key: cord-0998002-ym81lce9 authors: barasa, s. title: The major predictors of testing positive for COVID-19 among symptomatic hospitalized patients date: 2020-09-13 journal: nan DOI: 10.1101/2020.09.11.20192963 sha: 39a7e95f48bf278597c3f483dd1b24a9ed445e33 doc_id: 998002 cord_uid: ym81lce9 The major predictors of testing positive for COVID-19 among symptomatic hospitalized patients Samson Barasa,1 Amy Ballard,1 Josephine Kiage-Mokaya, 1 Michael Friedlander,1 Geraldine Luna,2 1PeaceHealth Sacred Heart 2University of Illinois at Chicago Introduction: Increasing corona virus disease 2019 (COVID-19) pre-test probability can minimize testing patients who are less likely to have COVID-19 and therefore reducing personal protective equipment and COVID-19 testing kit use. The aim of this study was to identify patients who were likely to test positive for COVID-19 among symptomatic patients suspected of having COVID-19 during hospitalization by comparing COVID-19 positive and negative patients. Method: We conducted a retrospective chart review of patients who were [≥]18 years old and underwent COVID-19 Polymerase chain reaction test because they presented with symptoms thought to be due to COVID-19. A Poisson regression analysis was conducted after clinical presentation, demographic, medical co-morbidities, laboratory and chest image data was retrieved from the medical records. Results: Charts of 277 and 18 COVID-19 negative and positive patients respectively were analyzed. Dyspnea (61%) was the most common symptom among COVID-19 negative patients, while 72% and 61% COVID-19 positive patients had cough and fever respectively. COVID-19 positive patients were more likely to present initially with cough [1.082 (1.022 - 1.145)], fever [1.066 (1.014 - 1.121)] and be 50 to 69 years old [1.094 (1.021 - 1.172)]. Dyspnea, weakness, lymphopenia and bilateral chest image abnormality were not associated with COVID-19 positivity. COVID-19 positive patients were less likely to have non-COVID-19 respiratory viral illness [1.068 (1.019 - 1.119)], human immunodeficiency virus [0.849 (0.765 - 0.943)] and heart failure history [0.093 (0.891 - 0.978)]. Other chronic medical problems (hypertension, diabetes mellitus, chronic obstructive pulmonary disease and coronary artery disease) were not associated with testing positive for COVID-19. Conclusion: Cough, fever and being 50 to 69 years old are better predictors of symptomatic COVID-19 positivity during hospitalization. Despite published studies reporting a high prevalence of lymphopenia among COVID-19 positive patients, lymphopenia is not associated with the risk of testing positive for COVID-19. Key Words: COVID-19, Predictors, Symptomatic, Hospitalized The major predictors of testing positive for COVID-19 among symptomatic hospitalized patients The center for disease control (CDC) has recommended corona virus 2019 (COVID-19) testing for patients who have fever and or respiratory symptoms such as cough and dyspnea among hospitalized patients, healthcare workers and elderly patients, besides those exposed to COVID-19 and those in high prevalence COVID-19 communities 1 . Patients with chronic obstructive pulmonary disease (COPD), 2 asthma 3 or congestive heart failure (CHF) 4 exacerbation can present with cough and dyspnea; while patients with bacterial pneumonia, non-COVID-19 viral pneumonia, bronchitis or upper respiratory tract infections 5 can present with fever besides cough and dyspnea. The initial COVID-19 publication from Mainland, China found that 83 % COVID-19 positive patients had lymphopenia and 58.3% had bilateral chest image abnormality. 6 Subsequent studies have also reported a high lymphopenia prevalence among COVID-19 positive patients. 7, 8 However, these published studies did not compare the prevalence of lymphopenia and or bilateral chest image abnormality among COVID-19 positive and negative patients presenting with cough, dyspnea and or fever in the hospital. Our study sought to determine whether lymphopenia and or bilateral chest image abnormality in association with cough, dyspnea, fever or weakness increased the risk of testing positive for COVID-19. Increasing the COVID-19 pre-test probability will minimize testing patients who are less likely to have COVID-19 and therefore reducing personal protective equipment (PPE) and COVID-19 testing kit use. In addition, increasing the pre-test probability will further increase the positive predictive value of COVID-19 polymerase chain reaction (PCR) tests. A retrospective chart review of patients who were tested for COVID-19 using the PCR test after presenting in the hospital with symptoms thought to be due to COVID-19, between 2 nd February 2020 and 2 nd June 2020 was conducted in Eugene, Oregon. The study enrollees were 18 years and older. The PeaceHealth institutional review board (IRB) approved the study and waived the written informed consent requirement. The Microsoft Access software was used to manage data after being extracted from the electronic medical records. Data was obtained from documents, laboratory tests and chest images completed when the patient initially arrived in the hospital. Information on whether the patient had cough, fever, dyspnea, fatigue or weakness was retrieved from the hospital triage note. Lymphopenia data was gathered from the complete blood count results, while bilateral chest image abnormality was determined by reviewing the radiologist's chest image report. The non-COVID-19 respiratory viral illness data was collected from the respiratory viral panel results. The following risk factors were also examined: age, diabetes mellitus, stroke, dementia, CHF, COPD, asthma, systemic lupus erythromatosus (SLE), organ transplant, coronary artery disease (CAD), smoking, hypertension and body mass index (BMI. The study outcome was the COVID-19 PCR test result. Our study hypothesized that COVID-19 positive patients were more likely to have lymphopenia and or bilateral chest image abnormality in association with cough, fever, dyspnea or weakness compared to COVID-19 negative patients. The Generalized Poisson regression analysis was used to determine whether COVID-19 positive patients were more likely to have bilateral chest image abnormality, lymphopenia, cough, fever, dyspnea or weakness adjusting for non-COVID-19 respiratory viral illness, history of smoking, asthma, diabetes mellitus, chronic kidney disease, SLE, COPD, CHF, hypertension and BMI. The statistical analysis was performed using STATA version 15. 0 (0) 0 (0) InfluenzaAH1 0 (0) 1 (0.40 ) InfluenzaA2009H1N1 0 (0) 3 (1.19) InfluenzaAH3 0 (0) 0 (0) Parainfluenza1 0 (0) 3 (1.19) Parainfluenza2 0 (0) 0 (0) Parainfluenza3 0 (0) 0 (0) Parainfluenza4 0 (0) 1 (0.40) Coronavirus229E 0 (0) 1 (0.4) CoronavirusNL63 0 (0) 0 (0) CoronavirusOC43 0 (0) 0 (0) CoronavirusHKU1 0 (0) 4 (1. The median age and the interquartile age range for COVID-19 positive and negative patients was not significantly different, although the age range of COVID-19 positive patients was 47 -85 years, while the age range of COVID-19 negative patients was 23 to 96 years. Most COVID-19 positive enrollees were males (72%) compared to the equal gender distribution among the COVID-19 negative enrollees. The prevalence of medical comorbidities among COVID-19 positive and negative patients was not significantly different apart from CHF. None of the COVID-19 positive patients had prior history of CHF, while 18% COVID-19 negative patients had prior history of CHF. Hypertension was the most common medical comorbidity among COVID-19 positive (44%) and negative (54%) patients. Similarly, diabetes mellitus was the second most common chronic medical problem among COVID-19 positive and negative enrollees. On the other hand, 5.6% COVID-19 positive patients had history of COPD compared to 24% among COVID-19 negative patients. None of the COVID-19 positive patients were current smokers, while 18% COVID-19 negative patients were current smokers. 62.5 % and 42.3 % COVID-19 positive and negative patients respectively were never smokers. . CC-BY-NC-ND 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) preprint The copyright holder for this this version posted September 13, 2020. . https://doi.org/10.1101/2020.09.11.20192963 doi: medRxiv preprint Figure 1 below shows the prevalence of the initial clinical features for COVID-19 positive and negative patients during hospitalization. COVID-19 positive patients had a significantly higher prevalence of cough compared to the COVID-19 negative patients. Cough (72%) was the most common symptom followed by fever (61%) and dyspnea (50%) among COVID-19 positive patients. Dyspnea (61.4%) was the most common symptom among COVID-19 negative patients. 61% COVID-19 positive patients had bilateral chest image abnormality compared to 33% COVID-19 negative patients. The prevalence of lymphopenia among COVID-19 positive (33%) and negative (38%) patients was not significantly different. Table 2 below shows the association between COVID-19 status and coughing. COVID-19 positive patients were more likely to present with cough, be 50 to 69 years old and not have non-COVID-19 respiratory viral illness. Moreover, lymphopenia was not associated with COVID-19 positivity. On the other hand, COVID-19 positive patients were less likely to have history of CHF or HIV. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted September 13, 2020. As indicated in Table 4 below, COVID-19 positive patients were more likely to have fever. Besides that, COVID-19 positive patients were more likely to be 50 to 69 years old and less likely to have history of CHF, organ transplant or HIV. Lymphopenia was not associated with COVID-19 status. . CC-BY-NC-ND 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) preprint The copyright holder for this this version posted September 13, 2020. . https://doi.org/10.1101/2020.09.11.20192963 doi: medRxiv preprint The bilateral chest image analysis (Table 5) demonstrated that COVID-19 status was not associated with bilateral chest image abnormality and reaffirmed that COVID-19 positive patients were less likely to have non-COVID-19 respiratory viral illness, history of CHF or HIV. We found that COVID-19 positive patients were more likely to initially present with cough, fever and be 50 to 70 years old during hospitalization. Furthermore, COVID-19 positivity was not associated with dyspnea, weakness or bilateral chest image abnormality. Despite published studies reporting a high prevalence of lymphopenia among COVID-19 positive patients, 6,7,8 COVID-19 negative patients too had a high prevalence of lymphopenia. Lymphopenia was not associated with an increased risk of testing positive for COVID-19. Medical comorbidities such as diabetes mellitus, hypertension, coronary artery disease, COPD and SLE didn't increase the risk of testing positive for COVID-19. However, COVID-19 positive patients were less likely to present with non-COVID-19 respiratory viral illness and have CHF, HIV or history of organ transplant. . CC-BY-NC-ND 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 this version posted September 13, 2020. . The initial COVID-19 published (Mainland, China; 6 New York, USA; 9 and Seattle, USA 8 ) studies identified the characteristics of COVID-19 positive patients. However, these studies and subsequent studies 10, 11 didn't compare patients who tested positive and negative for COVID-19 among patients who presented in the hospital with symptoms thought to be due to COVID-19. Our study compared the initial clinical presentation of patients who tested positive and negative for COVID-19 among patients who presented in the hospital with symptoms suspected to be due to COVID-19. Although the individualized risk prediction study compared COVID-19 positive and negative patients, it was conducted in Cleveland clinics, included drive-thru sites and didn't report on chest image abnormality or lymphopenia; 12 moreover, COVID-19 positive patients in the Cleveland clinics Ohio development cohort (sample 818) had a very low prevalence of cough (15%), fever (13%) and dyspnea (8%) among COVID-19 positive patients. 12 In contrast, the hospitalized COVID-19 positive patients in our study, the Seattle study, the New York study and the Mainland China study had a high prevalence of cough, fever and dyspnea. 6, 8, 9 COVID-19 positive patients in our study had comparable demographic and baseline characteristics to the New York study (with 5700 enrollees) at the epicenter of the COVID-19 pandemic in USA. 9 On the other hand, the mainland China study (with 1099 enrollees) had younger patients with a low prevalence of medical comorbidities. 6 The interquartile range of COVID-19 positive patients was between 54 and 70 years, while the median age was 60.5 years in our study. Similarly, COVID-19 positive patients in the New York study had an interquartile range of 52-75 years and a median age of 63 years. 9 In contrast, patients in the Mainland, China study were younger with a median age of 47 years and an interquartile range of 35 to 58 years. 6 Our study found that COVID-19 positive patients were more likely to be 50 to 69 years old. In congruence, the Cleveland study found that COVID-19 positivity risk increased with age. 12 72% of COVID-19 positive patients in our study and approximately 60% COVID-19 positive patients in the New York and China studies were males. 6, 9 Gender was not associated with COVID-19 status in our study, however the Cleveland study with an equal gender distribution, found that men had an increased risk of being COVID-19 positive. 12 Our study found that medical comorbidities were not associated with an increased risk of testing positive for COVID-19. The prevalence of medical comorbidities in our study and the New York study was comparable. 9 The medical comorbidities examined in our study among COVID-19 patients were: hypertension 44.4%, diabetes mellitus 27.8%, CAD 11.1%, COPD 5.6%, CKD 11.1%, asthma 11.1% and BMI (≥ 30) 53.3%. While the prevalence of medical comorbidities analyzed in the New York study was: hypertension 56.6%, diabetes mellitus 33.8%, CAD 11.1%, COPD 5.4%, CKD 5%, asthma 9% and BMI (≥ 30 ) 41.7%. 9 The Mainland, China study reported a lower prevalence of medical comorbidities, namely: hypertension (15%), diabetes mellitus (7.4%), CAD (2.5%), COPD (1.1%) and CKD (0.7%). 6 The China study didn't publish asthma or BMI data. 6 The China publication and our study found a stroke prevalence of 1.4% and 11.1% respectively among COVID-19 positive patients, while the New York study didn't report on stroke prevalence. 6, 9 The prevalence of CHF, HIV and organ transplant among COVID-19 positive patients in the New York study was 6.9%, 0.8% and 1 % respectively; 9 while none of the COVID-19 positive patients in our study had these medical comorbidities. Moreover, our study found that COVID-19 positive patients were less likely to have CHF, HIV and Organ transplant. Similarly, COVID-19 positive patients were less likely to have non-COVID-19 respiratory viral illness in our study. The prevalence of non-COVD-19 respiratory viral illness was 0% in our study, while in the New York study it was 2.1%. 9 The mainland, China study didn't report the prevalence of non-COVID-19 respiratory viral illness. 6 67%, 43.8%, 18.7% and 38.1% COVID-19 positive patients initially presented with cough, confirmed fever (≥37.5 o C), dyspnea and fatigue respectively in the Mainland, China study. 6 While 30.7% COVID-19 positive patients had confirmed fever (>38 o C) in the New York study; however this New York study didn't report the prevalence of cough, subjective fever, dyspnea, weakness or fatigue. 9 A study of 393 COVID-19 positive patients conducted in two New York hospitals, with comparable prevalence of medical comorbidities to the aforementioned (larger) New York study and our study, found that the initial COVID-19 positive patients' symptoms on presentation were cough (79.4%), subjective fever (77.1%) and dyspnea (56.5%), while 25.5% had confirmed fever ( >38 o C) on hospital arrival. 10 Other studies also found that cough was the most common initial COVID-19 presenting symptom. 8, 12, 11 In our study 72%, 61%, 50% and 33% COVID-19 positive patients had cough, subjective fever, dyspnea and fatigue respectively. Cough was the most common initial symptom among hospitalized COVID-19 patients followed with fever. COVID-19 positive patients were more likely to have cough or fever in our study while dyspnea and weakness were not associated with COVID-19 positivity. 36.5% of all hospitalized COVID-19 positive patients and 58.3% of those with severe COVID-19 disease had bilateral chest image abnormality during hospital admission in Mainland, China. 6 On the other hand, the New York study didn't publish data on chest image abnormality. 9 However, the New York study with 393 COVID-19 positive enrollees found that 59.8% enrollees had bilateral chest image abnormality during hospital admission. 10 61.1% COVID-19 positive patients in our study had bilateral chest image abnormality; however COVID-19 status was not associated with bilateral chest image abnormality. 83% COVID-19 positive patients in the Mainland, China study had a lymphopenia of ≤ 1500 compared to 66.67% in our study. 6 The New York study and our study found that 60% and 44.44% COVID-19 positive patients respectively had a lymphopenia of ≤ 1000. 9 The prevalence of lymphopenia was not significantly different between COVID-19 positive and negative patients in our study. Furthermore, lymphopenia was not associated with COVID-19 positivity. . CC-BY-NC-ND 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) preprint The copyright holder for this this version posted September 13, 2020. . https://doi.org/10.1101/2020.09.11.20192963 doi: medRxiv preprint Limitations of our study included missing data and not all patients had laboratory and chest image tests done. Non-COVID-19 respiratory viral illness data was missing for some patients, because the hospital stopped testing for non-COVID-19 respiratory viral illness in the middle of the pandemic. In addition, we didn't have data on how long those with history of smoking had quit smoking as well as whether their presenting cough symptom was new, an exacerbation or their baseline smokers' cough. Based on this study, cough, fever and being 50 to 69 years old are better predictors of testing positive for COVID-19 among patients presenting in the hospital with symptoms suspected to be due to COVID-19. Moreover, bilateral chest image abnormality is not associated with COVID-19 status. The findings of this study also suggest that COVID-19 positive patients are less likely to have non-COVID-19 respiratory viral illness, HIV or CHF. Despite published studies reporting a high prevalence of lymphopenia among COVID-19 positive patients, the prevalence of lymphopenia among COVID-19 positive and negative patients is not significantly different. Lastly, non-lymphopenic patients and those without medical comorbidities are not at a lower risk of testing positive for COVID-19. . CC-BY-NC-ND 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) preprint The copyright holder for this this version posted September 13, 2020. . https://doi.org/10.1101/2020.09.11.20192963 doi: medRxiv preprint Supplementary 1 Table 6 . CC-BY-NC-ND 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) preprint The copyright holder for this this version posted September 13, 2020. . https://doi.org/10.1101/2020.09.11.20192963 doi: medRxiv preprint CDC. Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19 Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications. 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