pISSN : 3058-423X eISSN: 3058-4302
Open Access, Peer-reviewed
pISSN : 3058-423X eISSN: 3058-4302
Open Access, Peer-reviewed
Ji Hyun Lee,Hwa Jung Yook
10.17966/JMI.2020.25.3.47 Epub 2020 October 06
Abstract
Keywords
Co-infection Corona virus COVID-19 Dermatologic department Fungus
Coronavirus Disease-2019 (COVID-19) was announced on November 16, 2019 when the first patient was diagnosed. Subsequently, the World Health Organization declared COVID- 19 as a pandemic disease caused by SARS-CoV-21 on March 11, 2020.
A total of 25,051,178 confirmed patients were reported worldwide with 843,586 COVID-19 related deaths by August 31, 2020. The COVID-19 pandemic has caused a serious health crisis worldwide. There were 19,947 confirmed cases and 324 deaths in South Korea, and the trend is increasing rapidly. Approximately 14% of COVID-19 patients have severe symptoms of breathing difficulties and low oxygen saturation, and 5% of patients have respiratory failure, septic shock, and fatal symptoms such as complex organ failure, resulting in death in 2.3% of patients2, even though they mostly improved with conservative treatment. The mortality of COVID-19 in- creases in patients with comorbidities. The fatality rate was 10.5% in patients with cardiovascular disease, 7.3% in people with diabetes, 6.3% in chronic respiratory disease, and 6.0% in hypertension. However, there are still insufficient data on the association between COVID-19 and fungal infection. Therefore, we would like to review fungal infection related to COVID-19.
Coronavirus belongs to the family Coronaviridae which are enveloped and single-stranded RNA viruses. Coronaviruses are classified into 4 groups: α, β, γ, and δ-coronavirus. Severe acute respiratory syndrome (SARS)-CoV-2 belongs to the beta-coronaviruses and is similar to bat COV and SARS-CoV-13. SARS-CoV-2 has a specific spike glycoprotein that has a strong binding affinity to the angiotensinogen-converting enzyme 2 (ACE2) receptors, which is approximately 20 times higher than that of SARS-CoV-14,5.
SARS-CoV-2 is a highly contagious disease transmitted through the respiratory droplets of infected patients, including asymptomatic carriers directly or indirectly6. Fever, cough, fatigue, anorexia, myalgia, and diarrhea are the most com- mon symptoms of COVID-197. Severe symptoms are dyspnea, hypoxemia, and rapid progression of respiratory failure8. The overall mortality rate is 2.3%2. CUTANEOUS MANIFESTATIONS
A variety of cutaneous manifestations can accompany viral infection9,10. Previous reports showed COVID-19 patients with urticarial rash11-14. Since then, several related symptoms have been reported. Recalcati demonstrated that 20.4% of COVID-19 patients in Italy developed cutaneous manifesta- tions, and the patients had cutaneous manifestations such as erythematous rash, urticaria, and chickenpox-like vesicles15. Skin findings, including chilblain-like (40.2%), maculopapular (22.7%), urticarial (8.9%), vesicular (6.4%), livedoid and ne- crotic (2.8%), and other skin lesions (19.8%), were reviewed by Jia et al.10. Furthermore, patients may complain of pain, burning, or itching. On the other hand, cutaneous symptoms were subdivided into 6 patterns by Marzano et al., as fol- lows: urticarial rash, confluent erythematous-maculopapular-morbilliform rash, papulovesicular exanthem, chilblain-like acral pattern, livedo reticularis-livedo racemosa-like pattern, and purpuric "vasculitic" pattern9. As such, there have been few reports of additional fungal or bacterial infections in patients with COVID-19 who visited a dermatology clinic.
It has been suggested that COVID-19 might increase the risk of co-infection or superinfections. Zhu et al. reported SARS-CoV-2 co-infection with other pathogens in laboratory-confirmed COVID-19 patients16, where 94.2% of patients had co-infection with one or more pathogens, with bacterial co-infection being dominant. Furthermore, 31.5% of patients had viral co-infection, 91.8% had a bacterial co-infection such as Streptococcus pneumonia, Klebsiella pneumonia, or Haemophilus influenza, among others, and 23.3% had fungal co-infection. The co-infection fungal pathogens included Aspergillus (23.3%), Mucor (2.5%), Candida (0.8%), and Cryptococcus (0.4%). The rates of viral co-infection (35.3%), fungal co-infection (29.5%), and bacterial-fungal co-infection (29.5%) were the highest in severe COVID-19 patients16. Three cases of Candida albicans, 1 case of Candida glabrata, and 1 case of Aspergillus flavus co-infection among 99 COVID-19 patients were presented by Chen et al.17. Yang et al. found 3 cases including Aspergillus flavus, Aspergillus fumigatus, and Candida albicans among 52 COVID-19 patients18. Zhang et al. also found that co-infections in severe patients with COVID-19 were significantly higher than those in non-severe patients. They suggested that this is due to a decrease in host immune function and the presence of invasive catheters. This may lead to increased susceptibility to secondary infections by multidrug-resistant pathogens19. Therefore, clinicians should consider co-infection when diag- nosing COVID-19.
Co-infection with COVID-19 and invasive pulmonary asper- gillosis was found20. It has recently been reported that COVID-19-associated pulmonary aspergillosis (CAPA) causes serious pulmonary abnormalities that require therapy in intensive care unit (ICU) due to its high mortality21,22. CAPA was found in 33% of ICU patients admitted for COVID-19 in France, and 26% in Germany23,24. Severe COVID-19 is associated with impaired immune regulation, affecting both T-helper cell 2 (Th2) and Th1 responses, thus explaining the mechanism behind co-infection. CAPA due to Aspergillus fumigatus requires early diagnosis with the identification of a triazole-resistant isolate21. However, exposure to antifungal drugs may reduce sensitivity of the serum galactomannan test and delay the diagnosis.
Meanwhile, it has been reported that co-infection of bacteria or fungi is associated with the use of empirical anti- microbial agents in patients with coronavirus-related respira- tory infections25. Approximately 60% of the articles did not mention bacterial/fungal infections. Regarding COVID-19, 8% of patients had bacterial/fungal co-infection during hospitali- zation25. There were not many simultaneous bacterial/fungal infections, as expected, even though patients with coronavirus-related respiratory infections actually use a wide range of empirical antimicrobial agents. Hughes et al. also reported no evidence of risk of concomitant fungal infections in the early stages of COVID-19 in the UK26.
The skin provides a shield against external stimuli and is a major part of the immune system. Loss of the skin barrier increases the risk of multiple infections, despite the lack of reports of fungal co-infection in the dermatologic department. More attention should therefore be paid to the COVID-19 pandemic era.
Diagnosis of COVID-19 and fungal co-infection can be delayed, missed, or misdiagnosed. Afterwards, COVID-19 can cause impairment of cellular immune responses and lead to high mortality.
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