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Management of antineutrophil cytoplasmic antibody–Associated vasculitis with COVID-19: A single center experience


 Nephrology Division, Superspeciality Hospital, Government Medical College, Srinagar, Jammu and Kashmir, India

Date of Submission07-Oct-2021
Date of Acceptance28-Apr-2022
Date of Web Publication29-Sep-2022

Correspondence Address:
Muzamil Latief,
2nd Floor Dialysis Unit, Superspeciality Hospital Shireenbagh, Government Medical College, Srinagar - 190 010, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijn.ijn_423_21

  Abstract 


Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) patients particularly presenting as rapidly progressive glomerulonephritis (RPGN) are at extremely high risk of progressing to end-stage kidney disease (ESKD); therefore, timely intervention is important. We describe our experience of managing six AAV patients who were on treatment (induction phase) and developed COVID-19. Cyclophosphamide was stopped till RT-PCR for SARS-CoV-2 was reported negative and patient had improved symptomatically. Out of our six patients, one died. Subsequently, cyclophosphamide was successfully resumed in all the surviving patients. In patients of AAV with COVID-19, close monitoring and withholding of cytotoxic medication and continuing steroids till active infection subsides is an effective treatment strategy until more and more data from well-conducted largescale studies become available for guidance.

Keywords: AAV, ANCA, COVID-19, cyclophosphamide



How to cite this URL:
Latief M, Mir TH, Wani ML. Management of antineutrophil cytoplasmic antibody–Associated vasculitis with COVID-19: A single center experience. Indian J Nephrol [Epub ahead of print] [cited 2022 Dec 10]. Available from: https://www.indianjnephrol.org/preprintarticle.asp?id=357227


  Introduction Top


As the pandemic of coronavirus disease 2019 (COVID-19) continues to rage, it is creating more and more challenges for the healthcare fraternity to deal with the complex interplay of disease processes. As COVID-19 situation continues to unfold, the guidance for management of COVID-19 and its ramifications on other disease management is derived from experiences from different centers across the globe. COVID-19-related clinical practice continues to be updated with respect to various kidney diseases, dialysis and kidney transplantation.[1–3] Remdesivir, among other medications, has emerged as a potential candidate for the management of COVID-19. As remdesivir has low water solubility, sulfobutylether-β-cyclodextrin (SBECD) is added to it. SBECD is dialyzable and hence can be used in patients with renal failure and subsequently removed using renal replacement therapy (RRT).[4],[5] The temporal relation of ANCA vasculitis with COVID-19 observed includes pre-infection, during infection and following infection. Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) patients particularly presenting as rapidly progressive glomerulonephritis (RPGN) are at extremely high risk of progressing to end-stage kidney disease (ESKD) and therefore timely intervention cannot be overemphasized.[6] The guidance on management of AAV patients on immunosuppression (induction phase in particular) who develop COVID-19 remains largely based on case reports and small case series.[1],[3],[4],[7],[8],[9] We describe our experience of managing AAV patients who were on treatment (induction phase) and developed COVID-19.


  Case Series Top


The age range of our series was 36–76 years with 3 males and 3 females [Table 1] and [Table 2]. All of our patients were on cyclophosphamide and steroids as part of induction therapy, and two of them had received plasmapheresis previously; none of our patient had received rituximab as induction agent. Four of our patients required oxygen support and two did not require any oxygen support. One patient with anti-PR3 AAV, who had received methylprednisolone 500 mg daily for 3 days and cyclophosphamide pulse 10 days prior to COVID-19, expired. This patient had been severely hypoxemic, had leucopenia and required mechanical ventilation. She received remdesivir, antibiotics, anticoagulation and expired on day 5 of hospitalization. In the rest of the patients, cyclophosphamide was stopped till RT-PCR result was negative and patient had improved symptomatically. All of our surviving patients were RT-PCR negative at hospital discharge. Subsequently, cyclophosphamide was successfully resumed in all of the surviving patients [Table 2]. We observed that interruption of cytotoxic agent and continuing steroids along with other measures, particularly anticoagulation, are viable options in the management of this complex situation.
Table 1: Patient summary prior to developing COVID-19

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Table 2: Clinical and demographic characteristics, and management strategies

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  Discussion Top


As immunosuppression puts patients at increased risk of COVID-19 infection and complications thereof, a careful balance between the intensity of immunosuppression (needed for active renal or systemic disease) and COVID-19 severity is needed. The management guidance regarding COVID-19 per se and the underlying renal diseases like lupus, glomerulonephritis, and vasculitis continues to evolve as more and more data accumulates. So far, the evidence is based on smaller studies and case series. In a case series by Nupur N. Uppal et al.,[10] two patients with COVID-19 and Pauci-immune glomerulonephritis (GN) were managed with steroids and rituximab and both patients improved. In another study, two patients were reported by Tugba Izci Duran et al.[11] who had developed AAV following COVID-19 and were managed with IVMP/CYC and with plasmapheresis in one patient who continues to be dialysis dependent. Sam Kant et al.[8] suggested that induction immunosuppressive agents can be employed shortly after improvement of acute COVID-19 presentation to treat AAV. Our study too suggests that immunosuppressive agents can be resumed as soon as COVID-19 settles. Sam Kant et al.,[9] in another study, concluded that the incidence of COVID-19 in patients with AAV is similar to that of the general population and that the care of AAV patients has been affected by the ongoing pandemic. They suggested that reduction of immunosuppression may not be needed or may prove detrimental because of the risk of AAV relapse. We suggest that in patients on AAV induction contracting COVID-19, withholding cytotoxic agent and close monitoring till infection settles is a pragmatic course to take. International Registry of COVID infection in glomerulonephritis (IRoc-GN) compared 40 patients with glomerulonephritis and COVID-19 to 80 COVID-positive control cases without glomerulonephritis and found that patients with GN had higher mortality (15%) compared to patients without GN (5%). Similarly, acute kidney injury (AKI) was higher in the GN group (39% vs 14% respectively), and therefore patients with GN and COVID-19 must be monitored closely, particularly when patients have hypoalbuminemia.[7] In a recent study that included 16 patients with COVID-19 who were on AAV induction treatment, it was found that seven (44%) of these patients required hospitalization and four patients died.[12] In our study, five of the six patients (83.3%) required hospitalization and one patient (16.6%) died. [Table 3] shows a comparison of our study with the other studies.
Table 3: Comparison of our study with other studies

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  Conclusion Top


In patients of AAV with COVID-19, close monitoring and withholding cytotoxic medication and continuation of steroids till active infection subsides is an effective treatment strategy till more and more data from well-conducted largescale studies becomes available for guidance.

Acknowledgement

We are thankful to Mr. Qayoom and Mr. Tariq for the help in the conduct of this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kronbichler A, Gauckler P, Windpessl M, Il Shin J, Jha V, Rovin BH, Oberbauer R. COVID-19: Implications for immunosuppression in kidney disease and transplantation. Nat Rev Nephrol 2020;16:365-7.  Back to cited text no. 1
    
2.
Latief M, Shafi O, Hassan Z, Farooq S, Abbas F. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in Kidney transplant patients: A case series and literature review. Med J Islam Repub Iran 2021;35:17. doi: 10.47176/mjiri.35.17.  Back to cited text no. 2
    
3.
Guilpain P., Le Bihan C., Foulongne V. Rituximab for granulomatosis with polyangiitis in the pandemic of covid-19: Lessons from a case with severe pneumonia. Ann Rheum Dis 2020;80:e10.  Back to cited text no. 3
    
4.
Daniel P, Raad M, Waked R. COVID-19 in a patient treated for granulomatosis with polyangiitis: Persistent viral shedding with no cytokine storm. Eur J Case Rep Intern Med 2020;7:001922. doi: 10.12890/2020_001922.  Back to cited text no. 4
    
5.
Luke DR, Wood ND, Tomaszewski KE, Damle B. Pharmacokinetics of sulfobutylether-b-cyclodextrin (SBECD) in subjects on hemodialysis. Nephrol Dial Transplant 2012;27:1207-12.  Back to cited text no. 5
    
6.
Kitching AR, Anders HJ, Basu N, Brouwer E, Gordon J, Jayne DR, et al. ANCA-associated vasculitis. Nat Rev Dis Primers 2020;6:71. doi: 10.1038/s41572-020-0204-y.  Back to cited text no. 6
    
7.
Waldman M, Soler MJ, García-Carro C, Lightstone L, Turner-Stokes T, Griffith M, et al. Results from the IRoc-GN international registry of patients with COVID-19 and glomerular disease suggest close monitoring. Kidney Int 2021;99:227-37.  Back to cited text no. 7
    
8.
Kant S, Raman G, Damera P, Antiochos B, Seo P, Geetha D. Characteristics and outcomes of COVID-19 in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Kidney Int Rep 2021;6:806-9.  Back to cited text no. 8
    
9.
Kant S, Morris A, Ravi S, Floyd L, Gapud E, Antichos B, et al. The impact of COVID-19 pandemic on patients with ANCA associated vasculitis. J Nephrol 2021;34:185-90.  Back to cited text no. 9
    
10.
Uppal NN, Kello N, Shah HH, Khanin Y, De Oleo IR, Epstein E, et al. De Novo ANCA-associated vasculitis with glomerulonephritis in COVID-19. Kidney Int Rep 2020;5:2079-83.  Back to cited text no. 10
    
11.
Izci Duran T, Turkmen E, Dilek M, Sayarlioglu H, Arik N. ANCA-associated vasculitis after COVID-19. Rheumatol Int 2021;41:1523-9.  Back to cited text no. 11
    
12.
Salas A, Kant S, Floyd L, Kratky V, Brix SR, Prendecki M, et al. ANCA vasculitis induction management during the COVID-19 pandemic. Kidney Int Rep 2021;6:2903-7.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

 
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