Clinical trial NCT05967039: Assessment of Functional Capacity in Long-COVID
Official title: Evaluation of Lung Function, Lung Ultrasound and Functional Capacity in Long-COVID Patients Who Underwent Physical Therapy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Post-COVID-19 Syndrome
Long COVID
Keywords: Functional capacity;
Six-minute walk test;
Spirometry;
Oscillometry;
Lung Ultrasound;
Ventilometry;
Lead sponsor: Centro Universitário Augusto Motta
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with long-COVID-19 syndrome

Brief summary: A paucity of prognostic studies in patients with post-COVID-19 syndrome (long-COVID) shows the need to identify the main effects on functional capacity in the short and medium term. In this regard, the evaluation of lung function, lung structure and functional capacity in long-COVID patients is essential to estimate the impact of the disease. This retrospective observational study aims to compare functional capacity, lung function, and lung ultrasound findings in patients who underwent physical therapy to those who did not.

Detailed description: Introduction: The pandemic caused by the Severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) has been presented as a one of the greatest health challenges on a global scale at the beginning of this millennium. Many patients need physical therapy in their recovery process. A paucity of prognostic studies in patients with long-COVID shows the need to identify the main repercussions on functional capacity in the short and medium term. In this regard, the evaluation of lung function, lung structure and functional capacity in long-COVID patients is essential to estimate the impact of the disease.

Objective: The present study aims to compare functional capacity, lung function, and lung ultrasound findings between patients diagnosed with long-COVID who underwent physical therapy to those who did not.

Methods: This is a retrospective observational study with quantitative data analysis. The study will be carried out at the Pulmonary Function Laboratory of the Policlínica Universitária Piquet Carneiro, from the State University of Rio de Janeiro. First, a clinical evaluation will be performed. In the survey, it will be asked whether the patient had undergone physical therapy treatment, so they can be allocated in the control or intervention group. After that, they will answer to the Post-COVID-19 Functional Status Scale (PCFS), a tool to measure functional status over time after COVID-19. Then, patients will have their lung function evaluated through spirometry and impulse oscillometry (IOS). In addition, lung ultrasound (LUS) images will be analyzed. And their functional capacity will be assessed using the six-minute walk test (6MWT) coupled to pulmonary ventilation measurement using Spiropalm® (Spiropalm 6MWT, Cosmed, Rome, Italy).

It is expected that understanding the consequences of long-COVID on pulmonary ventilation can help to design therapeutic strategies in rehabilitation services.

Eligibility criteria: Inclusion Criteria:

Individuals with an established diagnosis of COVID-19 (RT-PCR) who required hospitalization or not, regardless of whether or not they were treated in the ICU.

Exclusion Criteria:

Patients unable to perform the tests. Patients with musculoskeletal disorders not associated with COVID-19. Patients with lung, heart or cerebrovascular diseases not associated with COVID-19.

Primary outcomes:
measure: Six-minute walk test coupled into the measurement of pulmonary ventilation
timeFrame: October 2023
Secondary outcomes:
measure: Impulse oscillometry
timeFrame: October 2023
measure: Spirometry
timeFrame: October 2023
measure: Lung ultrasound
timeFrame: October 2023
measure: Functional Status scale PCFS
timeFrame: October 2023
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Agnaldo José Lopes
city: Rio De Janeiro
country: Brazil
facility: Centro Universitario Augusto Motta
Study officials:
References:
citation: Ahmad FB, Cisewski JA, Minino A, Anderson RN. Provisional Mortality Data - United States, 2020. MMWR Morb Mortal Wkly Rep. 2021 Apr 9;70(14):519-522. doi: 10.15585/mmwr.mm7014e1.
citation: Al-Ani F, Chehade S, Lazo-Langner A. Thrombosis risk associated with COVID-19 infection. A scoping review. Thromb Res. 2020 Aug;192:152-160. doi: 10.1016/j.thromres.2020.05.039. Epub 2020 May 27.
citation: Albuquerque CG, Andrade FM, Rocha MA, Oliveira AF, Ladosky W, Victor EG, Rizzo JA. Determining respiratory system resistance and reactance by impulse oscillometry in obese individuals. J Bras Pneumol. 2015 Sep-Oct;41(5):422-6. doi: 10.1590/S1806-37132015000004517.
citation: American Thoracic Society; American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003 Jan 15;167(2):211-77. doi: 10.1164/rccm.167.2.211. No abstract available.
citation: Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med. 2020 Apr;26(4):450-452. doi: 10.1038/s41591-020-0820-9. No abstract available.
citation: Bahl P, Doolan C, de Silva C, Chughtai AA, Bourouiba L, MacIntyre CR. Airborne or Droplet Precautions for Health Workers Treating Coronavirus Disease 2019? J Infect Dis. 2022 May 4;225(9):1561-1568. doi: 10.1093/infdis/jiaa189.
citation: Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020 May-Jun;14(3):247-250. doi: 10.1016/j.dsx.2020.03.013. Epub 2020 Mar 25.
citation: Barker-Davies RM, O'Sullivan O, Senaratne KPP, Baker P, Cranley M, Dharm-Datta S, Ellis H, Goodall D, Gough M, Lewis S, Norman J, Papadopoulou T, Roscoe D, Sherwood D, Turner P, Walker T, Mistlin A, Phillip R, Nicol AM, Bennett AN, Bahadur S. The Stanford Hall consensus statement for post-COVID-19 rehabilitation. Br J Sports Med. 2020 Aug;54(16):949-959. doi: 10.1136/bjsports-2020-102596. Epub 2020 May 31.
citation: Beraldo GL, Fonseca EKUN, Yokoo P, Matos MJR, Rosa MEE, Silva MMA, Chate RC, Shoji H, Ishikawa WY. Novel coronavirus pneumonia and acute pulmonary thromboembolism: casualty or causality? Einstein (Sao Paulo). 2020 Jun 3;18:eAI5750. doi: 10.31744/einstein_journal/2020AI5750. eCollection 2020. No abstract available.
citation: Berger KI, Reibman J, Oppenheimer BW, Vlahos I, Harrison D, Goldring RM. Lessons from the World Trade Center disaster: airway disease presenting as restrictive dysfunction. Chest. 2013 Jul;144(1):249-257. doi: 10.1378/chest.12-1411.
citation: Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, Greninger AL, Pipavath S, Wurfel MM, Evans L, Kritek PA, West TE, Luks A, Gerbino A, Dale CR, Goldman JD, O'Mahony S, Mikacenic C. Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020 May 21;382(21):2012-2022. doi: 10.1056/NEJMoa2004500. Epub 2020 Mar 30.
citation: Biryukov J, Boydston JA, Dunning RA, Yeager JJ, Wood S, Ferris A, Miller D, Weaver W, Zeitouni NE, Freeburger D, Dabisch P, Wahl V, Hevey MC, Altamura LA. SARS-CoV-2 is rapidly inactivated at high temperature. Environ Chem Lett. 2021;19(2):1773-1777. doi: 10.1007/s10311-021-01187-x. Epub 2021 Feb 3.
citation: Buonsenso D, Sali M, Pata D, De Rose C, Sanguinetti M, Valentini P, Delogu G. Children and COVID-19: Microbiological and immunological insights. Pediatr Pulmonol. 2020 Oct;55(10):2547-2555. doi: 10.1002/ppul.24978. Epub 2020 Jul 30.
citation: Butzko RP, Sotolongo AM, Helmer DA, Klein-Adams JC, Osinubi OY, Berman AR, Ortiz-Pacheco R, Falvo MJ. Forced oscillation technique in veterans with preserved spirometry and chronic respiratory symptoms. Respir Physiol Neurobiol. 2019 Feb;260:8-16. doi: 10.1016/j.resp.2018.11.012. Epub 2018 Nov 30.
citation: Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.
citation: Chan JF, To KK, Tse H, Jin DY, Yuen KY. Interspecies transmission and emergence of novel viruses: lessons from bats and birds. Trends Microbiol. 2013 Oct;21(10):544-55. doi: 10.1016/j.tim.2013.05.005. Epub 2013 Jun 14.
citation: Colavita F, Lapa D, Carletti F, Lalle E, Bordi L, Marsella P, Nicastri E, Bevilacqua N, Giancola ML, Corpolongo A, Ippolito G, Capobianchi MR, Castilletti C. SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19 in Italy With Prolonged Viral RNA Detection. Ann Intern Med. 2020 Aug 4;173(3):242-243. doi: 10.7326/M20-1176. Epub 2020 Apr 17. No abstract available.
citation: Costa IBSDS, Bittar CS, Rizk SI, Araujo Filho AE, Santos KAQ, Machado TIV, Andrade FTA, Gonzalez TB, Arevalo ANG, Almeida JP, Bacal F, Oliveira GMM, Lacerda MVG, Barberato SH, Chagas ACP, Rochitte CE, Ramires JAF, Kalil Filho R, Hajjar LA. The Heart and COVID-19: What Cardiologists Need to Know. Arq Bras Cardiol. 2020 May 11;114(5):805-816. doi: 10.36660/abc.20200279. English, Portuguese.
citation: Demeco A, Marotta N, Barletta M, Pino I, Marinaro C, Petraroli A, Moggio L, Ammendolia A. Rehabilitation of patients post-COVID-19 infection: a literature review. J Int Med Res. 2020 Aug;48(8):300060520948382. doi: 10.1177/0300060520948382.
citation: Enright PL, Sherrill DL. Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1384-7. doi: 10.1164/ajrccm.158.5.9710086.
citation: Gonzalez J, Zuil M, Benitez ID, de Gonzalo-Calvo D, Aguilar M, Santisteve S, Vaca R, Minguez O, Seck F, Torres G, de Batlle J, Gomez S, Barril S, Moncusi-Moix A, Monge A, Gort-Paniello C, Ferrer R, Ceccato A, Fernandez L, Motos A, Riera J, Menendez R, Garcia-Gasulla D, Penuelas O, Labarca G, Caballero J, Barbera C, Torres A, Barbe F. One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients. Front Med (Lausanne). 2022 Jul 14;9:897990. doi: 10.3389/fmed.2022.897990. eCollection 2022.
citation: Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 May 1;171(9):972-7. doi: 10.1164/rccm.200407-855OC. Epub 2005 Jan 21.
citation: Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, Oropez CE, Rosenfeld M, Stanojevic S, Swanney MP, Thompson BR. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019 Oct 15;200(8):e70-e88. doi: 10.1164/rccm.201908-1590ST.
citation: Guler MA, Guler K, Guneser Gulec M, Ozdoglar E. Working From Home During a Pandemic: Investigation of the Impact of COVID-19 on Employee Health and Productivity. J Occup Environ Med. 2021 Sep 1;63(9):731-741. doi: 10.1097/JOM.0000000000002277.
citation: Hui DS, Wong KT, Ko FW, Tam LS, Chan DP, Woo J, Sung JJ. The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors. Chest. 2005 Oct;128(4):2247-61. doi: 10.1378/chest.128.4.2247.
citation: Hussain A, Baleanu D, Adeel M. Existence of solution and stability for the fractional order novel coronavirus (nCoV-2019) model. Adv Differ Equ. 2020;2020(1):384. doi: 10.1186/s13662-020-02845-0. Epub 2020 Jul 25.
citation: Ianniello S, Di Giacomo V, Sessa B, Miele V. First-line sonographic diagnosis of pneumothorax in major trauma: accuracy of e-FAST and comparison with multidetector computed tomography. Radiol Med. 2014 Sep;119(9):674-80. doi: 10.1007/s11547-014-0384-1. Epub 2014 Jan 28.
citation: van Kampen JJA, van de Vijver DAMC, Fraaij PLA, Haagmans BL, Lamers MM, Okba N, van den Akker JPC, Endeman H, Gommers DAMPJ, Cornelissen JJ, Hoek RAS, van der Eerden MM, Hesselink DA, Metselaar HJ, Verbon A, de Steenwinkel JEM, Aron GI, van Gorp ECM, van Boheemen S, Voermans JC, Boucher CAB, Molenkamp R, Koopmans MPG, Geurtsvankessel C, van der Eijk AA. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat Commun. 2021 Jan 11;12(1):267. doi: 10.1038/s41467-020-20568-4.
citation: Kang N, Shin SH, Gu S, Kang D, Cho J, Jeong HJ, Suh GY, Lee H, Park HY. The impact of low forced vital capacity on behavior restrictions in a population with airflow obstruction. J Thorac Dis. 2019 Apr;11(4):1316-1324. doi: 10.21037/jtd.2019.03.77.
citation: Kanne JP, Little BP, Chung JH, Elicker BM, Ketai LH. Essentials for Radiologists on COVID-19: An Update-Radiology Scientific Expert Panel. Radiology. 2020 Aug;296(2):E113-E114. doi: 10.1148/radiol.2020200527. Epub 2020 Feb 27. No abstract available.
citation: Lopes AJ, de Menezes SL, Dias CM, de Oliveira JF, Mainenti MR, Guimaraes FS. Comparison between cardiopulmonary exercise testing parameters and computed tomography findings in patients with thoracic sarcoidosis. Lung. 2011 Oct;189(5):425-31. doi: 10.1007/s00408-011-9316-1. Epub 2011 Aug 20.
citation: Lopes AJ, Mafort TT, da Cal MS, Monnerat LB, Litrento PF, Ramos I, de Oliveira RFJ, da Costa CH, Rufino R. Impulse Oscillometry Findings and Their Associations With Lung Ultrasound Signs in COVID-19 Survivors. Respir Care. 2021 Nov;66(11):1691-1698. doi: 10.4187/respcare.09193. Epub 2021 Sep 7.
citation: Lutchmansingh DD, Knauert MP, Antin-Ozerkis DE, Chupp G, Cohn L, Dela Cruz CS, Ferrante LE, Herzog EL, Koff J, Rochester CL, Ryu C, Singh I, Tickoo M, Winks V, Gulati M, Possick JD. A Clinic Blueprint for Post-Coronavirus Disease 2019 RECOVERY: Learning From the Past, Looking to the Future. Chest. 2021 Mar;159(3):949-958. doi: 10.1016/j.chest.2020.10.067. Epub 2020 Nov 4.
citation: Mafort TT, Rufino R, da Costa CH, da Cal MS, Monnerat LB, Litrento PF, Parra LLZ, Marinho ASES, Lopes AJ. One-month outcomes of patients with SARS-CoV-2 infection and their relationships with lung ultrasound signs. Ultrasound J. 2021 Apr 9;13(1):19. doi: 10.1186/s13089-021-00223-9.
citation: Mitchell JH, Levine BD, McGuire DK. The Dallas Bed Rest and Training Study: Revisited After 50 Years. Circulation. 2019 Oct 15;140(16):1293-1295. doi: 10.1161/CIRCULATIONAHA.119.041046. Epub 2019 Oct 14. No abstract available.
citation: NEWS MEDICAL. Spiropalm Handheld Spirometer from COSMED. Medical Devices, Spirometers, 2022. Disponível em: <https://www.news- medical.net/Spiropalm-Handheld-Spirometer-from-COSMED>. Acesso em 10 de novembro de 2022
citation: Ngai JC, Ko FW, Ng SS, To KW, Tong M, Hui DS. The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology. 2010 Apr;15(3):543-50. doi: 10.1111/j.1440-1843.2010.01720.x. Epub 2010 Mar 19.
citation: Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA. 2020 May 12;323(18):1775-1776. doi: 10.1001/jama.2020.4683. No abstract available.
citation: Oostveen E, Boda K, van der Grinten CP, James AL, Young S, Nieland H, Hantos Z. Respiratory impedance in healthy subjects: baseline values and bronchodilator response. Eur Respir J. 2013 Dec;42(6):1513-23. doi: 10.1183/09031936.00126212. Epub 2013 Apr 18.
citation: Oreshkova N, Molenaar RJ, Vreman S, Harders F, Oude Munnink BB, Hakze-van der Honing RW, Gerhards N, Tolsma P, Bouwstra R, Sikkema RS, Tacken MG, de Rooij MM, Weesendorp E, Engelsma MY, Bruschke CJ, Smit LA, Koopmans M, van der Poel WH, Stegeman A. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Euro Surveill. 2020 Jun;25(23):2001005. doi: 10.2807/1560-7917.ES.2020.25.23.2001005.
citation: Pasnick S, Carlos WG, Dela Cruz CS, Gross JE, Garrison G, Jamil S. SARS-CoV-2 Transmission and the Risk of Aerosol Generating Procedures. Am J Respir Crit Care Med. 2020 Jun 30. doi: 10.1164/rccm.2020C11. Online ahead of print. No abstract available.
citation: Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020 Mar 3;12(1):9. doi: 10.1038/s41368-020-0075-9.
citation: Sant'Anna M Jr, Carvalhal RF, Oliveira FDFB, Zin WA, Lopes AJ, Lugon JR, Guimaraes FS. Respiratory mechanics of patients with morbid obesity. J Bras Pneumol. 2019 Oct 17;45(5):e20180311. doi: 10.1590/1806-3713/e20180311. eCollection 2019.
citation: Savioli F, Rocha LL. Coagulation profile in severe COVID-19 patients: what do we know so far? Rev Bras Ter Intensiva. 2020 Jun;32(2):197-199. doi: 10.5935/0103-507x.20200031. Epub 2020 Jun 24. No abstract available.
citation: Sibila M, Guevara G, Cuadrado R, Pleguezuelos P, Perez D, Perez de Rozas A, Huerta E, Llorens A, Valero O, Perez M, Lopez C, Krejci R, Segales J. Comparison of Mycoplasma hyopneumoniae and porcine circovirus 2 commercial vaccines efficacy when applied separate or combined under experimental conditions. Porcine Health Manag. 2020 May 4;6:11. doi: 10.1186/s40813-020-00148-0. eCollection 2020.
citation: Soldati G, Smargiassi A, Inchingolo R, Buonsenso D, Perrone T, Briganti DF, Perlini S, Torri E, Mariani A, Mossolani EE, Tursi F, Mento F, Demi L. Proposal for International Standardization of the Use of Lung Ultrasound for Patients With COVID-19: A Simple, Quantitative, Reproducible Method. J Ultrasound Med. 2020 Jul;39(7):1413-1419. doi: 10.1002/jum.15285. Epub 2020 Apr 13.
citation: Sutton D, Fuchs K, D'Alton M, Goffman D. Universal Screening for SARS-CoV-2 in Women Admitted for Delivery. N Engl J Med. 2020 May 28;382(22):2163-2164. doi: 10.1056/NEJMc2009316. Epub 2020 Apr 13. No abstract available.
citation: Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
citation: Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, Clark C, Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 May;18(5):1023-1026. doi: 10.1111/jth.14810. Epub 2020 Apr 27. No abstract available.
citation: Torres-Castro R, Vasconcello-Castillo L, Alsina-Restoy X, Solis-Navarro L, Burgos F, Puppo H, Vilaro J. Respiratory function in patients post-infection by COVID-19: a systematic review and meta-analysis. Pulmonology. 2021 Jul-Aug;27(4):328-337. doi: 10.1016/j.pulmoe.2020.10.013. Epub 2020 Nov 25.
citation: Caglar Tosun BN, Zeren M, Barlik M, Demir E, Gulen F. Investigation of dynamic hyperinflation and its relationship with exercise capacity in children with bronchiectasis. Pediatr Pulmonol. 2022 Sep;57(9):2218-2226. doi: 10.1002/ppul.26028. Epub 2022 Jun 14.
citation: Williams FMK, Muirhead N, Pariante C. Covid-19 and chronic fatigue. BMJ. 2020 Jul 30;370:m2922. doi: 10.1136/bmj.m2922. No abstract available.
citation: 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 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
citation: Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. 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 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
citation: Ye Z, Wang Y, Colunga-Lozano LE, Prasad M, Tangamornsuksan W, Rochwerg B, Yao L, Motaghi S, Couban RJ, Ghadimi M, Bala MM, Gomaa H, Fang F, Xiao Y, Guyatt GH. Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis. CMAJ. 2020 Jul 6;192(27):E756-E767. doi: 10.1503/cmaj.200645. Epub 2020 May 14.
citation: Zhang T, Wu Q, Zhang Z. Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak. Curr Biol. 2020 Apr 6;30(7):1346-1351.e2. doi: 10.1016/j.cub.2020.03.022. Epub 2020 Mar 19.
citation: Du Z, Xu X, Wu Y, Wang L, Cowling BJ, Meyers LA. Serial Interval of COVID-19 among Publicly Reported Confirmed Cases. Emerg Infect Dis. 2020 Jun;26(6):1341-1343. doi: 10.3201/eid2606.200357. Epub 2020 Jun 17.