key: cord-0762175-lfrzkrzq
authors: Meshram, Hari Shankar; Kumar, Deepak; Kute, Vivek B
title: Rare and unusual follow-up sequelae of COVID-19: Splenic mucormycosis in a renal transplant recipient.
date: 2021-10-02
journal: Transplant Proc
DOI: 10.1016/j.transproceed.2021.09.010
sha: 0e2a6ff151945e4b51c4f355f9981c5514d0333f
doc_id: 762175
cord_uid: lfrzkrzq

Background Coronavirus disease (COVID-19) has been reported with adverse outcomes in the transplantation communities. Mucormycosis even though a rare infection, has been classically being linked to organ transplantation and is associated with exceptionally high morbidity and mortality. The double infection of mucormycosis in COVID-19 is a lethal combination to be encountered in this pandemic era but is sparsely described in organ transplantation. Case presentation Here we report a young diabetic kidney transplant recipient who acquired severe COVID-19, followed by disseminated mucormycosis. The patient was a health care worker who developed severe COVID-19 for which he received remdesivir, anticoagulation and dexamethasone. There was no immunomodulatory therapy used. His maximum oxygen support was bilevel positive pressure ventilation (Bi-PAP). His sugars were frequently deranged during the stay. He developed secondary sepsis with Klebsiella, followed by non-healing lung consolidation. Later on, he developed pleural effusion and splenic abscess which was detected incidentally. He underwent an emergency splenectomy, the culture of which yielded mucormycosis. He was started with liposomal amphotericin B 5mg/kg was started. The patient deteriorated, and a repeat laparotomy yielded gastric perforation, with pus culture showing mucormycosis. The patient succumbed to death after an extensive long course of hospital stay. Conclusion We conclude that the diagnosis and management of this dual infection in this pandemic era is extremely challenging. The unusual location of mucormycosis complicating the COVID-19 course in our report, calls for a meticulous approach to opportunistic fungal infections in COVID-19 positive organ transplant recipients, especially with diabetes.

Here we report a young diabetic kidney transplant recipient who acquired severe COVID-19, followed by disseminated mucormycosis. The patient was a health care worker who developed severe COVID-19 for which he received remdesivir, anticoagulation and dexamethasone. There was no immunomodulatory therapy used. His maximum oxygen support was bilevel positive pressure ventilation (Bi-PAP). His sugars were frequently deranged during the stay. He developed secondary sepsis with Klebsiella, followed by non-healing lung consolidation. Later on, he developed pleural effusion and splenic abscess which was detected incidentally. He underwent an emergency splenectomy, the culture of which yielded mucormycosis. He was started with liposomal amphotericin B 5mg/kg was started. The patient deteriorated, and a repeat laparotomy yielded gastric perforation, with pus culture showing mucormycosis. The patient succumbed to death after an extensive long course of hospital stay.

We conclude that the diagnosis and management of this dual infection in this pandemic era is extremely challenging. The unusual location of mucormycosis complicating the COVID-19 course in our report, calls for a meticulous approach to opportunistic fungal infections in COVID-19 positive organ transplant recipients, especially with diabetes.

Organ transplantation is an established risk factor for COVID-19 morbidity and mortality. 1 Mucormycosis is well described as an opportunistic infection that is exclusive to immunosuppressed individuals and hence, they are more prone to the dual infection of COVID-19 and mucormycosis amid this pandemic. COVID-19 outcomes in organ transplantation have been extensively reviewed, but data about mucormycosis complicating the COVID-19 course is majorly limited to the general population. In addition, there are only a few such reports on organ transplant recipients. 2, 3 The logistics, diagnosis, and management of this dual infection are enormous, and so is the linked fatality. A multidisciplinary approach to the problem is required to improve the outcomes in such cases, but in pandemic times it becomes a difficult task to accomplish. In recent times, the Indian subcontinent dealt with the twin crisis of mucormycosis and COVID-19 in the second wave of the pandemic. 4, 5 Herein we describe a case of severe COVID-19 who developed disseminated mucormycosis in the follow-up period. This report will help in creating awareness for such complications in COVID-19 among transplant physicians, as the presentation of this entity was camouflaged.

The patient was a 41-year-old gentleman with IgA nephropathy who was transplanted 2 years back with a brother donor and thymoglobulin induction (3 mg/kg). He had an excellent graft function (baseline serum creatinine of 1.01 m/dl) and was on a combination of steroid 5mg, mycophenolate 360mg TDS and tacrolimus 0.05 mg/kg. He had developed post-transplant diabetes mellitus and had good glycemic control before COVID-19. He was unvaccinated for COVID-19. He got admitted with symptoms of fever, cough and breathlessness, and was diagnosed with severe COVID-19. The mainstay of COVID-19 therapy was oxygen support (BiPAP was the highest oxygen support required); IV remdesivir, anticoagulation and dexamethasone (8 mg once daily for 5 days). His blood sugars were frequently high during the stay. Among the laboratory markers, he had lymphopenia (300 cells/mm 3 ), thrombopenia (80,000 cells/mm 3 ), high ferritin (1239 ng/ml), D-dimers (3400 mmol/L) and interleukin-6 levels (67 ng/ml), C-reactive protein(102 mg/L). Figure 1 shows the detailed summary of the case. He developed secondary sepsis, evidenced by blood culture on day 6 of admission with klebsiella sensitive to meropenem and colistin. He was discharged and had a homestay of 3 days before his re-admission for persistent breathing difficulty. He was on IV antibiotics at home also. His repeat chest scans during this readmission reported necrotizing left lobe pneumonia, for which I V colistin was added. No prophylactic antifungal was added. As fever and dyspnea persisted even after appropriate antibiotics, his X-ray chest was repeated which showed large left-sided effusion along with splenic abscess in concurrent abdominal sonography. He underwent emergency splenectomy and the pus culture showed Rhizopus mucormycosis. He was started with I V liposomal Amphotericin B 5mg/kg treatment for mucormycosis bur he developed secondary sepsis when he developed fever and abdominal tenderness, and so he was re-explored which showed stomach perforation and pus drainage of around 500ml. He died 2 days after surgery. The pus culture reported the same species of mucormycosis again.

COVID-19 outcomes in renal transplantation have been vastly studied but there are fewer data about this dual infection of mucormycosis in transplant patients. The world has seen a surprisingly high number of this dual infection in this pandemic. 6 The exact reason for this surge of mucormycosis after COVID-19 is multiple, but chronic immunosuppression and diabetes are considered some possible reasons for this lethal combination as in our case. 7 The reasons for death in our report is also contributed to the delay in diagnosis. But, the unusual location in our scenario was unexpected and splenic mucormycosis is most difficult to diagnose compared to rhino cerebral mucormycosis which has some obvious signs and symptoms. The non-remitting nature of fever in COVID-19, despite good antibiotic coverage would have prompted us for an underlying fungal infection.

Another important point is that that patient was unvaccinated for COVID-19. This underscores the importance of vaccination, especially for such high-risk patients. The novelty of this report lies in the fact that there are no previously reported cases of splenic mucormycosis in a transplant patient with COVID-19. The most common presentation of mucormycosis is this pandemic is rhino-orbital. The unusual occurrence of mucormycosis in our report emphasizes the need for a meticulous approach in cases with persistent fever after COVID-19. We also suggest controlling sugars in a standardized manner, as steroids and stress from infection may lead to further deranged sugars in a COVID-19 patient. This step is important as various published literature of this dual infection, has accompanying diabetes as a co-morbidity. The exact dosing of amphotericin B and tailoring of immunosuppression in such cases is not known, but the goal is to maintain a balance between infection and rejection. We consider the elderly, diabetes, and severe COVID-19 to be the most important risk factors for developing this dual infection in this pandemic. Henceforth, we suggest screening for mucormycosis to all such organ transplant patients with COVID-19. The screening must include symptoms like eye swelling, diplopia, face swelling, abdominal pain, black discharge from nose or mouth, breathlessness after discharge. We also suggest all such prone discharged patients be properly informed about the danger signs of developing mucormycosis and look for any signs post-discharge.

In conclusion, dealing with mucormycosis in COVID-19 is associated with high morbidity and mortality. A multidisciplinary approach to transplant patients with post-COVID-19 sequelae is required to avoid any undesirable consequences. Increasing awareness and timely treatment is the key step in the management of this dual infection.

Legend for figure 1: Detailed summary of the case.

Clinical Profile and Outcome of COVID-19 in 250 Kidney Transplant Recipients: A Multicenter Cohort Study From India

Mucormycosis in post-COVID-19 renal transplant patients: A lethal complication in follow-up

Mucormycosis associated with covid19 in two kidney transplant patients

BBC. Mucormycosis: the black fungus hitting Covid-19 patients

Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis

Mucor in a Viral Land: A Tale of Two Pathogens

Mucormycosis in renal transplant recipients: review of 174 reported cases