -p r o o f bilateral dense shadows or ground-glass opacity when positive COVID-19 nucleic acid was detected (Tables 2 and 3 and Figure 1 ). Two (11.76%) of them showed typical multiple patchy ground-glass shadows in the lungs and were diagnosed by clinical symptoms and signs (Tables 2,   3 ). Typical dynamic changes in the chest CT files of Patient #5 are shown in Figure 2A and were compared with medical staff infected by Patient #4 ( Figure 2B ). nucleic acid (eFigure 1). Unfortunately, she died 8 days later due to acute respiratory distress.

Blood gas analysis showed that PaO 2 (110 mmHg) and PaCO 2 (42 mmHg) were in the normal ranges when she was diagnosed with COVID-19 pneumonia. However, PaO 2 (26 mmHg) and oxygenation index (58 mmHg) but not PaCO 2 (42 mmHg) levels were significantly decreased 2 hours before she died (eTable 2 in the Supplement).

Patient #4 and Patient #5 stayed in the same ward after surgery, and the attending clinician of patient #4 experienced fever and suffered from COVID-19 pneumonia 9 days later. Person-toperson transmission, from surgical patients to medical staff, mainly happened in ward area (15 [93.75%]), few in operating room (1 [6.25%]) and none in intensive care unit. Sixteen staff members (9.47%) had a definitive diagnosis and needed hospitalized therapy: 6 surgeons (11.76%), 1 anesthesiologist (2.94%), and 9 ward nurses (23.68%) ( pneumonia, which is related to low immunity and resistance. 11 Signs and symptoms were not typical before surgery, 12 and most surgical patients received elective surgeries before COVID-19 was diagnosed. Although body temperature was measured when entering the operating room, these patients were not screened out, which meant that fever was not highly related to COVID-19 pneumonia diagnosis before surgery. A single neutrophil or lymphocyte count could not predict COVID-19 infection, 13,14 but the NLR was sensitive for surgical patients infected with COVID-19 pneumonia, especially those with an NLR >3.5, which is considered significant in the diagnosis of COVID-19 pneumonia. Another study also showed that the NLR could predict the progression of pneumonia. 15 In this study, patients with a high NLR (>3.5) had a higher rate of mortality and long hospital stays after COVID-19 infection. , and complication incidence rates were also higher compared with surgical patients without COVID-19 infection. 16 Although the SAPS Ⅱ scores in surgical patients with COVID-19 were not higher than that in normal surgical patients, 17 two surgical patients (11.76%) died of COVID-19-associated complications, which was much higher than the reported overall case-fatality rate of 4.3% in COVID-19 patients without surgery 3 and was also higher than the case-fatality rate of 7.9% in noncardiac surgical patients. 16 Currently, no specialized medication is available for the treatment of COVID-19 infection. 18 The main treatment is antiviral and symptomatic support. 19 Thus, a patient's immune function is a major determinant of disease severity. 20 Interestingly, the numbers, not the distribution, of CD3+ and CD4+ cells in COVID-19 surgical patients were lower than those in mild COVID-19 patients without surgery and were similar to those in severe COVID-19 patients, 21 which meant that COVID-19 seriously inhibited the immune function of T lymphocytes after surgery. These findings would help to guide glucocorticoid or immunoglobulin therapies. A similar study also showed that cellular immunity was found to be a good prognostic indicator for predicting admission to the ICU in patients with SARS compared with age and leucocyte count. 22 Thus, the high mortality in surgical patients infected with COVID-19 may be associated with abnormal cellular immune function.

Studies have indicated that COVID-19 acts on the ACE II receptor, 2 which is mainly distributed on type II alveolar epithelial cells regulating lung compliance, 23 but few are distributed on type I alveolar epithelial cells. 24 COVID-19 pneumonia can lead to dyspnea and chest tightness, even respiratory failure, so patients need high-flow oxygen support, even ventilator therapy. The dynamic profile of arterial blood gas in Patient #4 receiving pulmonary surgery showed that COVID-19 pneumonia led to death, mainly by decreasing oxygen exchange but not carbon dioxide excretion, which suggested that pulmonary surgery may exacerbate the worse prognosis of COVID-19 pneumonia.

More importantly, patient #4 and patient #5 stayed in the same ward after surgery, and the attending doctor of patient #4 suffered from COVID-19 pneumonia 9 days later, suggesting that person-to-person transmission occurs in the surgical ward and that infection transmission may start even earlier. The time from hospitalization to diagnosis of COVID-19 was 9.0 days (6.5-12.5), and another study showed that the median time from symptom onset to first hospital admission was 7 days (4.0-8.0), 10 so COVID-19 transmission infection mostly occurred in hospitals. Infection of hospitalized medical staff with COVID-19 pneumonia mainly occurred in the surgical ward, and one anesthesiologist was infected in the operating room, which might be related to the delay in diagnosis, endotracheal intubation and invasive procedures without taking effective protection measures.

COVID-19 mainly includes three modes of transmission: droplet transmission, contact transmission, and aerosol transmission caused by long-term exposure to high-concentration aerosols in a relatively closed environment. 25, 26 Therefore, during the perioperative period, first, medical staff were required to undergo training regarding the infection control management procedures for COVID-19. All patients' blood, body fluids, secretions, and excreta should be J o u r n a l P r e -p r o o f treated as infective agents, and medical staff should take patient-to-staff two-sided protective measures and take measures such as droplet isolation, contact isolation and air isolation. 27 Second, medical staff and patients followed the established biosafety procedures when entering and leaving the operating room. Third, patients wore a surgical mask before endotracheal intubation, and medical staff must use PPE including protective suits surgical masks, N95 respirators and face shields when contacting surgical patients with confirmed or suspected COVID-19, especially during the endotracheal intubation period. 25 Fourth, the working area of medical staff was isolated from the ward, and critical workers caring for patients with coronavirus should use PPE. 28 There are several limitations in our study. First, as the total enrollment was affected by the Spring Festival and Wuhan lockdown, hospitals in Wuhan only accepted emergency patients, and elective surgeries could not be performed normally from January 23 to March 12. The infection of COVID-19 in general population was increased in the early stage of COVID-19

outbreak, but the incidence rate in surgical patients was not increased after January 23 (see in Table 1 ), which was mainly because of the efficient control, few patients transferred from primary hospitals and decreased number of surgeries. Second, surgical patients did not receive preoperative SARS-CoV-2 confirmation tests before January 23, so the data lacked the reservoir of infection and accurate infection onset of each patient due to the understanding of the epidemic situation and the shortage of 2019-nCoV confirmation kits at that time.

In summary, in this series of 1586 surgical patients, the COVID-19 infection rate was 1.07%, with an especially high incidence among patients with thoracic diseases, and the median age was infected with COVID-19 during the perioperative period and must wear protective equipment to protect themselves.

The authors declare no conflicts of interest. J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f 

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Middle-aged and elderly patients with preoperative pulmonary infection are more susceptible to COVID-19 infection after surgery

It's difficult to diagnose based on chest CT and fever before surgery

Name of the registry: Chinese Clinical Trial Registry

Unique Identifying number or registration ID: ChiCTR2000031245

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We acknowledge all health-care workers involved in the diagnosis and treatment of patients in Wuhan; we thank the surgical, imaging and clinical laboratory staff in our hospital for coordinating data collection for patients with COVID-19 infection.Provenance and peer review: Not commissioned, externally peer-reviewed.J o u r n a l P r e -p r o o f

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This study was supported by grants from the National Natural Science Foundation of China (81471844) and the Fundamental Research Funds for the Central Universities (2042019kf0061).

This retrospective clinical study was approved by the Medical Ethical Committee of Renmin Hospital of Wuhan University (No. WDRY-2020-K024).

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