Early transmission dynamics, spread, and genomic characterization of SARS-CoV-2 in Panama
Authors: Franco Danilo , Gonzalez Claudia , Abrego Leyda E. , Carrera Jean Paul , Diaz Yamilka , Caisedo Yaset , Moreno Ambar , Chavarria Oris , Gondola Jessica , Castillo Marlene , Valdespino Elimelec , Gaitán Melissa , Martínez-Mandiche Jose , Hayer Lizbeth , Gonzalez Pablo , Lange Carmen , Molto Yadira , Mojica Dalis , Ramos Ruben , Mastelari Maria , Cerezo Lizbeth , Moreno Lourdes , Donnelly Christl A. , Faria Nuno Rodrigues , Pascale Juan Miguel , Lopez-Verges Sandra , Martinez Alexander A 
Published: August 2020

SummaryBackgroundWith more than 50000 accumulated cases, Panama has one of the highest incidences of SARS-CoV-2 in Central America, despite the fast implementation of disease control strategies. We investigated the early transmission patterns of the virus and the outcomes of mitigation measures in the country.MethodsWe collected information from epidemiological surveillance, including contact tracing, and genetic data from SARS-CoV-2 whole genomes, of the first five weeks of the outbreak. These data were used to estimate the exponential growth rate, doubling time and the time-varying effective reproductive number (Rt) using date of symptom onset in a Bayesian framework. The time of most recent ancestor for the introduced and circulating lineages was estimated by Bayesian analysis.FindingsA total of 4210 subjects were SARS-CoV-2 positive during the period evaluated, of them we sequenced 313 cases, detecting the circulation of 10 SARS-CoV-2 lineages. Whole genomes analysis identified the local transmission of one cryptic lineage as early as 2 weeks before it was detected by surveillance systems. Analysis of transmission dynamics showed that lockdown reduced Rt and increased the doubling time, however, these measures did not stop the circulation of this lineage in the country.InterpretationThese results demonstrate the value of epidemiological modeling and genome surveillance to assess mitigation strategies. At the same time, an active search for cryptic transmission clusters is crucial to interrupt local transmission of SARS-CoV-2 in a region.FundingMinistry of Health, Contribution from private donors and Secretaría Nacional de Ciencia y Tecnología.Research in ContextEvidence before this studyIn May 2020, we searched for published studies in PubMed and web of Science related to genetic variability and dynamics of SARS-CoV-2 transmission in Latin America, and there was none. On July 2020, there was one study of this type on SARS-CoV-2 transmission in Brazil and none in Central America. We were particularly interested in SARS-CoV-2 cryptic transmission that could allow the virus spread through locals without being detected by respiratory health system surveillance, and no publication was reported. On July 2020, seven papers (five in preprint) were about SARS-CoV-2 cryptic transmission, one in China, another in UK and five in the US. None in Central America. All of them showed the importance of genomic surveillance to detect different lineage introductions, cryptic transmission and its role in early spread in a region or in health-care setting.Added value of this studyWe integrate data collected from tested individual during national surveillance of COVID19 suspected cases or contact of cases, as part of the National COVID19 Laboratory network. This data was used to estimate epidemiological parameters of the outbreak as well as the effect of mitigation measures on the epidemic dynamic. We sequence the whole genome of SARS-COV-2 of 7.4% of RT-PCR confirmed cases at the national level, and with phylogenetic analysis we identified SARS-CoV-2 lineages introduced in the country and estimate date of their introductions. Epidemiological and genetic data was compared and we observed the cryptic transmission of one introduced lineage and the rise of a local lineage that was not detected by the active contact tracing implemented by the health system surveillance. This cryptic lineage could explain the fact that early implementation measures decreased the transmission rate and the increased the doubling time, however they were not able to eliminate totally the virus spread.Implications of all the available evidenceThis is the first study that analyzed the epidemiology and transmission dynamics of the early COVID19 epidemic in a Central American country using both epidemiological and genomic surveillance. Our findings suggest that strict containment measures and movement restrictions in Panama might have contributed to decrease the early spread of the virus, but that cryptic local transmission allowed a continual basal virus diffusion that could explain, in part, the high incidence of cases in the country. More broadly, our findings are crucial to inform intervention policy in real-time, for countries in similar situations and the importance of constant monitoring of SARS-CoV-2 lineages to understand its transmission in a region.