Research on pneumonia exacerbation in patients infected with SARS-CoV-2 in Wuhan, China

Research on pneumonia exacerbation in patients infected with SARS-CoV-2 in Wuhan, China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Research on pneumonia exacerbation in patients infected with SARS-CoV-2 in Wuhan, China Yan-Ping Tang, Guo-Xi Chen, Lin Wang, Xing Lan, Chen Ji, Xiao-Pan Li, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-22154/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background SARS-CoV-2 pneumonia occasionally exacerbates to critical condition that is hard to manage. We aim to describe exacerbations of SARS-CoV-2 pneumonia among inpatients. Methods We included confirmed SARS-CoV-2 patients with pneumonia exacerbation admitted to Wuhan Pulmonary Hospital, Hubei Province, China between January 6 and February 17, 2020 and discharged or died before February 25. Their demographic characteristics, clinical symptoms, laboratory tests, CT manifestations, complications and clinical outcomes were collected. Results A total of 158 patients were collected, among them 107 patients were stable and discharged after recovery, 24 patients were already critically severe at hospital admission. 14 patients were excluded for insufficient clinical data. Eventually, 13 confirmed cases were included. The mean age was 65 (± 9.81) years. Ten of the 13 (76.9%) patients were female. Nine (69.2%) had underlying comorbidities. Fever and cough were the most common symptoms (12/13, 92.3%). 10/13(76.9%) patients had their exacerbation in the second week of disease course. All patients had both negative and positive nucleic acid test (NAT) results during the course. Increased range of ground-glass opacity (GGO) on CT imaging are consistent to disease exacerbation. ARDS, MODS, respiratory failure were found in 5/13(38.5%), 3/13(23.1%), 6/13(46.2%) patients respectively. Five (38.5%) patients did not survive. Conclusions SARS-CoV-2 pneumonia exacerbations often occurs in the second week of disease course. Negative NAT result could not exclude exacerbation. CT manifestation is consistent with disease progression. Early admissions have positive effects on reducing complications and mortality. Pulmonology SARS-CoV-2 exacerbation pneumonia Figures Figure 1 Figure 2 Figure 3 Background Since December 2019, the outbreak of novel coronavirus diseases COVID-19 has exerted profound influence globally. The World Health Organization (WHO) has declared COVID-19 as a pandemic. Up to March 17,2020, a total of 571678 confirmed cases and 26494 deaths were reported 1 . The highly pathogenic virus is now named as SARS-CoV-2 (initially as 2019-nCoV) 2 . Some studies have reported the epidemiological features, clinical characteristics and computed tomography (CT) changes of the SARS-CoV-2 pneumoina 3 – 7 . The aim of this study is to report the disease exacerbation during hospitalization. Methods Study design and material This is a retrospective, single ¬center, observational study. Laboratory-confirmed SARS-CoV-2 patients with pneumonia exacerbation after admitted to Wuhan Pulmonary Hospital, Hubei Province, China (a COVID-19-designated hospital in the event of epidemic outbreak) between January 6 and February 17, 2020 and discharged or died before February 25 are included. Diagnosis of SARS-CoV-2 pneumonia were confirmed by viral nucleic acid test (NAT) using high-throughput sequencing or ramplification of open reading frame 1ab (ORF1ab) and nucleocapsid protein (NP) genes fragments from sputum, pharyngeal swab or lower respiratory tract samples as descried in previous study 3 . In this study, sampling site also included urine and stool. NAT-confirmed patients were divided into three types according to the severity grading: 1) moderate: with fever and respiratory symptoms, or with pneumonia performance on imaging. 2) severe: met one of the following criteria: respiratory distress, respiratory rate>=30 times/min; pulse oxygen saturation 50% lesion within 24-48 hours as shown on CT. 3) critically severe: met one of the following criteria: respiratory failure and mechanical ventilation required; shock; multi-organ failure required intensive care unit (ICU) care. Disease exacerbation is defined as the escalation of severity grading during the course of disease. We counted the detection results of ORF1ab and NP genes, respectively. Double-positive is defined as both ORF1ab and NP positive while double-negative is defined as both ORF1ab and NP negative. Data collection We extracted the age, gender, underlying comorbidities, clinical symptoms, vital signs, laboratory findings on admission and CT during hospitalization. All laboratory testing and examinations are performed according to the clinical care needs of the patient. Definitions The course of illness of non-survivor cases was defined as the duration from onset to death. The course of illness of survivor cases was defined as the duration from onset to the sampling date of the second negative NAT of two consecutive NATs before discharge. We adopted this new method of definition to reflect the duration of detectable SARS-CoV-2 RNA as accurate as possible. Early Admission was defined as hospitalized within 7 days from onset. Late admission was defined as hospitalized after 7 days from onset. Lymphopenia was defined as lymphocyte count<0.8*10^9/L. Thrombocytopenia is defined as platelet count < 100*10^9/L. Anemia is defined as hemoglobin < 110g/L. Hyponatremia is defined as serum sodium < 135mmol/L. Hypokalemia is defined as serum potassium < 3.5mmol/L. Hypoalbuminemia is defined as plasma albumin < 35g/L. Elevation or reduction criteria of each laboratory value were listed on Table1. The survival outcome was defined as survival to hospital discharge. Statistical analysis All continuous variables were described as mean (standard deviation (SD), range) and categorical variables were defined as number and percentage. SPSS software (version 19) was used for the statistical analysis. Results Demographic data and clinical symptoms Of the 13 patients, the average age was 65 (SD: 9.81, range: 39–80) years old. Ten (76.9%) were women and 9 (69.2%) had one or more underlying comorbidities, including hypertension, diabetes, heart disease, chronic kidney disease, hepatic disease, etc. With respect to initial symptoms, fever and cough are most common symptoms (12/13, 92.3%). 1/13 (7.7%) patient had hypodynamia, 4/13 (30.8%) patients had shortness of breath, 3/13 (23.1%) patients had chest distress, 1/13 (7.7%) patient had abdominal pain and diarrhea,1/13 (7.7%) patient had palpitation (shown in Table 1). At admission, 7/13(53.8%) patients were diagnosed as moderate pneumonia, 6/13(46.2%) were diagnosed as severe pneumonia. Figure 1 shows the course of illness of all patients. Nucleic acid tests All NAT results and the corresponding sampling sites of 13 patients are collected and shown on Fig. 2. All cases had both double-negative result and double-positive result in different during disease course. NP gene positive with ORF1Ab negative result are shown in four cases (case 6,8,9,13). It is worth noting that two cases (case 2 and 4) tested positive post hospital discharge whereas their two consecutive NAT tests showed double-negative results before discharge. Laboratory tests Laboratory values are shown in Table 1. 1/13(7.7%) had procalcitonin elevation. 7/13 (53.8%) had elevated D-Dimer. 13/13 (100%) had elevated C-reaction protein. 3/13(23.1%) had leukopenia. 11/13(84.6%) had lymphopenia. Increased neutrophilic granulocyte count and decreased monocyte count are observed in 4/13(30.8%) patients separately. 1/13(7.7%) had thrombocytopenia. 3/13(23.1%) had anemia. 12/13 (92.3%) had elevated lactate dehydrogenase. Elevation of total bilirubin and direct bilirubin are not detected. 2/13(15.4%) had increased glutamic-pyruvic transaminase, 4/13(30.7%) had increased glutamic-oxaloacetic transaminase. 2/13(15.4%) had abnormal creatinine. 8/13(61.5%) decrease of plasma albumin. 5/13(38.5%) presented blood urea nitrogen increase. 3/13(23.1%) had hyponatremia. 3/13(23.1%) had hypokalemia. 2/13(15.4%) had prolonged active partial thromboplastin time. 3/13(23.1%) had cardiac troponin elevation. 6/13(46.2%) had elevated creatine kinase. Imaging examinations Intact CT imaging of all cases except case 7 and case 8 are available. Features of CT imaging, including location, proportion, numbers of associated lung lobes and manifestation, were shown in the table2-supplementary table. CT imaging of case2 and case10 are shown in Fig. 3. Ground-glass opacity in both lungs were characteristically observed on CT (11/11,100%). Peripheral distribution and bilateral sides involvement were observed in 11/11 (100%) and 10/11 (90.9%) patients, respectively. One patient with unilateral abnormality at onset progressed to bilateral in 3 days. As the disease progressed, the lesions became consolidated, and central zone and more lung lobes were involved. Pleural effusion and thickened pleura were detected in 2 different patients. Treatment Antiviral drugs and glucocorticoids were given to all patients (13/13, 100%).Antibiotics were given to 12/13 (92.3%) patients. Mechanical ventilation was given to 6/7 (85.7%) critically severe patients. Exacerbations,complications and outcome Seven cases (case 1,2,3,4,11,12,13) presented as moderate type at admission, among them only case11 progressed to the critically severe type. The other six cases progressed to the severe type. The cases presented as the severe type (case5,6,7,8,9,10) at admission all deteriorated to be critically severe. 10/13(76.9%) patients had their exacerbation in the second week of disease course. Among all included cases, 5/13 (38.5%) had ARDS, 3/13 (23.1%) had MODS, 6/13 (46.2%) had respiratory failure, 8/13 (61.5%) had hypoalbuminemia. 42.8% (3/7) early admission cases and 66.6% (4/6) late admission cases developed to critically severe type. The majority of critically severe type (case5,6,7,8,10) (5/7,71.4%) did not survive. The overall survival rate is 53.8% (7/13). Mortality rate is 28.6% (2/7) in the early group and 50.0% (3/6) in the late group. Incidence of ARDS is 28.6% (2/7) vs. 50.0% (3/6), MODS 28/6% (2/7) vs. 16.6% (1/6), respiratory failure 33.3% (2/6) vs. 66.6% (4/6), hypoalbuminemia 28.6% (2/7) vs. 100.0% (6/6) respectively. Discussion We analyzed 13 confirmed cases of SARS-CoV-2 pneumonia patients with disease exacerbation after admission. Exacerbation of SARS-CoV-2 pneumonia does not always but indeed happen (13/120, 10.8%) among inpatients. Review the age distribution of 13 patients, 11(11/13 85%) had exceeded 60 years old. The majority of patients (9/13 69%) had underlying comorbidities, including but limited to hypertension, diabetes, heart disease, chronic kidney disease, hepatic disease. Two patients under 60 years of age had obesity, hyperlipidemia (case1), and coronary artery disease, hypertension (case2) separately. Aging and underlying diseases may collaborate and contribute to the decline of host immunity that is the prerequisite of virus infection and disease exacerbation. In this study, 10/13(76.9%) cases were female. This ratio seems to be quite contradictory to previous report on COVID-19 that claimed approximately 70% infections occur in male8. and also inconsistent with the proportion of male patients (67%) in severe SARS-CoV-2 pneumonia reported in another study 8 . Since this study had excluded patients admitted but has not been discharged or died before February 25, the total number and proportion of male patients could be underestimated. Disease exacerbation mostly occurred in the second week of disease course (10/13, 76.9%). Patients (case 1,4,5,10,11,12,13) admitted early (within 7days) of the disease course had a relatively better prognosis than those (case 2,3,6,7,8,9) admitted later (after the first 7days). The early group demonstrated lower probability of complications and death. These results indicate that early admission is crucial to restrain deterioration and reduce mortality. The overall mortality rate was 38.4%(5/13), and in critically severe cases,the mortality rate was 71.4%(5/7), slightly higher than former study 8 . These results may be attributed to the fact that the inclusion criteria of this study are different from those of the above studies. These data do not apply to the entire herd of infected patients. In our study, fever and cough were the most common symptoms at hospital admission. Initial reports of the COVID-19 virus suggested that symptoms of SAR-CoV-2 pneumonia are similar to that of SARS and MERS, since most patients presenting with fever, cough, fatigue and hypodynamia 9 , 10 . However, one patient (case12) did not manifest fever during the entire course of disease. This is an 80 years old female patient presented to clinic with a complain of chest distress and palpitation. Since she was in the epidemic area, she underwent a CT scan which demonstrated pneumonia. Then nucleic acid test was administrated and this case is confirmed. Besides, patients presented diarrhea as the initial symptom of disease have been reported 11 . These extra-pulmonary initial symptoms deserve more attention outside of fever clinic. Elevation of C-reaction protein, D-Dimer and lactate dehydrogenase, reduction of lymphocyte count and albumin are observed in more than half of the cases. Anemia, transaminase abnormality, elevated myocardial index and renal dysfunction are also detected as disease exacerbate. These changes are consistent with previous reports 3 , 12 , 13 . Ground-glass opacity and consolidation are the main changes in CT imaging. CT manifestations are indicative of the exacerbation of pneumonia. In the process of exacerbation, more lobes were involved, range of GGOs were expanded and density of consolidation was increased. Additional signs on CT imaging include vascular enlargement, interlobular septal thickening in crazy-paving pattern, air bronchogram sign and discrete pulmonary nodules, which were previously reported in some studies 14 , 15 . CT imaging may serve as a standard method in the rapid diagnosis of COVID-19. Previous studies have reported that the sensitivity of chest CT is significantly greater than that of RT-PCR (98% vs 71%, respectively, p < .001) 16 . And false negative rate is very low (3.9%)16. Nevertheless, CT is still incapable of distinguish between different viruses. Nucleic acid RT-PCR testing is a standard test for suspected cases to confirm the SARS-CoV-2 infection. Sampling site plays an important role in virus detection. Case 10 was sampled at 4 sites (pharyngeal swab, urine, venous blood, stool) on the same day, only stool sample demonstrated positive result. The patient’s medical records showed severe diarrhea and significant weight loss, which suggests that stool specimen in patients presenting gastrointestinal symptoms is probably more sensitive to the virus than pharyngeal swabs. Controversial NAT results were also observed in case 8 whose sputum and urine sample were taken on the same day. Urine sampling is not of high priority in clinical routine due to lack of sufficient data to support it as a usual shedding route of coronavirus. For different sampling sites, bronchoalveolar lavage fluid exhibited the highest positive rate, followed by sputum, nasal and pharyngeal swabs showing poor positive rate in patients with fever 17 . Another study reported the detection rates of SARS-CoV-2 from sputum specimens are significantly higher than throat swabs 18 . SARS-CoV-2 has the ability to transmit through multiple routes 19 , 20 and manifest diverse clinical symptoms which should be taken into account while sampling. We infer that while determine where specimens are collected, considering the location of initial symptoms may increase positive rate. In 4 cases (case 6, 8, 9, 13), NAT showed ORF1ab negative and NP positive result. Low viral load might lead to this result since PCR kits currently used in clinical practice are generally more sensitive to the amplification of the N protein gene than ORF1ab. On the other hand, crossovers of other coronaviruses may cause the same result since ORF1ab sequence is more conservative than N protein gene. Patients presented single-positive result should be re-checked by test kits from a different manufacture or different test method. NAT results has turned out to be controversial in 2 cases(case2,4). After discharge from hospital (20 days for case 2, 14 days for case 4), their NAT result reversed to be positive. It is not clear that whether these patients are still contagious. Virus isolation and antibody test may provide further confirmation. The shedding mode of virus might be relevant to a re-positive result of NAT. Intermittent shedding have been found in Epstein-Barr-virus infected patients 21 and pulsed shedding of viruses in wildlifes 22 have been reported. This may also suggest that SARS-CoV-2 has acquired the ability of chronic infection, as HIV integrates itself into the host's genome by reverse transcription 23 , 24 and Hepatitis B virus invades into liver cells and transforms into covalently closed circular DNA 25 . But this hypothesis is yet unfounded and requires further investigation. All medical treatment administrated in our cases suits clinical demands. The efficacy of antibiotics, antivirals, glucocorticoids is not discussed here since sample size is too small to summarize any conclusion. This study has obvious limitations. First, only 13 cases were eventually involved. However, all included cases have intact medical records available to trace back and changes in severity grading over time is recorded in details. Second, due to the diversity of clinical needs, NAT sample site choosing changes in every case and CT examinations not administrated in 2 cases. Third, the course of illness is defined as the time interval between onset and outcome event in this study. Disregarding the incubation period leads to an underestimation of the actual span of disease course. Last but not least, as a retrospective study, recall bias and selection bias inevitably affected our assessment. Further studies on aggravating factors of pneumonia, early identification and prevention methods of exacerbation are needed. Conclusion In conclusion, our study provides a preliminary sight into the exacerbation of SARS-CoV-2 pneumonia. Disease exacerbation mostly occurs in the second week of disease course. Negative NAT does not exclude exacerbation. CT manifestations may provide evidence of the exacerbation of pneumonia. Early admission appears to have positive effects on reducing complications and mortality. Abbreviations NAT nucleic acid test GGO ground-glass opacity CT computed tomography ARDS acute respiratory distress syndrome MODS multiple organ dysfunction syndrome COVID-19 coronavirus disease 2019 WHO the World Health Organization RT-PCR real-time reverse-transcriptase–polymerase-chain-reaction ORF1ab open reading frame 1ab NP nucleocapsid protein PaO2/FiO2 artery partial pressure of oxygen / inspired oxygen fraction ICU intensive care unit SARS severe acute respiratory syndrome MERS middle east respiratory syndrome Declarations Ethics approval and consent to participate Informed consent was exempted with the approval of Medical Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China (No. XHEC-D-2020-030). Consent for publication Not applicable. Availability of data and materials The datasets used during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research is supported by Zhejiang University special scientific research fund for COVID-19 prevention and control(2020XGZX065) and Shanghai Jiaotong University's Technology Promotion Project 2019(ZT201903). Authors' contributions GX Chen and X Lan collected the data, C Ji and XP Li accomplished data analysis, Y An, D Zhang and GW Zeng performed imaging processing, YP Tang and L Wang drafted the manuscript and made literature review, L Yang, YY Cai and H Huang designed the study and reviewed the manuscript. All authors read and approved the final manuscript. Co-first authors: YP Tang, GX Chen, L Wang, X Lan and C Ji contributed equally to this work. Correspondence authors: YY Cai, L Yang and H Huang. Acknowledgements Not applicable. References World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report – 68. . Accessed 29 Mar 2020. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–33. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. 10.1001/jama.2020.2648 Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. Jama. 2020;2019. doi:. Tian S, Hu N, Lou J, Chen K, Kang X, Xiang Z, et al. Characteristics of COVID-19 infection in Beijing. J Infect. 2020; PG-. doi:. Bernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N, et al. Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection. Radiology. 2020;19:200463. doi:. Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China. J Infect. 2020;80:388–93. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;2600:1–7. Chafekar A, Fielding BC. MERS-CoV: Understanding the latest human coronavirus threat. Viruses. 2018;10. Hui DS-C, Wong P-C, Wang C. SARS: clinical features and diagnosis. Respirology. 2003;8 Suppl:S20-4. Song Y, Liu P, Shi XL, Chu YL, Zhang J, Xia J, et al. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut. 2020;:gutjnl-2020-320891. doi:. Zhang J-J, Dong X, Cao Y-Y, Yuan Y-D, Yang Y-B, Yan Y-Q, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–13. Zhou S, Wang Y, Zhu T, Xia L. CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China. AJR Am J Roentgenol. 2020;October:1–8. doi:. Li Y, Xia L. Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management. AJR Am J Roentgenol. 2020;October:1–7. doi:. Fang Y, Zhang H, Xie J, Lin M, Ying L, Pang P, et al. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology. 2020;2013:200432. doi:. Liu R, Han H, Liu F, Lv Z, Wu K, Liu Y, et al. Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020. Clin Chim Acta. 2020. doi:. Lin C, Xiang J, Yan M, Li H, Huang S, Shen C. Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2) infected pneumonia (COVID-19). medRxiv. 2020;:2020.02.21.20026187. Gu J, Han B, Wang J. COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission. Gastroenterology. 2020. doi:. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395:809–15. Niederman JC, Miller G, Pearson HA, Pagano JS, Dowaliby JM. Infectious mononucleosis. Epstein-Barr-virus shedding in saliva and the oropharynx. N Engl J Med. 1976;294:1355–9. Páez DJ, Giles J, McCallum H, Field H, Jordan D, Peel AJ, et al. Conditions affecting the timing and magnitude of Hendra virus shedding across pteropodid bat populations in Australia. Epidemiol Infect. 2017;145:3143–53. Marini B, Kertesz-Farkas A, Ali H, Lucic B, Lisek K, Manganaro L, et al. Nuclear architecture dictates HIV-1 integration site selection. Nature. 2015;521:227–31. Allweiss L, Dandri M. The role of cccDNA in HBV maintenance. Viruses. 2017;9. Schröder ARW, Shinn P, Chen H, Berry C, Ecker JR, Bushman F. HIV-1 integration in the human genome favors active genes and local hotspots. Cell. 2002;110:521–9. Tables Due to technical limitations, the tables are only available as a download in the supplemental files section. Supplementary Files Table2supplementary.xlsx Table1.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Zhang","email":"","orcid":"","institution":"Shanghai Jiaotong University School of Medicine Xinhua Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Di","middleName":"","lastName":"Zhang","suffix":""},{"id":491105,"identity":"5a06c520-930b-46b0-b5d3-e539593ea805","order_by":9,"name":"Guang-Wang Zeng","email":"","orcid":"","institution":"Shanghai Jiaotong University School of Medicine Xinhua Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guang-Wang","middleName":"","lastName":"Zeng","suffix":""},{"id":491106,"identity":"9263da6a-ff0a-40a5-be19-fae7d8978cd9","order_by":10,"name":"Ya-Ling Wang","email":"","orcid":"","institution":"Department of Tuberculosis ward2, Wuhan Pulmonary Hospital, Hubei 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Yang","email":"data:image/png;base64,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","orcid":"","institution":"","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Yang","suffix":""},{"id":491110,"identity":"6af44c86-5405-4743-b209-c632f47bf3cd","order_by":14,"name":"Hai Huang","email":"","orcid":"","institution":"Department of Tuberculosis ward2, Wuhan Pulmonary Hospital, Wuhan, Hubei Province","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hai","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2020-04-09 11:05:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-22154/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-22154/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":921573,"identity":"c6b29d75-4747-49e4-9f80-5e4b4a9f62b3","added_by":"auto","created_at":"2020-04-17 14:48:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":35631,"visible":true,"origin":"","legend":"The course of illness of all patients.","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-22154/v1/Fig1.png"},{"id":921575,"identity":"3ef8756c-89f3-4048-8cc7-20720cffb108","added_by":"auto","created_at":"2020-04-17 14:48:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21119,"visible":true,"origin":"","legend":"NAT results and the corresponding sampling sites of 13 patients.","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-22154/v1/Fig2.png"},{"id":921576,"identity":"6178c8ce-46f1-4250-9198-c61fd710ba41","added_by":"auto","created_at":"2020-04-17 14:48:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2025302,"visible":true,"origin":"","legend":"High-Resolution computed tomographic imaging of case 2 and case 10. \nThe imaging of these two cases showed us that the features of CT imaging were presented as ground glass opacity (GGO), peripheral distribution and bilateral lung involvement. As the disease progressed, the lesions became consolidated, central zone and more lung lobes are involved. Panel A1, A2 and A3 demonstrated an exacerbation process of case 10. Her condition rapidly deteriorated into critically severe type after admission and did not survive eventually. Meanwhile, CT imaging manifested increased range of GGO and consolidation. A typical “white lung” can be seen in Panel A3. CT imaging of case 2 was shown in Panel B1, B2 and B3. In Panel B1, the proportion of lesions were 35%. In the process of pneumonia exacerbation, the proportion climbed up to 90% (shown in Panel B2). The range of lesions decreased to 57.5% (shown in Panel B3) when her condition is relieved.\n\n*number of associated lung lobes\n※CT imaging was unavailable because CT examination was completed before admission in another hospital.\n# CT imaging of case7 and case 8 are absent because their critical condition does not permit a CT scan.","description":"","filename":"3.PNG","url":"https://assets-eu.researchsquare.com/files/rs-22154/v1/3.PNG"},{"id":13499001,"identity":"74d14c9e-b87f-4808-8452-3c64529e64ab","added_by":"auto","created_at":"2021-09-16 23:00:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":460230,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-22154/v1/325881fc-128d-4520-b2b3-7d8e434e6902.pdf"},{"id":921574,"identity":"b45fedc9-2183-4596-9174-3db7fcecc1b8","added_by":"auto","created_at":"2020-04-17 14:48:10","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":13940,"visible":true,"origin":"","legend":"","description":"","filename":"Table2supplementary.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-22154/v1/Table2supplementary.xlsx"},{"id":921572,"identity":"79170647-d7c2-41ec-8742-632d65be65bb","added_by":"auto","created_at":"2020-04-17 14:48:10","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":13037,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-22154/v1/Table1.xlsx"}],"financialInterests":"","formattedTitle":"Research on pneumonia exacerbation in patients infected with SARS-CoV-2 in Wuhan, China","fulltext":[{"header":"Background","content":" \u003cp\u003eSince December 2019, the outbreak of novel coronavirus diseases COVID-19 has exerted profound influence globally. The World Health Organization (WHO) has declared COVID-19 as a pandemic. Up to March 17,2020, a total of 571678 confirmed cases and 26494 deaths were reported\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. The highly pathogenic virus is now named as SARS-CoV-2 (initially as 2019-nCoV)\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Some studies have reported the epidemiological features, clinical characteristics and computed tomography (CT) changes of the SARS-CoV-2 pneumoina\u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The aim of this study is to report the disease exacerbation during hospitalization.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eStudy design and material\u003c/p\u003e\n\u003cp\u003eThis is a retrospective, single \u0026not;center, observational study. Laboratory-confirmed SARS-CoV-2 patients with pneumonia exacerbation after admitted to Wuhan Pulmonary Hospital, Hubei Province, China (a COVID-19-designated hospital in the event of epidemic outbreak) between January 6 and February 17, 2020 and discharged or died before February 25 are included.\u003c/p\u003e\n\u003cp\u003eDiagnosis of SARS-CoV-2 pneumonia were confirmed by viral nucleic acid test (NAT) using high-throughput sequencing or ramplification of open reading frame 1ab (ORF1ab) and nucleocapsid protein (NP) genes fragments from sputum, pharyngeal swab or lower respiratory tract samples as descried in previous study\u003csup\u003e3\u003c/sup\u003e. In this study, sampling site also included urine and stool.\u003c/p\u003e\n\u003cp\u003eNAT-confirmed patients were divided into three types according to the severity grading: 1) moderate: with fever and respiratory symptoms, or with pneumonia performance on imaging. 2) severe: met one of the following criteria: respiratory distress, respiratory rate\u0026gt;=30 times/min; pulse oxygen saturation \u0026lt;93% at rest; oxygenation index (artery partial pressure of oxygen / inspired oxygen fraction (PaO2/FiO2) \u0026le; 300 mmHg; obvious progression of \u0026gt;50% lesion within 24-48 hours as shown on CT. 3) critically severe: met one of the following criteria: respiratory failure and mechanical ventilation required; shock; multi-organ failure required intensive care unit (ICU) care. Disease exacerbation is defined as the escalation of severity grading during the course of disease.\u003c/p\u003e\n\u003cp\u003eWe counted the detection results of ORF1ab and NP genes, respectively. Double-positive is defined as both ORF1ab and NP positive while double-negative is defined as both ORF1ab and NP negative.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData collection\u003c/p\u003e\n\u003cp\u003eWe extracted the age, gender, underlying comorbidities, clinical symptoms, vital signs, laboratory findings on admission and CT during hospitalization. All laboratory testing and examinations are performed according to the clinical care needs of the patient.\u003c/p\u003e\n\u003cp\u003eDefinitions\u003c/p\u003e\n\u003cp\u003eThe course of illness of non-survivor cases was defined as the duration from onset to death. The course of illness of survivor cases was defined as the duration from onset to the sampling date of the second negative NAT of two consecutive NATs before discharge. We adopted this new method of definition to reflect the duration of detectable SARS-CoV-2 RNA as accurate as possible.\u003c/p\u003e\n\u003cp\u003eEarly Admission was defined as hospitalized within 7 days from onset. Late admission was defined as hospitalized after 7 days from onset.\u003c/p\u003e\n\u003cp\u003eLymphopenia was defined as lymphocyte count\u0026lt;0.8*10^9/L. Thrombocytopenia is defined as platelet count \u0026lt; 100*10^9/L. Anemia is defined as hemoglobin \u0026lt; 110g/L. Hyponatremia is defined as serum sodium \u0026lt; 135mmol/L. Hypokalemia is defined as serum potassium \u0026lt; 3.5mmol/L. Hypoalbuminemia is defined as plasma albumin \u0026lt; 35g/L. Elevation or reduction criteria of each laboratory value were listed on Table1.\u003c/p\u003e\n\u003cp\u003eThe survival outcome was defined as survival to hospital discharge.\u003c/p\u003e\n\u003cp\u003eStatistical analysis\u003c/p\u003e\n\u003cp\u003eAll continuous variables were described as mean (standard deviation (SD), range) and categorical variables were defined as number and percentage. SPSS software (version 19) was used for the statistical analysis.\u003c/p\u003e"},{"header":"Results","content":" \u003cp\u003eDemographic data and clinical symptoms\u003c/p\u003e \u003cp\u003eOf the 13 patients, the average age was 65 (SD: 9.81, range: 39\u0026ndash;80) years old. Ten (76.9%) were women and 9 (69.2%) had one or more underlying comorbidities, including hypertension, diabetes, heart disease, chronic kidney disease, hepatic disease, etc. With respect to initial symptoms, fever and cough are most common symptoms (12/13, 92.3%). 1/13 (7.7%) patient had hypodynamia, 4/13 (30.8%) patients had shortness of breath, 3/13 (23.1%) patients had chest distress, 1/13 (7.7%) patient had abdominal pain and diarrhea,1/13 (7.7%) patient had palpitation (shown in Table\u0026nbsp;1). At admission, 7/13(53.8%) patients were diagnosed as moderate pneumonia, 6/13(46.2%) were diagnosed as severe pneumonia. Figure\u0026nbsp;1 shows the course of illness of all patients.\u003c/p\u003e \u003cp\u003eNucleic acid tests\u003c/p\u003e \u003cp\u003eAll NAT results and the corresponding sampling sites of 13 patients are collected and shown on Fig.\u0026nbsp;2. All cases had both double-negative result and double-positive result in different during disease course. NP gene positive with ORF1Ab negative result are shown in four cases (case 6,8,9,13). It is worth noting that two cases (case 2 and 4) tested positive post hospital discharge whereas their two consecutive NAT tests showed double-negative results before discharge.\u003c/p\u003e \u003cp\u003eLaboratory tests\u003c/p\u003e \u003cp\u003eLaboratory values are shown in Table\u0026nbsp;1. 1/13(7.7%) had procalcitonin elevation. 7/13 (53.8%) had elevated D-Dimer. 13/13 (100%) had elevated C-reaction protein. 3/13(23.1%) had leukopenia. 11/13(84.6%) had lymphopenia. Increased neutrophilic granulocyte count and decreased monocyte count are observed in 4/13(30.8%) patients separately. 1/13(7.7%) had thrombocytopenia. 3/13(23.1%) had anemia. 12/13 (92.3%) had elevated lactate dehydrogenase. Elevation of total bilirubin and direct bilirubin are not detected. 2/13(15.4%) had increased glutamic-pyruvic transaminase, 4/13(30.7%) had increased glutamic-oxaloacetic transaminase. 2/13(15.4%) had abnormal creatinine. 8/13(61.5%) decrease of plasma albumin. 5/13(38.5%) presented blood urea nitrogen increase. 3/13(23.1%) had hyponatremia. 3/13(23.1%) had hypokalemia. 2/13(15.4%) had prolonged active partial thromboplastin time. 3/13(23.1%) had cardiac troponin elevation. 6/13(46.2%) had elevated creatine kinase.\u003c/p\u003e \u003cp\u003eImaging examinations\u003c/p\u003e \u003cp\u003eIntact CT imaging of all cases except case 7 and case 8 are available. Features of CT imaging, including location, proportion, numbers of associated lung lobes and manifestation, were shown in the table2-supplementary table. CT imaging of case2 and case10 are shown in Fig.\u0026nbsp;3. Ground-glass opacity in both lungs were characteristically observed on CT (11/11,100%). Peripheral distribution and bilateral sides involvement were observed in 11/11 (100%) and 10/11 (90.9%) patients, respectively. One patient with unilateral abnormality at onset progressed to bilateral in 3 days. As the disease progressed, the lesions became consolidated, and central zone and more lung lobes were involved. Pleural effusion and thickened pleura were detected in 2 different patients.\u003c/p\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003cp\u003eAntiviral drugs and glucocorticoids were given to all patients (13/13, 100%).Antibiotics were given to 12/13 (92.3%) patients. Mechanical ventilation was given to 6/7 (85.7%) critically severe patients.\u003c/p\u003e \u003cp\u003eExacerbations,complications and outcome\u003c/p\u003e \u003cp\u003eSeven cases (case 1,2,3,4,11,12,13) presented as moderate type at admission, among them only case11 progressed to the critically severe type. The other six cases progressed to the severe type. The cases presented as the severe type (case5,6,7,8,9,10) at admission all deteriorated to be critically severe. 10/13(76.9%) patients had their exacerbation in the second week of disease course.\u003c/p\u003e \u003cp\u003eAmong all included cases, 5/13 (38.5%) had ARDS, 3/13 (23.1%) had MODS, 6/13 (46.2%) had respiratory failure, 8/13 (61.5%) had hypoalbuminemia. 42.8% (3/7) early admission cases and 66.6% (4/6) late admission cases developed to critically severe type.\u003c/p\u003e \u003cp\u003eThe majority of critically severe type (case5,6,7,8,10) (5/7,71.4%) did not survive. The overall survival rate is 53.8% (7/13). Mortality rate is 28.6% (2/7) in the early group and 50.0% (3/6) in the late group. Incidence of ARDS is 28.6% (2/7) vs. 50.0% (3/6), MODS 28/6% (2/7) vs. 16.6% (1/6), respiratory failure 33.3% (2/6) vs. 66.6% (4/6), hypoalbuminemia 28.6% (2/7) vs. 100.0% (6/6) respectively.\u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eWe analyzed 13 confirmed cases of SARS-CoV-2 pneumonia patients with disease exacerbation after admission. Exacerbation of SARS-CoV-2 pneumonia does not always but indeed happen (13/120, 10.8%) among inpatients.\u003c/p\u003e \u003cp\u003eReview the age distribution of 13 patients, 11(11/13 85%) had exceeded 60\u0026nbsp;years old. The majority of patients (9/13 69%) had underlying comorbidities, including but limited to hypertension, diabetes, heart disease, chronic kidney disease, hepatic disease. Two patients under 60\u0026nbsp;years of age had obesity, hyperlipidemia (case1), and coronary artery disease, hypertension (case2) separately. Aging and underlying diseases may collaborate and contribute to the decline of host immunity that is the prerequisite of virus infection and disease exacerbation.\u003c/p\u003e \u003cp\u003eIn this study, 10/13(76.9%) cases were female. This ratio seems to be quite contradictory to previous report on COVID-19 that claimed approximately 70% infections occur in male8. and also inconsistent with the proportion of male patients (67%) in severe SARS-CoV-2 pneumonia reported in another study\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Since this study had excluded patients admitted but has not been discharged or died before February 25, the total number and proportion of male patients could be underestimated.\u003c/p\u003e \u003cp\u003eDisease exacerbation mostly occurred in the second week of disease course (10/13, 76.9%). Patients (case 1,4,5,10,11,12,13) admitted early (within 7days) of the disease course had a relatively better prognosis than those (case 2,3,6,7,8,9) admitted later (after the first 7days). The early group demonstrated lower probability of complications and death. These results indicate that early admission is crucial to restrain deterioration and reduce mortality.\u003c/p\u003e \u003cp\u003eThe overall mortality rate was 38.4%(5/13), and in critically severe cases,the mortality rate was 71.4%(5/7), slightly higher than former study\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. These results may be attributed to the fact that the inclusion criteria of this study are different from those of the above studies. These data do not apply to the entire herd of infected patients.\u003c/p\u003e \u003cp\u003eIn our study, fever and cough were the most common symptoms at hospital admission. Initial reports of the COVID-19 virus suggested that symptoms of SAR-CoV-2 pneumonia are similar to that of SARS and MERS, since most patients presenting with fever, cough, fatigue and hypodynamia\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. However, one patient (case12) did not manifest fever during the entire course of disease. This is an 80\u0026nbsp;years old female patient presented to clinic with a complain of chest distress and palpitation. Since she was in the epidemic area, she underwent a CT scan which demonstrated pneumonia. Then nucleic acid test was administrated and this case is confirmed. Besides, patients presented diarrhea as the initial symptom of disease have been reported\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. These extra-pulmonary initial symptoms deserve more attention outside of fever clinic.\u003c/p\u003e \u003cp\u003eElevation of C-reaction protein, D-Dimer and lactate dehydrogenase, reduction of lymphocyte count and albumin are observed in more than half of the cases. Anemia, transaminase abnormality, elevated myocardial index and renal dysfunction are also detected as disease exacerbate. These changes are consistent with previous reports\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGround-glass opacity and consolidation are the main changes in CT imaging. CT manifestations are indicative of the exacerbation of pneumonia. In the process of exacerbation, more lobes were involved, range of GGOs were expanded and density of consolidation was increased. Additional signs on CT imaging include vascular enlargement, interlobular septal thickening in crazy-paving pattern, air bronchogram sign and discrete pulmonary nodules, which were previously reported in some studies\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. CT imaging may serve as a standard method in the rapid diagnosis of COVID-19. Previous studies have reported that the sensitivity of chest CT is significantly greater than that of RT-PCR (98% vs 71%, respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;.001) \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. And false negative rate is very low (3.9%)16. Nevertheless, CT is still incapable of distinguish between different viruses.\u003c/p\u003e \u003cp\u003eNucleic acid RT-PCR testing is a standard test for suspected cases to confirm the SARS-CoV-2 infection. Sampling site plays an important role in virus detection. Case 10 was sampled at 4 sites (pharyngeal swab, urine, venous blood, stool) on the same day, only stool sample demonstrated positive result. The patient\u0026rsquo;s medical records showed severe diarrhea and significant weight loss, which suggests that stool specimen in patients presenting gastrointestinal symptoms is probably more sensitive to the virus than pharyngeal swabs. Controversial NAT results were also observed in case 8 whose sputum and urine sample were taken on the same day. Urine sampling is not of high priority in clinical routine due to lack of sufficient data to support it as a usual shedding route of coronavirus. For different sampling sites, bronchoalveolar lavage fluid exhibited the highest positive rate, followed by sputum, nasal and pharyngeal swabs showing poor positive rate in patients with fever\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Another study reported the detection rates of SARS-CoV-2 from sputum specimens are significantly higher than throat swabs\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. SARS-CoV-2 has the ability to transmit through multiple routes\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e and manifest diverse clinical symptoms which should be taken into account while sampling. We infer that while determine where specimens are collected, considering the location of initial symptoms may increase positive rate.\u003c/p\u003e \u003cp\u003eIn 4 cases (case 6, 8, 9, 13), NAT showed ORF1ab negative and NP positive result. Low viral load might lead to this result since PCR kits currently used in clinical practice are generally more sensitive to the amplification of the N protein gene than ORF1ab. On the other hand, crossovers of other coronaviruses may cause the same result since ORF1ab sequence is more conservative than N protein gene. Patients presented single-positive result should be re-checked by test kits from a different manufacture or different test method.\u003c/p\u003e \u003cp\u003eNAT results has turned out to be controversial in 2 cases(case2,4). After discharge from hospital (20 days for case 2, 14 days for case 4), their NAT result reversed to be positive. It is not clear that whether these patients are still contagious. Virus isolation and antibody test may provide further confirmation. The shedding mode of virus might be relevant to a re-positive result of NAT. Intermittent shedding have been found in Epstein-Barr-virus infected patients\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e and pulsed shedding of viruses in wildlifes\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e have been reported. This may also suggest that SARS-CoV-2 has acquired the ability of chronic infection, as HIV integrates itself into the host's genome by reverse transcription\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e and Hepatitis B virus invades into liver cells and transforms into covalently closed circular DNA\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. But this hypothesis is yet unfounded and requires further investigation.\u003c/p\u003e \u003cp\u003eAll medical treatment administrated in our cases suits clinical demands. The efficacy of antibiotics, antivirals, glucocorticoids is not discussed here since sample size is too small to summarize any conclusion.\u003c/p\u003e \u003cp\u003eThis study has obvious limitations. First, only 13 cases were eventually involved. However, all included cases have intact medical records available to trace back and changes in severity grading over time is recorded in details. Second, due to the diversity of clinical needs, NAT sample site choosing changes in every case and CT examinations not administrated in 2 cases. Third, the course of illness is defined as the time interval between onset and outcome event in this study. Disregarding the incubation period leads to an underestimation of the actual span of disease course. Last but not least, as a retrospective study, recall bias and selection bias inevitably affected our assessment. Further studies on aggravating factors of pneumonia, early identification and prevention methods of exacerbation are needed.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eIn conclusion, our study provides a preliminary sight into the exacerbation of SARS-CoV-2 pneumonia. Disease exacerbation mostly occurs in the second week of disease course. Negative NAT does not exclude exacerbation. CT manifestations may provide evidence of the exacerbation of pneumonia. Early admission appears to have positive effects on reducing complications and mortality.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNAT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enucleic acid test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGGO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eground-glass opacity\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute respiratory distress syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMODS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emultiple organ dysfunction syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOVID-19\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoronavirus disease 2019\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethe World Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRT-PCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ereal-time reverse-transcriptase\u0026ndash;polymerase-chain-reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eORF1ab\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eopen reading frame 1ab\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enucleocapsid protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePaO2/FiO2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eartery partial pressure of oxygen / inspired oxygen fraction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSARS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esevere acute respiratory syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMERS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emiddle east respiratory syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eInformed consent was exempted with the approval of Medical Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China (No. XHEC-D-2020-030).\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research is supported by Zhejiang University special scientific research fund for COVID-19 prevention and control(2020XGZX065) and Shanghai Jiaotong University's Technology Promotion Project 2019(ZT201903).\u003c/p\u003e\n\u003cp\u003eAuthors' contributions\u003c/p\u003e\n\u003cp\u003eGX Chen and X Lan collected the data, C Ji and XP Li accomplished data analysis, Y An, D Zhang and GW Zeng performed imaging processing, YP Tang and L Wang drafted the manuscript and made literature review, L Yang, YY Cai and H Huang designed the study and reviewed the manuscript. \u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eCo-first authors: YP Tang, GX Chen, L Wang, X Lan and C Ji contributed equally to this work.\u003c/p\u003e\n\u003cp\u003eCorrespondence authors: YY Cai, L Yang and H Huang.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e \u003cspan\u003eWorld Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report \u0026ndash; 68. . Accessed 29 Mar 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eZhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727\u0026ndash;33.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eHuang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497\u0026ndash;506.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cdiv class=\"BibBookDOI\"\u003e10.1001/jama.2020.2648\u003c/div\u003e \u003cspan\u003eWu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. Jama. 2020;2019. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eTian S, Hu N, Lou J, Chen K, Kang X, Xiang Z, et al. Characteristics of COVID-19 infection in Beijing. J Infect. 2020; PG-. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eBernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N, et al. Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection. Radiology. 2020;19:200463. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eYang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China. J Infect. 2020;80:388\u0026ndash;93.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eYang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;2600:1\u0026ndash;7.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eChafekar A, Fielding BC. MERS-CoV: Understanding the latest human coronavirus threat. Viruses. 2018;10.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eHui DS-C, Wong P-C, Wang C. SARS: clinical features and diagnosis. Respirology. 2003;8 Suppl:S20-4.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eSong Y, Liu P, Shi XL, Chu YL, Zhang J, Xia J, et al. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut. 2020;:gutjnl-2020-320891. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eZhang J-J, Dong X, Cao Y-Y, Yuan Y-D, Yang Y-B, Yan Y-Q, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eChen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507\u0026ndash;13.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eZhou S, Wang Y, Zhu T, Xia L. CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China. AJR Am J Roentgenol. 2020;October:1\u0026ndash;8. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eLi Y, Xia L. Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management. AJR Am J Roentgenol. 2020;October:1\u0026ndash;7. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eFang Y, Zhang H, Xie J, Lin M, Ying L, Pang P, et al. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology. 2020;2013:200432. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eLiu R, Han H, Liu F, Lv Z, Wu K, Liu Y, et al. Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020. Clin Chim Acta. 2020. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eLin C, Xiang J, Yan M, Li H, Huang S, Shen C. Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2) infected pneumonia (COVID-19). medRxiv. 2020;:2020.02.21.20026187.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eGu J, Han B, Wang J. COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission. Gastroenterology. 2020. doi:.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eChen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395:809\u0026ndash;15.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eNiederman JC, Miller G, Pearson HA, Pagano JS, Dowaliby JM. Infectious mononucleosis. Epstein-Barr-virus shedding in saliva and the oropharynx. N Engl J Med. 1976;294:1355\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eP\u0026aacute;ez DJ, Giles J, McCallum H, Field H, Jordan D, Peel AJ, et al. Conditions affecting the timing and magnitude of Hendra virus shedding across pteropodid bat populations in Australia. Epidemiol Infect. 2017;145:3143\u0026ndash;53.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eMarini B, Kertesz-Farkas A, Ali H, Lucic B, Lisek K, Manganaro L, et al. Nuclear architecture dictates HIV-1 integration site selection. Nature. 2015;521:227\u0026ndash;31.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eAllweiss L, Dandri M. The role of cccDNA in HBV maintenance. Viruses. 2017;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eSchr\u0026ouml;der ARW, Shinn P, Chen H, Berry C, Ecker JR, Bushman F. HIV-1 integration in the human genome favors active genes and local hotspots. Cell. 2002;110:521\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eDue to technical limitations, the tables are only available as a download in the supplemental files section.\u003c/P\u003e "}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"SARS-CoV-2, exacerbation, pneumonia","lastPublishedDoi":"10.21203/rs.3.rs-22154/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-22154/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSARS-CoV-2 pneumonia occasionally exacerbates to critical condition that is hard to manage. We aim to describe exacerbations of SARS-CoV-2 pneumonia among inpatients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe included confirmed SARS-CoV-2 patients with pneumonia exacerbation admitted to Wuhan Pulmonary Hospital, Hubei Province, China between January 6 and February 17, 2020 and discharged or died before February 25. Their demographic characteristics, clinical symptoms, laboratory tests, CT manifestations, complications and clinical outcomes were collected.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 158 patients were collected, among them 107 patients were stable and discharged after recovery, 24 patients were already critically severe at hospital admission. 14 patients were excluded for insufficient clinical data. Eventually, 13 confirmed cases were included. The mean age was 65 (\u0026plusmn;\u0026thinsp;9.81) years. Ten of the 13 (76.9%) patients were female. Nine (69.2%) had underlying comorbidities. Fever and cough were the most common symptoms (12/13, 92.3%). 10/13(76.9%) patients had their exacerbation in the second week of disease course. All patients had both negative and positive nucleic acid test (NAT) results during the course. Increased range of ground-glass opacity (GGO) on CT imaging are consistent to disease exacerbation. ARDS, MODS, respiratory failure were found in 5/13(38.5%), 3/13(23.1%), 6/13(46.2%) patients respectively. Five (38.5%) patients did not survive.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSARS-CoV-2 pneumonia exacerbations often occurs in the second week of disease course. Negative NAT result could not exclude exacerbation. CT manifestation is consistent with disease progression. Early admissions have positive effects on reducing complications and mortality.\u003c/p\u003e","manuscriptTitle":"Research on pneumonia exacerbation in patients infected with SARS-CoV-2 in Wuhan, China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-04-17 14:48:05","doi":"10.21203/rs.3.rs-22154/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b5fdb5f5-befe-45fa-b0eb-35f0f2acbbc1","owner":[],"postedDate":"April 17th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":85058,"name":"Pulmonology"}],"tags":[],"updatedAt":"2020-04-21T17:45:19+00:00","versionOfRecord":[],"versionCreatedAt":"2020-04-17 14:48:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-22154","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-22154","identity":"rs-22154","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}