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Covid-19-associated mucormycosis in patients with renal failure
[To cite: Patil A, Rao N, Kumar K, Modi T, Gandhi C, Deb S, et al. Covid-19-associated mucormycosis in patients with renal failure [Correspondence]. Natl Med J India 2022;35:187–9.]
A surge of an invasive fungal infection, mucormycosis has been reported in association with Covid-19. There is no reported literature yet in a subset of patients with renal failure. These patients tend to have severe Covid-19, warranting the use of steroids, which can potentially increase the risk of mucormycosis. Uraemia and metabolic acidosis are additional risk factors for this fungal infection in these patients.
Three hundred and eighty-seven patients were admitted with Covid-19 and renal failure between March 2020 and May 2021 at a tertiary care centre in western India. We studied 4 of these patients (1%) who developed mucormycosis and 1 patient who had a mild respiratory illness 2 weeks after the Covid-19 (Covishield) vaccine. The reported efficacy of these vaccines is 60%–65%, 4 weeks after a single dose.1 Hence, it is likely that this patient had Covid-19 due to high community transmission. As the patient did not visit the hospital during this illness, the diagnosis of Covid-19 could not be made.
All these patients were on haemodialysis for either acute kidney injury (AKI), AKI on chronic kidney disease (CKD), or end-stage renal disease (ESRD; Table I). Four patients with uncontrolled diabetes had received high-dose steroids and had hypoxaemia on admission. All patients had rhino-orbital involvement with 3 patients having additional cerebral involvement and 1 had pulmonary involvement. Median (interquartile range) time to onset after diagnosis of Covid-19 was 13 (9–22.5) days. Uncontrolled diabetes was defined as fasting blood sugar >130 mg/dl or post-prandial blood sugar >180 mg/dl or HbA1c >7% according to the glycaemic recommendations given by the American Diabetes Association.2
| Age, gender | Diagnosis | Serum creatinine (rng/dl) | Severity Covid- 19* |
Diabetes | Hypoxaemia | Cumulative steroid dose equivalent to dexamethasone (mg) |
Time of onset post Covid-19‡ |
Site of involve-ment |
Micro- biological diagnosis (KOH smear and fungal culture) | Antifungal therapy§ | Timing of surgical intervention (if done) | Renal outcome |
Patient outcome |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Base-line | On admission | Un- controlled† | Blood sugar on admission (mg/dl) | HbAlc (if available) | Timing | Duration (days) | |||||||||||
| 30, woman | ESRD | na | na | Severe | No | 93 | na | Yes | 75 | Day 15 | Rhino- orbital- cerebral |
Rhizopus sp | Day 2 | 45 | Day 7 | ESKD | Alive |
| 50, man | AKI on CKD |
1.8 | 8.6 | Severe | Yes | 353 | Not available |
Yes | 460 | Day 12 | Rhino- orbital |
Rhizopus sp and Mucor sp |
Day 2 | 45 | Day 7 | Serum creatinine 1.8 on discharge, stable after 3 months follow-up |
Alive |
| 70, man | AKI | na | 4.4 | Severe | Yes | 567 | 8.6% | Yes | 24 | Day 6 | Rhino- orbital |
Patient expired before complete evaluation |
Day 3 | 10 | Not done |
na | Died on day 14 |
| 55, man | AKI on CKD |
2.5 | 9 | Severe | Yes | 468 | 12% | Yes | 68 | Day 13 | Rhino- orbital- cerebral |
No growth | Day 1 | 45 | Day 6 | Serum creatinine 2.7 on dis- charge, lost to follow-up |
Alive |
| 40, man | AKI on CKD |
Not available | 18.5 | Mild Covid-19-like illness day 15 post-first dose of Covishield vaccine | Yes | 250 | Not available |
No | 0 | Day 30 after mild Covid-19- like illness |
Rhino- orbital- cerebral and pulmonary |
No growth | Day 1 | 30 | Day 25 | na | Died on day 30 |
CAM occurrence of proven mucormycosis in patients with Covid-19, the diagnosis of Covid-19 was made by RT-PCR (reverse transcription-polymerase chain reaction), mucormycosis was defined as compatible with clinical, radiological manifestations with a microbiological diagirosis of fungi of tire order Mucorales with either KOH smear and/or fungal culture. * mild: as^nptomatic/s^nptomatic upper respiratory infection with or without comorbid conditions (>60 years, obesity, diabetes mellitirs, hypertension, coronary artery disease, chronic lung disease, chronic kidney disease,immunocompromised state, immunosuppressive drugs) severe SpOj (oxygen satirration) <94% or requiring oxygen (hypoxaemia) t fasting blood sugar >130 mg/dl or postprandial blood sugar >1S0 m g/dl or HbAlc >7% t diagnosis of Covid-19 being day 0§ amphotericin B deoxycholate (conventional) at 0.7-1 mgkg/day DM diabetes mellitirs AKI acute kidney injury CKD chronic kidney disease ESRD end-stage renal disease NA not applicable 1 based on clinical presentation and radiological extent
We also included detailed data on the timing of medical and surgical intervention after the diagnosis of mucormycosis. All patients were treated with amphotericin B deoxycholate (conventional) at dosages of 0.7–1 mg/kg/day and 4 patients underwent immediate surgical intervention. Median (IQR) duration of antifungal therapy was 45 (20–45) days and was continued until clinical and radiological resolution of active disease, which was assessed after surgical intervention. Timely surgical intervention could not be done in 2 patients due to haemodynamic instability. These 2 patients died within 6 weeks of the onset of illness. One had AKI, the other had AKI on CKD and they died while being on dialysis. Of the remaining 3 patients, one was on dialysis as a result of ESRD, 2 had AKI on CKD. Serum creatinine of both these patients returned to baseline on discharge. One of these 2 patients had followed up after 3 months of illness and had stable kidney function, whereas the other was lost to follow-up.
This study emphasizes that renal failure is an important risk factor for Covid-19-associated mucormycosis (CAM). Severe metabolic acidosis and uraemia, which is associated with impaired neutrophil chemotaxis, impaired activation of helper T cells make this group of patients a vulnerable population for acquiring this fungal infection. Our patients had uncontrolled diabetes, hypoxaemia and received high-dose steroids which were concurrent with the results of Patel et al.,3 who reported that high-dose steroids and hypoxaemia were independently associated with the development of mucormycosis.The majority of our patients were managed with a combination of surgery and antifungal therapy. Mortality in 2 patients was possibly due to an inability to do and a delay in surgical intervention, respectively. These results were similar to that from the existing literature,3 which reported that the combination of surgery and antifungal therapy was associated with better survival.
To conclude, a high degree of suspicion of mucormycosis is required in patients with Covid-19 and renal failure with an immediate medical and surgical intervention being necessary to reduce mortality.
References
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- Multicenter epidemiologic study of coronavirus disease-associated mucormycosis, India. Emerg Infect Dis. 2021;27:2349-59.
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