Clinical Review

Atypical Features of COVID-19: A Literature Review

Journal of Clinical Outcomes Management. 2020 May;27(3):131-134 | 10.12788/jcom.0005

References

1. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020 [press release]. World Health Organization; March 11, 2020.

2. Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. Johns Hopkins CSSE. https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 Accessed May 15, 2020.

3. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020;27(2):taaa021. doi:10.1093/jtm/taaa021

4. Li Z, Wu M, Guo J, et al. Caution on kidney dysfunctions of 2019-nCoV patients. medRxiv preprint. doi: 10.1101/2020.02.08.20021212

5. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450-454. doi: 10.1038/nature02145.

6. 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. doi:10.1001/jama.2020.1585

7. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020;323:1612‐1614. doi:10.1001/jama.2020.4326

8. Chen C, Zhou Y, Wang DW. SARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020;45:230-232. doi: 10.1007/s00059-020-04909-z

9. Hu H, Ma F, Wei X, Fang Y. Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin. Eur Heart J. 2020 Mar 16;ehaa190. doi: 10.1093/eurheartj/ehaa190

10. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846-848. doi:10.1007/s00134-020-05991-x

11. Akhmerov A, Marban E. COVID-19 and the heart. Circ Res. 2020;126:1443-1455. doi:10.1161/CIRCRESAHA.120.317055

12. Xiao F, Tang M, Zheng X, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158:1831-1833. doi: 10.1053/j.gastro.2020.02.055

13. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1078-1720. doi: 10.1056/NEJMoa2002032

14. 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 Mar 31;e201291. doi: 10.1001/jamaophthalmol.2020.1291

15. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020 Apr 10. doi: 10.1001/jamaneurol.2020.1127

16. Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and ageusia: common findings in COVID-19 patients. Laryngoscope. 2020 Apr 1. doi: 10.1002/lary.28692

17. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-coronavirus-2. Int J Infect Dis. 2020;94:55-58. doi: 10.1016/j.ijid.2020.03.062

18. Toscano G, Palmerini F, Ravaglia S, et al. Guillain–Barré syndrome associated with SARS-CoV-2. N Engl J Med. 2020 Apr 17;NEJMc2009191. doi:10.1056/nejmc2009191

19. Dafer RM, Osteraas ND, Biller J. Acute stroke care in the coronavirus disease 2019 pandemic. J Stroke Cerebrovascular Dis. 2020 Apr 17:104881. doi: 10.1016/j.jstrokecerebrovasdis.2020.104881

20. Terpos E, Ntanasis-Stathopoulos I, Elalamy I, et al. Hematological findings and complications of COVID-19. Am J Hematol. 2020;10.1002/ajh.25829. doi:10.1002/ajh.25829

21. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med. 2020;S2213-2600(20)30216-2. doi:10.1016/S2213-2600(20)30216-2

22. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020 Mar 26. doi: 10.1111/jdv.16387

23. Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. J Am Acad Dermatol. 2020;82(5):e177. doi: 10.1016/j.jaad.2020.03.036

24. Alramthan A, Aldaraji W. A Case of COVID‐19 presenting in clinical picture resembling chilblains disease. First report from the Middle East. Clin Exp Dermatol. 2020 Apr 17. doi: 10.1111/ced.14243

25. Kolivras A, Dehavay F, Delplace D, et al. Coronavirus (COVID-19) infection–induced chilblains: a case report with histopathologic findings. JAAD Case Rep. 2020 Apr 18. doi: 10.1016/j.jdcr.2020.04.011

From the University of Florida College of Medicine, Division of Infectious Diseases and Global Medicine, Gainesville, FL.

Abstract

Objective: To review current reports on atypical manifestations of coronavirus disease 2019 (COVID-19).
Methods: Review of the literature.
Results: Evidence regarding atypical features of COVID-19 is accumulating. SARS-CoV-2 can infect human cells that express the angiotensin-converting enzyme 2 receptor, which would allow for a broad spectrum of illnesses affecting the renal, cardiac, and gastrointestinal organ systems. Neurologic, cutaneous, and musculoskeletal manifestations have also been reported. The potential for SARS-CoV-2 to induce a hypercoagulable state provides another avenue for the virus to indirectly damage various organ systems, as evidenced by reports of cerebrovascular disease, myocardial injury, and a chilblain-like rash in patients with COVID-19.
Conclusion: Because the signs and symptoms of COVID-19 may occur with varying frequency across populations, it is important to keep differentials broad when assessing patients with a clinical illness that may indeed be COVID-19.

Keywords: coronavirus; severe acute respiratory syndrome coronavirus-2; SARS-CoV-2; pandemic.

Coronavirus disease 2019 (COVID-19), the syndrome caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, China, in early December 2019.¹ Since then, the virus has spread quickly around the world, with the World Health Organization (WHO) declaring the coronavirus outbreak a global pandemic on March 11, 2020. As of May 21, 2020, more than 5,000,000 cases of COVID-19 have been confirmed, and more than 328,000 deaths related to COVID-19 have been reported globally.² These numbers are expected to increase, due to the reproduction number (R0) of SARS-CoV-2. R0 represents the number of new infections generated by an infectious person in a totally naïve population.³ The WHO estimates that the R0 of SARS-CoV-2 is 1.95, with other estimates ranging from 1.4 to 6.49.³ To control the pathogen, the R0 needs to be brought under a value of 1.

A fundamental tool in lowering the R0 is prompt testing and isolation of those who display signs and symptoms of infection. SARS-CoV-2 is still a novel pathogen about which we know relatively little. The common symptoms of COVID-19 are now well known—including fever, fatigue, anorexia, cough, and shortness of breath—but atypical manifestations of this viral continue to be reported and described. To help clinicians across specialties and settings identify patients with possible infection, we have summarized findings from current reports on COVID-19 manifestations involving the renal, cardiac, gastrointestinal (GI), and other organ systems.

Renal

During the 2003 SARS-CoV-1 outbreak, acute kidney injury (AKI) was an uncommon complication of the infection, but early reports suggest that AKI may occur more commonly with COVID-19.⁴ In a study of 193 patients with laboratory-confirmed COVID-19 treated in 3 Chinese hospitals, 59% presented with proteinuria, 44% with hematuria, 14% with increased blood urea nitrogen, and 10% with increased levels of serum creatinine.⁴ These markers, indicative of AKI, may be associated with increased mortality. Among this cohort, those with AKI had a mortality risk 5.3 times higher than those who did not have AKI.⁴ The pathophysiology of renal disease in COVID-19 may be related to dehydration or inflammatory mediators, causing decreased renal perfusion and cytokine storm, but evidence also suggests that SARS-CoV-2 is able to directly infect kidney cells.⁵ The virus infects cells by using angiotensin-converting enzyme 2 (ACE2) on the cell membrane as a cell entry receptor; ACE2 is expressed on the kidney, heart, and GI cells, and this may allow SARS-CoV-2 to directly infect and damage these organs. Other potential mechanisms of renal injury include overproduction of proinflammatory cytokines and administration of nephrotoxic drugs. No matter the mechanism, however, increased serum creatinine and blood urea nitrogen correlate with an increased likelihood of requiring intensive care unit (ICU) admission.⁶ Therefore, clinicians should carefully monitor renal function in patients with COVID-19.