The effect of age on fever response among nursing home residents with SARS-COV-2 infection.

Over 15,000 veterans in 135 VA nursing homes were systematically tested for SARS-CoV-2 and had daily temperatures assessed from March to August, 2020. Lower baseline temperatures, and in SARS-CoV-2+ , lower maximum temperatures were observed with advancing age. Clinicians should be aware of the potential diminished fever response in the elderly with SARS-CoV-2.

Deletion of P2X7 attenuates hyperoxia-induced acute lung injury via inflammasome suppression.

Increasing evidence shows that hyperoxia is a serious complication of oxygen therapy in acutely ill patients that causes excessive production of free radicals leading to hyperoxia-induced acute lung injury (HALI). Our previous studies have shown that P2X7 receptor activation is required for inflammasome activation during HALI. However, the role of P2X7 in HALI is unclear. The main aim of this study was to determine the effect of P2X7 receptor gene deletion on HALI. Wild-type (WT) and P2X7 knockout (P2X7 KO) mice were exposed to 100% O2 for 72 h. P2X7 KO mice treated with hyperoxia had enhanced survival in 100% O2 compared with the WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1ß, TNF-α, monocyte chemoattractant protein-1, and IL-6 levels were attenuated in P2X7 KO mice. P2X7 deletion decreased lung edema and alveolar protein content, which are associated with enhanced alveolar fluid clearance. In addition, activation of the inflammasome was suppressed in P2X7-deficient alveolar macrophages and was associated with suppression of IL-1ß release. Furthermore, P2X7-deficient alveolar macrophage in type II alveolar epithelial cells (AECs) coculture model abolished protein permeability across mouse type II AEC monolayers. Deletion of P2X7 does not lead to a decrease in epithelial sodium channel expression in cocultures of alveolar macrophages and type II AECs. Taken together, these findings show that deletion of P2X7 is a protective factor and therapeutic target for the amelioration of hyperoxia-induced lung injury.

Is the mechanism of COVID-19 coagulopathy still a rabbit's hole?

The pathophysiology of COVID-19 is an enigma with its severity often determined by the extent of coagulopathy. Several regulatory pathways targeted by the SARS-CoV-2 include the renin-angiotensin system, von Willebrand Factor, and most importantly, the complement pathway. This article discusses these pathways to help design potential future therapies.

Dementia prevalence, a contextual factor associated with SARS-CoV-2 in veterans affairs community living centers.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) impact the diagnosis and infection control of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in nursing homes (NH) by influencing the behavior of residents and their caregivers. Health system data show an association between ADRD and SARS-CoV-2. Whether this association is present in NH populations remains unknown. How increased SARS-CoV-2 risk among residents with ADRD impacts the greater NH population also remains unknown. METHODS: This retrospective cohort study used electronic health record data on Veterans residing in 133 Veterans Affairs Community Living Centers (CLC) and 15 spinal cord injury units from March 1, 2020 to December 13, 2020. We measured ADRD using diagnostic codes 12 months before an index SARS-CoV-2 test date for each resident. We used Poisson regression to determine the relative risk of SARS-CoV-2 for the highest quartile of facility ADRD prevalence versus the lowest, stratifying by individual ADRD status, and adjusting for covariates, with and without a random intercept to account for facility clustering. RESULTS: Across the study period, 15,043 residents resided in CLCs, 1952 (13.0%) had SARS-CoV-2, and 8067 (53.6%) had ADRD. There was an estimated 60% increased risk of SARS-CoV-2 in facilities with highest dementia prevalence versus lowest (relative risk, 1.6 [95% confidence interval 0.95, 2.7]). CONCLUSIONS: CLC residents had a greater likelihood of SARS-CoV-2 infection in facilities with greater ADRD prevalence. Facility characteristics other than ADRD prevalence may account for this association.

Can we use temperature measurements to identify pre-symptomatic SARS-CoV-2 infection in nursing home residents?

BACKGROUND: COVID-19 has had a severe impact on morbidity and mortality among nursing home (NH) residents. Earlier detection of SARS-CoV-2 may position us to better mitigate the risk of spread. Both asymptomatic and pre-symptomatic transmission are common in outbreaks, and threshold temperatures, such as 38C, for screening for infection could miss timely detection in the majority of residents. We hypothesized that in long-term care residents, temperature trends with SARS-CoV-2 infection could identify infection in pre-symptomatic individuals earlier than standard screening. METHODS: We conducted a retrospective cohort study using electronic health records in 6176 residents of the VA NHs who underwent SARS-CoV-2 testing triggered by symptoms. We collected information about age and other demographics, baseline temperature, and specific comorbidities. We created standardized definitions, and a hypothetical model to test measures of temperature variation and compare outcomes to the VA standard of care. RESULTS: We showed that a change from baseline of 0.4C identified 47% of NH residents who became SARS-CoV-2 positive, earlier than standard testing by an average of 42.2 h. Temperature variability of 0.5C over 3 days when paired with a 37.2C temperature cutoff identified 55% of NH residents who became SARS-CoV-2 positive earlier than the standard of care testing by an average of 44.4 h. A change from baseline temperature of 0.4C when combined with temperature variability of 0.7C over 3 days identified 52% of NH residents who became SARS-CoV-2 positive, earlier than standard testing by an average of 40 h, and by more than 3 days in 22% of the residents. This earlier detection comes at the expense of triggering 57,793 tests, as compared to the number of trigger tests ordered in the VA system of 40,691. CONCLUSIONS: Our model suggests that early temperature trends with SARS-CoV-2 infection may identify infection in pre-symptomatic long-term care residents.

Can we clinically identify pre-symptomatic and asymptomatic COVID-19?

OBJECTIVES: COVID-19 has had a severe impact on morbidity and mortality among nursing home (NH) residents. Earlier detection of SARS-CoV-2 may position us to better mitigate risk of spread. Both asymptomatic or pre-symptomatic transmission are common in outbreaks, and threshold temperatures, such as 38C, for screening for infection could miss timely detection in the majority. DESIGN: Retrospective cohort study using electronic health records. METHODS: We hypothesized that in long-term care residents, temperature trends with SARS-CoV-2 infection could identify infection in pre-symptomatic and asymptomatic individuals earlier. We collected information about age and other demographics, baseline temperature, and specific comorbidities. We created standardized definitions, and an alternative hypothetical model to test measures of temperature variation and compare outcomes to the VA reality. SETTINGS AND PARTICIPANTS: Our subjects were 6,176 residents of the VA NHs who underwent SARS-CoV-2 trigger testing. RESULTS: We showed that a change from baseline of >0.4C identifies 47% of the SARS-CoV-2 positive NH residents early, and achieves earlier detection by 42.2 hours. Range improves early detection to 55% when paired with a 37.2C cutoff, and achieves earlier detection by 44.4 hours. Temperature elevation >0.4C from baseline, when combined with a 0.7C range, would detect 52% early, leading to earlier detection by more than 3 days in 22% of the residents. This earlier detection comes at the expense of triggering 57,793 tests, as compared to the number of trigger tests ordered in the VA system of 40,691. CONCLUSION AND IMPLICATIONS: Our model suggests that current clinical screening for SARS-CoV-2 in NHs can be substantially improved upon by triggering testing using a patient-derived baseline temperature with a 0.4C degree relative elevation or temperature variability of 0.7C trigger threshold for SARS-CoV2 testing. Such triggers could be automated in facilities that track temperatures in their electronic records.

A rare presentation of spontaneous atheroembolic renal disease: A case report.

BACKGROUND: Atheroembolic renal disease (AERD) is caused by occlusion of the small renal arteries from embolized cholesterol crystals arising from ulcerated atherosclerotic plaques. This usually manifests as isolated renal disease or involvement from systemic atheroembolic disease. Here we report a case of AERD that responded well to steroid therapy. CASE SUMMARY: A 62-year-old woman with a history of hypertension and stage IIIa chronic kidney disease was referred for rapidly worsening renal function over a 4-mo period. She complained of swollen legs, dyspnea on exertion, and two episodes of epistaxis about a month prior to admission. She reported no history of invasive vascular procedures, use of radio contrast agents, or treatment with anticoagulants or thrombolytic agents. Urinalysis showed a few red blood cells and granular casts. Serology was positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Non-contrast-enhanced computed tomography of the chest, abdomen, and pelvis showed diffuse atherosclerotic changes in the aortic arch. Thus, c-ANCA-associated vasculitis was suspected, and the patient was started on pulse intravenous methylprednisolone. Her renal biopsy showed evidence of AERD. She was discharged with oral prednisone, and her renal function continued to improve during the initial follow-up. CONCLUSION: In cases of non-vasculitis-associated ANCA, a high degree of clinical suspicion is required to pursue the diagnosis of spontaneous AERD in patients with clinical or radiological evidence of atherosclerotic burden. Although no specific treatment is available, the potential role of statins and steroids requires exploration.

SOCS-1 rescues IL-1ß-mediated suppression of epithelial sodium channel in mouse lung epithelial cells via ASK-1.

BACKGROUND: Acute lung injury (ALI) is characterized by alveolar damage, increased levels of pro-inflammatory cytokines and impaired alveolar fluid clearance. Recently, we showed that the deletion of Apoptosis signal-regulating kinase 1 (ASK1) protects against hyperoxia-induced acute lung injury (HALI) by suppressing IL-1ß and TNF-α. Previously, our data revealed that the suppressor of cytokine signaling-1 (SOCS-1) overexpression restores alveolar fluid clearance in HALI by inhibiting ASK-1 and suppressing IL-1ß levels. Furthermore, IL-1ß is known to inhibit the expression of epithelial sodium channel α-subunit (ENaC) via a p38 MAPK signaling pathway. OBJECTIVE: To determine whether SOCS-1 overexpression in MLE-12 cells would protect against IL-1ß-mediated depletion of αENaC by suppressing ASK-1 expression. METHODS: We co-transfected MLE-12 cells with SOCS-1 overexpressing plasmid with or without IL-1ß in the presence or absence of sodium channel inhibitor, amiloride. We measured potential difference, transepithelial current, resistance, and sodium uptake levels across MLE-12 cells. We studied the effect of ASK-1 depletion, as well as ASK-1 and SOCS-1 overexpression on αENaC expression. RESULTS: SOCS-1 overexpression sufficiently restored transepithelial current and resistance in MLE-12 cells treated with either IL-1ß or amiloride. The αENaC mRNA levels and sodium transport were increased in SOCS-1 overexpressing MLE-12 cells exposed to IL-1ß. Depletion of ASK-1 in MLE-12 cells increased αENaC mRNA levels. Interestingly, SOCS-1 overexpression restored αENaC expression in MLE-12 cells in the presence of ASK-1 overexpression. CONCLUSION: Collectively, these findings suggest that SOCS-1 may exert its protective effect by rescuing αENaC expression via suppression of ASK-1.