Invasive cryptococcal disease in COVID-19: systematic review of the literature and analysis

Abstract

During the Coronavirus Disease 2019 (COVID-19) pandemic, an increasing number of fungal infections associated with SARS-CoV-2 infection have been reported. Among them, cryptococcosis could be a lifethreatening disease. We performed a Systematic Review (PRISMA Statement) of cryptococcosis and CO-VID-19 co-infection, case report/series were included: a total of 34 cases were found, then we added our case report. We collected patients' data and performed a statistical analysis comparing two groups of patients sorted by outcome: "dead" and "alive". Three cases were excluded for lack of information. To compare categorical data, we used a Fisher-exact test (a=0.05). To compare quantitative variables a U Mann-Whitney test was used (a=0.05), with a 95% Confidence Interval. A total of 32 co-infected patients were included in the statistical analysis. Mortality rate was 17/32 (53.1%): these patients were included in "dead" group, and 15/32 (46.9%) patients survived and were included in "alive" group. Overall, males were 25/32 (78.1%), the median age was 60 years (IQR 53-70) with non-statistically significant difference between groups (p=0.149 and p=0.911, respectively). Three variables were associated with mortality: ARDS, ICU admission and inadequate treatment. Overall, 21 out of 24 (87.5%) patients were in ARDS with a statistically significant difference among two groups (p=0.028). ICU admission for COVID-19 was observed in 18/26 (69.2%), more frequently among dead group (p=0.034). Finally, 15/32 (46.9%) patients had adequate treatment (amphotericin B + flucytosine for invasive cryptococcosis) mostly among alive patients (p=0.039). In conclusion, mortality due to cryptococcal infection among COVID-19 patients remains high but an early diagnosis and appropriate treatment could reduce mortality.

COVID-19 associated with cryptococcosis: a scoping review

“…Previously, ICU admission and MV were reported as important risk factors in literature reviews on the subject. 50 , 72 Our findings were similar for both variables; in addition to these, we also found that secondary infections/co-infections (the majority being bacterial infections) turned out to be a risk factor associated with mortality. It should be noted that it was difficult to distinguish between both according to the information provided by the papers, thus for the patients in the present review it would be an additional infection to cryptococcosis and COVID-19 and could be either a co-infection or secondary infection.…”

“…Overall, cryptococcosis in COVID-19 patients is not as frequent compared to other fungal infections such as mucormycosis 70 and aspergillosis, 71 widely reported in the literature, in COVID-19 patients, although it can still be life-threatening in light of the high mortality, ranging between 50% and 65%. 23 , 50 , 72 , 73 Our analysis showed that the majority of patients were men and around 60 years of age, and in addition, it was determined that both male sex and age are risk factors associated with mortality. The male sex is related to the incidence, severity, and mortality of COVID-19.…”

“…The review by Pipitone et al . 50 reported that inadequate cryptococcal treatment (non-CAT) and mortality were associated, unlike a meta-analysis in which the duration and type of antifungal therapy (CAT versus monotherapy) were not associated with all-cause mortality in patients with COVID-19 and fungal secondary infections. 89 The latter is similar to what we found in our analysis.…”

“…Of the total number of patients, the male sex was affected in 48 cases while the median age was 60 years, with statistically significant differences between the two groups: alive versus dead in both variables ( p value = 0.0203 and 0.0332, respectively). Of 60 patients with available information, 31 were from the United States 15 , 16 , 19 – 40 (51.6%), 8 from Peru 41 (13.3%), 7 from Brazil 14 , 42 – 47 (11.6%), and 2 from India 48 , 49 and Italy 50 , 51 (3.3% each), while the rest were from Canada, 52 Colombia, 53 China, 54 the Czech Republic, 55 the UK, 56 Uganda, 57 Qatar, 58 Lebanon, 59 Spain, 60 and Germany 61 ( n = 1; 1.7% each).…”