A Systematic Review of Coronavirus Disease 2019 with Respiratory Distress Syndrome in Adult: Focus on Risk Factors, Mechanism, Diagnosis, and Treatment

Claudia Jodhinata, Andree Kurniawan, Devina Adella Halim


Context: Coronavirus disease 2019 (COVID-19) is a newly discovered disease, caused by SARS-CoV-2 and currently has become a pandemic. Acute respiratory distress syndrome (ARDS) is the most common complication in COVID-19. There were numerous conflicting results among articles related to it. The aim of this study is to ascertain the most compelling evidence about ARDS in COVID-19.

Evidence Acquisition: This systematic review was registered in PROSPERO (CRD42020180379). A systematic search was conducted in PubMed, PubMed central, and Google Scholar on April 16, 2020. Two reviewers independently searched and selected the articles. The risk of bias was evaluated using the Newcastle-Ottawa Quality assessment tool.

Results: A total of 1,647 articles were screened, 9 articles were included. Patients were classified as having various degrees of ARDS, the diagnosis of COVID-19 was confirmed by PCR nasopharyngeal swab.  Risk factors of ARDS in COVID-19 reported were older age, male gender, and pre-existing medical conditions. Cytokine storm was thought to play a role in the mechanism of ARDS. The main treatment for COVID-19 was supportive and symptomatic. To date, there is no antiviral treatment recommended for COVID-19 and the given treatment for ARDS in COVID-19 was similar to other pneumonia-induced ARDS. No additional therapy specific for ARDS in COVID-19 has been proposed.

Conclusion: Our synthesis of the literature showed that there was no good evidence in the mechanism and treatment of ARDS. Further translation research in the mechanism of ARDS and continuing with clinical trials evaluating drug efficacy for ARDS in COVID-19 is needed.


ARDS; COVID-19; risk factors; diagnosis; treatment

DOI: http://dx.doi.org/10.19166/med.v8i2.3442

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1. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020 Jan 29; 395:507-13(10223): 7. https://doi.org/10.1016/S0140-6736(20)30211-7

2. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. 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;2600(20):1-7. https://doi.org/10.1016/S2213-2600(20)30079-5

3. Sun P, Qie S, Liu Z, Ren J, Li K, Xi J. Clinical characteristics of 50 466 hospitalized patients with 2019-nCoV infection. J Med Virol 2020;0-2. https://doi.org/10.1101/2020.02.18.20024539

4. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis [Internet] 2020 (February):101623. https://doi.org/10.1016/j.tmaid.2020.101623

5. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 2020;1-10. https://doi.org/10.1001/jamainternmed.2020.0994

6. Centre for Reviews and Dissemination (CRD): PROSPERO: inter-nation prospective register for systematic reviews, University of York, UK, 2019.

7. Schardt C, Adams MB, Owens T. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med Inform Decis Mak 2007(7):16. https://doi.org/10.1186/1472-6947-7-16

8. Polus S, Pieper D, Burns J. Heterogeneity in application, design, and analysis characteristics was found for controlled before-after and interrupted time series studies included in Cochrane reviews. J Clin Epidemiol 2017;91:56-69. https://doi.org/10.1016/j.jclinepi.2017.07.008

9. Moher D, Liberati A, Tetzlaff J. Preferred reporting items for systematic reviews and meta-analysis: the PRISMA statement. J Clin Eppidemiol 2009;62:1006-12. https://doi.org/10.1016/j.jclinepi.2009.06.005

10. Higgins JP, Altman DG, Gotzsche PC. The Cochrane collaboration's tool for assessing risk of bias in randomized trials. BMJ 2011;343:d5928. https://doi.org/10.1136/bmj.d5928

11. Margulis AV, Pladevall M, Riera-Guardia N, et al. Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa scale and RTI item bank. Clin Epidemil 2014;6:359-68. https://doi.org/10.2147/CLEP.S66677

12. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. 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 [Internet] 2020;2600(20):1-7. https://doi.org/10.1016/S2213-2600(20)30079-5

13. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020;63(3):364-74. https://doi.org/10.1007/s11427-020-1643-8

14. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5

15. Zhou Y, Zhang Z, Tian J, Xiong S. Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Ann Palliat Med 2020;9(2):428-36.

16. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 2020;368:m1091.

17. Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, et al. [A pathological report of three COVID-19 cases by minimally invasive autopsies]. Zhonghua bing li xue za zhi = Chinese J Pathol [Internet] 2020 [cited 2020 Apr 11];49(0):E009. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32172546

18. Yao W, Wang T, Jiang B, Gao F, Wang L, Zheng H, et al. Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan , China : lessons learnt and international expert recommendations. 2020;(March):1-10.

19. Tu W-J, Cao J, Yu L, Hu X, Liu Q. Clinicolaboratory study of 25 fatal cases of COVID-19 in Wuhan. Intensive Care Med [Internet] 2020;(Table 1):1-4.

20. Tang X, Du R, Wang R, Cao T, Guan L, Yang C, et al. Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1. 2020;(January).

21. Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ [Internet] 2020.

22. Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis [Internet] 2020;2019(20):2019-20.

23. Dennis McGonagle, et al. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmunity Reviews [Internet] 2020; 19(6):102537.

24. Matthay MA, Aldrich JM, Gotts JE. Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet Respir Med [Internet] 2020;2600(20):2019-20. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32203709

25. Guo Y-R, Cao Q-D, Hong Z-S, Tan Y-Y, Chen S-D, Jin H-J, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res 2020;7(1):1-10.

26. Guan W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med [Internet] 2020;1-13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32109013

27. Hariyanto TI, Japar KV, Kwenandar F, Damay V, Siregar JI, Lugito NPH, et al. Inflammatory and hematologic markers as predictors of severe outcomes in COVID-19 infection: A systematic review and meta-analysis. Am J Emerg Med [Internet]. 2021;41:110-9.

28. Hariyanto TI, Kwenandar F, Japar KV, Damay V, Kurniawan A. The Effectiveness and Safety of Remdesivir for the Treatment of Patients With COVID-19: A Systematic Review and Meta-Analysis. Anti-Infective Agents (2020) 18: 1.

29. Hariyanto TI, Kristine E, Hardi CJ, Kurniawan A. Efficacy of Lopinavir/Ritonavir Compared With Standard Care for Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review. Infectious Disorders - Drug Targets (2020) 20: 1. https://doi.org/10.2174/1871526520666201029125725

30. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med [Internet]. 2020 Jul 17 [cited 2021 Jan 27]; Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2021436

31. Hariyanto TI, Kurniawan A. Tocilizumab administration is associated with the reduction in biomarkers of coronavirus disease 2019 infection. J Med Virol. 2020;(July):1-5.

32. Hariyanto TI, Hardyson W, Kurniawan A. Efficacy and Safety of Tocilizumab for Coronavirus Disease 2019 (Covid-19) Patients: A Systematic Review and Meta-analysis.

33. Drug Res (Stuttg). 2021 Jan 5. doi: 10.1055/a-1336-2371. Epub ahead of print. PMID: 33401328.

34. Hariyanto TI, Japar KV, Damay V, Kwenandar F, Sieto NL, Kurniawan A. The Use of ACE inhibitor/ARB in SARS-CoV-2 Patients: A Comprehensive Narrative Review. Asian J Med Sci. 2020;11(6):113-20.

35. Hariyanto TI, Kurniawan A. Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection. Obes Med. 2020 Sep 1;19:100290.

36. Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr Clin Res Rev. 2020 Nov 1;14(6):1613-5.


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