Histopathology of Middle East respiratory syndrome coronovirus (MERS‐CoV) infection – clinicopathological and ultrastructural study

Aims

The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome – coronavirus (MERS‐CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS‐CoV infection and represent a base of MERS‐CoV histopathology.

Methods and results

We analysed the post‐mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33‐year‐old male patient of T cell lymphoma, who acquired MERS‐CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles.

Conclusion

The results highlight the pulmonary and extrapulmonary pathological changes of MERS‐CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS‐CoV in kidney.

     

Non-pulmonary infections but not specific pathogens are associated with increased risk of AKI in septic shock

Introduction

Little is known regarding the relationship between the anatomic infection site and etiologic pathogen with the occurrence of acute kidney injury (AKI) in severe infections. We set out to determine the association between the site of infection, type of pathogen in septic shock and occurrence of AKI.

Methods

Using a large, international multicenter database that included data from 28 academic and community hospitals, we retrospectively analyzed adult (age >18 years) cases of septic shock occurring between January 1996 and December 2008. Early acute kidney injury (AKI) was classified by the RIFLE criteria at or within 24 h of shock diagnosis. Multivariate logistic regression was used to determine the association between the infection site/microbial pathogen and occurrence of AKI. Analyses were adjusted for demographics, illness severity, comorbidities and intensive care unit interventions (partial adjustment) ± site of infection and microbial pathogen (full adjustment).

Results

After exclusions, 4,493 cases from potentially eligible patients in the database were included in the analytic cohort of whom 3,298 (73.4 %) experienced AKI. Patients with AKI were older (p < 0.0001), had a higher mean Acute Physiology and Chronic Health Evaluation score (p < 0.0001), and had greater laboratory and hemodynamic abnormalities. The most common site of infection among septic shock patients with AKI was the lung (34.5 %), followed by gastrointestinal (GI) (26.2 %) and urinary (15.3 %) sources. Likewise, the most common infecting organism among septic shock patients with AKI was E. coli (23.9 %) followed by S. aureus (GI) (16.1 %) and other enterobacteriaceae (15.7 %). There was a large degree of variability in the occurrence of AKI based on the site of infection and the pathogen in unadjusted analysis (p < 0.0001), which persisted with partial (excluding infection site and microbial pathogen grouping) adjustment (p < 0.0001). Fully adjusted multivariate analysis showed significant variations in AKI only in relation to the anatomic source of infection, with non-pulmonary infections having higher risk than pulmonary infections. The pathogen group/pathogen had no significant independent impact on AKI.

Conclusion

This study demonstrates that the presence of septic AKI varies significantly based on the site of infection but not the type of causative organism.     

Clinical characteristics,sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

Introduction

Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.

Methods

We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.

Results

Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).

Conclusions

The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.