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Advancing Science for Global Health
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Home > Global Health Matters Nov/Dec 2023 > COVID-19 modelling and phylogenetic studies Print

COVID-19 modelling and phylogenetic studies

November/December 2023 | Volume 22 Number 6

A graph depicting the flow of SARS-CoV-2 lineages into Malta. The number between square brackets depicts the number of sequences attributed to the specific reconstructed origin location (left side) or SARS-CoV-2 variant (right side).Adapted from “Evolutionary and spatiotemporal analyses reveal multiple introductions and cryptic transmission of SARS-CoV-2 VOC/VOI in Malta,” courtesy Nídia Trovão, et al.The flow of SARS-CoV-2 lineages into Malta. The numbers between brackets represent sequences attributed to the specific reconstructed origin (left side) or SARS-CoV-2 variant (right side). Full image and description.

Understanding the diversity and relatedness of early Omicron strains in Pakistan

Drs. David Spiro, Nídia Trovão and Zeba Rasmussen contributed to this BMC Genomics study that sought to understand the diversity and phylogenetic relatedness of SARS-CoV-2 strains in various regions of Pakistan. The team analyzed data on 276,525 COVID-19 cases and 1,031 genomes sequenced from December 2021 to August 2022. They found the highest case numbers and deaths recorded in Sindh and Punjab, Pakistan's most populous provinces. Omicron variants comprised 93% of all genomes, with subvariants BA.2 (32.6%) and BA.5 (38.4%) predominating. Analysis identified Sindh as a hotspot for viral dissemination. 

Determining the incubation period of the Delta variant of SARS-CoV-2

Fogarty's Dr. Kaiyuan Sun co-authored this analysis of a successfully contained local outbreak of SARS-CoV-2 (Delta variant) that took place in Hunan, China, in July–August, 2021. The team leveraged data on infections and contacts and then estimated epidemiological parameters, including the incubation period and generation time. The paper, published in China CDC Weekly, suggests the mean incubation period of Delta ranges from three to six days, while the estimated mean generation time is 4.4 days. Importantly, children were more likely to be infected than adults. Two doses of inactivated vaccine had an estimated 54% effectiveness. 

  • Publication: China CDC Weekly

Quantifying transmission trends in South Africa during the COVID-19 pandemic

Dr. Cécile Viboud contributed to this PloS One study that aimed to quantify transmission trends in South Africa during the COVID-19 pandemic. Roughly 17% of South African residents have access to private healthcare, while 83% rely on the public system. Accessing data from public and private health service providers, the authors compared estimates for reproduction number (R)— the expected number of people an infected individual will pass the virus to. The authors found general agreement between R estimates, and so believe public and private sector clients had similar pandemic experiences. Results also indicate that data from either source could be used in the early stages of any future pandemic. 

Using phylodynamic analysis to inform public health response to COVID-19

Dr. Nídia Trovão contributed to this JMIR Formative Research study. Between June 2020 and June 2021, four focus groups discussed how phylodynamic tools can inform the public health response to the ongoing COVID-19 pandemic. Participating molecular epidemiologists, clinical-researchers, infectious disease experts and public health professionals from Europe, the U.S., and the Caribbean identified nine key themes: translational/implementation science; precision public health; fundamental unknowns; proper scientific communication; methods of epidemiological investigation; sampling bias; interoperability standards; academic/public health partnerships; and resources. They called for interoperability standards in sequence data sharing, urged careful reporting to prevent misinterpretations, proposed tailored responses to specific variants, and cited issues that need to be addressed in future outbreaks. 

How impaired mitochondrial function due to COVID-19 may cause serious symptoms and complications

Published in Science Translational Medicine, this study analyzed human nasopharyngeal samples and autopsy tissues from patients with COVID-19 and tissues from SARS-CoV-2-infected rodents. The data suggest viral suppression of mitochondrial gene transcription and activation of glycolysis (cellular reactions whereby energy is extracted from glucose) are part of the response to the infection. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired. Such chronically impaired mitochondrial function may cause serious COVID-19 symptoms and complications, such as organ failure, Dr. Nídia Trovão and her co-authors concluded.

  • Publication: Science Translational Medicine

What gives SARS-CoV-2 the ability to evolve increasingly transmissible variants?

Dr. Cécile Viboud contributed to this study examining the ability of SARS-CoV-2 to evolve increasingly transmissible variants. The researchers mapped genomic diversity over time and found SARS-CoV-2 followed a pattern of punctuated evolution; periods of genetic drift were interrupted by sudden, large increases in diversity, followed by abrupt collapses. A mathematical model showed this pattern can result from rare saltations (sudden evolutionary jumps) occurring alongside epistasis (suppression of a gene's effects due to modifier genes). One possible explanation is accelerated evolution within immunocompromised hosts, another less likely explanation would be reverse zoonosis (transmission from humans to animals), according to the authors who published in PloS Computational Biology.

Using a multiple-model approach to support COVID-19 reopening strategies

Dr. Cécile Viboud co-authored this PNAS study that examined multiple modeling teams' evaluations of COVID-19 reopening strategies for a mid-sized U.S. county early in the pandemic. While projections from 17 distinct models were inconsistent in magnitude, they were highly congruent when ranking interventions. Aggregate results showed that, with full workplace reopening, up to half the population could be infected. By contrast, workplace restrictions reduced median cumulative infections by 82%, the authors noted.

Quantifying the impact of COVID-2019 in Africa

Published in Clinical Infectious Diseases and co-authored by Dr. Cécile Viboud, this study attempted to estimate the actual burden of COVID-19 on the African continent. The researchers used serosurveillance and postmortem surveillance data to construct a "multiplicative factor"—a ratio of seroprevalence to the proportion of people reported to have COVID-19 for each of 12 African nations studied. Using these factors, they estimated ratios of infections to reported cases since March 2020. Multiplicative factors suggested COVID-19 reporting rates ranged from one in two (Cape Verde)—one case reported for every two estimated infections—to one in 3,795 (Malawi). Reported low case burden in many African nations is due to significant underdetection and underreporting, not to younger population age or other factors, the authors concluded. Results suggest an additional four COVID-19 waves occurred, unseen, on the continent.

How could vaccinating children impact the spread of COVID-19?

The Lancet Regional Health—Americas published this COVID-19 Scenario Modeling Hub study assessing potential effects of immunizing children 5 to 11 years old in the U.S. prior to approval of a vaccine for this age group. Co-senior author Dr. Cécile Viboud and colleagues considered four scenarios: with and without childhood vaccination, and with and without the emergence of a hypothetical variant (50% more transmissible than the then circulating viruses). Vaccination of children was associated with reductions in cases (7.2%), hospitalizations (8.7%), and deaths (9.2%) for all age groups when compared to no childhood vaccination. In the scenario with the hypothetical variant, benefits of childhood vaccination, assuming similar vaccine effectiveness, increased. 

Exploring behavioral factors and SARS-CoV-2 transmission in household settings in Costa Rica

Fogarty's Dr. Kaiyuan Sun led the data analysis of this study, co-authored by Dr. Cécile Viboud and published in Communications Medicine. The researchers conducted a household serologic study in Costa Rica to explore behavioral determinants of SARS-CoV-2 transmission. Overall seroprevalence was 53% among household contacts, while the estimated household secondary attack rate—the number of people infected compared to total people exposed to a primary infection—was 34%.  Mask wearing was associated with a 67% household transmission risk reduction; not sharing a bedroom with the index case (first patient) was associated with a 78% risk reduction. The team estimated 30% of index cases as the source for 80% of secondary cases. 

  • Publication:  Communications Medicine

Comparing the incubation period and transmission rate of SARS-CoV-2 variants

This PNAS study, co-authored by Drs. Kaiyuan Sun and Cécile Viboud, investigated whether people with Omicron infections developed symptoms earlier (shorter incubation period) and transmitted faster (shorter generation interval) than those infected with Delta variants. In the Netherlands, Omicron infections during December 2021 had similar incubation periods, but shorter generation intervals, as compared to Delta infections from the same period. Omicron's shorter generation intervals could be due to its higher reproduction number—the expected number of people an infected individual will pass the virus to—which leads to a faster depletion of susceptible people, the authors noted.

A look at how targeted non-pharmaceutical interventions could have contained the pandemic

Dr. Kaiyuan Sun, one of two first authors of this China CDC Weekly study, demonstrates through empirical data and modeling analysis that targeted non-pharmaceutical interventions (NPIs) could have contained outbreaks caused by the original SARS-CoV-2 strain. The NPIs include case isolation, contact tracing, targeted lockdowns, and mobility restrictions. Mass testing could have further improved the efficacy and speed of containment, the authors wrote: "In retrospect, had the virus been successfully contained in the early stage of the pandemic, a great deal of the global morbidity, mortality and tremendous socioeconomic costs could have been avoided."

Analyzing transmission of SARS-CoV-2 in Malta

Fogarty's Dr. Nídia Trovão led this Microbiology Spectrum study of the evolution of the COVID-19 pandemic in Malta. The authors analyzed epidemiological and phylodynamic data to investigate trends in the number of new cases, deaths, tests, positivity rates, viral introductions, and dispersal patterns from August 2020 to January 2022. Their reconstructions inferred 173 independent introductions of SARS-CoV-2 from various global regions. Positivity rates remained low to moderate, likely due to public health interventions. 

Updated December 11, 2023

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