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 Rare Presentation of IgA Nephropathy in a 62-Year-Old Hispanic Female.

A case of immunoglobulin A (IgA) nephropathy is presented here that demonstrates an unusual clinical presentation in multiple ways and is vitally important for clinicians to consider. The patient is a Hispanic female in her 7th decade of life that presented with nephrotic-range proteinuria without hematuria ultimately leading to a diagnosis of IgA nephropathy. After diagnosis, her clinical course was complicated by continued poorly controlled type II diabetes mellitus and hypertension, and ultimately her kidney disease progressed to chronic kidney disease IV and then end-stage renal disease requiring hemodialysis. Though IgA nephropathy predominantly presents as nephritic syndrome, it can also present as nephrotic range proteinuria and even rapidly progressive glomerulonephritis which should be considered even when the patient's ethnicity and age group carry a smaller risk.

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.

Streptococcus intermedius Bacteremia and Pyogenic Liver Abscess in a Patient With No Risk Factors.

This case report depicts a 39-year-old male with no significant past medical history who was admitted for fever of unknown origin and sepsis. He was then found to have Streptococcus intermedius bacteremia and pyogenic liver abscess. The treatment course was complicated by pleural empyema leading to readmission. The case presented here adds to the medical literature, where a clear underrepresentation has been noted, and outlines a unique case of S. intermedius liver abscess complicated by pleural empyema in a patient without significant medical history, risk factors, or typical physical exam findings.

A Case of Multisystem Inflammatory Syndrome in an Immunosuppressed Adult.

Multisystem inflammatory syndrome in an adult (MIS-A) is a rare immunological complication that gained prominence after the coronavirus disease 2019 pandemic. Patients with MIS-A often clinically present with non-specific generalized symptoms, such as fever, myalgia, or fatigue, making the diagnosis difficult. In this article, we present an unusual case of MIS-A in a 50-year-old male that raises the question of whether the immune system's dysregulation will demonstrate differing criteria of signs and symptoms for a patient on sustained immunosuppression as opposed to the non-immunosuppressed population.

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.

Chronic elevation of cardiac troponin I predicts the extent of coronary disease in hemodialysis patients presenting with acute enzyme elevation.

Introduction: Elevation of cardiac troponin I (cTn-I) is associated with coronary artery disease (CAD) in asymptomatic patients with end-stage renal disease (ESRD) receiving hemodialysis. We aim to investigate the diagnostic value of chronically elevated cTn-I in ESRD patients presenting with an acute rise in serum cTn-I levels. Methods: We performed a retrospective analysis of 364 patients. Using coronary angiography, we correlated baseline elevation of cTn-I with the severity of CAD when hemodialysis patients present with acute symptomatic elevation in serum cTn-I. Results: In hemodialysis patients presenting with a rise in serum cTn-I above baseline levels, 59% had severe CAD, and 17% had no angiographic evidence of CAD. Hemodialysis patients with severe CAD had significantly higher baseline cTn-I levels compared to patients with non-severe CAD or normal coronaries (p < 0.0001). Baseline elevation of cTn-I in the severe CAD group was correlated with the degree of CAD occlusion (r2 0.56, p < 0.0001), fitting a positive linear model. Furthermore, baseline cTn-I differentiates between patients with and without severe CAD with a test accuracy of 0.72 (95% CI, 0.69-0.75, p < 0.001). At a value of ≥0.2 ng/mL (cutoff for myocardial necrosis), the specificity of baseline cTn-I for underlying severe CAD was 0.95. Conclusions: Elevated baseline cTn-I has good accuracy for anticipating more advanced angiographic CAD when hemodialysis patients present with a symptomatic rise in serum cTn-I above baseline levels. Baseline elevation of cTn-I can be used for cardiac disease risk management in hemodialysis patients presenting with symptoms suggestive of CAD.