Self-Reported Symptoms of SARS-CoV-2 Infection in a Nonhospitalized Population in Italy: Cross-Sectional Study of the EPICOVID19 Web-Based Survey

Fulvio Adorni, Federica Prinelli, Fabrizio Bianchi, Andrea Giacomelli, Gabriele Pagani, Dario Bernacchia, Stefano Rusconi, Stefania Maggi, Caterina Trevisan, Marianna Noale, Sabrina Molinaro, Luca Bastiani, Loredana Fortunato, Nithiya Jesuthasan, Aleksandra Sojic, Carla Pettenati, Marcello Tavio, Massimo Andreoni, Claudio Mastroianni, Raffaele Antonelli Incalzi, Massimo Galli, Fulvio Adorni, Federica Prinelli, Fabrizio Bianchi, Andrea Giacomelli, Gabriele Pagani, Dario Bernacchia, Stefano Rusconi, Stefania Maggi, Caterina Trevisan, Marianna Noale, Sabrina Molinaro, Luca Bastiani, Loredana Fortunato, Nithiya Jesuthasan, Aleksandra Sojic, Carla Pettenati, Marcello Tavio, Massimo Andreoni, Claudio Mastroianni, Raffaele Antonelli Incalzi, Massimo Galli

Abstract

Background: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce.

Objective: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population.

Methods: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19-like infection in the nontested population.

Results: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection.

Conclusions: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection.

Trial registration: ClinicalTrials.gov NCT04471701; https://ichgcp.net/clinical-trials-registry/NCT04471701.

Keywords: COVID-19; SARS-CoV-2; cross-sectional; nasopharyngeal swab testing; self-reported symptom; voluntary respondents; web-based survey.

Conflict of interest statement

Conflicts of Interest: None declared.

©Fulvio Adorni, Federica Prinelli, Fabrizio Bianchi, Andrea Giacomelli, Gabriele Pagani, Dario Bernacchia, Stefano Rusconi, Stefania Maggi, Caterina Trevisan, Marianna Noale, Sabrina Molinaro, Luca Bastiani, Loredana Fortunato, Nithiya Jesuthasan, Aleksandra Sojic, Carla Pettenati, Marcello Tavio, Massimo Andreoni, Claudio Mastroianni, Raffaele Antonelli Incalzi, Massimo Galli. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 18.09.2020.

Figures

Figure 1
Figure 1
Comparison of the survey response rates and the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per 100,000 inhabitants by Italian region. A: Response rates × 100,000. B: Incidence rates of SARS-CoV-2 × 100,000.
Figure 2
Figure 2
Self-reported symptoms by 171,310 survey respondents. Error bars are ±2*standard error (normal approximation).

References

    1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727–733. doi: 10.1056/nejmoa2001017.
    1. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. World Health Organization. 2020. Mar 11, [2020-04-14]. .
    1. COVID-19 repository, Dipartimento di Protezione Civile. Webpage in Italian. GitHub. [2020-07-14]. .
    1. 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 Feb 24; doi: 10.1001/jama.2020.2648.
    1. Lavezzo E, Franchin E, Ciavarella C, Cuomo-Dannenburg G, Barzon L, Vecchio C. Suppression of COVID-19 outbreak in the municipality of Vo, Italy. medRxiv. 2020 Apr 18; doi: 10.1101/2020.04.17.20053157.
    1. Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection. Ann Intern Med. 2020 Jun 03; doi: 10.7326/m20-3012.
    1. Cohen PA, Hall LE, John JN, Rapoport AB. The Early Natural History of SARS-CoV-2 Infection: Clinical Observations From an Urban, Ambulatory COVID-19 Clinic. Mayo Clin Proc. 2020 Jun;95(6):1124–1126. doi: 10.1016/j.mayocp.2020.04.010.
    1. Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli M. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020 Mar 26;:330. doi: 10.1093/cid/ciaa330.
    1. Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med. 2020 May 11; doi: 10.1038/s41591-020-0916-2.
    1. Wu D, Jha P, Lam T, Brown P, Gelband H, Nagelkerke N. Determinants of self reported symptoms and testing for COVID-19 in Canada using a nationally representative survey. medRxiv. 2020 doi: 10.1101/2020.05.29.20109090.
    1. EPICOVID19: Indagine Epidemiologica Nazionale COVID-19. Istituto di Tecnologie Biomediche, Consiglio Nazionale della Richerche. [2020-07-14].
    1. Global COVID-19: clinical platform: novel coronavius (‎‎COVID-19)‎‎: rapid version. World Health Organization. 2020. [2020-07-14]. .
    1. Case Record Form Instructions Severe Acute Respiratory Infection Clinical Characterisation Data Tools. World Health Organization. 2017. Dec 20, [2020-07-14]. .
    1. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Initial Interview Questionnaire of Cases v2. World Health Organization. 2017. May, [2020-07-14]. .
    1. EUSurvey. [2020-07-14]. .
    1. Popolazione residente al 1° Gennaio. I.Stat. 2019. [2020-07-14]. .
    1. Joint ECDC-WHO/Europe weekly influenza update. Flu News Europe. [2020-07-14]. .
    1. Epidemia COVID-19 Aggiornamento nazionale. Istituto Superiore di Sanità (ISS) 2020. Apr 24, [2020-07-14]. .
    1. Bi Q, Wu Y, Mei S, Ye C, Zou X, Zhang Z, Liu X, Wei L, Truelove S, Zhang T, Gao W, Cheng C, Tang X, Wu X, Wu Y, Sun B, Huang S, Sun Y, Zhang J, Ma T, Lessler J, Feng T. Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study. Lancet Infect Dis. 2020 Apr doi: 10.1016/s1473-3099(20)30287-5.
    1. Oh J, Lee J, Schwarz D, Ratcliffe HL, Markuns JF, Hirschhorn LR. National Response to COVID-19 in the Republic of Korea and Lessons Learned for Other Countries. Health Syst Reform. 2020 Jan 01;6(1):e1753464. doi: 10.1080/23288604.2020.1753464.
    1. Yong SEF, Anderson DE, Wei WE, Pang J, Chia WN, Tan CW, Teoh YL, Rajendram P, Toh MPHS, Poh C, Koh VTJ, Lum J, Suhaimi NM, Chia PY, Chen MI, Vasoo S, Ong B, Leo YS, Wang L, Lee VJM. Connecting clusters of COVID-19: an epidemiological and serological investigation. Lancet Infect Dis. 2020 Jul;20(7):809–815. doi: 10.1016/s1473-3099(20)30273-5.
    1. Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, Holden KA, Read JM, Dondelinger F, Carson G, Merson L, Lee J, Plotkin D, Sigfrid L, Halpin S, Jackson C, Gamble C, Horby PW, Nguyen-Van-Tam JS, Ho A, Russell CD, Dunning J, Openshaw PJ, Baillie JK, Semple MG, ISARIC4C investigators Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020 May 22;369:m1985. doi: 10.1136/bmj.m1985.
    1. Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, Aaron JG, Claassen J, Rabbani LE, Hastie J, Hochman BR, Salazar-Schicchi J, Yip NH, Brodie D, O'Donnell MR. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020 Jun;395(10239):1763–1770. doi: 10.1016/s0140-6736(20)31189-2.
    1. de Lusignan S, Dorward J, Correa A, Jones N, Akinyemi O, Amirthalingam G, Andrews N, Byford R, Dabrera G, Elliot A, Ellis J, Ferreira F, Lopez Bernal J, Okusi C, Ramsay M, Sherlock J, Smith G, Williams J, Howsam G, Zambon M, Joy M, Hobbs Fdr. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Infect Dis. 2020 May;:a. doi: 10.1016/s1473-3099(20)30371-6.
    1. Beltrán‐Corbellini A, Chico-García JL, Martínez-Poles J, Rodríguez-Jorge F, Natera-Villalba E, Gómez-Corral J, Gómez‐López A, Monreal E, Parra‐Díaz J, Cortés‐Cuevas J, Galán C, Fragola‐Arnau C, Porta‐Etessam J, Masjuan J, Alonso‐Cánovas A. Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study. Eur J Neurol. 2020 Apr 22; doi: 10.1111/ene.14273.
    1. Popovic M, Moccia C, Isaevska E, Moirano G, Pizzi C, Zugna D. COVID-19-like symptoms and their relation to SARS-CoV-2 epidemic in children and adults of the Italian birth cohort. Research Sqaure. 2020 Jun 07; doi: 10.21203/-34027/v1.
    1. Denis F, Galmiche S, Dinh A, Fontanet A, Scherpereel A, Benezit F, Lescure F. Epidemiological Observations on the Association Between Anosmia and COVID-19 Infection: Analysis of Data From a Self-Assessment Web Application. J Med Internet Res. 2020 Jun 11;22(6):e19855. doi: 10.2196/19855.
    1. Attems J, Walker L, Jellinger KA. Olfaction and Aging: A Mini-Review. Gerontology. 2015;61(6):485–90. doi: 10.1159/000381619.
    1. Flaxman S, Mishra S, Gandyet A, Unwin H, Coupland H, Mellan T, et al Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries. Imperial College London. 2020 Mar 30; doi: 10.25561/77731. doi: 10.25561/77731.
    1. Bai Y, Yao L, Wei T, Tian F, Jin D, Chen L, Wang M. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406. doi: 10.1001/jama.2020.2565.
    1. Zhou X, Li Y, Li T, Zhang W. Follow-up of asymptomatic patients with SARS-CoV-2 infection. Clin Microbiol Infect. 2020 Jul;26(7):957–959. doi: 10.1016/j.cmi.2020.03.024.
    1. Simons D, Shahab L, Brown J, Perski O. The association of smoking status with SARS-CoV-2 infection, hospitalisation and mortality from COVID-19: A living rapid evidence review (version 4) Qeios. 2020 Jun 11; doi: 10.32388/ujr2aw.5.
    1. Engin AB, Engin ED, Engin A. Two important controversial risk factors in SARS-CoV-2 infection: Obesity and smoking. Environ Toxicol Pharmacol. 2020 Aug;78:103411. doi: 10.1016/j.etap.2020.103411.
    1. Wright KB. Researching Internet-Based Populations: Advantages and Disadvantages of Online Survey Research, Online Questionnaire Authoring Software Packages, and Web Survey Services. J Comput-Mediat Commun. 2006 Jun 23;10(3) doi: 10.1111/j.1083-6101.2005.tb00259.x.
    1. Luo H, Lie Y, Prinzen FW. Surveillance of COVID-19 in the General Population Using an Online Questionnaire: Report From 18,161 Respondents in China. JMIR Public Health Surveill. 2020 Apr 27;6(2):e18576. doi: 10.2196/18576.

Source: PubMed

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