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
Keywords:
SARS-CoV- 2 infection, COVID-19, signs and symptoms, extra-respiratory manifestationsAbstract
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.
References
European Centre for Disease Prevention and Control. COVID-19 situation update worldwide, as of 7 September 2020. https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases.
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.
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.
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.
Canatan D, De Sanctis V. The impact of MicroRNAs (miRNAs) on the genotype of coronaviruses. Acta Biomed. 2020;91:195-198.
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.
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.
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.
Dong M, Zhang J, Ma X et.al.ACE2, 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.
Xiao F, Tang M, Zheng X. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158:1831–1833.
Wang W, Xu Y, Gao R. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323:1843–1844.
Yang Y, Lu Q, Liu M, et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. medRxiv. 2020; https://doi.org/10.1016/j.cmi.2020.02.005.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Russell CA, Jones TC, Barr IG, et al.Vaccine. 2008; 26 (Suppl 4):31-34.
World Health Organization. International travel and health: seasonal influenza and influenza A (H1N1) April 2020, https://www.who.int/ith/diseases/si_iAh1n1/en/.
World Health Organization. Up to 650,000 people die of respiratory diseases linked to seasonal flu each year. April 2020, http://www.who.int/mediacentre/news/releases/2017/seasonal-flu/en/.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sofia S, Boccatonda A, Montanari M, et al. Thoracic ultrasound and SARS-COVID-19: a pictorial essay. J Ultrasound. 2020;23:217-221.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
ACG News Team, Joint GI Society Message on COVID-19, American College of Gastroenterology, 2020, https://gi.org/2020/03/15/joint-gi-society-message-oncovid-19/.
Zhang C , Shi L , Wang FS . Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020; 5:428–30.
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/.
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.
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.
Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. J Clin Neurosci. 2020;77:8-12.
Filatov A., Sharma P., Hindi F. Neurological complications of coronavirus disease (COVID-19): encephalopathy. Cureus. 2020;12(3):e7352. doi: 10.7759/cureus.7352.
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.
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.
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.
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.
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.
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.
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.
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.
Jiang G, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol. 2007;170:1136–1147.
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.
Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020;98:209-218.
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.
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.
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.
Sun DQ, Wang TY, Zheng KI, et al. Subclinical acute kidney injury in COVID-19 patients: a retrospective cohort study. Nephron. 2020:1-4. https://doi.org/10.1159/000508502.
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.
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.
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.
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.
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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