Diaphragm impairment in patients admitted for severe COVID-19


Submitted: 14 March 2022
Accepted: 10 June 2022
Published: 21 June 2022
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Authors

Among patients affected by the virus COVID-19, physicians have observed ventilation disorders. It is relevant to assess neurological involvement, including the role of diaphragmatic function. Its possible impairment could be related to the systemic inflammatory response and disease progression that both typify COVID-19 infection. We distinguished two groups (severe group (SG) and mild group (MG)) according to the severity of respiratory symptomatology. We performed neurophysiological and sonography studies to evaluate the diaphragmatic function. Regarding the sonography variables, we identified statistically significant differences in the right mean diaphragmatic thickness along with the expiration, showing 1.56 mm (SEM: 0.11) in the SG vs 1.92 mm (SEM: 0.19) in the MG (p = 0.042). The contractibility of both hemidiaphragms was 15% lower in the severe group, though this difference is not statistically significant. In our examination of the neurophysiological variables, in the amplitude responses, we observed a greater difference between responses from both phrenic nerves as follows: the raw differences in amplitude were 0.40 μV (SEM: 0.14) in the SG vs 0.35 μV (SEM: 0.19) in the MG and the percentage difference was 25.92% (SEM: 7.22) in the SG vs 16.28% (SEM: 4.38%) in the MG. Although diaphragmatic dysfunction is difficult to detect, our combined functional and morphological approach with phrenic electroneurograms and chest ultrasounds could improve diagnostic sensitivity. We suggest that diaphragmatic dysfunction could play a relevant role in respiratory disturbance in hospitalised patients with severe COVID-19.


Brosnahan SB, Jonkman AH, Kugler MC, Munger JS, Kaufman DA. COVID-19 and Respiratory System Disorders: Current Knowledge, Future Clinical and Translational Research Questions. Arterioscler Thromb Vasc Biol. 2020 Nov;40(11):2586-2597. Epub 2020 Sep 22. DOI: https://doi.org/10.1161/ATVBAHA.120.314515

Hund E. Critical illness polyneuropathy. Curr Opin Neurol. 2001 Oct;14(5):649-53. DOI: https://doi.org/10.1097/00019052-200110000-00015

Gu J, Gong E, Zhang B, Zheng J, Gao Z, Zhong Y, Zou W, Zhan J, Wang S, Xie Z, Zhuang H, Wu B, Zhong H, Shao H, Fang W, Gao D, Pei F, Li X, He Z, Xu D, Shi X, Anderson VM, Leong AS. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005 Aug 1;202(3):415-24. Epub 2005 Jul 25. DOI: https://doi.org/10.1084/jem.20050828

Kokatnur L, Rudrappa M. Diaphragmatic Palsy. Diseases. 2018 Feb 13;6(1):16. DOI: https://doi.org/10.3390/diseases6010016

Tsao BE, Ostrovskiy DA, Wilbourn AJ, Shields RW Jr. Phrenic neuropathy due to neuralgic amyotrophy. Neurology. 2006 May 23;66(10):1582-4. Erratum in: Neurology. 2006 Jul 25;67(2):299. DOI: https://doi.org/10.1212/01.wnl.0000216140.25497.40

Nardone R, Bernhart H, Pozzera A, Taddei M, Tezzon F. Respiratory weakness in neuralgic amyotrophy: report of two cases with phrenic nerve involvement. Neurol Sci. 2000 Jun;21(3):177-81. DOI: https://doi.org/10.1007/s100720070094

Jeon JS, Park JS. An early treated neuralgic amyotrophy with bilateral phrenic nerve involvement with a favorable outcome. Neurol India. 2016 May-Jun;64(3):566-9. DOI: https://doi.org/10.4103/0028-3886.181578

Lahrmann H, Grisold W, Authier FJ, Zifko UA. Neuralgic amyotrophy with phrenic nerve involvement. Muscle Nerve. 1999 Apr;22(4):437-42. DOI: https://doi.org/10.1002/(SICI)1097-4598(199904)22:4<437::AID-MUS2>3.0.CO;2-F

Asadi-Pooya AA, Simani L. Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci. 2020 Jun 15;413:116832. DOI: https://doi.org/10.1016/j.jns.2020.116832

Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020 Jul;92(7):699-702. DOI: https://doi.org/10.1002/jmv.25915

Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, Gibson-Corley KN, Meyerholz DK, McCray PB Jr. Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4. J Infect Dis. 2016 Mar 1;213(5):712-22. Epub 2015 Oct 20. DOI: https://doi.org/10.1093/infdis/jiv499

Rudrappa M, Kokatnur L, Chernyshev O. Neurological Respiratory Failure. Diseases. 2018 Jan 10;6(1):7. DOI: https://doi.org/10.3390/diseases6010007

Ricoy J, Rodríguez-Núñez N, Álvarez-Dobaño JM, Toubes ME, Riveiro V, Valdés L. Diaphragmatic dysfunction. Pulmonology. 2019 Jul-Aug;25(4):223-235. Epub 2018 Dec 1. DOI: https://doi.org/10.1016/j.pulmoe.2018.10.008

Vincent M, Court-Fortune I, Costes F, Antoine JC, Camdessanché JP. Phrenic Nerve Conduction in Healthy Subjects. Muscle Nerve. 2019 Apr;59(4):451-456. Epub 2019 Jan 24. DOI: https://doi.org/10.1002/mus.26414

Maranhão AA, Carvalho SRDS, Caetano MR, Alamy AH, Peixoto EM, Filgueiras PDEP. Phrenic nerve conduction studies: normative data and technical aspects. Arq Neuropsiquiatr. 2017 Dec;75(12):869-874. DOI: https://doi.org/10.1590/0004-282x20170153

Resman-Gaspersc A, Podnar S. Phrenic nerve conduction studies: technical aspects and normative data. Muscle Nerve. 2008 Jan;37(1):36-41. DOI: https://doi.org/10.1002/mus.20887

Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. Epub 2020 Feb 18. Erratum in: Lancet Respir Med. 2020 Feb 25. DOI: https://doi.org/10.1016/S2213-2600(20)30076-X

Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han H, Li X, Kang W, Weng D, Liang P, Jiang S. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol. 2004 Jun;203(2):622-30. DOI: https://doi.org/10.1002/path.1560

Fox RJ, Galetta SL, Mahalingam R, Wellish M, Forghani B, Gilden DH. Acute, chronic, and recurrent varicella zoster virus neuropathy without zoster rash. Neurology. 2001 Jul 24;57(2):351-4. DOI: https://doi.org/10.1212/WNL.57.2.351

Kolson DL, Gonzalez-Scarano F. HIV-associated neuropathies: role of HIV-1, CMV, and other viruses. J Peripher Nerv Syst. 2001 Mar;6(1):2-7. DOI: https://doi.org/10.1046/j.1529-8027.2001.006001002.x

Wulff EA, Wang AK, Simpson DM. HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment. Drugs. 2000 Jun;59(6):1251-60. DOI: https://doi.org/10.2165/00003495-200059060-00005

Mahadevan A, Gayathri N, Taly AB, Santosh V, Yasha TC, Shankar SK. Vasculitic neuropathy in HIV infection: a clinicopathological study. Neurol India. 2001 Sep;49(3):277-83.

Martínez Rodríguez L, Carvajal P, Morís G. Neuralgia amiotrófica en relación con infección por el virus de la hepatitis E [Neuralgic amyotrophy associated to hepatitis E virus infection]. Med Clin (Barc). 2015 Nov 20;145(10):462-3. Spanish. Epub 2015 Mar 24. DOI: https://doi.org/10.1016/j.medcli.2015.01.021

Verma R, Sahu R, Holla V. Neurological manifestations of dengue infection: a review. J Neurol Sci. 2014 Nov 15;346(1-2):26-34. Epub 2014 Sep 6. DOI: https://doi.org/10.1016/j.jns.2014.08.044

Podnar S. Nosology of idiopathic phrenic neuropathies. J Neurol. 2015 Mar;262(3):558-62. Epub 2014 Dec 6. DOI: https://doi.org/10.1007/s00415-014-7596-0

Sierra A, Prat J, Bas J, Romeu A, Montero J, Matos JA, Bella R, Ferrer I, Buendia E. Blood lymphocytes are sensitized to branchial plexus nerves in patients with neuralgic amyotrophy. Acta Neurol Scand. 1991 Mar;83(3):183-6. DOI: https://doi.org/10.1111/j.1600-0404.1991.tb04674.x

Waki Y, Nobeyama Y, Fukuchi O, Mukai T, Takagi M, Asahina A. Case of herpes zoster complicated by diaphragmatic paralysis. J Dermatol. 2019 Sep;46(9):e322-e324. Epub 2019 Apr 2. DOI: https://doi.org/10.1111/1346-8138.14878

Djukic M, Larsen J, Lingor P, Nau R. Unilateral phrenic nerve lesion in Lyme neuroborreliosis. BMC Pulm Med. 2013 Jan 18;13:4. DOI: https://doi.org/10.1186/1471-2466-13-4

Melero MJ, Mazzei ME, Bergroth B, Cantardo DM, Duarte JM, Corti M. Bilateral diaphragmatic paralysis in an HIV patient: Second reported case and literature review. Lung India. 2014 Apr;31(2):149-51. DOI: https://doi.org/10.4103/0970-2113.129846

Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008 Aug;82(15):7264-75. Epub 2008 May 21. DOI: https://doi.org/10.1128/JVI.00737-08

Xu J, Zhong S, Liu J, Li L, Li Y, Wu X, Li Z, Deng P, Zhang J, Zhong N, Ding Y, Jiang Y. Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clin Infect Dis. 2005 Oct 15;41(8):1089-96. Epub 2005 Sep 12. DOI: https://doi.org/10.1086/444461

van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008 Oct;7(10):939-50. DOI: https://doi.org/10.1016/S1474-4422(08)70215-1

Brosnahan SB, Jonkman AH, Kugler MC, Munger JS, Kaufman DA. COVID-19 and Respiratory System Disorders: Current Knowledge, Future Clinical and Translational Research Questions. Arterioscler Thromb Vasc Biol. 2020 Nov;40(11):2586-2597. Epub 2020 Sep 22. DOI: https://doi.org/10.1161/ATVBAHA.120.314515

Chetta A, Rehman AK, Moxham J, Carr DH, Polkey MI. Chest radiography cannot predict diaphragm function. Respir Med. 2005 Jan;99(1):39-44. DOI: https://doi.org/10.1016/j.rmed.2004.04.016

Noda Y, Sekiguchi K, Kohara N, Kanda F, Toda T. Ultrasonographic diaphragm thickness correlates with compound muscle action potential amplitude and forced vital capacity. Muscle Nerve. 2016 Apr;53(4):522-7. Epub 2015 Oct 10. DOI: https://doi.org/10.1002/mus.24902

Pinto S, Alves P, Pimentel B, Swash M, de Carvalho M. Ultrasound for assessment of diaphragm in ALS. Clin Neurophysiol. 2016 Jan;127(1):892-897. Epub 2015 Apr 25. DOI: https://doi.org/10.1016/j.clinph.2015.03.024

Lisboa C, Paré PD, Pertuzé J, Contreras G, Moreno R, Guillemi S, Cruz E. Inspiratory muscle function in unilateral diaphragmatic paralysis. Am Rev Respir Dis. 1986 Sep;134(3):488-92.

Hart N, Nickol AH, Cramer D, Ward SP, Lofaso F, Pride NB, Moxham J, Polkey MI. Effect of severe isolated unilateral and bilateral diaphragm weakness on exercise performance. Am J Respir Crit Care Med. 2002 May 1;165(9):1265-70. DOI: https://doi.org/10.1164/rccm.2110016

López-Viñas, L., Vega-Villar, J., Rocío-Martín, E., García-García, P., De La Rosa Santiago, E., Galván-Román, J. M., & Wix-Ramos, R. (2022). Diaphragm impairment in patients admitted for severe COVID-19. European Journal of Translational Myology, 32(2). https://doi.org/10.4081/ejtm.2022.10460

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