RESUMEN
IntroductionThis study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during Englands Delta wave, by age group, dose, and over time. MethodsWe used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine. ResultsCompared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18-29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60-69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose. ConclusionImportant demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during Englands Delta wave, with evidence of waning predominantly restricted to those aged 70+.
RESUMEN
IntroductionTools to detect SARS-Coronavirus-2 variants of concern and track the ongoing evolution of the virus are necessary to support public health efforts and the design and evaluation of novel COVID-19 therapeutics and vaccines. Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality. MethodsAn allele-specific probe polymerase chain reaction (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil. Probit regression models were developed to compare ASP-PCR performance against 1,771 NGS results for the same cohorts. ResultsIndividual SNPs were shown to readily identify specific variants of concern. ASP-PCR was shown to discriminate SARS-CoV-2 lineages with a higher likelihood than NGS over a wide range of viral loads. Comparative advantage for ASP-PCR over NGS was most pronounced in samples with Ct values between 26-30 and in samples that showed evidence of degradation. Results for samples screened by ASP-PCR and NGS showed 99% concordant results. DiscussionASP-PCR is well-suited to augment but not replace NGS. The method can differentiate SARS-COV-2 lineages with high accuracy and would be best deployed to screen samples with lower viral loads or that may suffer from degradation. Future work should investigate further destabilization from primer:target base mismatch through altered oligonucleotide chemistry or chemical additives.
RESUMEN
BackgroundTreatment of COVID-19 patients with convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation as a means of reducing viral loads, ameliorating disease outcomes, and reducing mortality. However, its efficacy might be reduced in those infected with the emerging B.1.1.7 SARS-CoV-2 variant. Here, we report the diverse virological characteristics of UK patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial. MethodsSARS-CoV-2 viral RNA was detected and quantified by real-time PCR in nasopharyngeal swabs obtained from study subjects within 48 hours of admission to intensive care unit. Antibody status was determined by spike-protein ELISA. B.1.1.7 strain was differentiated from other SARS-CoV-2 strains by two novel typing methods detecting the B.1.1.7-associated D1118H mutation with allele-specific probes and by restriction site polymorphism (SfcI). FindingsOf 1260 subjects, 90% were PCR-positive with viral loads in nasopharyngeal swabs ranging from 72 international units [IUs]/ml to 1.7x1011 IU/ml. Median viral loads were 45-fold higher in those who were seronegative for IgG antibodies (n=314; 28%) compared to seropositives (n=804; 72%), reflecting in part the latter groups possible later disease stage on enrolment. Frequencies of B.1.1.7 infection increased from early November (<1%) to December 2020 (>60%). Anti-SARS-CoV-2 seronegative individuals infected with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians of 1.2x106 and 3.4 x104 IU/ml respectively; p=2x10-9). However, viral load distributions were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (13.4x106 and 7.6x106 IU/ml; p=0.18). InterpretationHigh viral loads in seropositive B.1.1.7-infected subjects are consistent with increased replication capacity and/or less effective clearance by innate or adaptive immune response of B.1.1.7 strain than wild-type. As viral genotype was associated with diverse virological and immunological phenotypes, metrics of viral load, antibody status and infecting strain should be used to define subgroups for analysis of treatment efficacy.
