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The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data.

 

In this work, the COVID-19 pandemic burden in Ukraine is investigated retrospectively using the excess mortality measures during 2020–2021. In particular, the epidemic impact on the Ukrainian population is studied via the standardized both all-cause and cause-specific mortality scores before and during the epidemic. The excess mortality counts during the pandemic were predicted based on historic data using parametric and nonparametric modeling and then compared with the actual reported counts to quantify the excess. The corresponding standardized mortalityP-score metrics were also compared with the neighboring countries. In summary, there were three “waves” of excess all-cause mortality in Ukraine in December 2020, April 2021 and November 2021 with excess of 32%, 43% and 83% above the expected mortality. Each new “wave” of the all-cause mortality was higher than the previous one and the mortality “peaks” corresponded in time to three “waves” of lab-confirmed COVID-19 mortality. The lab-confirmed COVID-19 mortality constituted 9% to 24% of the all-cause mortality during those three peak months. Overall, the mortality trends in Ukraine over time were similar to neighboring countries where vaccination coverage was similar to that in Ukraine. For cause-specific mortality, the excess observed was due to pneumonia as well as circulatory system disease categories that peaked at the same times as the all-cause and lab-confirmed COVID-19 mortality, which was expected. The pneumonias as well as circulatory system disease categories constituted the majority of all cases during those peak times. The seasonality in mortality due to the infectious and parasitic disease category became less pronounced during the pandemic. While the reported numbers were always relatively low, alcohol-related mortality also declined during the pandemic.

 

Abstract Background Investigation of outbreaks to identify the primary case is crucial for the interruption and prevention of transmission of infectious diseases. These individuals may have a higher risk of participating in near future transmission events when compared to the other patients in the outbreak, so directing more transmission prevention resources towards these individuals is a priority. Although the genetic characterization of intra-host viral populations can aid the identification of transmission clusters, it is not trivial to determine the directionality of transmissions during outbreaks, owing to complexity of viral evolution. Here, we present a new computational framework, PYCIVO: primary case inference in viral outbreaks. This framework expands upon our earlier work in development of QUENTIN, which builds a probabilistic disease transmission tree based on simulation of evolution of intra-host hepatitis C virus (HCV) variants between cases involved in direct transmission during an outbreak. PYCIVO improves upon QUENTIN by also adding a custom heterogeneity index and identifying the scenario when the primary case may have not been sampled. Results These approaches were validated using a set of 105 sequence samples from 11 distinct HCV transmission clusters identified during outbreak investigations, in which the primary case was epidemiologically verified. Both models can detect the correct primary case in 9 out of 11 transmission clusters (81.8%). However, while QUENTIN issues erroneous predictions on the remaining 2 transmission clusters, PYCIVO issues a null output for these clusters, giving it an effective prediction accuracy of 100%. To further evaluate accuracy of the inference, we created 10 modified transmission clusters in which the primary case had been removed. In this scenario, PYCIVO was able to correctly identify that there was no primary case in 8/10 (80%) of these modified clusters. This model was validated with HCV; however, this approach may be applicable to other microbial pathogens. Conclusions PYCIVO improves upon QUENTIN by also implementing a custom heterogeneity index which empowers PYCIVO to make the important ‘No primary case’ prediction. One or more samples, possibly including the primary case, may have not been sampled, and this designation is meant to account for these scenarios. 

Abstract Public health intervention to contain the ongoing COVID-19 pandemic significantly differed by country since the SARS-CoV-2 spread varied regionally in time and in scale. Since vaccinations were not available until the end of 2020 non-pharmaceutical interventions (NPIs) remained the only strategies to mitigate the pandemic spread at that time. Belarus in Europe is one of a few countries with a high Human Development Index where no lockdowns have ever been implemented and only limited NPIs have taken place for a period of time. Therefore, the Belarusian case was evaluated and compared in terms of the mortality burden. Since the COVID-19 mortality was low, the excess overall mortality was studied for Belarus. Since no overall mortality data have been reported past June 2020 the analysis was complemented by the study of Google Trends funeral-related search queries up until August 2021. Depending on the model, the Belarusian mortality for June of 2020 was 29 to 39% higher than otherwise expected with the corresponding estimated excess death was from 2953 to 3690 while the reported COVID-19 mortality for June 2020 was only 157 cases. The Belarusian excess mortality for June 2020 was higher than for all neighboring countries with an excess of 5% for Poland, 5% for Ukraine, 8% for Russia, 11% for Lithuania and 11% for Latvia. The relationship between Google Trends and mortality time series was studied using Granger’s test and the results were statistically significant. The results for Google Trends searches did vary by key phrase with the largest excess of 138% for April 2020 and 148% for September 2020 was observed for a key phrase “coffin”, while the largest excess of 218% for January 2021 was observed for “funeral services”. In summary, there are indications of the excess overall mortality in Belarus, which is larger than the reported COVID-19-related mortality.