Background A subset of patients with COVID-19 develops a hyperinflammatory syndrome that has similarities with other hyperinflammatory disorders. However, clinical criteria specifically to define COVID-19-associated hyperinflammatory syndrome (cHIS) have not been established. We aimed to develop and validate diagnostic criteria for cHIS in a cohort of inpatients with COVID-19. Methods We searched for clinical research articles published between Jan 1, 1990, and Aug 20, 2020, on features and diagnostic criteria for secondary haemophagocytic lymphohistiocytosis, macrophage activation syndrome, macrophage activation-like syndrome of sepsis, cytokine release syndrome, and COVID-19. We compared published clinical data for COVID-19 with clinical features of other hyperinflammatory or cytokine storm syndromes. Based on a framework of conserved clinical characteristics, we developed a six-criterion additive scale for cHIS: fever, macrophage activation (hyperferritinaemia), haematological dysfunction (neutrophil to lymphocyte ratio), hepatic injury (lactate dehydrogenase or asparate aminotransferase), coagulopathy (D-dimer), and cytokinaemia (C-reactive protein, interleukin-6, or triglycerides). We then validated the association of the cHIS scale with in-hospital mortality and need for mechanical ventilation in consecutive patients in the Intermountain Prospective Observational COVID-19 (IPOC) registry who were admitted to hospital with PCR-confirmed COVID-19. We used a multistate model to estimate the temporal implications of cHIS. Findings We included 299 patients admitted to hospital with COVID-19 between March 13 and May 5, 2020, in analyses. Unadjusted discrimination of the maximum daily cHIS score was 0·81 (95% CI 0·74–0·88) for in-hospital mortality and 0·92 (0·88–0·96) for mechanical ventilation; these results remained significant in multivariable analysis (odds ratio 1·6 [95% CI 1·2–2·1], p=0·0020, for mortality and 4·3 [3·0–6·0], p<0·0001, for mechanical ventilation). 161 (54%) of 299 patients met two or more cHIS criteria during their hospital admission; these patients had higher risk of mortality than patients with a score of less than 2 (24 [15%] of 138 vs one [1%] of 161) and for mechanical ventilation (73 [45%] vs three [2%]). In the multistate model, using daily cHIS score as a time-dependent variable, the cHIS hazard ratio for worsening from low to moderate oxygen requirement was 1·4 (95% CI 1·2–1·6), from moderate oxygen to high-flow oxygen 2·2 (1·1–4·4), and to mechanical ventilation 4·0 (1·9–8·2). Interpretation We proposed and validated criteria for hyperinflammation in COVID-19. This hyperinflammatory state, cHIS, is commonly associated with progression to mechanical ventilation and death. External validation is needed. The cHIS scale might be helpful in defining target populations for trials and immunomodulatory therapies. Fundi...

Background Neutralizing monoclonal antibodies (MAb) are a promising therapy for early COVID-19, but effectiveness has not been confirmed in a real-world setting. Methods In this quasi-experimental pre-/post-implementation study, we estimated the effectiveness of MAb treatment within 7 days of symptom onset in high-risk ambulatory adults with COVID-19. The primary outcome was a composite of emergency department visit or hospitalization within 14 days of positive test. Secondary outcomes included adverse events and 14-day mortality. The average treatment effect in the treated for MAb therapy was estimated using inverse probability of treatment weighting and the impact of MAb implementation using propensity-weighted interrupted time series analysis. Results Pre-implementation (July-November, 2020), 7404 qualifying patients were identified. Post-implementation (December 2020-January 2021), 594 patients received MAb treatment and 5536 did not. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls and 1525 (20.6%) historical controls. MAb treatment was associated with decreased likelihood of emergency care or hospitalization, odds ratio 0.69 (95% CI 0.60-0.79). After implementation, the weighted probability that a given patient would require an emergency department visit or hospitalization decreased significantly (0.7% per day, 95% CI 0.03%-0.10%). Mortality was 0.2% (n=1) in the MAb group compared to 1.0% (n=71) and 1.0% (n=57) in pre- and post-implementation controls, respectively. Adverse events occurred in 7 (1.2%); 2 (0.3%) were considered serious. Conclusions MAb treatment of high-risk ambulatory patients with early COVID-19 was well-tolerated and likely effective at preventing the need for subsequent emergency department or hospital care.

NCT03245879.

Improving antibiotic prescribing in outpatient settings is a public health priority. In the United States, urgent care (UC) encounters are increasing and have high rates of inappropriate antibiotic prescribing. Our objective was to characterize antibiotic prescribing practices during UC encounters, with a focus on respiratory tract conditions. This was a retrospective cohort study of UC encounters in the Intermountain Healthcare network. Among 1.16 million UC encounters, antibiotics were prescribed during 34% of UC encounters and respiratory conditions accounted for 61% of all antibiotics prescribed. Of respiratory encounters, 50% resulted in antibiotic prescriptions, yet the variability at the level of the provider ranged from 3% to 94%. Similar variability between providers was observed for respiratory conditions where antibiotics were not indicated and in first-line antibiotic selection for sinusitis, otitis media, and pharyngitis. These findings support the importance of developing antibiotic stewardship interventions specifically targeting UC settings.

Rationale: The coronavirus disease (COVID-19) pandemic struck an immunologically naive, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates. Objectives: To assess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19. Methods: We performed a randomized clinical trial of hydroxychloroquine versus azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID ordinal outcomes scale at Day 14. Secondary endpoints included hospital-, intensive care unit–, and ventilator-free days at Day 28. The trial was stopped early after the enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective. Results: We enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine versus azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithromycin. Secondary outcomes displayed a similar slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The 20 safety outcomes were similar between arms, with the possible exception of postrandomization-onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than those in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury. Conclusions: Although early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation. Clinical trial registered with www.clinicaltrials.gov (NCT04329832).

There is substantial variation in patterns of antibiotic use among SCHs. Overall usage in SCHs is similar to usage in LCHs. Small hospitals need to become a focus of stewardship efforts.

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We evaluated the impact of nursing education and stewardship interventions on Clostridium difficile testing and treatment appropriateness. Diarrhea documentation increased for those with positive tests (45% to 70%); pretreatment laxative use decreased (50% to 19%). Appropriate treatment increased for severe infection (57% to 93%), but all asymptomatically colonized patients were treated.