Sociodemographic variables as predictors of adverse outcome in SARS-CoV-2 infection: an Irish hospital experience.

INTRODUCTION: Our hospital found itself at the epicentre of the Irish COVID-19 pandemic. We describe the organisational challenges faced in managing the surge and identified risk factors for mortality and ICU admission among hospitalised SARS-CoV-2-infected patients. METHODS: All hospitalised SARS-CoV-2 patients diagnosed between March 13 and May 1, 2020, were included. Demographic, referral, deprivation, ethnicity and clinical data were recorded. Multivariable regression, including age-adjusted hazard ratios (HR (95% CI), was used to explore risk factors associated with adverse outcomes. RESULTS: Of 257 inpatients, 174 were discharged (68%) and 39 died (15%) in hospital. Two hundred three (79%) patients presented from the community, 34 (13%) from care homes and 20 (8%) were existing inpatients. Forty-five percent of community patients were of a non-Irish White or Black, Asian or minority ethnic (BAME) population, including 34 Roma (13%) compared to 3% of care home and 5% of existing inpatients, (p < 0.001). Twenty-two patients were healthcare workers (9%). Of 31 patients (12%) requiring ICU admission, 18 were discharged (58%) and 7 died (23%). Being overweight/obese HR (95% CI) 3.09 (1.32, 7.23), p = 0.009; a care home resident 2.68 (1.24, 5.6), p = 0.012; socioeconomically deprived 1.05 (1.01, 1.09), p = 0.012; and older 1.04 (1.01, 1.06), p = 0.002 were significantly associated with death. Non-Irish White or BAME were not significantly associated with death 1.31 (0.28, 6.22), p = 0.63 but were significantly associated with ICU admission 4.38 (1.38, 14.2), p = 0.014 as was being overweight/obese 2.37 (1.37, 6.83), p = 0.01. CONCLUSION: The COVID-19 pandemic posed unprecedented organisational issues for our hospital resulting in the greatest surge in ICU capacity above baseline of any Irish hospital. Being overweight/obese, a care home resident, socioeconomically deprived and older were significantly associated with death, while ethnicity and being overweight/obese were significantly associated with ICU admission.

Inhibition of PGE2 production by nimesulide compared with diclofenac in the acutely inflamed joint of patients with arthritis.

OBJECTIVE: Cyclo-oxygenase (COX) exists in two isoforms, COX-1 and COX-2. COX-1 is responsible for homeostatic functions, whereas COX-2 is inducible and responsible for the inflammatory effects of prostaglandins. Nimesulide, a selective inhibitor of COX-2, has been shown to relieve pain rapidly in arthritis. We examined the effect of nimesulide on prostaglandin formation in arthritis, to evaluate if this compound gains access to the site of inflammation and whether this is required for analgesia. STUDY DESIGN: This was a single-dose, double-blind, double-dummy, parallel group study of nimesulide 100mg compared with diclofenac 50mg. METHODS: Serial sampling of synovial fluid, whole blood and plasma was performed at baseline and 0.5, 1, 2, 3 and 4 hours after drug administration. Synovial tissue was obtained by needle biopsy at completion of the study period. Synovial fluid prostaglandin E2 (PGE2) was measured by enzyme immunoassay. COX-1 and COX-2 activities in whole blood were estimated by serum thromboxane B2 (TxB2) and endotoxin-induced PGE2 concentrations respectively. Synovial tissue COX-1 and COX-2 mRNA and protein expression were studied by reverse transcriptase polymerase chain reaction and immunohistochemistry respectively. Twenty patients with acute knee inflammation on a background of arthritis of all types completed the study. RESULTS: Patients were allocated randomly to groups to receive nimesulide (n = 10) or diclofenac (n = 10). The mean (+/- SEM) plasma concentration of PGE2 in the nimesulide group decreased from 24.45 +/- 2.71 ng/mL at baseline to 1.74 +/- 2.71 ng/ mL at 2 hours. Diclofenac also inhibited PGE2, but at a later time point (28.15 +/- 2.86 ng/mL at baseline and 0.85 +/- 2.86 ng/mL at 4 hours). The mean (+/- SEM) synovial fluid concentration of PGE2 was 319 +/- 89 pg/mL before treatment; it remained unaltered over 4 hours after the administration of nimesulide or diclofenac (235 +/- 72 pg/mL). In contrast, in six patients receiving long-term treatment with nimesulide or a non-selective NSAID, synovial PGE2 was 61 +/- 24 pg/ mL, suggesting that inhibition of synovial prostaglandin formation is delayed compared with that in plasma. Nimesulide caused partial inhibition of serum TxB2 (a decrease from a mean of 268 +/- 24 ng/mL to one of 164 +/- 27 ng/mL at 2 hours), whereas diclofenac had a greater effect (a decrease from 224 +/- 33 ng/mL, to 76 +/- 27 ng/mL at 3 hours). CONCLUSIONS: Nimesulide, a COX-2 selective inhibitor, has a rapid onset of action in the blood compartment, with early inhibition of PGE2 generation, an index of COX-2 activity. In contrast, it exhibits a delay in achieving therapeutic concentrations in the synovial fluid. Thus factors other than local inhibition of prostaglandins may explain the rapid onset of analgesia that is associated with nimesulide, including a possible central mechanism of pain relief.

The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes.

Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8 mRNA expression was increased in hSFs upon stimulation with proinflammatory cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL-1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore, although IL-1beta protein levels were increased in inflamed human and mouse joint tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were similar to or lower than those in matched serum samples, suggesting that the joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and septic shock, and did not correlate with inflammatory status. Interestingly however, we observed high IL-1F8 levels in several serum samples in all groups. In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. It remains to be determined whether circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis.