ABSTRACT
We here report the first case of anti-proteinase 3-positive anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis following the severe acute respiratory syndrome coronavirus 2 Pfizer-BioNTech vaccine presenting with prominent liver involvement and alveolar haemorrhage. Two weeks after vaccination, a 49-year-old man developed inflammatory arthralgias and hypertransaminasaemia. Two months later, fever and haemoptysis appeared; the patient tested positive for anti-proteinase 3 autoantibodies. High-dose steroids and rituximab were started, and complete remission was achieved. Systemic autoimmune diseases, including ANCA-associated vasculitis, should always be considered in the differential diagnosis of hypertransaminasaemia, especially when the clinical context is suspicious.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , COVID-19 , Male , Humans , Middle Aged , Antibodies, Antineutrophil Cytoplasmic , COVID-19 Vaccines/adverse effects , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/prevention & control , Myeloblastin , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/etiology , Vaccination , LiverABSTRACT
Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.
Subject(s)
Acute Lung Injury/etiology , Blood Coagulation Disorders/etiology , COVID-19/pathology , Cytokine Release Syndrome/etiology , Hemorrhage/etiology , Lipopolysaccharides/adverse effects , Lung Diseases/etiology , Receptor, Angiotensin, Type 1/metabolism , STAT Transcription Factors/metabolism , Signal Transduction , Acute Lung Injury/pathology , Animals , Blood Coagulation Disorders/pathology , COVID-19/etiology , Cytokine Release Syndrome/pathology , Disease Models, Animal , Hemorrhage/pathology , Janus Kinases , Lung Diseases/pathology , Male , Rats , Rats, WistarABSTRACT
BACKGROUND: Early diagnosis of diffuse alveolar haemorrhage (DAH) can be extremely difficult, as the common clinical picture is often attributed to more common clinical conditions. High degree of suspicion is key to diagnosis which can be much more difficult during the coronavirus disease 2019 (COVID-19) pandemic. CASE SUMMARY: A 61-year-old man with inferolateral ST-segment elevation myocardial infarction treated by a stent to the left circumflex artery and intravenous abciximab treatment was started for the high thrombus burden. Two hours later, the patient developed dyspnoea and hypoxaemia. Chest examination revealed diffuse rales over both lung fields. Chest X-ray revealed bilateral diffuse alveolar infiltrates, while the echocardiography was normal. Chest computed tomography (CT) was performed and the 'crazy paving appearance', which is the typical radiological finding of COVID-19, was reported. The patient was considered to be suspected of COVID-19 and was transferred to a quarantine unit. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test was obtained and azithromycin and hydroxychloroquine were initiated. 48 h later, 2.6 mmol/L reduction was observed in haemoglobin levels and haemoptysis was developed. After the second negative RT-PCR with an interval of 24 h, CT was repeated and the patient was diagnosed to have abciximab-induced DAH. The patient was later followed up conventionally and discharged after two weeks without additional complications. DISCUSSION: DAH and COVID-19 might share common clinical and radiological findings during examination. The physicians must be aware of the high motivation of the COVID-19 pandemic which can lead to misdiagnosis by overlooking other important clinical conditions.