Maite Aubry

Background: Effective Coronavirus Disease 2019 (COVID-19) response relies on good knowledge of population infection dynamics, but owing to under-ascertainment and delays in symptom-based reporting, obtaining reliable infection data has typically required large dedicated local population studies. Although many countries implemented Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing among travellers, it remains unclear how accurately arrival testing data can capture international patterns of infection, because those arrival testing data were rarely reported systematically, and predeparture testing was often in place as well, leading to nonrepresentative infection status among arrivals. Methods and findings: In French Polynesia, testing data were reported systematically with enforced predeparture testing type and timing, making it possible to adjust for nonrepresentative infection status among arrivals. Combining statistical models of polymerase chain reaction (PCR) positivity with data on international travel protocols, we reconstructed estimates of prevalence at departure using only testing data from arrivals. We then applied this estimation approach to the United States of America and France, using data from over 220,000 tests from travellers arriving into French Polynesia between July 2020 and March 2022. We estimated a peak infection prevalence at departure of 2.1% (95% credible interval: 1.7, 2.6%) in France and 1% (95% CrI: 0.63, 1.4%) in the USA in late 2020/early 2021, with prevalence of 4.6% (95% CrI: 3.9, 5.2%) and 4.3% (95% CrI: 3.6, 5%), respectively, estimated for the Omicron BA.1 waves in early 2022. We found that our infection estimates were a leading indicator of later reported case dynamics, as well as being consistent with subsequent observed changes in seroprevalence over time. We did not have linked data on traveller demography or unbiased domestic infection estimates (e.g., from random community infection surveys) in the USA and France. However, our methodology would allow for the incorporation of prior data from additional sources if available in future. Conclusions: As well as elucidating previously unmeasured infection dynamics in these countries, our analysis provides a proof-of-concept for scalable and accurate leading indicator of global infections during future pandemics.

Estimation of the impact of vaccination and non-pharmaceutical interventions (NPIs) on COVID-19 incidence is complicated by several factors, including the successive emergence of SARS-CoV-2 variants of concern and changing population immunity resulting from vaccination and previous infection. We developed an age-structured multi-strain COVID-19 transmission model and inference framework that could estimate the impact of vaccination and NPIs while accounting for these factors. We applied this framework to French Polynesia, which experienced multiple large COVID-19 waves from multiple variants over the course of the pandemic, interspersed with periods of elimination. We estimated that the vaccination programme averted 49.6% (95% credible interval (CI) 48.7–50.5%) of the 5830 hospitalisations and 64.2% (95% CI 63.1–65.3%) of the 1540 hospital deaths that would have occurred in a baseline scenario without any vaccination up to May 2022. Vaccination also averted an estimated 34.8% (95% CI 34.5–35.2%) of 223,000 symptomatic cases in the baseline scenario. We estimated the booster campaign contributed 4.5%, 1.9% and 0.4% to overall reductions in cases, hospitalisations and hospital deaths respectively. Our results suggested that removing, or altering the timings of, the lockdowns during the first two waves had non-linear effects on overall incidence owing to the resulting effect on accumulation of population immunity. Our estimates of vaccination and booster impact differ from those for other countries due to differences in age structure, previous exposure levels and timing of variant introduction relative to vaccination, emphasising the importance of detailed analysis that accounts for these factors.

In French Polynesia, Wuhan, Delta and Omicron SARS-CoV-2 variants-of-concern (VOCs) caused epidemics with variable severities. We assessed the prevalence and titers of anti-SARS-CoV-2 antibodies related to natural infection and/or vaccination, from a representative sample (N=673) of the adult population of Tahiti recruited during November-December 2021 (after the Delta outbreak and just before the Omicron epidemic). Of the 673 participants tested, 644 (95.7%) had detectable antibodies against SARS-CoV-2-S and/or -N proteins resulting from natural infection and/or vaccination, and 388 (57.7%) were positive only for the detection of anti-N antibodies indicating natural infection. SARS-CoV-2 seroprevalence extrapolated to the adult population of Tahiti was estimated at 95.9%. Concentrations of anti-SARS-CoV-2-S antibodies significantly increased with age, number of self-reported SARS-CoV-2 infections (0 or ≥1), and number of COVID-19 vaccine doses (0, 1, 2, or 3) received by the participants. Elderly people, who are at higher risk of severe outcomes, had received more vaccine doses than younger individuals both in our sample and in the general population. The high level of antibody responses related to past infections and vaccination, especially booster doses, has likely contributed to reducing the severity of the Omicron outbreak in French Polynesia.

Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-β). Remarkably, this IFNAR1 variant has a minor allele frequency >1% in Samoa and is also observed in the Cook, Society, Marquesas, and Austral islands, as well as Fiji, whereas it is extremely rare or absent in the other populations tested, including those of the Pacific region. Inherited IFNAR1 deficiency should be considered in individuals of Polynesian ancestry with severe viral illnesses.

In French Polynesia, following the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in March 2020, several control measures were implemented to prevent virus spread, including a population lockdown and the interruption of international air traffic. SARS-CoV-2 local transmission rapidly stopped, and circulation of dengue virus serotypes 1 and 2, the only arboviruses being detected at that time, decreased. After the borders re-opened, a surveillance strategy consisting of the testing by SARS-CoV-2 RT-PCR of travelers entering French Polynesia, and isolating those with ongoing infection, was implemented. This strategy proved efficient to limit the introduction of SARS-CoV-2, and should be considered to prevent the importation of other pathogens, including mosquito-borne viruses, in geographically isolated areas such as French Polynesia.

In French Polynesia, the first case of SARS-CoV-2 infection was detected on March 10^th, 2020, in a resident returning from France. Between March 28^th and July 14^th, international air traffic was interrupted and local transmission of SARS-CoV-2 was brought under control, with only 62 cases recorded. The main challenge for reopening the air border without requiring travelers to quarantine on arrival was to limit the risk of re-introducing SARS-CoV-2. Specific measures were implemented, including the obligation for all travelers to have a negative RT-PCR test for SARS-CoV-2 carried out within 3 days before departure, and to perform another RT-PCR testing 4 days after arrival. Because of limitation in available medical staff, travelers were provided a kit allowing self-collection of oral and nasal swabs. In addition to increase our testing capacity, self-collected samples from up to 10 travelers were pooled before RNA extraction and RT-PCR testing. When a pool tested positive, RNA extraction and RT-PCR were performed on each individual sample. We report here the results of COVID-19 surveillance (COV-CHECK PORINETIA) conducted between July 15^th, 2020, and February 15^th, 2021, in travelers using self-collection and pooling approaches. We tested 5,982 pools comprising 59,490 individual samples, and detected 273 (0.46%) travelers positive for SARS-CoV-2. A mean difference of 1.17 Ct (CI 95% 0.93–1.41) was found between positive individual samples and pools (N = 50), probably related to the volume of samples used for RNA extraction (200 μL versus 50 μL, respectively). Retrospective testing of positive samples self-collected from October 20^th, 2020, using variants-specific amplification kit and spike gene sequencing, found at least 6 residents infected by the Alpha variant. Self-collection and pooling approaches allowed large-scale screening for SARS-CoV-2 using less human, material and financial resources. Moreover, this strategy allowed detecting the introduction of SARS-CoV-2 variants of concern in French Polynesia.

In French Polynesia, the first case of SARS-CoV-2 infection was detected on March 10 ^th , 2020, in a resident returning from France. Between March 28 ^th and July 14 ^th , international air traffic was interrupted and local transmission of SARS-CoV-2 was brought under control, with only 62 cases recorded. The main challenge for reopening the air border without requiring travelers to quarantine on arrival was to limit the risk of re-introducing SARS-CoV-2. Specific measures were implemented, including the obligation for all travelers to have a negative RT-PCR test for SARS-CoV-2 carried out within 3 days before departure, and to perform another RT-PCR testing 4 days after arrival. Because of limitation in available medical staff, travelers were provided a kit allowing self-collection of oral and nasal swabs. In addition to increase our testing capacity, self-collected samples from up to 10 travelers were pooled before RNA extraction and RT-PCR testing. When a pool tested positive, RNA extraction and RT-PCR were performed on each individual sample. We report here the results of COVID-19 surveillance (COV-CHECK PORINETIA) conducted between July 15 ^th , 2020, and February 15 ^th , 2021, in travelers using self-collection and pooling approaches. We tested 5,982 pools comprising 59,490 individual samples, and detected 273 (0.46%) travelers positive for SARS-CoV-2. A mean difference of 1.17 Ct (CI 95% 0.93 – 1.41) was found between positive individual samples and pools (N=50), probably related to the volume of samples used for RNA extraction (200 µL versus 50 µL, respectively). Retrospective testing of positive samples self-collected from October 20 ^th , 2020, using variants-specific amplification kit and spike gene sequencing, found at least 6 residents infected by the B1.1.7 UK variant. Self-collection and pooling approaches allowed large-scale screening for SARS-CoV-2 using less human, material and financial resources. Moreover, this strategy allowed detecting the introduction of SARS-CoV-2 variants in French Polynesia.

Understanding the transition of epidemic to endemic dengue transmission remains a challenge in regions where serotypes co-circulate and there is extensive human mobility. French Polynesia, an isolated group of 117 islands of which 72 are inhabited, distributed among five geographically separated subdivisions, has recorded mono-serotype epidemics since 1944, with long inter-epidemic periods of circulation. Laboratory confirmed cases have been recorded since 1978, enabling exploration of dengue epidemiology under monotypic conditions in an isolated, spatially structured geographical location. A database was constructed of confirmed dengue cases, geolocated to island for a 35-year period. Statistical analyses of viral establishment, persistence and fade-out as well as synchrony among subdivisions were performed. Seven monotypic and one heterotypic dengue epidemic occurred, followed by low-level viral circulation with a recrudescent epidemic occurring on one occasion. Incidence was asynchronous among the subdivisions. Complete viral die-out occurred on several occasions with invasion of a new serotype. Competitive serotype replacement has been observed previously and seems to be characteristic of the South Pacific. Island population size had a strong impact on the establishment, persistence and fade-out of dengue cases and endemicity was estimated achievable only at a population size in excess of 175 000. Despite island remoteness and low population size, dengue cases were observed somewhere in French Polynesia almost constantly, in part due to the spatial structuration generating asynchrony among subdivisions. Long-term persistence of dengue virus in this group of island populations may be enabled by island hopping, although could equally be explained by a reservoir of sub-clinical infections on the most populated island, Tahiti. Dengue virus is the most significant arthropod-borne virus infecting man. Understanding how long dengue virus can persist in populations of varying size is key to understanding its epidemiology. This is, however, impossible to achieve in settings where dengue is endemic, because of continued human movement and is further complexified by the occurrence of several co-circulating serotypes. By contrast, French Polynesia, an isolated group of 72 inhabited islands in the South Pacific, has had intermittent majoritarily monotypic dengue epidemics since the 1940s and offers a unique opportunity to address questions of viral persistence, turnover and the importance of spatial sub-structure in determining dengue epidemiology. Collating and analyzing a database of laboratory-confirmed dengue cases from across French Polynesia over a 35 year period we were able to show that dengue virus die-out can occur with or without replacement by a new serotype, monotypic transmission of dengue viruses fails to be maintained within small island populations but can persist for years among isolated islands connected via air and sea links. This remarkable long-term persistence of dengue virus in French Polynesia could be maintained by asynchronous viral transmission among connected islands and/or by repeated seeding from a reservoir of sub-clinical infections in the most populated island, Tahiti.