The Multifacets of COVID-19 in Adult Patients: A Concise Clinical Review on Pulmonary and Extrapulmonary Manifestations for Healthcare Physicians Covid-19 and Pulmonary and Extrapulmonary Manifestations

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Duran Canatan
Joan Lluis Vives Corrons
Vincenzo De Sanctis


SARS-CoV- 2 infection, COVID-19, signs and symptoms, extra-respiratory manifestations


Summary. COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Most people with COVID-19 have a mild to moderate respiratory illness; others experience severe illness, such as COVID-19 pneumonia. The first and most accessible diagnostic information is from symptoms and signs from clinical examination. Infected patients present with a variety of manifestations. Formal diagnosis requires laboratory analysis of nose and throat samples, or imaging tests like CT scans. Emerging data suggest that coronavirus disease 2019 (COVID-19) has extrapulmonary manifestations. Sometimes these extra-respiratory manifestations may be the initial or only symptom of COVID-19, prior to fever or respiratory manifestations. In summary, our concise review shows that there is a wide range of symptoms that can be presented by COVID-19 patients. Extra-respiratory manifestations of SARS-CoV-2 infection have recently been observed in the rapidly increasing number of COVID-19 cases. Considering the broad spectrum of clinical manifestations and the increasing worldwide burden of the disease, there is an urgent need to rapidly scale up the diagnostic capacity to detect COVID-19 and its complications.


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1. European Centre for Disease Prevention and Control. COVID-19 situation update worldwide, as of 7 September 2020.

2. 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;10.1001/jama.2020.2648. doi:10.1001/jama.2020.2648.

3. Nikolich-Zugich J, Knox KS, Rios CT, Natt B, Bhattacharya D, Fain MJ. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. GeroScience. 2020;42:505–514.

4. Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020;10.1002/jmv.26234. doi:10.1002/ jmv.26234.

5. Canatan D, De Sanctis V. The impact of MicroRNAs (miRNAs) on the genotype of coronaviruses. Acta Biomed. 2020;91:195-198.

6. Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat Rev Microbiol. 2009; 7:226-236.

7. Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116:1097–1100.

8. Di Gennaro F, Pizzol D, Marotta C, et al. Coronavirus Diseases (COVID-19) Current Status and Future Perspectives: A Narrative Review. Int J Environ Res Public Health. 2020;17(8):2690. Published 2020 Apr 14. doi:10.3390/ijerph17082690.

9. Dong M, Zhang J, Ma X, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19. Biomed Pharmacother. 2020 Aug 24;131:110678. doi: 10.1016/j.biopha.2020.110678.

10. Xiao F, Tang M, Zheng X. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158:1831–1833.

11. Wang W, Xu Y, Gao R. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323:1843–1844.

12.Yang Y, Lu Q, Liu M, et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. medRxiv. 2020;

13. Wu Y, Guo C, Tang L, et al. Prolonged presence of SARS-CoV- 2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol. doi:10.1016/S2468-1253(20)30083-2.

14. Atri D, Siddiqi HK, Lang J. COVID-19 for the cardiologist: a current review of the virology, clinical epidemiology, cardiac and other clinical manifestations and potential therapeutic strategies. JACC Basic Transl Sci. 2020;5:518-536.

15. Struyf T, Deeks JJ, Dinnes J, et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database Syst Rev. 2020;7(7): CD013665. doi:10.1002/14651858.CD013665.

16. Zheng Q, Lu Y, Lure F, Jaeger S, Lu P. Clinical and radiological features of novel coronavirus pneumonia. J Xray Sci Technol. 2020;28:391-404.

17. Han W, Quan B, Guo Y, et al. The course of clinical diagnosis and treatment of a case infected with coronavirus disease 2019. J Med Virol. 2020;92:461–463.

18. Liu X, Zhou H, Zhou Y, et al. Risk factors associated with disease severity and length of hospital stay in COVID-19 patients. J Infect. 2020;81:e95-e97.

19. Zhao J, Yang Y, Huang H et al. Relationship between the ABO Blood Group and the COVID-19 Susceptibility Clin Infect Dis. 2020 Aug 4;ciaa1150. doi: 10.1093/cid/ciaa1150.

20. Lippi G, Simundic AM, Plebani M. Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clin Chem Lab Med. 2020;58:1070-1076.

21. Frater JL, Zini G, d'Onofrio G, Rogers HJ. COVID-19 and the clinical hematology laboratory. Int J Lab Hematol. 2020;42 Suppl 1:11-18.

22. Lopez C, Kim J, Pandey A, Huang T, DeLoughery TG. Simultaneous Onset of COVID-19 and Autoimmune Haemolytic Anaemia. Br J Haematol. 2020;190:31-32.

23. Russell CA, Jones TC, Barr IG, et al.Vaccine. 2008; 26 (Suppl 4):31-34.
24. World Health Organization. International travel and health: seasonal influenza and influenza A (H1N1) April 2020,
25. World Health Organization. Up to 650,000 people die of respiratory diseases linked to seasonal flu each year. April 2020,

26. Rothe C, Schunk M, Sothmann P, et al. Transmission of COVID-19 Infection from an asymptomatic contact in Germany. N Engl J Med. 2020; 382:970-971.

27. Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based SARS-CoV-2 tests by time since exposure. Ann Intern Med. 2020;173:262-267.

28. Long C, Xu H, Shen Q, et al. Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? Eur J Radiol. 2020;126:108961. doi:10.1016/j.ejrad.2020.108961.

29. Watson J, Whiting PF, Brush JE. Interpreting a covid-19 test result. BMJ. 2020;369:m1808. Published 2020 May 12. doi:10.1136/bmj.m1808.

30. Self WH, Courtney DM, McNaughton CD, Wunderink RG, Kline JA. High discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ed patients: implications for diagnosing pneumonia. Am J. Emerg Med. 2013;31:401–405.
31. Rubin GD, Ryerson CJ, Haramati LB, et al. The Role of Chest Imaging in Patient Management During the COVID-19 Pandemic: A Multinational Consensus Statement From the Fleischner Society. Chest. 2020;158:106-116.

32. Kanne JP, Little BP, Chung JH, Elicker BM, Ketai LH. Essentials for Radiologists on COVID-19: An Update-Radiology Scientific Expert Panel. Radiology. 2020;296:E113-E114.

33. Bernheim A, Mei X, Huang M, et al. Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection. Radiology. 2020;295(3):200463. doi:10.1148/radiol.2020200463.

34. Onigbinde SO, Ojo AS, Fleary L, Hage R. Chest Computed Tomography Findings in COVID-19 and Influenza: A Narrative Review. Biomed Res Int. 2020;2020:6928368. Published 2020 Jun 5. doi:10.1155/ 2020/6928368.

35. Testa A, Soldati G, Copetti R, Giannuzzi R, Portale G, Gentiloni-Silveri N. Early recognition of the 2009 pandemic influenza A (H1N1) pneumonia by chest ultrasound. Crit Care. 2012 Feb 17; 16(1):R30.

36. Sofia S, Boccatonda A, Montanari M, et al. Thoracic ultrasound and SARS-COVID-19: a pictorial essay. J Ultrasound. 2020;23:217-221.

37. Zou X, Chen K, Zou J, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020;14:185–192.

38. Martinez-Rojas MA, Vega-Vega O, Bobadilla NA. Is the kidney a target of SARS-CoV-2? Am J Physiol Renal Physiol. 2020;318:F1454-F1462.

39. Galván Casas C, Català A, Carretero Hernández G. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020 Apr 29:10.1111/bjd.19163. doi: 10.1111/bjd.19163.

40. Landa N, Mendieta-Eckert M, Fonda-Pascual P, Aguirre T. Chilblain-like lesions on feet and hands during the COVID-19 Pandemic. Int J Dermatol. 2020;59:739- 743.

41.Tang K, Wang Y, Zhang H, Zheng Q, Fang R, Sun Q. Cutaneous manifestations of the Coronavirus Disease 2019 (COVID-19): A brief review. Dermatol Ther. 2020;e13528. doi:10.1111/dth.13528.

42. Cogan E, Foulon P, Cappeliez O, Dolle N, Vanfraechem G, De Backer D. Multisystem Inflammatory Syndrome With Complete Kawasaki Disease Features Associated With SARS-CoV-2 Infection in a Young Adult. A Case Report. Front Med (Lausanne). 2020;7:428. Published 2020 Jul 14. doi:10.3389/ fmed.2020.00428.

43. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069.

44. Fried JA, Ramasubbu K, Bhatt R, et al. The variety of cardiovascular presentations of COVID-19 [published online April 3, 2020]. Circulation. doi: 10.1161/CIRCULATIONAHA.120.047164.

45. Lang JP, Wang X, Moura FA, Siddiqi HK, Morrow DA, Bohula EA. A current review of COVID-19 for the cardiovascular specialist. Am Heart J. 2020;226:29-44.

46. Boukhris M, Hillani A, Moroni F, et al. Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective. Can J Cardiol. 2020;36:1068-1080.

47. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020;18:1421-1424.

48. 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;18:844–847.

49. Moores LK, Tritschler T, Brosnahan S, et al. Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST guideline and expert panel report. Chest. 2020;3692:31625-31621.

50. Tian Y, Rong L, Nian W, He Y: Review article: gastrointestinal features in COVID-19 and the
possibility of faecal transmission. Aliment Pharmacol Ther 2020, 51:843-851.

51. Huang C, Wang Y, Li X, et al: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.

52.Tran J, Glavis-Bloom J, Bryan T, Harding KT, Chahine C, Houshyar R. COVID-19 patient presenting with initial gastrointestinal symptoms. Eurorad. 2020:Case 16654.

53. Han C, Duan C, Zhang S, et al. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes.Am J Gastroenterol. 2020;115:916-923.

54. ACG News Team, Joint GI Society Message on COVID-19, American College of Gastroenterology, 2020,

55. Zhang C , Shi L , Wang FS . Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020; 5:428–30.

56. Cascella M, M. Rajnik M, A. Cuomo A, et al., Features, evaluation and treatment coronavirus (COVID-19), StatPearls [Internet], StatPearls Publishing, Treasure Island (FL), 2020https://www.ncbi. nlm.nih. gov/ books/ NBK554776/.

57. Wang F, Wang H, Fan J, Zhang Y, Wang H, Zhao Q. Pancreatic Injury Patterns in Patients With Coronavirus Disease 19 Pneumonia. Gastroenterology. 2020;159:367-370.

58. Soliman AT, Al-Amri M, Alleethy K, Alaaraj N, Hamed N, De Sanctis V. Newly-onset type 1 diabetes mellitus precipitated by COVID-19 in an 8-month-old infant. Acta Biomed. 2020;91(3).Published 2020 Jul 13. doi:10.23750/abm.v91i3.10074.

59. Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. J Clin Neurosci. 2020;77:8-12.

60. Filatov A., Sharma P., Hindi F. Neurological complications of coronavirus disease (COVID-19): encephalopathy. Cureus. 2020;12(3):e7352. doi: 10.7759/cureus.7352.

61. Baig A.M., Khaleeq A., Ali U., Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11: 995–998.

62. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020:77:1–9.

63. Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277:2251-2261.

64. Chen L, Deng C, Chen X, et al. Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: a cross-sectional study. Acta Ophthalmol. 2020;10.1111/aos.14472. doi:10.1111 /aos. 14472.

65.Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. 2020;138:575-578.

66. Khavandi S, Tabibzadeh E, Naderan M, Shoar S. Corona virus disease-19 (COVID-19) presenting as conjunctivitis: atypically high-risk during a pandemic. Cont Lens Anterior Eye. 2020;43:211-212.
67. Ulhaq ZS, Soraya GV. The prevalence of ophthalmic manifestations in COVID-19 and the diagnostic value of ocular tissue/fluid. Graefe’s Arch Clin Exp Ophthalmol. 2020;258:1351–1352.

68. Ho D, Low R, Tong L, Gupta V, Veeraraghavan A, Agrawal R. COVID-19 and the Ocular Surface: A Review of Transmission and Manifestations. Ocul Immunol Inflamm. 2020;28:726-734.

69. Jiang G, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol. 2007;170:1136–1147.

70. Kunutsor SK, Laukkanen JA. Renal complications in COVID-19: a systematic review and meta-analysis. Ann Med. 2020;1-9. doi:10.1080/07853890.2020.1790643.

71. Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020;98:209-218.

72. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395:1763-1770.

73. Farouk SS, Fiaccadori E, Cravedi P, Campbell KN. COVID-19 and the kidney: what we think we know so far and what we don't. J Nephrol. 2020;1-6. doi:10.1007/s40620-020-00789-y.

74. Kunutsor SK, Laukkanen JA. Renal complications in COVID-19: a systematic review and meta-analysis. Ann Med. 2020;1-9. doi:10.1080/07853890.2020.1790643.

75. Sun DQ, Wang TY, Zheng KI, et al. Subclinical acute kidney injury in COVID-19 patients: a retrospective cohort study. Nephron. 2020:1-4.

76. Diao B, Wang C, Wang R, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. medRxiv. 2020:2020.03.04.20031120.

77. Shen Q, Xiao X, Aierken A, et al. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection [published online ahead of print, 2020 Jun 28]. J Cell Mol Med. 2020;24:9472-9477.

78. Wang Z, Xu X. scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in Spermatogonia, Leydig and Sertoli cells. Cells 2020;9(4):920.

79. Ma L, Xie W, Li D. Effect of SARS-CoV-2 infection upon male gonadal function: a single center-based study. medRxiv. 2020 doi: 10.1101/2020.03.21.20037267.

80. Chen F. Rising Concern on Damaged Testis of COVID-19 Patients. Urology. 2020;142: 42.
doi: 10.1016/j.urology.2020.04.069.

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