Background A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival. Methods In this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model. Findings We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62–2·87]) after adjustment for age, sex, and comorbidity. Interpretation Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design. Funding None.

Introduction: The type 1 interferon pathway is known to play a role in the immunopathology of Systemic Lupus Erythematosus (SLE). As a result, biologic agents targeting this pathway have been developed and are currently being investigated in clinical trials. Areas covered: We review the biologic agents which have been developed to antagonise type I interferons in SLE. We focus on anifrolumab, a type I interferon receptor antagonist, and consider the complexities of defining efficacy in SLE clinical trials. Expert opinion: Anifrolumab shows promise as an addition to the SLE therapeutic armamentarium. Despite discordant results between its two phase III studies, there is a convincing suggestion of benefit in both trials to encourage the view that this approach might be effective. Data acquired thus far look particularly useful for cutaneous disease. We await data on its effect on renal, pulmonary, cardiac and central nervous system involvement, on patient reported outcomes, and its safety and efficacy with long term use.

Objectives Transplacental passage of certain biologic- and targeted synthetic DMARDs leads to detectable levels in the neonate, which may impact on the safety of live vaccines. Guidelines advise delaying live vaccine administration in biologic exposed infants until they are 7 months old. Methods A systematic review of Embase, Medline and Cochrane identified live vaccine outcomes in infants exposed to biologic or targeted synthetic DMARDs in-utero. Results Studies included 276 in-utero exposures to adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and ustekinumab. Live vaccine exposures <12 months of age included BCG (n = 215), rotavirus (n = 46) and MMR (n = 12). We identified no reactions following MMR, 7 mild reactions to rotavirus vaccination, and 8 reactions to BCG including one death. All infants with an adverse reaction to BCG had been exposed to infliximab in-utero, and 6 had received BCG in the first month of life. A freedom of information request to the Medicines and Healthcare products Regulatory Agency revealed 4 fatal disseminated BCG infections in infants exposed to TNF inhibitors in-utero, including infliximab, adalimumab and one unspecified TNF inhibitor. Conclusion Most evidence for clinically harmful effect was for early administration of the BCG vaccine to infants exposed in-utero to TNF inhibitors with high transplacental transfer rates.

Background/Aims  Increasing utilisation of biologic disease modifying anti-rheumatic drugs (DMARDs) and targeted synthetic (ts)DMARDs in women of reproductive age has potential for informed or accidental use in pregnancy and impact on fetal immunity. Transplacental passage of certain biologic DMARDs result in detectable drug levels in the neonate. Current British Society for Rheumatology (BSR) guidelines recommend all live vaccines be delayed in infants until 7 months of age after in-utero exposure in later pregnancy to the tumour necrosis factor inhibitors (TNFi) etanercept, adalimumab or infliximab. This advice affects administration of rotavirus, BCG and potentially MMR vaccination. Therefore, we performed a systematic review to evaluate vaccine safety in infants exposed to bDMARDs or tsDMARDs in pregnancy. Methods  A systematic review of Embase, Medline and Cochrane identified live vaccine outcomes in the infants of mothers who took bDMARDs or tsDMARDs during pregnancy, focussing on drugs used in standard rheumatology practice. Studies were reviewed in accordance with the PRISMA guidelines. Results  A total of 226 titles and abstracts were screened and 8 papers selected for final analysis. Studies included in-utero exposures to adalimumab (n = 326), certolizumab pegol (n = 18), etanercept (n = 1), infliximab (n = 408), golimumab (n = 1), rituximab (n = 1), tocilizumab (n = 3) and ustekinumab (n = 1). No relevant articles on tsDMARDs were identified. Maternal disease included inflammatory bowel disease (n = 849), rheumatoid arthritis (n = 3) and Burkitt’s lymphoma (n = 1). For infants exposed to biologic medications in utero, we identified infant vaccination to: BCG (n = 111) and/or rotavirus (n = 48) in the first year of life, many < 6 months; and MMR (n = 605) at 12 months (n = 590), 6-9 months (n = 12) and at 1, 2 or 4 months (n = 3). Adverse events with BCG vaccination included 1 death, 2 large local skin reactions, and 1 infant with axillary lymphadenopathy. A freedom of information request to the MHRA revealed 4 further suspected fatal BCG infections in infants exposed to TNFi in-utero (2 infliximab, 1 adalimumab, 1 unspecified TNFi). Side-effects noted in infants given rotavirus vaccination were mild and at similar frequency to those in non-biologic exposed infants. No complications were reported with MMR vaccination. Conclusion  Overall, we found most evidence of clinically harmful effects after administration of BCG to infants < 3 months of age and after in-utero exposure to infliximab. In contrast, outcomes following rotavirus (mostly < 6 months) and MMR (mostly at a year) vaccinations were reassuring. These findings are limited to live vaccine usage at standard time points in Europe/USA following maternal use of TNFis with significant placental transfer. Therefore, further understanding of live vaccine safety after exposure to any bDMARD or tsDMARD is required, including confirmation of the presumed safety of live vaccine use following maternal usage of bDMARDs with negligible rates of placental transfer. Disclosure  B. Goulden: None. N. Chua: None. E. Parker: None. I. Giles: Consultancies; Educational grant from UCB; speakers fees from UCB; travel fees from UCB. Other; Chair of guideline group on prescribing anti-rheumatic drugs in pregnancy for British Society of rheumatology.