Evolution of case fatality rates in the second wave of coronavirus in England: effects of false positives, a Variant of Concern and vaccination.

Objective: To track the statistical case fatality rate (CFR) in the second wave of the UK coronavirus outbreak, and to understand its variations over time. Design: Publicly available UK government data and clinical evidence on the time between first positive PCR test and death are used to determine the relationships between reported cases and deaths, according to age groups and across regions in England. Main Outcome Measures: Estimates of case fatality rates and their variations over time. Results: Throughout October and November 2020, deaths in England can be broadly understood in terms of CFRs which are approximately constant over time. The same CFRs prove a poor predictor of deaths when applied back to September, when prevalence of the virus was comparatively low, suggesting that the potential effect of false positive tests needs to be taken into account. Similarly, increasing CFRs are needed to match cases to deaths when projecting the model forwards into December. The growth of the S gene dropout VOC in December occurs too late to explain this increase in CFR alone, but at 33% increased mortality, it can explain the peak in deaths in January. On our analysis, if there were other factors responsible for the higher CFRs in December and January, 33% would be an upper bound for the higher mortality of the VOC. From the second half of January, the CFRs for older age groups show a marked decline. Since the fraction of the VOC has not decreased, this decline is likely to be the result of the rollout of vaccination. However, due to the rapidly decreasing nature of the raw cases data (likely due to a combination of vaccination and lockdown), any imprecisions in the time-to-death distribution are greatly exacerbated in this time period, rendering estimates of vaccination effect imprecise. Conclusions: The relationship between cases and deaths, even when controlling for age, is not static through the second wave of coronavirus in England. An apparently anomalous low case-fatality ratio in September can be accounted for by a modest 0.4% false-positive fraction. The large jump in CFR in December can be understood in terms of a more deadly new variant B1.1.7, while a decline in January correlates with vaccine roll-out, suggesting that vaccine reduce the severity of infection, as well as the risk.