key: cord-0711395-k1pfx0di authors: Wei, Xiao-Shan; Wang, Xiao-Rong; Zhang, Jian-Chu; Yang, Wei-Bing; Ma, Wan-Li; Yang, Bo-Han; Jiang, Nan-Chuan; Gao, Zhan-Cheng; Shi, Huan-Zhong; Zhou, Qiong title: A Cluster of Health Care Workers with COVID-19 Pneumonia Caused by SARS-CoV-2 date: 2020-04-27 journal: J Microbiol Immunol Infect DOI: 10.1016/j.jmii.2020.04.013 sha: 2f51cb4a08bdfeef1f20e9b8119c830edac08fe6 doc_id: 711395 cord_uid: k1pfx0di Abstract Background The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international borders. Methods We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China. Results Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significently elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%). Conclusions Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection. from Wuhan city, Hubei province, China, 1-4 has become a global health concern. 5-8 As of March 18, 2020, a total of 191, 127 confirmed cases had been reported globally, with 7807 deaths. 9 80928 comfirmed cases and 3245 death cases were documented in China, as of March 18, 2020 . 10 The overwheliming burden of illness stressed the health system capacity and increased the risk of infection among health care workers (HCWs). As of February 11, 2020, the Chinese Center for Disease Control and Prevention reported that a total of 1716 HCWs were confirmed to be COVID-19 patients in China. 11 Among them, 63% (1080) were in Wuhan, at least 5 had been dead. 11 During the early outbreak of COVID-19 in Wuhan, inadequate personal protection of healthcare workers maybe an important reason for the COVID-19 infection in HCWs. Here, we report a cluster of infected HCWs from department of neurosurgery in Wuhan Union Hospital. One male patient (69 years old) was admitted to the department of neurosurgery of Wuhan Union Hospital for pituitary adenoma resection on December 25, 2019. He demonstrated a fever of 38 °C on January 6 and pulmonary computed tomography (CT) revealed "virus pneumonia" on January 11. Another patient in the same ward also compained of fever, on January 11. Both of them were confirmed to be COVID-19 patients with positive result of SARS-CoV-2 on January 16 and 18, respectively. They were transferred to an isolation ward for patients with infectious diseases, immediately. Meanwhile, all health care workers in the neurosurgery deparment, not only those exposed to the two index patients, were enquired if they had any uncomfort, took test for SARS-CoV-2 from throat swab and CT scan, to see if they had been infected. Medical College, Huazhong University of Science and Technology (2020-0120). Oral consent was obtained from all patients and infected HCWs. Written informed consents were exempted according to the approved ehics approval (2020-0120). All the infected 14 health care workers were hospitalized in isolation wards. All the medical records were extracted and analyzed. The critiria for confirmed and suspected cases of COVID-19 were followed "the diagnosis and treatment protocol for novel coronavirus pneumonia" (trial version 7, released by National Health Commission & State Administration of Traditional Chinese Medicine on March 3, 2020) . 10 Throat-swab specimens from the upper respiratory tract were obtained from all patients and infected HCWs, and the detection of SARS-CoV-2 was performed according to WHO recommendation. 12 SARS-CoV-2 was confirmed by real-time RT-PCR using the same protocol as previously described in the studies from Wuhan Jinyintan Hospital. 3, 4 Serum cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were assayed using the BD Biosciences Th1/Th2 cytokine kit, as per the manufacturer's instructions (BD Ltd., Franklin Lakes, NJ, USA). For those confirmed infected HCWs, they were permitted to discharge, if (1) their body temperature was back to normal for more than three days, (2) respiratory symptoms improve obviously, (3) pulmonary imaging shows obvious absorption of inflammation (4) and nuclei acid tests negative twice consecutively on nasopharyngeal swabs (sampling interval being at least 24 hours). 10 For those suspected infected HCWs, they also were permitted to discharge if they met the the above criteria (1), (2) and (3). All discharged HCWs were required to live in an isolation hotel for another 14 days, before they could go home. We describe demographics, clinical presentation, laboratory results, pulmonary CT findings, response to therapy, and clinical outcomes. Continuous measurements are presented as mean (SD) and categorical variables as count (%). Comparisons were determined by paired t test or repeated measures analysis of variance as appropriate. We also assessed whether the laboratory results were outside the normal range. All statistical analyses were performed with SPSS22.0 (SPSS Inc., Chicago, IL). As of January 31, fourteen HCWs in the neurosurgery department were hospitalized to isolation wards. According "the diagnosis and treatment protocol for novel coronavirus turned to be negative in the 12 confirmed HCWs (Figure 1 ). In addition, all infected HCWs were tested for the nucleic acid of influenza viruses A and B as well as local common bacteria and fungi spectra, and influenza virus A test was positive in one patient (patient 2). The mean age of the infected HCWs was 36 years (SD, 6 years), and 4 of the 14 infected HCWs (29%) were male (Table 1) . No one was smoker and had been exposed to Huana seafood wholesale market in Wuhan, which was thought to be associated with the early outbreak of COVID-19 pneumonia. 3, 4, 13 Except patient 13 had cough variant asthma, none of the remaining 13 infected HCWs had any kinds of underlying chronic illness. The main symptoms included myalgia or fatigue (100% of the patients), fever (86%), dry cough (71%), diarrhea (64%), headache (57%), and pharyngalgia (50%), on admission to hospital (Table 1) . Myalgia or fatigue, fever, dry cough, diarrhea ( Figure 2 ) and the other symptoms resolved within two weeks after the disease onset. On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia ( Table 2 ). The numbers of white blood cells and lymphocytes in most infected HCWs with leucopenia and/or lymphopenia increasd to normal range within 10 days after admission. Unlik the laboratory findings previously reported in the first and second cohorts, 3, 4 all blood biochemical and the other parameters determined in our cohort were not outside the normal range, although a couple of parameters, such as aspartate aminotransferase and albumin, demonstrated some an extent of fluctuation (Table 2 ). It was noted that COVID-19 pneumonia onset did not influence the proportion of lymphocytes subsets (Appendix Table 1 ) and the concentrations of immunoglobulins (Appendix Table 2 ). Reduced complement C3 could be seen in 57% of the infected HCWs at day 1 and 29% at day 7, while complement C4 was not affected (Appendix Table 2 ). We determined the concentrations of IL-2, IL-4, IL-6, IL-10, TNF-α, as well as IFN-γ, and found that IL-6 was the only one cytokine whose level was significently elevated in serum of COVID-19 pneumonia infected HCWs, indicating IL-6 may play an important role in the pathogenesis of COVID-19 pneumonia (Appendix Table 3 ). Pulmonary involvement was seen on CT images of all infected HCWs, and most of the CT abnormalities were bilateral pneumonia (Appendix Table 4 ). The CT scans of the two suspected infeted HCWs were shown in figure 3 . The most frequent findings on CT images were ground-glass opacifications (86%), which located in peripheral parenchiyma (50%) or in both peripheral and central parenchiyma (36%). The ground-glass opacifications in all infected HCWs were multifocal. Subsegmental areas of consolidation could be identified in six (43%) infected HCWs and patchy reticular changes subpleural areas in two (14%). Importantly, ground-glass opacification and/or consolidation stably resolved in 10 (86%) infected HCWs on serial CT images during hospitalization; however, such abnormalities demonstrated a deterioration for a couple of days and then an improvement in 4 (29%) infected HCWs. Bilateral pleural effusion appeared in one (7%). During hospitalization, all these 14 HCWs received antibiotic and antiviral treatments. The antiviral treatment they took were arbidol(200mg tid) and recombinant human interferon α2b(5 million U each time for adults, adding 2ml of sterilized water, atomization inhalation twice daily). Three infected HCWs needed oxygen inhalation through nasal tube. None of these infected HCWs were given systematic corticosteroids, non-invasive ventilation, or ICU admission. As of February 26, all the 14 HCWs had discharged and none of them died. In the beginning of the outbreak of COVID-19 in China, COVID-19 patients increased substancially and HCWs were a high-risk group to get infected . Of the 138 admmitted patients in Zhongnan Hospital from Wuhan during January 1 to January 28, 40 patients were health care workers. 14 Here, we describe a cluster of COVID-19 infected HCWs who worked in the same department. In the present study, when the first index patient was hospitalized for pituitary adenoma resection, he did not have fever or any respiratory symptom, his chest X-ray did not shown any signs of virus pneumonia on admission. Thus he was not suspected to be a COVID-19 patient. Eleven days after hospitalization, he accepted the pituitary adenoma resection and had a fever of 38℃ after the surgery. Postoperative fever was considered to the cause of the patient's fever. However, five days after the fever onset, the patient had a chest CT scan with typical signs of viral pneumonia. Meanwile, another patient who lived in the same ward had fever, too. Further, several days later, the two patients were confirmed to be COVID-19 patients with positive results for SARS-CoV-2 from throat swab and transferred to isolation wards. However, during their stay in the department of neurosurgery, especially before the day of the first patient's chest CT scan, HCWs did not have enough personal protective equipment. Sometimes, they weared nursing mask but not the surgical mask, when they contact these two patient, as we did not know that was a COVID-19 patient at None of these 14 infected HCWs were admitted to ICU or dead. One explanation might be that all these HCWs with COVID-19 pneumonia were young people and mild cases. Another explanation might be that our infected HCWs did not had significant underlying chronic diseases. In the largest case series to date of COVID-19 in mainland China(72314 cases, updated February 11, 2020) , no deaths were reported in mild and severe cases. 11 But in critical cases, the overall case-fatality rate (CFR) was 49.0%. 11 CFR was increased in those with underlying deseases, such as cardiovascular disease, diabetes, chronic respiratory diseas, hypertension and cancer. 11 We noticed that IL-6 was significantly elevated in 86% of the infected HCWs and complement C3 was decreased in 57% of them. It indicated that a dysregulated and excessive host inflammatory response may exist in COVID-19 pneumonia. 15 As a multieffective cytokine with anti-inflammatory and pro-inflammatory effects, IL-6 plays an important role in cytokine release syndrome of COVID-19 patients. 15 Blocking the signal transduction pathway of IL-6 maybe a promising method for the treatment of COVID-19 patients. 16 A latest small single-centre study has revealed the effectiveness of Tocilizumab (IL-6R blocker) in treating COVID-19 patients. 16 However, multicenter randomized controlled trial is still needed to document the effectiveness of Tocilizumab in COVID-19. The proportion of lymphocytes subsets were within normal range in these 14 infected HCWs, including CD4 + T cells and CD8 + T cells. Published studies indicated that CD4 + T cells and CD8 + T cells decreased significantly in severe cases, as compared with mild cases. 17, 18 All these 14 infected HCWs were mild cases, it might be the reason that the proportion of lymphocytes subsets did not exceed the normal range, as well as the concentration of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ in this small case series. It was quite reasonable to consider that some of the HCWs were infected by the two index patients, as they did not contact any other COVID-19 patients. However, the laboratory-confirmed evidence of SARS-CoV-2 transmission chain among them was not availabe yet. Another limitation of this study was the small number of cases. Observation with a large number of infected HCWs is needed to document the route of nosocomial transmission. Our current study demonstrated a cluster of HCWs in the same department due to unsufficient personal protective equipment. Future studies are necessary to determine what is the best protocol to protect HCWs from infected with SAR-CoV-2 while they contact the COVID-19 patients. showed patchy shadows and ground glass density in the middle lobe of the right lung, (E) the lesion was reduced in the middle lobe of the right lung, and newly small patchy shadows appeared in the left lower lobe of the lung, (F) the lesions in the middle lobe of the right lung and the lower lobe of the left lung were almost resloved, showing as ground-glass opacity. * means ±SD. 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