Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Systemic BK Virus Infection in a Pediatric Patient With Severe Combined Immunodeficiency.

Human BK virus (BKV) infection is known to occur mostly during childhood with the establishment of latent infection with no tissue damage or clinical manifestations. However, conditions causing immunosuppression can lead to increased virus replication and tissue damage. Although the tissues most commonly involved are the kidneys, bladder, ureters and, to some extent, brain tissue, there are some reports that suggest that BKV may cause multisystemic infections. In this case, a 12-month-old child was seen to suffer from multiple gastrointestinal infections. This prompted a search for immunodeficiencies, which revealed the presence of severe combined immunodeficiency. The child was eventually hospitalized and continued showing recurrent bouts of gastroenteritis as well as lower respiratory infection. After multiple antibiotic courses, he developed acute kidney injury, a hemophagocytic syndrome, and eventually respiratory failure, which led to his death a year later. Autopsy findings revealed the presence of a disseminated BKV infection involving the kidneys, ureters, leptomeninges, and pancreas. Analysis of the literature failed to show any previous case of BKV pancreatitis. The present case suggests that BKV can damage more tissues than previously reported and may be responsible for systemic infections in immunosuppressed patients.

Nephrotic syndrome in the setting of LECT2 amyloidosis: Take a look at the podocyte.

Amyloid light-chain (AL) amyloidosis represents the most common type of amyloid affecting the kidneys. As AL amyloidosis is frequently clinically manifested as nephrotic syndrome, this glomerular syndrome has been improperly linked to all other types of kidney amyloidosis. In this report, we highlight the importance of amyloid typing, as the deposition of several amyloidotic proteins in the kidneys is not associated with heavy proteinuria. We present two cases of patients who presented with sudden-onset nephrotic syndrome and kidney biopsies showing interstitial, vascular, and/or mesangial LECT2 amyloidosis. Further examination by electron microscopy demonstrated diffuse foot process effacement consistent with minimal change disease and no amyloid deposition in the glomerular basement membrane. Both patients had complete remission after glucocorticoid treatment. We conclude that the presence of nephrotic syndrome in a patient with LECT2 amyloidosis must alert for a potential concurrent podocytopathy.

LECT2 Amyloidosis in Kidney Transplantation: A Report of 5 Cases.

Leukocyte chemotactic factor 2 (LECT2) amyloidosis is a recently recognized entity that often affects the kidneys. Little information is available regarding kidney transplant outcomes in patients with LECT2 amyloidosis or who received kidney allografts containing LECT2 amyloid. We present clinical findings and allograft outcomes of 5 patients who received kidneys with donor-derived LECT2 amyloidosis. In all 5, LECT2 amyloidosis was discovered during protocol biopsies or in evaluation of suspected rejection. Less than 10% of kidney parenchyma was involved, with mostly interstitial and vascular deposits. Allograft function was not impaired and the amyloid deposits persisted for up to 8 years of follow-up. We conclude that kidneys with limited and localized LECT2 amyloid deposits that are otherwise suitable for transplantation need not be automatically discarded.

Immune gene expression in kidney biopsies of lupus nephritis patients at diagnosis and at renal flare.

BACKGROUND: Up to 50% of lupus nephritis (LN) patients experience renal flares after their initial episode of LN. These flares contribute to poor renal outcomes. We postulated that intrarenal immune gene expression is different in flares compared with de novo LN, and conducted these studies to test this hypothesis. METHODS: Glomerular and tubulointerstitial immune gene expression was evaluated in 14 patients who had a kidney biopsy to diagnose LN and another biopsy at their first LN flare. Ten healthy living kidney donors were included as controls. RNA was extracted from laser microdissected formalin-fixed paraffin-embedded kidney biopsies. Gene expression was analyzed using the Nanostring nCounter® platform and validated by quantitative real-time polymerase chain reaction. Differentially expressed genes were analyzed by the Ingenuity Pathway Analysis and Panther Gene Ontology tools. RESULTS: Over 110 genes were differentially expressed between LN and healthy control kidney biopsies. Although there was considerable molecular heterogeneity between LN biopsies at diagnosis and flare, for about half the LN patients gene expression from the first LN biopsy clustered with the repeated LN biopsy. However, in all patients, a set of eight interferon alpha-controlled genes had a significantly higher expression in the diagnostic biopsy compared with the flare biopsy. In contrast, nine tumor necrosis factor alpha-controlled genes had higher expression in flare biopsies. CONCLUSIONS: There is significant heterogeneity in immune-gene expression of kidney tissue from LN patients. There are limited but important differences in gene expression between LN flares, which may influence treatment decisions.

Effect of Pinocembrin Isolated from Mexican Brown Propolis on Diabetic Nephropathy.

Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds, wounds, rheumatism, heart disease and diabetes. Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are few alternatives. The present study aimed to determine the chemical composition of three propolis samples collected in Chihuahua, Durango and Zacatecas and to evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo. Previous research demonstrated that propolis of Chihuahua possesses hypoglycemic and antioxidant activities. Two different schemes were assessed, preventive (before renal damage) and corrective (once renal damage is established). In the preventive scheme, pinocembrin treatment avoids death of the rats, improves lipid profile, glomerular filtration rate, urinary protein, avoid increases in urinary biomarkers, oxidative stress and glomerular basement membrane thickness. Whereas, in the corrective scheme, pinocembrin only improves lipid profile without showing improvement in any other parameters, even pinocembrin exacerbated the damage. In conclusion, pinocembrin ameliorates diabetic nephropathy when there is no kidney damage but when it is already present, pinocembrin accelerates kidney damage.

Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS: The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS: The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.

Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: a retrospective cohort study.

INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

[Incidence of acute rejection in patients with renal graft dysfunction]. / [Incidencia de rechazo agudo en pacientes con disfunción del injerto renal].

INTRODUCTION: Acute rejection has been identified as the main cause of renal graft dysfunction during the first year after transplantation; it is associated with chronic structural and functional damage, which causes loss of graft and decrease in patient survival. MATERIAL AND METHODS: We performed a retrospective and descriptive research consisting in a review of the final reports of biopsies performed due to renal graft dysfunction during the postransplant period. Patients included were transplanted at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) from January 2007 to December 2011. RESULTS: A total number of 223 patients underwent renal transplantation during the period considered for this study purpose, 222 biopsies were performed due to renal graft dysfunction in 118 patients (52.9%). 74.5% of patients developed graft dysfunction in the first year after transplantation. The main histopathological findings reported were immunologic events in both living donor (LDRTR) and deceased donor renal transplant recipients (DDRTR), borderline changes were the most common diagnosis. The median time to detect immune events as cause of dysfunction was shorter for DDRTR and they tend to occur in the first 4 months after transplantation. CONCLUSION: We observed an incidence of 11.8% for acute rejection in the first year after transplantation for LDRTR and 17.4% for DDRTR. Further studies are needed to determine the causes of immunological events and their implications in the evolution of renal graft and patient's survival.

Leukocyte Chemotactic Factor 2 Amyloidosis (ALECT2) Distribution in a Mexican Population.

OBJECTIVES: To assess the prevalence of leukocyte cell-derived chemotactic 2 (LECT2), its organ involvement, and its clinical association in autopsies from an ethnically biased population. METHODS: The tissues from all autopsies of individuals diagnosed with amyloidosis were reassessed and typed for amyloid light chain (AL) amyloidosis, amyloid A (AA) amyloidosis, transthyretin amyloidosis (ATTR), and leukocyte chemotactic factor 2 amyloidosis (ALECT2) by immunohistochemistry. Organ involvement was described and correlated with its clinical associations. RESULTS: Of 782 autopsies, 27 (3.5%) had a confirmed diagnosis of amyloidosis. Of these, 14 (52%) corresponded to ALECT2, 5 (19%) to AL amyloidosis, 2 (7%) to ATTR amyloidosis, 1 (4%) to AA amyloidosis, and 5 (21%) as undetermined-type amyloidosis. The LECT2 amyloid deposits were found in the kidneys, liver, spleen, and adrenal glands in most individuals. Except for the kidneys, there were no clinical signs suggestive of amyloid deposition in most of the affected organs. LECT2 amyloidosis was not associated with the cause of death in any case. No cases had heart or brain involvement. Potential subclinical effects of amyloid deposition in organs such as adrenal glands and spleen require further study. CONCLUSIONS: This autopsy study confirms the high prevalence of LECT2 amyloidosis in the Mexican population, with frequent amyloid deposition in the kidneys, liver, spleen, and adrenal glands.

Is the Sars-CoV-2 virus a possible trigger agent for the development of achalasia?

BACKGROUND: Achalasia is an autoimmune disease whose probable causal agent is a neurotropic virus that chronically infects the myenteric plexus of the esophagus and induces the disease in a genetically susceptible host. The association between achalasia and coronaviruses has not been reported. AIMS: To evaluate the presence of the SARS-CoV-2 virus, the ACE2 expression, the tissue architecture, and immune response in the lower esophageal sphincter muscle (LESm) of achalasia patients who posteriorly had SARS-CoV-2 (achalasia-COVID-19) infection before laparoscopic Heller myotomy (LHM) and compare the findings with type II achalasia patients and transplant donors (controls) without COVID-19. METHODS: The LESm of 7 achalasia-COVID-19 patients (diagnosed by PCR), ten achalasia patients, and ten controls without COVID-19 were included. The presence of the virus was evaluated by in situ PCR and immunohistochemistry. ACE2 receptor expression and effector CD4 T cell and regulatory subsets were determined by immunohistochemistry. KEY RESULTS: Coronavirus was detected in 6/7 patients-COVID-19. The SARS-CoV-2 was undetectable in the LESm of the achalasia patients and controls. ACE2 receptor was expressed in all the patients and controls. One patient developed achalasia type II post-COVID-19. The percentage of Th22/Th17/Th1/pDCreg was higher in achalasia and achalasia-COVID-19 pre-HLM vs. controls. The Th2/Treg/Breg cell percentages were higher only in achalasia vs. controls. CONCLUSION & INFERENCES: SARS-CoV2 and its receptor expression in the LESm of achalasia patients who posteriorly had COVID-19 but not in the controls suggests that it could affect the myenteric plexus. Unlike achalasia, patients-COVID-19 have an imbalance between effector CD4 T cells and the regulatory mechanisms.

Down-Regulation-Resistant STAT4 Risk Haplotype Contributes to Lupus Nephritis Through CD4+ T Cell Interferon-γ Production.

OBJECTIVE: Variants in STAT4 are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. We undertook this study to investigate how disease-associated variants affect STAT4 expression, in particular in CD4+ T cells where STAT4 plays an essential role. METHODS: We compared Th1 differentiation between naive CD4+ T cells from healthy donors homozygous for the risk (R/R) or nonrisk (NR/NR) alleles. We analyzed epigenetic marks in STAT4 and evaluated the relevance of its third intron, assessed the consequences of Stat4 overexpression in vivo in mice, and analyzed the effects of the STAT4 genotype in patients with lupus nephritis. RESULTS: Naive CD4+ T cells from NR/NR healthy donors down-regulated STAT4 in response to interleukin-12 (IL-12). In contrast, cells from R/R healthy donors maintained high levels. R/R cells exhibited a higher abundance of transcriptionally active STAT4 and increased interferon-γ production. Accordingly, R/R healthy donors exhibited a stronger induction of local active enhancer marks. Genetic editing confirmed the presence of a negative regulatory region in the STAT4 third intron, where most of the SLE-associated STAT4 single-nucleotide polymorphisms (SNPs) are located. In vivo forced expression demonstrated that increases in Stat4 levels in T cells enhanced glomerulonephritis in mice. Accordingly, the R/R genotype was associated with suboptimal response to treatment and with worse clinical outcomes in patients with proliferative lupus nephritis. CONCLUSION: The SLE-associated STAT4 haplotype correlates with an abnormal IL-12-mediated STAT4 transcriptional regulation. Carriers of the risk variant exhibit exaggerated CD4+ proinflammatory capacities that, in the context of SLE, contribute to more severe disease. R/R patients may benefit from blockade of the IL-12/STAT4 pathway.

[The Mexican Board of Pathology: microscopy examination before and after digital microscopy]. / Consejo Mexicano de Médicos Anatomopatólogos: su examen de microscopia, antes y después de su digitalización.

INTRODUCTION: The examination carried out by the COMMAP for the certification process assessed pathologist formed in dissimilar institutions. In 2007 COMMAP's governing body in turn, decided to digitize it. The purpose of this study is to investigate whether the conversion to virtual slides in the microscopy section, compared with the traditional have had an impact on the scores of the candidates. METHOD: The slides were scanned with high resolution. The virtual microscope is a standard computer screen where there is a program (Aperio Scope Image Viewer) that can display the scanned slides. The results of the microscopy section of the past nine years were compared; two groups were formed: 1) those without digitized examination, and 2) with it. The results were compared by Student t-test and Mann-Whitney. RESULTS: Of a 461 results 240 belonged to the first group and 221 to the second one. On a scale of 1-10, the average scores were 6.6 and 6.8, respectively (p > 0.6 and > 0.5).The minimum and maximum scores were also similar in each group. CONCLUSIONS: According to the results, the digitized exam in the COMMAP's certification process shows no difference between the digitized and the conventional versions.

Autoantigen characterization in the lower esophageal sphincter muscle of patients with achalasia.

BACKGROUND: Serum anti-myenteric autoantibodies define autoimmune achalasia and tissue MMP-9 activity may locally process autoantigenic proteins in the muscle of the lower esophageal sphincter (LES) of achalasia patients. METHODS: Biopsies of the LES muscle from 36 achalasia patients, 6 esophagogastric junction outflow obstruction (EGJOO) patients, and 16 transplant donors (TD) were compared in a blind cross-sectional study. Histological characteristics such as inflammation, fibrosis, presence of ganglion cells, cells of Cajal, GAD65, PNMA2, S-100, P substance, and MMP-9 proteoforms in tissue were assessed by H&E and Picrosirius Red staining and immunohistochemistry analysis. Anti-neuronal antibodies, onconeural antigens, recoverin, SOX-1, titin, zic4, GAD65, and Tr were evaluated by immunoblot/line assay. KEY RESULTS: Tissue of achalasia patients had heterogeneous inflammatory infiltrates with fibrosis and contrasting higher levels of activated MMP-9, as compared with EGJOO and TD. Moreover, lower ganglion cell percentages and cell of Cajal percentages were determined in esophageal tissues of achalasia patients versus TD. The tissues of achalasia versus EGJOO patients had higher GAD65 and PNMA2 protein expression. Unexpectedly, these proteins were absent in TD tissue. S-100 and P substance had similar expression levels in tissues of achalasia patients versus TD and EGJOO. Most of the achalasia sera had anti-GAD65 (83%) and anti-PNMA2 (90%) autoantibodies versus EGJOO (17% and 33%, respectively) and healthy volunteers (10% and 0%, respectively). CONCLUSIONS AND INFERENCES: Tissue-specific ectopic expression of GAD65 and PNMA/Ta2 and active MMP-9, associated with the presence of specific autoantibodies directed against these proteins, might participate in the pathophysiology of achalasia triggering and/or perpetuating autoimmune disease.

ANCA-associated vasculitis and IgG4-related disease overlap syndrome: a case report and literature review.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are infrequent autoimmune diseases characterized by inflammation of the walls of small vessels leading to tissue and endothelial damage. On the other hand, IgG4-related disease is a fibroinflammatory disease characterized histologically by lymphoplasmacytic infiltrates with IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis that may affect nearly every organ of the body. There are similarities in clinical, serological, radiological, and histopathological features between both diseases, and hence, they usually mimic each other complicating the differential diagnosis. Furthermore, reports of patients with the coexistence of both conditions (overlap syndrome) have been reported. We herein report a patient with an unequivocal diagnosis of ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (posterior uveitis, polyneuropathy, pauci-immune glomerulonephritis with crescent formation and granulomas, and MPO-ANCA positivity) and IgG4-related disease (thoracic aortitis, tubulointerstitial nephritis with prominent IgG4+ plasma cell infiltration, fibrosis, and obliterative arteritis, high levels of serum IgG4, and eosinophilia) overlap syndrome.

Sub-classification of borderline changes into diffuse or focal and its impact on long-term renal transplant outcomes.

BACKGROUND: Borderline changes (BL) with stable renal function is a controversial category in renal transplantation, given its contradictory outcomes. The aim of this study was to compare the clinical outcomes of BL in patients with stable renal function classified as focal and diffuse according to the extent of tubulitis. METHODS: Patients with no history of rejection with a surveillance graft biopsy at 3 or 12 months showing BL (n = 40), acute cellular rejection (n = 20) or normal biopsies (n = 20), were included in this study. Biopsies with BL were divided into diffuse BL (BLD) and focal BL (BLF) according to the extent of tubulitis. Because of the low frequency of subclinical ACR (ACRND) (n = 12), biopsies with ACR and graft dysfunction (ACRD) (n = 8) were also included. A composite outcome that included the presence of rejection in subsequent biopsies, graft loss, patient death, decrease in GFR ≥30% or presence of de novo DSA (dnDSA) during the first year of follow-up was evaluated. RESULTS: The primary composite outcome occurred in five patients of each of the Normal, BLF and ACRND, eight patients with BLD and six patients with ACRD (p = 0.105). A trend towards more rejection episodes was observed in the ACRND and ACRD. Also, a shorter time to rejection in the BLD, ACRND and ACRD groups compared to BLF and Normal groups (p = 0.039) was observed. During the first year of follow-up, no patient in the ACRND group developed dnDSA, compared to 15-25% in the other groups. The median time of dnDSA development in the BLF group was 45 months, and in the BLD group was 10 months (p = 0.020). CONCLUSION: Classifying BL biopsies with stable renal function into focal and diffuse categories, is a simple and feasible strategy that helps to differentiate between BLD with a phenotype that shows a trend towards worse outcomes, and BLF that behaves more similar to normal biopsies.

Clinicopathologic characteristics of severe COVID-19 patients in Mexico City: A post-mortem analysis using a minimally invasive autopsy approach.

OBJECTIVE: Describe the histological findings of minimally ultrasound-guided invasive autopsies in deceased patients with severe SARS-CoV-2 and compare the diagnostic yield with open autopsies. DESIGN: Observational post-mortem cohort study. Minimally invasive ultrasound-guided autopsies were performed in fourteen deceased patients with a confirmed diagnosis of SARS-CoV-2 pneumonia. Histological and clinical findings of lung, kidney, and liver tissue are described and contrasted with those previously reported in the literature. SETTING: Single-center COVID-19 reference center in Mexico City. RESULTS: Fourteen minimally invasive autopsies revealed a gross correlation with open autopsies reports: 1) Lung histology was characterized mainly by early diffuse alveolar damage (12/13). Despite low lung compliances and prolonged mechanical ventilation, the fibrotic phase was rarely observed (2/13). 2) Kidney histopathology demonstrated acute tubular injury (12/13), interstitial nephritis (11/13), and glomerulitis (11/13) as the predominant features 3) Liver histology was characterized by neutrophilic inflammation in all of the cases, as well as hepatic necrosis (8/14) despite minimal alterations in liver function testing. Hepatic steatosis was observed in most cases (12/14). SARS-CoV-2 positivity was widely observed throughout the immunohistochemical analysis. However, endothelitis and micro thrombosis, two of the hallmark features of the disease, were not observed. CONCLUSION: Our data represents the largest minimally invasive, ultrasound-guided autopsy report. We demonstrate a gross histological correlation with large open autopsy cohorts. However, this approach might overlook major histologic features of the disease, such as endothelitis and micro-thrombosis. Whether this represents sampling bias is unclear.