key: cord-0940807-7y96s3u1 authors: Malik, A. A.; Bhatti, F. S. title: Presence of Mediastinal Lymphadenopathy in Hospitalized Covid-19 Patients in a Tertiary Care Hospital in Pakistan - A cross-sectional study date: 2022-03-14 journal: nan DOI: 10.1101/2022.03.10.22272193 sha: b4ba884a69a435499fd3480e2661bdd4ba416c08 doc_id: 940807 cord_uid: 7y96s3u1 Background The aim of this study was to investigate the presence of mediastinal lymphadenopathy in hospitalized Covid-19 patients in a tertiary care hospital in the metropolitan city of Lahore, Pakistan from September 2020 till July 2021. Methods We retrospectively collected data of Covid-19 patients hospitalized from September 2020 till July 2021. Only those patients who tested PCR positive through a nasopharyngeal swab, were enrolled in the study. Patients whose data were missing were excluded from this study. Our exclusion criteria included patients who tested negative on Covid-19 PCR, patients with comorbidities that may cause enlarged mediastinal lymphadenopathies such as haemophagocytic lymphohistiocytosis, neoplasia, tuberculosis, sarcoidosis or a systemic disease. The extent of lung involvement in Covid-19 patients was quantified by using a 25-point visual quantitative assessment called the Chest Computed Tomography Score. This score was then correlated with the presence of mediastinal lymphadenopathy. Findings Of the 210 hospitalized patients included in the study, 131 (62.4%) had mediastinal lymphadenopathy. The mean and median Severity Score of Covid-19 patients with mediastinal lymphadenopathy (mean: 17.1, SD:5.7; median: 17, IQR: 13-23) were higher as compared to those without mediastinal lymphadenopathy (mean: 12.3, SD:5.4; median: 12, IQR:9-16) Interpretation Our study documents a high prevalence of mediastinal lymphadenopathy in hospitalized patients with Covid-19 with the severity score being higher in its presence representing a more severe course of disease. Our study documents a high prevalence of mediastinal lymphadenopathy in hospitalized patients with Covid-19 with the severity score being higher in its presence representing a more severe course of disease. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 14, 2022 Coronavirus 2) . The main mode of transmission of Covid-19 is through respiratory droplets and via aerosols although transmission can occur through body fluids and from mother to child. Indirect transmission through fomites or contact with objects used on an infected patient can also occur. (4, 5) The clinical features of a Covid-19 infection can range from asymptomatic to mild symptoms of lethargy, fatigue, dry cough and fever to severe symptoms of an acute respiratory distress syndrome. (6) The standard criterion for diagnosing Covid-19 is by a real-time reverse transcriptase polymerase chain reaction through an oropharyngeal or a nasopharyngeal swab. Sensitivity for rRT-PCR ranges from 60-78%. (7, 8) In cases where lung involvement is suspected a non-enhanced high resolution chest CT scan is performed to supplement a Covid-19 diagnosis and to quantify lung involvement. (7, 9) CT imaging can have a sensitivity of up to 90% but it does have a low specificity. It is difficult to distinguish the viral cause of characteristic abnormalities on CT imaging. However, in PCR confirmed cases of Covid-19, CT imaging is an immensely valuable tool to assess the extent of lung involvement.(9, 10) According to recent studies, mediastinal lymphadenopathy is a commonly reported finding in Covid-19 patients (11) (12) (13) although some studies have shown conflicting data as well. (14) Mediastinal lymphadenopathy may be a sign of disease severity. Lymphadenopathy may be attributed to Cytokine Release Syndrome which commonly occurs in critical patients. (14) Currently, the prevalence of mediastinal lymphadenopathy in Covid-19 patients in Pakistan is not known. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) We conducted this retrospective cross-sectional study at a private, tertiary care hospital in the metropolitan city of Lahore, Pakistan. Lahore is Pakistan's second largest city with a population of 11.3 million and is the capital of the province of Punjab. It is home to some of Pakistan's most educated and affluent and is accessible by an international airport with flights from around the world. During the various peaks of the pandemic, Lahore had some of the highest cases of Covid-19 in the country. Our data collection was primarily done at Doctors Hospital & Medical Center, Lahore which is a private hospital where hospital fees are either borne out of pocket or paid for by insurance companies. All non-enhanced high-resolution chest CT Scans were performed using a 128 slice CT Scanner (Toshiba Aquilion) with the following parameters: 120 kV, tube voltage 100-200 mAs, rotation time 0·6 s, pitch 1·35. 1 mm slice thickness, sharp convolution kernel reconstructions with a window width of 1500 HU and a window length -500 HU was performed. All images were obtained using a standard dose scanning protocol. The scanning range was from the apex of the lung to the costophrenic angle. Intravenous contrast was not used for these scans. To the best ability of our technical team and the patient's cooperation to hold his or her breath optimally, the scan was captured in the end-inspiratory phase. The scans were interpreted by in-house qualified radiologists who were blinded to the clinical data. The high resolution non-enhanced CT were carefully reviewed for distinctive features such as ground glass opacification, consolidations, nodules, reticulation, interlobular septal thickening, . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 14, 2022. ; https://doi.org/10.1101/2022.03.10.22272193 doi: medRxiv preprint crazy paving pattern, linear opacities, subpleural curvilinear line, bronchial wall thickening, mediastinal lymphadenopathy, pleural effusion and pericardial effusion. Descriptive analysis was carried out and frequency tables were created to determine distribution of demographic and clinical factors in patients with Covid-19. Prevalence of mediastinal lymphadenopathy was calculated. Chi-square test was used to assess the bivariate association between categorical variables and mediastinal lymphadenopathy. T-test and/or Wilcoxon ranksum test were used to assess the bivariate association between continuous variables and mediastinal lymphadenopathy. All analysis was carried out on Stata (Version 16, StataCorp LP, College Station, TX, USA). This study was approved by the Institutional Review Boards (IRB) of Doctors Hospital & Medical Center, Lahore, Pakistan. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 14, 2022. ; https://doi.org/10.1101/2022.03.10.22272193 doi: medRxiv preprint The final sample size for our study was 210 after excluding 40 patients that did not meet the study criteria. Our study population comprised 72.9% (n=153) males and 27.1% (n=57) females. The overall mean age was 59.9 years (SD: 14.5) with median age being 61 (IQR: 50-71; table 1). The mean creatinine (available for 203 patients) was 1.39 (SD: 1.30) while the median creatinine (table 1) . . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 14, 2022. ; . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 14, 2022 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. in Germany reported lymph node enlargement in around half of their patients with critical disease. The volumetric expansion of lymph nodes may be attributed to a cytokine release syndrome (CRS), a common occurrence in critical patients. (24) Due to the retrospective nature of our study, we were unable to perform longitudinal assessment of non-enhanced high resolution CT scans. We did not follow how the mediastinal lymphadenopathy progressed over time in different patients. Since we didn't have previous CT scans for comparison, we had no way of knowing whether the patients comprising our study population didn't already have mediastinal lymphadenopathy before becoming ill with Covid-19. Smoking is a known contributor of mediastinal lymphadenopathy and data on smoking was not available. Another important consideration is that we did not perform invasive microbiological sampling so coexisting bacterial, fungal and mycobacterial infections could not be ruled out. No biopsies were performed to rule out other causes of mediastinal lymphadenopathy such as malignancies and Sarcoidosis. Lastly, Covid-19 patients with significant findings on nonenhanced high resolution CT chest scans but tested negative on RT-PCR were excluded from our study. More studies need to be carried out to study the presence of mediastinal lymphadenopathy in hospitalized Covid-19 patients as a prognostic factor. In the meantime, clinicians should be more wary about the presence of mediastinal lymphadenopathy and may want to focus on the timely use of steroids, step up to an intensive care setting, non-invasive ventilation, mechanical ventilation, antibiotics for superadded bacterial infection and early use of monoclonal antibodies. To the best of our knowledge this is the first study conducted on hospitalized Covid-19 patients in Pakistan to evaluate the presence of mediastinal lymphadenopathy. All our patients tested . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted March 14, 2022. ; is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 14, 2022. ; https://doi.org/10.1101/2022.03.10.22272193 doi: medRxiv preprint Factors associated with uptake of vaccination against pandemic influenza: a systematic review Covid-19: The first documented coronavirus pandemic in history 100 Years apart: Psychiatric admissions during Spanish flu and Covid-19 pandemic Covid-19 and its Modes of Transmission A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and Covid-19 as a Basis for Controlling the Pandemic Clinical and radiological features of novel coronavirus pneumonia Diagnosing Covid-19 in the Emergency Department: A Scoping Review of Clinical Examinations, Laboratory Tests, Imaging Accuracy, and Biases Real-time RT-PCR for Covid-19 diagnosis: challenges and prospects Covid-19 severity scoring systems in radiological imaging -a review Extrapulmonary manifestations of Covid-19: Radiologic and clinical overview The Clinical and Chest CT Features Associated With Severe and Critical Covid-19 Pneumonia Mediastinal lymphadenopathy in patients with severe Covid-19 Radiological findings from 81 patients with Covid-19 pneumonia in Wuhan, China: a descriptive study Mediastinal lymphadenopathy in Covid-19: A review of literature 2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation Imaging Features of Pediatric Covid-19 on Chest Radiography and Chest CT: A Retrospective, Single-Center Study Overview of chest involvement at computed tomography in children with coronavirus disease 2019 (Covid-19) CT characteristics and diagnostic value of Covid-19 in pregnancy Coronavirus disease 2019 (Covid-19) in Italy: features on chest computed tomography using a structured report system Association of mediastinal lymphadenopathy with Covid-19 prognosis The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia Covid-19 infection: the perspectives on immune responses FSB conceptualized the study and wrote the protocol; FSB and Amyn AM collected data under supervision from Adeel AM; FSB and Amyn AM performed and reviewed the analysis; FSB and Amyn AM wrote the initial draft of the manuscript. All authors helped interpret the findings, read and approved the final version of the manuscript. All other authors declare no conflict of interest.