• SARS-CoV-2
• adipose tissue
• diabetes
• liver
• pancreas
• skeletal muscle

• Humans
• COVID-19
• Pandemics
• SARS-CoV-2
• Diabetes Mellitus/epidemiology
• Energy Metabolism

• European Foundation for the Study of Diabetes
• Ministry of Culture
• Federal Ministry of Education and Research

Our understanding of the severe acute respiratory syndrome coronavirus 2 has evolved since the first reported cases in December 2019, and a greater emphasis has been placed on the hyper-inflammatory response in severely ill patients. The purpose of this study was to determine risk factors for mortality and the impact of anti-inflammatory therapies on survival.

To determine the impact of various therapies on outcomes in severe coronavirus disease 2019 patients with a focus on anti-inflammatory and immune-modulating agents.

A retrospective analysis was conducted on 261 patients admitted or transferred to the intensive care unit in two community hospitals between March 12, 2020 and June 17, 2020. Totally 167 patients received glucocorticoid (GC) therapy. Seventy-three patients received GC alone, 94 received GC and tocilizumab, 28 received tocilizumab monotherapy, and 66 received no anti-inflammatory therapy.

Patient survival was associated with GC use, either alone or with tocilizumab, and decreased vasopressor requirements. Delayed administration of GC was found to decrease the survival benefit of GC therapy. No difference in survival was found with varying anticoagulant doses, convalescent plasma, tocilizumab monotherapy; prone ventilation, hydroxychloroquine, azithromycin, or intravenous ascorbic acid use.

This analysis demonstrated the survival benefit associated with anti-inflammatory therapy of GC, with or without tocilizumab, with the combination providing the most benefit. More studies are needed to assess the optimal timing of anti-inflammatory therapy initiation.

• COVID-19
• Corticosteroids
• Intensive care unit
• Methylprednisolone
• Tociluzimab
• Anti-inflammatory

• COVID-19
• Fibrosis
• Growth factors
• Neutrophils
• Pulmonology

• COVID-19/complications
• COVID-19/diagnosis
• COVID-19/immunology
• COVID-19/physiopathology
• Cough/diagnosis
• Cough/etiology
• Dyspnea/diagnosis
• Dyspnea/etiology
• Female
• Hepatocyte Growth Factor/analysis
• Humans
• Lipocalin-2/analysis
• Lung/metabolism
• Lung/pathology
• Lung/physiopathology
• Male
• Matrix Metalloproteinase 7/analysis
• Middle Aged
• Neutrophil Activation/immunology
• Prognosis
• Pulmonary Fibrosis/diagnosis
• Pulmonary Fibrosis/etiology
• Pulmonary Fibrosis/metabolism
• Recovery of Function/immunology
• Respiratory Function Tests/methods
• Respiratory Function Tests/statistics & numerical data
• SARS-CoV-2
• Severity of Illness Index
• Post-Acute COVID-19 Syndrome

• K08 HL130557 NHLBI NIH HHS
• R01 HL142818 NHLBI NIH HHS
• UL1 TR001863 NCATS NIH HHS
• National Heart, Lung, and Blood Institute
• American Heart Association

Subjects recovering from COVID-19 frequently experience persistent respiratory ailments; however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity.

We performed a prospective cohort study of subjects with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors.

Sixty-one subjects were enrolled across two academic medical centers at a median of 9 weeks (interquartile range 6–10) after COVID-19 illness: n=13 subjects (21%) mild/non-hospitalized, n=30 (49%) hospitalized/non-critical, and n=18 subjects (30%) hospitalized/intensive care (“ICU”). Fifty-three subjects (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P<0.05), but did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered subjects by past COVID-19 severity. Lipocalin 2 (LCN2), matrix metalloproteinase-7 (MMP-7), and hepatocyte growth factor (HGF) identified by the model were significantly higher in the ICU group (P<0.05) and inversely correlated with FVC and DLCO (P<0.05), and were confirmed in a separate validation cohort (n=53).

Subjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.

The study was funded in part by the NHLBI (K08HL130557 to BDK and R01HL142818 to HJC), the DeLuca Foundation Award (AP), a donation from Jack Levin to the Benign Hematology Program at Yale, and Divisional/Departmental funds from Duke University.

Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of the body’s innate immune system; however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. We aim to comprehensively delineate monocyte heterogeneity in healthy and KD infants and to reveal the underlying mechanism for KD.

Peripheral monocytes were enriched from peripheral blood samples of two healthy infants and two KD infants. scRNA-seq was performed to acquire the transcriptomic atlas of monocytes. Bio-information analysis was utilized to identify monocyte subsets and explore their functions and differentiation states. SELL+CD14+CD16- monocytes were validated using flow cytometry.

Three monocyte subsets were identified in healthy infants, including CD14+CD16- monocytes, CD14+CD16+ monocytes, and CD14^LowCD16+ monocytes. Cell trajectory analysis revealed that the three monocyte subsets represent a linear differentiation, and possess different biological functions. Furthermore, SELL+CD14+CD16- monocytes, which were poorly differentiated and relating to neutrophil activation, were found to be expanded in KD.

Our findings provide a valuable resource for deciphering the monocyte heterogeneity in healthy infants and uncover the altered monocyte subsets in KD patients, suggesting potential biomarkers for KD diagnosis and treatment.

• Kawasaki disease
• monocyte subsets
• scRNA-seq

Following the decline in Physical Activity (PA) due to COVID-19 restrictions in the form of government mandated lockdowns and closures of public spaces, the modulatory effect of physical exercise on immunity is being heavily revisited. In an attempt to comprehend the wide discrepancy in patient response to COVID-19 and the factors that potentially modulate it, we summarize the findings relating PA to inflammation and immunity. A distinction is drawn between moderate intensity and high intensity physical exercise based on the high lactate production observed in the latter. We hypothesize that, the lactate production associated with high intensity anaerobic exercise is implicated in the modulation of several components of the innate and adaptive immunity. In this review, we also summarize these immunomodulatory effects of lactate. These include increasing serum IL-6 levels, the main mediator of cytokine storms, as well as affecting NK cells, Macrophages, Dendritic cells and cytotoxic T-lymphocytes. The implications of high lactate levels in athletic performance are highlighted where athletes should undergo endurance training to increase VO2 max and minimize lactate production. Tumor models of hypoxia were also reported where lactate levels are elevated leading to increased invasiveness and angiogenesis. Accordingly, the novel lactate blocking strategy employed in cancer treatment is evaluated for its potential benefit in COVID-19 in addition to the readily available beta-blockers as an antagonist to lactate. Finally, we suggest the diagnostic/prognostic purpose of the elevated lactate levels that can be determined through sweat lactate testing. It is the detrimental effect of lactate on immunity and its presence in sweat that qualify it to be used as a potential non-invasive marker of poor COVID-19 outcome.

• Covid-19
• Endurance training
• Lactate blockers
• Sweat lactate

• Adipose tissue hypoxia
• COVID-19
• HIF
• HIF1alpha switch to HIF2alpha
• Obesity related obstructive sleep apnea

• COVID-19
• Ferroptosis
• Hepcidin
• Hyperferritinemia
• Iron deficiency anemia
• RNA viruses

• COVID‐19
• Cytokine storm
• Immunotherapy
• Innate immune
• SARS‐CoV‐2
• T‐cell exhaustion

Symptomatic COVID-19 is prevalent in the community. We identify factors indicating COVID-19 positivity in non-hospitalized patients and prognosticators of moderate-to-severe disease.

Appeals conducted in April–June 2020 in social media, collaborating medical societies and patient advocacy groups recruited 20,476 participants ≥18 years who believed they had COVID-19 exposure. Volunteers consented on-line and reported height, weight, concomitant illnesses, medication and supplement use, residential, occupational or community COVID-19 exposure, symptoms and symptom severity on a 4-point scale. Of the 12,117 curated analytic population 2279 reported a COVID-19 viral test result: 865 positive (COVID+) and 1414 negative (COVID-).

The triad of anosmia, ageusia and fever best distinguished COVID+ from COVID-participants (OR 6.07, 95% CI: 4.39 to 8.47). COVID + subjects with BMI≥30, concomitant respiratory disorders or an organ transplant had increased risk of moderate-to- severe dyspnoea. Race and anti-autoimmunity medication did not affect moderate-to-severe dyspnea risk.

The triad of anosmia, ageusia and fever differentiates COVID-19. Elevated risks of severe symptoms outside the hospital were most evident among the obese and those with pulmonary comorbidity. Race and use of medication for autoimmune disease did not predict severe disease. These findings should facilitate rapid COVID-19 diagnosis and triage in settings without testing.

•

The triad of anosmia, ageusia and fever best distinguished those who tested positive from those who tested negative.

• Ageusia
• Anosmia
• COVID-19
• Direct to patient
• Epidemiology
• Infectious disease

• Adult
• Aged
• Aged, 80 and over
• COVID-19/diagnosis
• Female
• Humans
• Male
• Middle Aged
• Prognosis
• SARS-CoV-2
• Self Report
• Triage
• Young Adult