Edited by: Chia-Ter Chao, National Taiwan University Hospital Bei-Hu Branch, Taiwan
Reviewed by: Karl Martin Wissing, University Hospital Brussels, Belgium; Chih-Chin Kao, Taipei Medical University Hospital, Taiwan
This article was submitted to Nephrology, a section of the journal Frontiers in Medicine
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The rare and severe adverse effects associated with coronavirus disease of 2019 (COVID-19) vaccination have been under-appreciated, resulting in many instances of inappropriate management. We describe the case of an elderly woman who developed anti-neutrophil cytoplasmic antibody-associated vasculitis with pulmonary renal syndrome approximately 3 weeks after the first dose of COVID-19 mRNA vaccination (Moderna). Her nasopharyngeal polymerase chain reaction test for the COVID-19 RNA virus was negative. Gross hematuria, heavy proteinuria, acute renal failure (serum creatinine up to 6.5 mg/dL), and hemoptysis coupled with a marked increase in serum anti-myeloperoxidase-O antibody were observed. Renal biopsy showed severe vasculitis with pauci-immune crescent glomerulonephritis. The pulmonary hemorrhage was resolved and renal function improved following combined plasma exchange and the administration of systemic steroids and anti-CD20 therapy. The early examination of urinalysis and renal function may be crucial for identifying glomerulonephritis and acute renal failure in susceptible patients after COVID-19 vaccination.
The global pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to a significant loss of life, as well as severe disruptions to economies and social activities worldwide. Coronavirus disease of 2019 (COVID-19) infection will progress to acute respiratory distress syndrome in approximately 15–30% of hospitalized patients (
Due to the enhancement of the immune response by COVID-19 vaccinations, rare and serious adverse effects have been recently reported. These include vaccine-induced immune thrombotic thrombocytopenia and immune-mediated myocarditis associated with the use of viral vector vaccines and mRNA vaccines, respectively (
A 70-year-old healthy woman was hospitalized due to worsening hematuria, proteinuria, and acute renal failure. She did not have a history of prior COVID-19 infection or medical illness (with the exception of urinary tract infection, from which she had recovered in March). The patient reported that she experienced dizziness, headache, and hematuria 1 week after the first dose of mRNA-1273 COVID-19 vaccination (Moderna); this was followed by a progressive elevation of blood pressure, gross hematuria, and decreased urine levels 2 weeks later. She was diagnosed with acute renal failure (with an incremental serum creatinine level ranging from 1.0 to 3.5 mg/dL) at a district hospital and were subsequently referred to medical center.
The patient was alert and oriented on admission, but developed hemoptysis and exertional dyspnea. Her supine blood pressure, heart rate, and body temperature were 160/90 mmHg, 88 beats/min, and 37.8°C, respectively. Pulse oximetry indicated that her blood oxygen saturation was 96% with 28% oxygen support. The following features were noted: pale conjunctiva, shallow breathing, rhonchi, rales over the left lung field, and bilateral leg edema. The rest of her physical examination was unremarkable. Two nasopharyngeal swabs were obtained for the COVID-19 polymerase chain reaction test, both yielding negative results. Urinalysis revealed more than 100 red blood cells per high-power field and nephrotic-range proteinuria (urine protein creatinine ratio, 4,384 mg/g). Abnormal laboratory test values included hemoglobin (8.7 g/dL), creatinine (3.5 mg/dL), blood urea nitrogen (88 mg/dL), albumin (3.1 g/dL), and C-reactive protein (2.7 mg/dL) levels. Arterial blood gas analysis showed pH, partial pressure of carbon dioxide, partial pressure of oxygen, and HCO3 values of 7.45, 26.1 mmHg, 86.3 mmHg, and 17.5 mmol/L, respectively.
Pulmonary radiography and computed tomography showed bilateral peribronchial consolidations, which were predominantly located in the left upper lung (
The pulmonary hemorrhage was resolved and renal function was improved (serum creatinine, 2.5 mg/dL) 3 weeks later, following the continuous administration of combined plasma exchange, systemic steroid, and anti-CD20 therapy (500 mg) (
Time and therapeutic course of anti-neutrophil cytoplasmic antibody-associated vasculitis with rapidly progressive glomerulonephritis following COVID-19 vaccination. PE, plasma exchange; P.S., pulse steroid; ANCA, anti-neutrophil cytoplasmic antibody; Anti-MPO, anti-myeloperoxidase-O, mo., month. Daily pulse steroid dosage: intravenous methylprednisolone 1,000 mg daily in the first course, then 500 mg daily in the following three courses.
The patient in the present case showed typical features of AAV with RPGN and pulmonary involvement during the COVID-19 pandemic. While patients with COVID-19 infection may exhibit coexisting pneumonia and acute renal failure, thus mimicking pulmonary renal syndrome, this possibility was excluded by two negative COVID-19 polymerase chain reaction tests. As there were no other identifiable causes (e.g., other infections, malignancies, or drugs) of AAV, the etiological factor was concluded to be the patient's first dose of the COVID-19 mRNA vaccine.
To date, eight cases (including the present report) have shown temporal links between the development of
AAV with RPGN following COVID-19 vaccination.
18 | 52/M | HTN | Moderna | 2 weeks after 2nd dose | Headache Weakness | Dysmorphic RBC | SCr:8.4 mg/dL, | Anti-PR3 (+) | Pauci-immune necrotizing and crescentic GN | None | Hemodialysis Rituximab CYC | Dialysis-dependent |
29 | 81/M | Healthy | Moderna | Shortly after 2nd dose | Flu-like symptoms | NA | AKI | Anti-PR3 (+) | Pauci-immune crescentic GN with capillary necrosis & vasculitis | Pulmonary necrotic masses | Plasma exchange Pulse steroid CYC | Improved renal function |
310 | 77/M | Healthy | AstraZeneca | 4 weeks after 1st dose | Fever, Night sweating, |
NA | SCr:2.7 mg/dL, CRP: 20 mg/dL | NA | Non-caseating, non-necrotizing granuloma | None | Pulse steroid | Resolved renal function |
411 | 78/F | DM, HTN | Pfizer-BioNTech | Immediate after 2nd dose | Nausea, vomiting, diarrhea, lethargy | Dysmorphic RBC UACR:2,050 mg/g | SCr:3.5 mg/dL, | Anti-MPO (+) | Necrotizing crescentic GN | None | Rituximab | Improved renal function(SCr: 1.7mg/dL) |
512 | 29/F | Congenital cystic lung disease | Pfizer-BioNTech | 7 weeks after 2nd dose | NA | HematuriaUACR:633 mg/g | SCr: 1.9 mg/dL | Anti-MPO (71 AU/ml) | Pauci-immune crescent GN | Chronic lung infiltration | Pulse steroid Rituximab CYC | Improved renal function(SCr: 1.0 mg/dL) |
613 | 63/M | Healthy | AstraZeneca | 1 week after 1st dose | Hemoptysis Flu-like symptoms | Microscopic hematuria | SCr:2.9 mg/dL | Anti-MPO (12 IU/ml) | Focal class of pauci-immune crescent GN | Infiltration over LLL | Pulse steroid | Improved renal function(SCr: 2.1 mg/dL) |
714 | 79/F | HTN | Pfizer-BioNTech | 2 weeks after 2nd dose | Weakness Upper thigh pain | HematuriaUPCR: |
SCr: 6.57 mg/dL Eosinophils: |
Anti-MPO (>134 IU/ml) | Vasculitis with pauci-immune crescent GN | CK: 14,243 U/LMyoglobinemia >12,000 μg/L | Pulse steroid CYC | Resolved renal function |
8 | 70/F | UTI | Moderna | 3 weeks after 1st dose | Headache Hemoptysis Hematuria | Dysmorphic RBCUPCR:4,384 mg/g | SCr:3.5 |
Anti-MPO (378 IU/ml) | Vasculitis with pauci-immune crescent GN | Pulmonary vasculitis | Plasma exchange Pulse steroid Rituximab | Improved renal function(SCr: 2.5 mg/dL) |
COVID-19 vaccination with different strategies and designs can trigger and enhance innate and adaptive immunity by activating neutrophils, T cells, and B cells (
The wide-range timeline of AAV activation following COVID-19 vaccination has not been elucidated. AAV with RPGN after COVID-19 vaccination could be masked by initial non-specific prodromal symptoms, making early recognition difficult. For patients with the pre-existing asymptomatic or oligosymptomatic autoimmune diseases, COVID-19 vaccination may accelerate the immune activation more rapidly, compared to other
Given the persistent COVID-19 pandemic and the emergence of variants of concern, the rare incidence of severe adverse events after COVID-19 vaccination should not be a reason for vaccine hesitancy. Nevertheless, our patient highlighted the potential development of AAV with RPGN and pulmonary involvement following COVID-19 vaccination, suggesting that the early examination of urinalysis and renal function is imperative for the prompt recognition of glomerulonephritis and acute renal failure in vulnerable patients. The potential causal relationship between COVID-19 vaccination and the development of
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.
The studies involving human participants were reviewed and approved by Ethics Committee on Human Studies at Tri-Service General Hospital in Taiwan. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
C-CC authored the manuscript, with contribution from all authors. H-YC prepared the figure. C-CL was consulted for rheumatology problems. S-HL supervised the article. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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anti-neutrophil cytoplasmic antibody-associated vasculitis
rapidly progressive glomerulonephritis.