Dengue vaccine acceptability before and after the availability of COVID-19 vaccines in Puerto Rico.

Dengue is a growing public health threat, causing approximately 400 million infections annually. In June 2021, the Advisory Committee on Immunization Practices recommended the first dengue vaccine (CYD-TDV) for children aged 9-16 years with a previous dengue infection, living in endemic areas, such as Puerto Rico (PR). As the COVID-19 pandemic affected vaccine intention worldwide, we assessed dengue vaccine intention before (pre-COVID) and after (post-COVID) COVID-19 vaccine availability among participants enrolled in the Communities Organized to Prevent Arboviruses (COPA) cohort to prepare for dengue vaccine implementation in PR. We used logistic regression models to evaluate changes in dengue vaccine intention by interview timing and participant characteristics. Among 2,513 participants pre-COVID, 2,512 answered the dengue vaccine intention question for themselves, and 1,564 answered relative to their children. Post-COVID, dengue vaccine intention in adults increased for themselves from 73.4% to 84.5% (adjusted odds ratio (aOR) = 2.27, 95%CI: 1.90-2.71) and relative to their children from 75.6% to 85.5% (aOR = 2.21, 95%CI: 1.75-2.78). Among all participants, groups with higher dengue vaccine intention included those who reported previous year influenza vaccine uptake and those who reported being frequently bitten by mosquitos, compared to those who did not. Adult males were also more likely to intend to vaccinate themselves than females. Respondents who were employed or in school were less likely to intend to vaccinate compared to those who were not working. The primary reasons for vaccine hesitancy were concerns with side effects and not believing in vaccines, which should be considered during educational strategies prior to dengue vaccine implementation. In general, dengue vaccine intention is high in PR and has increased after COVID-19 vaccine availability, potentially due to increased awareness of vaccine importance during the COVID-19 pandemic.

Genomic Surveillance of SARS-CoV-2 Variants in the Dominican Republic and Emergence of a Local Lineage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that evolves over time, leading to new variants. In the current study, we assessed the genomic epidemiology of SARS-CoV-2 in the Dominican Republic. A total of 1149 SARS-CoV-2 complete genome nucleotide sequences from samples collected between March 2020 and mid-February 2022 in the Dominican Republic were obtained from the Global Initiative on Sharing All Influenza Data (GISAID) database. Phylogenetic relationships and evolution rates were analyzed using the maximum likelihood method and the Bayesian Markov chain Monte Carlo (MCMC) approach. The genotyping details (lineages) were obtained using the Pangolin web application. In addition, the web tools Coronapp, and Genome Detective Viral Tools, among others, were used to monitor epidemiological characteristics. Our results show that the most frequent non-synonymous mutation over the study period was D614G. Of the 1149 samples, 870 (75.74%) were classified into 8 relevant variants according to Pangolin/Scorpio. The first Variants Being Monitored (VBM) were detected in December 2020. Meanwhile, in 2021, the variants of concern Delta and Omicron were identified. The mean mutation rate was estimated to be 1.5523 × 10-3 (95% HPD: 1.2358 × 10-3, 1.8635 × 10-3) nucleotide substitutions per site. We also report the emergence of an autochthonous SARS-CoV-2 lineage, B.1.575.2, that circulated from October 2021 to January 2022, in co-circulation with the variants of concern Delta and Omicron. The impact of B.1.575.2 in the Dominican Republic was minimal, but it then expanded rapidly in Spain. A better understanding of viral evolution and genomic surveillance data will help to inform strategies to mitigate the impact on public health.

Preventive Measures among Healthcare Workers (HCWs) during the COVID-19 Pandemic

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), placed health systems worldwide under immense pressure, and healthcare workers (HCWs) were at the front lines. The Puerto Rico Department of Health confirmed the first case of COVID-19 in March 2020. We aimed to assess whether COVID-19 preventive measures implemented by HCWs were effective in a work scenario before vaccine availability. We conducted a descriptive cross-sectional study from July to December 2020 to evaluate the use of personal protective equipment (PPE), hygiene guidelines, and other measures taken by HCWs to prevent the spread of SARS-CoV-2. We collected nasopharyngeal specimens for molecular testing at the beginning of the study and follow-up. We recruited 62 participants aged 30–59 (79% women). Participants recruited from hospitals, clinical laboratories, and private practice included medical technologists (33%), nurses (28%), respiratory therapists (2%), physicians (11%), and others (26%). Among our participants, nurses were at higher risk (p < 0.05) of infection. We identified that 87% of participants followed the hygiene recommendation guidelines. In addition, all participants practiced handwashing or disinfection before or after caring for each patient. All participants tested negative for SARS-CoV-2 during the study period. On follow-up, all study participants reported being vaccinated against COVID-19. The implementation of PPE and hygiene measures showed high efficacy as a prevention method against SARS-CoV-2 infection when vaccines and treatment were not widely available in Puerto Rico.

SARS-CoV-2 Omicron Replacement of Delta as Predominant Variant, Puerto Rico.

We reconstructed the SARS-CoV-2 epidemic caused by Omicron variant in Puerto Rico by sampling genomes collected during October 2021-May 2022. Our study revealed that Omicron BA.1 emerged and replaced Delta as the predominant variant in December 2021. Increased transmission rates and a dynamic landscape of Omicron sublineage infections followed.

Preventive Measures among Healthcare Workers (HCWs) during the COVID-19 Pandemic.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), placed health systems worldwide under immense pressure, and healthcare workers (HCWs) were at the front lines. The Puerto Rico Department of Health confirmed the first case of COVID-19 in March 2020. We aimed to assess whether COVID-19 preventive measures implemented by HCWs were effective in a work scenario before vaccine availability. We conducted a descriptive cross-sectional study from July to December 2020 to evaluate the use of personal protective equipment (PPE), hygiene guidelines, and other measures taken by HCWs to prevent the spread of SARS-CoV-2. We collected nasopharyngeal specimens for molecular testing at the beginning of the study and follow-up. We recruited 62 participants aged 30-59 (79% women). Participants recruited from hospitals, clinical laboratories, and private practice included medical technologists (33%), nurses (28%), respiratory therapists (2%), physicians (11%), and others (26%). Among our participants, nurses were at higher risk (p < 0.05) of infection. We identified that 87% of participants followed the hygiene recommendation guidelines. In addition, all participants practiced handwashing or disinfection before or after caring for each patient. All participants tested negative for SARS-CoV-2 during the study period. On follow-up, all study participants reported being vaccinated against COVID-19. The implementation of PPE and hygiene measures showed high efficacy as a prevention method against SARS-CoV-2 infection when vaccines and treatment were not widely available in Puerto Rico.

Genomic surveillance of SARS-CoV-2 in Puerto Rico enabled early detection and tracking of variants.

Background: Puerto Rico has experienced the full impact of the COVID-19 pandemic. Since SARS-CoV-2, the virus that causes COVID-19, was first detected on the island in March of 2020, it spread rapidly though the island's population and became a critical threat to public health. Methods: We conducted a genomic surveillance study through a partnership with health agencies and academic institutions to understand the emergence and molecular epidemiology of the virus on the island. We sampled COVID-19 cases monthly over 19 months and sequenced a total of 753 SARS-CoV-2 genomes between March 2020 and September 2021 to reconstruct the local epidemic in a regional context using phylogenetic inference. Results: Our analyses reveal that multiple importation events propelled the emergence and spread of the virus throughout the study period, including the introduction and spread of most SARS-CoV-2 variants detected world-wide. Lineage turnover cycles through various phases of the local epidemic were observed, where the predominant lineage was replaced by the next competing lineage or variant after ~4 months of circulation locally. We also identified the emergence of lineage B.1.588, an autochthonous lineage that predominated in Puerto Rico from September to December 2020 and subsequently spread to the United States. Conclusions: The results of this collaborative approach highlight the importance of timely collection and analysis of SARS-CoV-2 genomic surveillance data to inform public health responses.

Clinical Features of COVID-19, Dengue, and Influenza among Adults Presenting to Emergency Departments and Urgent Care Clinics-Puerto Rico, 2012-2021.

Dengue and influenza are pathogens of global concern and cause febrile illness similar to COVID-19. We analyzed data from an enhanced surveillance system operating from three emergency departments and an urgent care clinic in Puerto Rico to identify clinical features predictive of influenza or dengue compared with COVID-19. Participants with fever or respiratory symptoms and aged ≥18 years enrolled May 2012-January 2021 with dengue, influenza, or SARS-CoV-2 confirmed by reverse transcriptase polymerase chain reaction were included. We calculated adjusted odds ratios (aORs) and 95% CIs using logistic regression to assess clinical characteristics of participants with COVID-19 compared to those with dengue or influenza, adjusting for age, subregion, and days from illness onset to presentation for clinical care. Among 13,431 participants, we identified 2,643 with dengue (N = 303), influenza (N = 2,064), or COVID-19 (N = 276). We found differences in days from onset to presentation among influenza (2 days [interquartile range: 1-3]), dengue (3 days [2-4]), and COVID-19 cases (4 days [2-7]; P < 0.001). Cough (aOR: 0.12 [95% CI: 0.07-0.19]) and shortness of breath (0.18 [0.08-0.44]) were less common in dengue compared with COVID-19. Facial flushing (20.6 [9.8-43.5]) and thrombocytopenia (24.4 [13.3-45.0]) were more common in dengue. Runny nose was more common in influenza compared with COVID-19 (8.3 [5.8-12.1]). In summary, cough, shortness of breath, facial flushing, and thrombocytopenia helped distinguish between dengue and COVID-19. Although few features distinguished influenza from COVID-19, presentation > 4 days after symptom onset suggests COVID-19. These findings may assist clinicians making time-sensitive decisions regarding triage, isolation, and management while awaiting pathogen-specific testing.

SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference.

The reliability of sequence-based inference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with a reverse transcription-PCR cycle threshold of ≤30 underwent whole-genome sequencing. Intrahost single-nucleotide variants (iSNV) were identified at a ≥5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole-genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had ≥1 consensus sequence that differed by 1 to 2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and in 6 of 11 with distinct ones. In multiple-infection households, whole-genome consensus sequences differed by 0 to 1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. IMPORTANCE We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings.

Genomic surveillance of SARS-CoV-2 in Puerto Rico enabled early detection and tracking of variants

Background Puerto Rico has experienced the full impact of the COVID-19 pandemic. Since SARS-CoV-2, the virus that causes COVID-19, was first detected on the island in March of 2020, it spread rapidly though the island’s population and became a critical threat to public health. Methods We conducted a genomic surveillance study through a partnership with health agencies and academic institutions to understand the emergence and molecular epidemiology of the virus on the island. We sampled COVID-19 cases monthly over 19 months and sequenced a total of 753 SARS-CoV-2 genomes between March 2020 and September 2021 to reconstruct the local epidemic in a regional context using phylogenetic inference. Results Our analyses reveal that multiple importation events propelled the emergence and spread of the virus throughout the study period, including the introduction and spread of most SARS-CoV-2 variants detected world-wide. Lineage turnover cycles through various phases of the local epidemic were observed, where the predominant lineage was replaced by the next competing lineage or variant after ~4 months of circulation locally. We also identified the emergence of lineage B.1.588, an autochthonous lineage that predominated in Puerto Rico from September to December 2020 and subsequently spread to the United States. Conclusions The results of this collaborative approach highlight the importance of timely collection and analysis of SARS-CoV-2 genomic surveillance data to inform public health responses. Plain language summary The COVID-19 pandemic reached Puerto Rico in March 2020. To understand the impact of SARS-CoV-2 on Puerto Rico, we formed a partnership with universities and local government to study the genetic sequence of viruses sampled from infected people between March 2020 and September 2021. Our results show that the local epidemic was initiated and sustained by frequent importation of a wide diversity of SARS-CoV-2 lineages and variants, some of which circulated for some time in the island. We also detected a lineage of SARS-CoV-2, named B.1.588, that was first detected in Puerto Rico and subsequently spread to the United States. This study highlights the importance of the study of viral genetic data to inform public health responses. Santiago et al. sequenced SARS-CoV-2 genomes sampled in Puerto Rico between March 2020 and September 2021. Phylogenetic analyses found multiple importations that increased infections and that variant turnover dynamics were similar to those seen in the USA.

COVID-19 Vaccination Intention in a Community Cohort in Ponce, Puerto Rico.

As of January 20, 2022, > 247,000 confirmed COVID-19 cases and 3,400 deaths were reported in Puerto Rico (PR). We interviewed participants aged ≥ 14 years in the Communities Organized to Prevent Arboviruses (COPA) study, a community-based cohort in PR, about COVID-19 vaccine intention from November 12, 2020, to June 25, 2021. We used univariate and adjusted analyses to identify participant characteristics associated with vaccine intention. Among 1,542 respondents, the median age was 37 years (interquartile range 23-45) and 914 (59%) were female. Most participants (83%) reported a willingness to receive a COVID-19 vaccine. The most common reason for vaccine hesitancy was concern about the safety or side effects (64%). Willingness to receive the COVID-19 vaccine was associated with a later interview date, higher household income, previous COVID-19 diagnosis among household members, COVID-19 risk perception, influenza vaccine uptake, dengue vaccine intention, and general positive perceptions of vaccines. While parents with minors (< 21 years old) were less likely to report vaccine intention for themselves than participants without minor children, we observed similar characteristics associated with parents' willingness to vaccinate their children. Overall, COVID-19 vaccine intention was high among COPA participants. It is important that public health messaging in PR addresses COVID-19 vaccine safety and possible side effects.

Precision health diagnostic and surveillance network uses S gene target failure (SGTF) combined with sequencing technologies to track emerging SARS‐CoV‐2 variants

Introduction The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic revealed a worldwide lack of effective molecular surveillance networks at local, state, and national levels, which are essential to identify, monitor, and limit viral community spread. SARS‐CoV‐2 variants of concern (VOCs) such as Alpha and Omicron, which show increased transmissibility and immune evasion, rapidly became dominant VOCs worldwide. Our objective was to develop an evidenced‐based genomic surveillance algorithm, combining reverse transcription polymerase chain reaction (RT‐PCR) and sequencing technologies to quickly identify highly contagious VOCs, before cases accumulate exponentially. Methods Deidentified data were obtained from 508,969 patients tested for coronavirus disease 2019 (COVID‐19) with the TaqPath COVID‐19 RT‐PCR Combo Kit (ThermoFisher) in four CLIA‐certified clinical laboratories in Puerto Rico (n = 86,639) and in three CLIA‐certified clinical laboratories in the United States (n = 422,330). Results TaqPath data revealed a frequency of S Gene Target Failure (SGTF) > 47% for the last week of March 2021 in both, Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021. The weekly SGTF rate in US samples was high (>8%) from late December to early January and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico was concurrent with a sharp increase in VOCs among all SARS‐CoV‐2 sequences from Puerto Rico uploaded to Global Influenza Surveillance and Response System (GISAID) (n = 461). Alpha variant frequency increased from <1% in the last week of January 2021 to 51.5% of viral sequences from Puerto Rico collected in the last week of March 2021. Conclusions According to the proposed evidence‐based algorithm, approximately 50% of all SGTF patients should be managed with VOCs self‐quarantine and contact tracing protocols, while WGS confirms their lineage in genomic surveillance laboratories. Our results suggest this workflow is useful for tracking VOCs with SGTF. The evidence‐based Molecular Epidemiology and Genomic Surveillance algorithm, developed in this study to quickly identify emerging Variants of Concern (VOCs), is a valuable tool for identifying individual carriers of highly infectious variants with the S Gene Target Failure (SGTF) feature, such as Alpha and Omicron, who can then be effectively triaged for isolation, contact tracing, and treatment purposes.

Precision health diagnostic and surveillance network uses S gene target failure (SGTF) combined with sequencing technologies to track emerging SARS-CoV-2 variants.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic revealed a worldwide lack of effective molecular surveillance networks at local, state, and national levels, which are essential to identify, monitor, and limit viral community spread. SARS-CoV-2 variants of concern (VOCs) such as Alpha and Omicron, which show increased transmissibility and immune evasion, rapidly became dominant VOCs worldwide. Our objective was to develop an evidenced-based genomic surveillance algorithm, combining reverse transcription polymerase chain reaction (RT-PCR) and sequencing technologies to quickly identify highly contagious VOCs, before cases accumulate exponentially. METHODS: Deidentified data were obtained from 508,969 patients tested for coronavirus disease 2019 (COVID-19) with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA-certified clinical laboratories in Puerto Rico (n = 86,639) and in three CLIA-certified clinical laboratories in the United States (n = 422,330). RESULTS: TaqPath data revealed a frequency of S Gene Target Failure (SGTF) > 47% for the last week of March 2021 in both, Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021. The weekly SGTF rate in US samples was high (>8%) from late December to early January and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico was concurrent with a sharp increase in VOCs among all SARS-CoV-2 sequences from Puerto Rico uploaded to Global Influenza Surveillance and Response System (GISAID) (n = 461). Alpha variant frequency increased from <1% in the last week of January 2021 to 51.5% of viral sequences from Puerto Rico collected in the last week of March 2021. CONCLUSIONS: According to the proposed evidence-based algorithm, approximately 50% of all SGTF patients should be managed with VOCs self-quarantine and contact tracing protocols, while WGS confirms their lineage in genomic surveillance laboratories. Our results suggest this workflow is useful for tracking VOCs with SGTF.

Reduced spread of influenza and other respiratory viral infections during the COVID-19 pandemic in southern Puerto Rico.

INTRODUCTION: Impacts of COVID-19 mitigation measures on seasonal respiratory viruses is unknown in sub-tropical climates. METHODS: We compared weekly testing and test-positivity of respiratory infections in the 2019-2020 respiratory season to the 2012-2018 seasons in southern Puerto Rico using Wilcoxon signed rank tests. RESULTS: Compared to the average for the 2012-2018 seasons, test-positivity was significantly lower for Influenza A (p<0.001) & B (p<0.001), respiratory syncytial virus (RSV) (p<0.01), respiratory adenovirus (AdV) (p<0.05), and other respiratory viruses (p<0.001) following March 2020 COVID-19 stay at home orders. CONCLUSIONS: Mitigation measures and behavioral social distancing choices may have reduced respiratory viral spread in southern Puerto Rico.

Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness - United States and Puerto Rico, April 2020-March 2021.

The diagnosis of dengue disease, caused by the dengue virus (DENV) (a flavivirus), often requires serologic testing during acute and early convalescent phases of the disease. Some symptoms of DENV infection, such as nonspecific fever, are similar to those caused by infection with SARS-CoV-2, the virus that causes COVID-19. In studies with few COVID-19 cases, positive DENV immunoglobulin M (IgM) results were reported with various serologic tests, indicating possible cross-reactivity in these tests for DENV and SARS-CoV-2 infections (1,2). DENV antibodies can cross-react with other flaviviruses, including Zika virus. To assess the potential cross-reactivity of SARS-CoV-2, DENV, and Zika virus IgM antibodies, serum specimens from 97 patients from Puerto Rico and 12 U.S.-based patients with confirmed COVID-19 were tested using the DENV Detect IgM Capture enzyme-linked immunosorbent assay (ELISA) (InBios International).* In addition, 122 serum specimens from patients with confirmed dengue and 121 from patients with confirmed Zika virus disease (all from Puerto Rico) were tested using the SARS-CoV-2 pan-Ig Spike Protein ELISA (CDC).† Results obtained for DENV, Zika virus IgM, and SARS-CoV-2 antibodies indicated 98% test specificity and minimal levels of cross-reactivity between the two flaviviruses and SARS-CoV-2. These findings indicate that diagnoses of dengue or Zika virus diseases with the serological assays described in this report are not affected by COVID-19, nor do dengue or Zika virus diseases interfere with the diagnosis of COVID-19.

Characteristics and clinical outcomes of patients hospitalized with laboratory-confirmed COVID-19-Puerto Rico, March-August 2020.

Hispanics are the majority ethnic population in Puerto Rico where we reviewed charts of 109 hospitalized COVID-19 patients to better understand demographic and clinical characteristics of COVID-19 and determine risk factors for poor outcomes. Eligible medical records of hospitalized patients with confirmed COVID-19 illnesses were reviewed at four participating hospitals in population centers across Puerto Rico and data were abstracted that described the clinical course, interventions, and outcomes. We found hospitalized patients had a median of 3 underlying conditions with obesity and diabetes as the most frequently reported conditions. Intensive care unit (ICU) admission occurred among 28% of patients and 18% of patients died during the hospitalization. Patients 65 or older or with immune deficiencies had a higher risk for death. Common symptoms included cough, dyspnea, and fatigue; less than half of patients in the study reported fever which was less frequent than reported elsewhere in the literature. It is important for interventions within Hispanic communities to protect high-risk groups.