Augmented renal clearance (ARC) is a manifestation of enhanced renal function seen in critically ill patients. The use of regular unadjusted doses of renally eliminated drugs in patients with ARC might lead to therapy failure. The purpose of this scoping review was to provide and up-to-date summary of the available evidence pertaining to the phenomenon of ARC. A literature search of databases of available evidence in humans, with no language restriction, was conducted. Databases searched were MEDLINE (1946 to April 2017), EMBASE (1974 to April 2017) and the Cochrane Library (1999 to April 2017). A total of 57 records were included in the present review: 39 observational studies (25 prospective, 14 retrospective), 6 case reports/series and 12 conference abstracts. ARC has been reported to range from 14 to 80%. ARC is currently defined as an increased creatinine clearance of greater than 130 mL/min/1.73 m2 best measured by 8–24 h urine collection. Patients exhibiting ARC tend to be younger (<50 years old), of male gender, had a recent history of trauma, and had lower critical illness severity scores. Numerous studies have reported antimicrobials treatment failures when using standard dosing regimens in patients with ARC. In conclusion, ARC is an important phenomenon that might have significant impact on outcome in critically ill patients. Identifying patients at risk, using higher doses of renally eliminated drugs or use of non-renally eliminated alternatives might need to be considered in ICU patients with ARC. More research is needed to solidify dosing recommendations of various drugs in patients with ARC.

ObjectivesWe intended to assess the effectiveness of all three US Food and Drug Administration approved COVID-19 vaccines at preventing SARS-CoV-2 infection and COVID-19 hospitalisation in a large cohort of individuals on immunosuppressants for a diverse range of conditions.MethodsWe studied the effectiveness of BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna) and Ad26.COV2.S (Johnson & Johnson–Janssen) vaccines among individuals who take immunosuppressants (including disease-modifying antirheumatic drugs and glucocorticoids) by comparing vaccinated (n=97688) and unvaccinated (n=42094) individuals in the Michigan Medicine healthcare system from 1 January to 7 December 2021, using Cox proportional hazards modelling with time-varying covariates.ResultsAmong vaccinated and unvaccinated individuals, taking immunosuppressants increased the risk of SARS-CoV-2 infection (adjusted HR (aHR)=2.17, 95% CI 1.69 to 2.79 for fully vaccinated and aHR=1.40, 95% CI 1.07 to 1.83 for unvaccinated). Among individuals taking immunosuppressants, we found: (1) vaccination reduced the risk of SARS-CoV-2 infection (aHR=0.55, 95% CI 0.39 to 0.78); (2) the BNT162b2 and mRNA-1273 vaccines were highly effective at reducing the risk of SARS-CoV-2 infection (n=2046, aHR=0.59, 95% CI 0.38 to 0.91 for BNT162b2; n=2064, aHR=0.52, 95% CI 0.33 to 0.82 for mRNA-1273); (3) with a smaller sample size (n=173), Ad26.COV2.S vaccine protection did not reach statistical significance (aHR=0.34, 95% CI 0.09 to 1.30, p=0.17); and (4) receiving a booster dose reduced the risk of SARS-CoV-2 infection (aHR=0.42, 95% CI 0.24 to 0.76).ConclusionsThe mRNA-1273 and BNT162b2 vaccines are effective in individuals who take immunosuppressants. However, individuals who are vaccinated but on immunosuppressants are still at higher risk of SARS-CoV-2 infection and COVID-19 hospitalisation than the broader vaccinated population. Booster doses are effective and crucially important for individuals on immunosuppressants.

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Background There is a lack of data regarding how the delta variant of coronavirus disease 2019 (COVID-19) has impacted the effectiveness of the BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson–Janssen) vaccines at preventing SARS-CoV-2 infection and COVID-19 hospitalization. Methods We compared the effectiveness of the three vaccines during the pre- and post-delta variant period (before and after July 1 st, 2021) in a large cohort of vaccinated and unvaccinated patients in the Michigan Medicine healthcare system. We assessed vaccine effectiveness using two analyses: an Inverse Propensity Weighted (IPW) Kaplan-Meier (KM) analysis based on time from vaccination, and a Cox model based on calendar time with vaccination as a time-varying covariate. Results Compared to Ad26.COV2.S recipients, the risk of hospitalization for COVID-19 in the post-delta variant period was lower for BNT162b2 recipients (HR=0.37; 95% CI: [0.14-0.98]; p=0.05) and mRNA-1273 recipients (HR=0.21; 95% CI: [0.07-0.64]; p=0.006). Recipients of the mRNA-1273 vaccine had a lower risk of SARS-CoV-2 infection than Ad26.COV2.S recipients (HR=0.6; 95% CI: [0.43-0.83]; p=0.003) and BNT162b2 recipients (HR=0.64; 95% CI: [0.54-0.76]; p&lt;0.001). After July 1 st, efficacy against SARS-CoV-2 infection declined for Ad26.COV2.S recipients (VE=76% before; VE=49% after; p=0.02), BNT162b2 recipients (VE=87% before; VE=52% after; p&lt;0.001), and mRNA-1273 recipients (VE=92% before; VE=70% after; p&lt;0.001). Waning immunity and the delta variant contributed independently and significantly to this decline. Discussion Although there is a substantial decline in effectiveness, the approved COVID-19 vaccines remain effective against infection and hospitalization due to the delta variant. The mRNA-based vaccines are more effective than the Ad26.COV2.S vaccine.

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