key: cord-0785863-roiquyvz authors: Gil-Agudo, Angel; Rodriguez-Cola, Miguel; Jimenez-Velasco, Irena; Gutierrez-Henares, Francisco; Lopez-Dolado, Elisa; Gambarrutta-Malfatti, Claudia; Vargas-Baquero, Eduardo title: Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury date: 2020-04-24 journal: nan DOI: 10.1101/2020.04.20.20072918 sha: 5e31c4100255110a24004507b81ee2f039fa4d16 doc_id: 785863 cord_uid: roiquyvz Study design: Cohort study of patients with spinal cord injury (SCI) Objectives: To describe the clinical and analytical features of a Covid-19 infected cohort with SCI to contribute new knowledge for a more accurate diagnosis and to outline prevention measures. Setting: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). Methods: A cohort analysis of seven patients with SCI infected by Covid-19 was carried out. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical and radiographic findings were registered. Results: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (5 out 7). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (6 out of 7). The second most common symptom was asthenia (4 out of 7), followed by dyspnea, cough and expectoration (3 out of 7 for each symptom). The MEWS score for Covid-19 severity rating was classified as severe in 5 out of 7. All but one patient showed radiological alterations evident in chest X-Rays at the time of diagnosis. All patients recovered gradually. Conclusion: Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection. In late December 2019, an epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan 1 4 . Several demographic and clinical factors associated with the more aggressive Covid-19 phenotype have been identified: male gender, age over 60 years and the presence of previous comorbidities such as hypertension, diabetes mellitus, obesity, cardiac ischemic disease, lung disease and immunosuppression 5 . It is reasonable to assume SCI as a high-risk comorbidity, mostly due to the presence of respiratory failure as a result of thoracoabdominal muscle weakness 10 and also because of systemic immunosuppression due to injury 6, 7 . Suppresion of the immune system after SCI is due to noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitaryadrenal axis stimulation 8 and also to autoimmunity 9 . Both phenomena, respiratory failure and injury-induced immunosuppression are more pronounced after cervical or high-thoracic compared with low-thoracic SCI levels, which explains why pneumonia is the leading cause of mortality in SCI patients 11 . As Covid-19 is a novel viral respiratory infection, its epidemiology and clinical course among people with SCI is yet unknown. However, recently the first survey has been published which addresses COVID-19-related practices and adaptations among health care professionals working with individuals with SCI 12 . So far, only one case of Covid 19 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04. 20.20072918 doi: medRxiv preprint infection with SCI has been reported 13 . Considering all the secondary complications associated with SCI, it is reasonable to expect a harsh prognosis with Covid-19 infection. In the present study, the authors aimed to describe the clinical features of the cohort of hospitalized SCI cases with confirmed Covid-19 infection in a monographic hospital in Spain, information which is especially important for a more accurate diagnosis and to prevent future outbreaks. An observational prospective analysis was made of a SCI patient cohort with confirmed Covid-19 infection from March 20 up to April 4, 2020, all of whom had been previously admitted for clinical care at the national SCI monographic hospital in Spain. All of the patients had attended an inpatient treatment regime during the present SARS-CoV2 pandemic. Those patients in whom this infection could not be confirmed were excluded. All participants provided their informed consent. The guidelines of the declaration of Helsinki were followed in every case and the study design was approved by the local Ethics Committee (Hospital Virgen de la Salud, Toledo, Spain, resolution number 504). The following demographic variables were recorded in the cohort: age, sex, SCI aetiology, neurological level and severity, with the last two variables assessed in accordance with the International Standards for Neurological Classification of SCI 14 . The main sources of data were the electronic medical records and clinical reports of each patient. Data were recorded of the history of recent physical contacts made between the confirmed case, the diagnostic time delay until RT-PCR confirmation, symptom and signs assessed at onset and evolution, and the laboratory and chest X-rays. In order to avoid biases and to ensure the patients' data confidentiality, all documents were handled after removing personal or identifying data. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04.20.20072918 doi: medRxiv preprint physical contact exposure was defined as a close contact with a family member, caregiver or healthcare professional diagnosed with Covid-19. Fever was defined as a temperature higher than 37.5ºC. Lymphocytopenia was defined as a lymphocyte count of less than 1500 cells per cubic millimeter (mm 3 ). Thrombocytopenia was defined as a platelet count of less than 150.000/ mm 3 . Pneumonia was defined based on the radiological report by a hospital radiologist, classified either as normal, with consolidation in only one lobe, bilateral multilobular, or with a ground glass pattern. In addition, the presence of atelectasis and or pleural effusion was recorded 15 . Laboratory tests included complete chemical analysis including liver and kidney function assessment, electrolytes, C-reactive protein (PCR), lactate dehydrogenase (LDH), ferritin, and blood count. The Covid-19 severity was defined using the Modified Early Warning System (MEWS) 16 . A nonsevere Covid-19 case was defined by a MEWS score ≤ 2. A severe Covid-19 case was defined by a MEWS score > 2 but <5. A critical Covid-19 case was defined by a MEWS score > 5. In the case of pneumonia, we included the CURB-65 score 17 . Data were expressed as mean or median +/-standard deviation as well as a percentage. As it is a case series with only 7 patients included, further statistical analysis was not performed. As of April 4, 2020, 7 cases of Covid-19 have been confirmed among patients with SCI admitted to the HNP. In two cases with an incubation period of 4 and 9 days respectively, the source of infection was a close contact with their relatives who were also subsequently confirmed with Covid-19. In the other five cases, no clear source of infection was identified. The clinical profile of the cohort is shown in Table 1 . The majority were male (5 out of 7; 71.4%), with an average age of 68 years (interquartile range, 34 to 75). A total of 5 out of 7 patients (71.4%) of the cohort presented with a cervical SCI that was sensorimotor complete AIS A in 4 out of 7 of cases (57.1%). A subacute SCI was present in more than half of the patients (4 out of 7), with less than 3 months time from injury. With respect to the SCI aetiology, 4 of the cases were traumatic, 2 of them were vascular and 1 of them, iatrogenic. A total of 4 of the cases had a tracheostomy, and 2 of them required frequent aspirations to remove respiratory secretions before Covid-19 infection. Four of patients had a history of risk All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. were either current or previous smokers and lung disease had been previously described. The median diagnostic time delay, defined as the time period from the onset of symptoms to confirmed Covid-19 infection with RT-PCR, was 4 days (interquartile range, 1-10), and was less than 6 days in 6 out of 7 (85.7%) of cases. Fever was presented in 6 out of 7 (85.7%) of patients at the time of diagnosis confirmation. The second most common symptom was asthenia (4 out of 7; 57.1%), followed by dyspnea, cough and expectoration (3 out of 7; 42.9% for each symptom). Neurological (2 out of 7; 28.6%) and gastrointestinal (1 out of 7; 14.3%) symptoms were less common. Only 2 of the patients (28.6%) presented one single symptom from onset, while other 2 of cases presented two symptoms and 3 with three or more symptoms. The MEWS score confirmed that Covid-19's infection was severe in 5 out 7 of the patients (71.4%). A total of 3 patients required oxygen therapy, which was always applied at a low flow (less than 3l/minute) to achieve ≥98% oxygen saturation in the capillary oximetry continuous measure. With respect to the radiographic findings, 2 out of 7 of our patients showed no radiological alterations at diagnosis (Fig. 1A) , 3 out of 7 of them presented bilateral multilobular pneumonia (Fig. 1B) , 1 with unilobular pneumonia (Fig. 1C) and another one with a ground glass pattern (Fig. 1D) . Only one case showed pleural effusion (Fig. 1C) . All of the patients have been gradually recovering, although the evolution was slower in the older patients, which were also depended on tracheostomy and suffered a cervical AIS A SCI. No deaths were recorded. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. To the author´s knowledge, this is the first work that describes the clinical profile of Covid-19 in a cohort of SCI patients. The vulnerability of people with SCI is well known [6] [7] [8] [9] [10] [11] . We have found that more than half of our patients showed one or two symptoms at the moment of Covid-19 confirmation, which is lower than the symptomatic expression in other published case series 18 . We hypothesized that the Covid-19 symptoms overlapped with some of the signs of respiratory failure due to SCI, which would have complicated the accurate clinical diagnosis. The average time delay between diagnosis in our case series was shorter than that found in other series, which may reflect rapid early identification of the initial Covid-19 symptoms in a cohort of hospitalized patients who were already receiving close attention for their SCI. At the onset of Covid-19 infection, fever and asthenia were the most frequently observed symptoms, which slightly differed from other published series that identified cough and fever as initial symptoms in the general population [18] [19] [20] . We agree with the previous case Covid 19 SCI in a patient with SCI which reported that cough was not the prevalent symptom 13 . However, despite the less evident symptomatology in our cohort, the MEWS score confirmed that they presented a higher risk of clinical worsening compared to the general population 18 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04. 20.20072918 doi: medRxiv preprint We consider it of vital importance to closely supervise the SCI population to identify early compatible Covid-19 symptoms and signs, as well as to implement follow up measures against infectious diseases contagion. These measures will be especially needed in long-term treatment facilities such as our hospital, where asymptomatic cases could become Covid-19 reservoirs, further complicating the eradication of the current epidemic or future outbreaks. The limitations of this study include the fact that none of the patients admitted to the HNP or their healthcare personnel were interviewed for symptoms of infection or received the SARS-CoV-2 screening test, which therefore may have led to an underestimation of the Covid-19 infection rate in the hospital, especially in those patients who were asymptomatic or who presented mild symptoms. As this is a descriptive case series study, there is no control group, the absence of which is justified given the urgency of pandemic and the lack of previous Covid-19 data among SCI population. Unfortunately, it is likely that our Covid-19 SCI case series will gradually increase until the end of the present pandemic, which will provide us with more clinical data with longer evolution times. In our case series, patients with SCI and confirmed Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, although they presented a similar or greater MEWS severity the clinical evolution of Covid-19 infection was not as pronounced as had been expected. This study recommends close active supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection. Dr. Julian Taylor (JTG) revised the manuscript and reviewed the English version (julian.taylor@jtgconsulting.org). The main sources of data were the electronic medical records and clinical reports of each one of the patients. The history of recent contact with a confirmed case, the diagnosis time delay, the symptom and signs of onset and evolution, the laboratory and chest X-rays were analyzed. In order to avoid biases and ensure the patients' data confidentiality, all documents were handled after removing their filiation data. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research. All participants provided their informed consent. The guidelines of the declaration of Helsinki were followed in every case and the study design was approved by the local ethics committee. Authors declare that were no real or apparent competing financial interests in relation to the work described. MRC was responsible for designing the clinical protocol and collecting clinical and analytical data, conducting the research, analysing data, interpreting results and writing the manuscript. IJV was responsible for designing the clinical protocol and collecting clinical and analytical data. JTG was responsible for content revision and correction of English version AGA was responsible for designing the clinical protocol, reviewing data quality and, conducting the research, analysing data, interpreting results and writing the manuscript. No financial assistance was received in support of the study (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04.20.20072918 doi: medRxiv preprint Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering Johns Hopkins Coronavirus Resource Center Protocolo de actuación frente a casos de infección por el Nuevo Coronavirus (SARS-CoV-2). Ministerio de Sanidad. Gobierno de España Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Multiple organ dysfunction and systemic inflammation after spinal cord injury: a complex relationship Spinal cord injury-induced immune depression syndrome (SCI-IDS) A Review on Response of Immune System in Spinal Cord Injury and Therapeutic Agents useful in Treatment Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies Respiratory management of the spinal cord injured patients Long-term functional outcome in patients with acquired infections after acute spinal cord injury COVID-19 and spinal cord injury and disease: results of an international survey COVID-19 tsunami: the first case of a spinal cord injury patient in Italy American Injury Association: International Standards of Neurological Classification of Spinal Cord Injury Coronavirus Disease 2019 (COVID-19): A Perspective from China Validation of a modified Early Warning Score in medical admissions Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 inChina Covid-19-Navigating the Uncharted Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 4000-10.000 per mm3 -no./total no. (%) was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted