Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 - implications for post COVID-19 conditions.

BACKGROUND: Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC). METHODS: The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10. RESULTS: Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals. CONCLUSIONS: This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.

A Case of COVID-Associated Nephropathy (COVAN).

Collapsing glomerulopathy is a variant of focal segmental glomerulosclerosis (FSGS) causing rapid renal failure. There has been an emergence of these cases among African American patients with COVID-19, especially those with the apolipoprotein L1 (APOL1) allele. We present a case of an African American patient with COVID-19 who tested positive for the APOL1 allele in the setting of acute renal deterioration. This provides a partial explanation for the increased burden of kidney failure in this population. As cases of COVID-19 persist, COVID-associated nephropathy (COVAN) should be suspected in patients with acute kidney injury and treatment tailored accordingly.

A Case of De Novo Membranous Nephropathy Causing Renal Transplant Rejection.

We present a novel case of de novo membranous nephropathy (DNMN) leading to transplant rejection in a 51-year-old female patient. The patient has a transplant history of two renal transplants for end-stage renal disease due to lupus nephritis. She had a prior unrelated, living donor kidney transplant that was subsequently replaced by a deceased donor kidney transplant due to graft failure. This patient's case is intriguing because DNMN is a rare cause of transplant rejection, and the literature demonstrates a scarcity of clinical examples. Interestingly, post-transplant DNMN has been suggested to be a separate disease from recurrent post-transplant MN and is associated with separate risk factors and diagnostic findings. As DNMN is considered a manifestation of antibody-mediated rejection, it should be treated with immunosuppressive therapy. As such, the presented case has received immunosuppressive therapy. In addition, DNMN is associated with humoral alloimmunity. Potentially other inflammatory processes (such as infection/potential UTI in our patient's case) could cause exposure to undetectable donor antigens on renal transplants leading to antibody-mediated rejection via DNMN.

Spontaneous rupture of thymoma.

We report a case of patient who presented to the hospital due to shoulder pain and was later diagnosed with ruptured thymoma. Shortly after being admitted to the hospital for the work up patient developed respiratory distress and underwent emergent endotracheal intubation. CT scan of the chest showed anterior mediastinal mass with associated right sided hemothorax. He subsequently underwent medial sternotomy with resection of the mass which turned out to be thymoma.

A Rare Case of Pulmonary Mucoepidermoid Carcinoma in an 81-Year-Old Male.

BACKGROUND Lung mucoepidermoid carcinoma is a form of non-small cell lung carcinoma that originates from the submucosal glands of the tracheobronchial tree; it is rare and causes 0.1% to 0.2% of lung malignancies. In this article, we report on an occurrence of this condition in an 81-year-old male, which is rare occurrence in this age group. In this case, we found a history of smoking and asbestos exposure which might suggest that exposure to both of these factors can possibly increase the risk for this malignancy. CASE REPORT An 81-year-old male presented with chronic cough and yellow sputum, associated with right upper back pain. The patient was a smoker of 30 packs per year and reported a history of asbestos exposure. He had past medical history of rectal cancer, but no previous history of salivary glands tumors. Physical examination was normal, laboratory investigations were unremarkable. Computed tomography chest showed endobronchial mass with post-obstructive atelectasis. Bronchoscopic evaluation revealed a whitish, endobronchial mass occluding the posterior segment of the right lower lobe. Biopsy showed benign squamous papilloma and malignancy was not excluded as only superficial parts of the mass were obtained. The decision was made to remove the lesion. A right lower lobectomy was done, and histopathology revealed a low grade mucoepidermoid carcinoma; immunohistochemical staining showed tumor cells positive for p40 and p63 supporting the diagnosis. No further adjuvant treatment was recommended, and follow-up imaging was planned for surveillance. CONCLUSIONS Mucoepidermoid carcinoma of the lung is a rare form of non-small cell lung carcinoma. Appropriate diagnosis requires correctly interpreted biopsy results along with immunohistochemical staining results.

Pulmonary strongyloidiasis causing septic shock in a patient with Crohn's disease.

A 58 years old male who was admitted to the intensive care unit for septic shock secondary to pneumonia, he has Crohn's disease currently treated with Vedolizumab and previously with infliximab. He was started on broad spectrum antibiotics and vasopressors for treatment of septic shock without improvement in the following days, sputum & blood cultures were negative. Bronchoscopy was done for non-resolving pneumonia work up, broncheoalveolar lavage smears and cultures were negative for bacteria, tuberculosis and Fungi. Bronchial washings cytology showed filariform larvae and serology was positive for Strongyloides, He was started on ivermectin and his condition improved significantly.