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

1AbstractObjectiveTo track the statistical case fatality rate (CFR) in the second wave of the UK coronavirus outbreak, and to understand its variations over time.DesignPublicly 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 MeasuresEstimates of case fatality rates and their variations over time.ResultsThroughout 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. Seasonal effects could be in part responsible for the early December increase in CFR, and if so, the estimate of increased mortality would be reduced. There is also evidence that the prevalence of B.1.1.7 may have been slower amongst older age groups, and if this is a factor, then 33% could be an underestimate of mortality. 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, any imprecisions in the time-to-death distribution are magnified in this time period, rendering estimates of vaccination’s effect less precise.ConclusionsThe 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 0.4% false-positive fraction. The rapid growth in CFR in December can be understood in part in terms of a more deadly new variant B.1.1.7, while a decline in January correlates with vaccine roll-out, suggesting that vaccine reduce the severity of infection, as well as the risk.Summary BoxWhat is already known on this topicThe case fatality rate (CFR) is a useful measure which enables one to estimate future deaths based on current infections. In England, there was a surge in Covid-19 CFR around the beginning of December.What the study addsUsing it, we monitor the case-fatality rate across time, region and age group from publicly available case data. This quantity is related to the lethality of the virus. It shows a sharp increase in December 2020, which parallels the spread of the B.1.1.7 variant. The January peak in actual deaths matches that predicted by cases if B.1.1.7 is about 33% more deadly; this estimate would be lower if there is a seasonal effect on deaths, and higher if at the peak the variant was less pervasive amongst older age groups. A steady drop in CFR from January suggests that vaccination not only reduces transmission but also the risk of serious illness among those infected. It is notable that these conclusions are reached with publicly available data independent of clinical studies.