Pharmacogenetics: ethnicity, treatment and health in Latin American populations.

The Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) studies Latin American populations to benefit from the implementation of personalized medicine. Since 2006, it has studied ethnicity to apply pharmacogenetics knowledge in autochthonous populations of Latin America, considering ancestral medicine. The meeting 'Pharmacogenetics: ethnicity, Treatment and Health in Latin American Populations' was held in Mexico City, Mexico, and presented the relevance of RIBEF collaboration with Latin American researchers and the governments of Mexico, Spain and the Autonomous Community of Extremadura. The results of 17 years of uninterrupted work by RIBEF, the Declaration of Mérida/T'Hó and the call for the Dr José María Cantú Award for studies focused on the pharmacogenetics of native populations in Latin America were presented.

Identification of the Genotypes Circulating in the Ecuadorian Population Infected with the Hepatitis C Virus (HCV).

Introduction: The hepatitis C virus (HCV) is responsible for 1.5 million new infections, and around 290 thousand deaths worldwide. 15 to 30% of the patients that go into a chronic phase of the disease will develop cirrhosis or hepatocellular carcinoma within 20 years and is the leading etiology for liver transplantation. HCV genetic characteristics display a remarkable genetic diversity, which divides HCV into 8 genotypes and 67 subgenotypes; the treatment and probability of chronic HCV depend on these genotypes and subgenotypes. In Ecuador, there is no available information regarding HCV genotypes and subgenotypes; therefore, this study aims to provide an overview of the main genotypes circulating in Ecuador. Methods: In a cross-sectional and descriptive study using the Ecuadorian Ministry of Health (MSP) registry of patients already diagnosed with Hepatitis C (HCV) between 2017 and 2019. From 51 patients identified by health ministry, blood samples from a total of 15 subjects (named HCV1 to HCV15) were collected using an appropriate venipuncture technique. Pandemic-related circumstances avoid reaching all patients identified by health ministry. Results: After the amplification of 11 samples from patients living in the Ecuadorian territory, the genotypes of HCV obtained were distributed as follows: 6 samples corresponding to subgenotype 2b (54.5%), 2 samples corresponding to subgenotype 1a (18.2%), 2 samples corresponding to subgenotype 4d (18.2%) and 1 corresponding to sample 1b (9.1%). Conclusion: These results represent the first epidemiological approach to genotype distribution in Ecuador, and it contributes to better management of patients. We emphasize the importance of the development of better strategies from the Healthcare Ministry of Ecuador (MSP) for the identification, treatment and tracking of HCV patients.

The Placental Function Beyond Pregnancy: Insights from Latin America.

Currently, more than 100,000 papers had been published studying the placenta in both physiological and pathological contexts. However, relevant health conditions affecting placental function, mostly found in low-income countries, should be evaluated deeper. This review will raise some - of what we think necessary - points of discussion regarding challenging topics not fully understood, including the paternal versus maternal contribution on placental genes imprinting, placenta-brain communication, and some environmental conditions affecting the placenta. The discussions are parts of an international effort to fulfil some gaps observed in this area, and Latin-American research groups currently evaluate that.

Widespread Clean Cooking Fuel Scale-Up and under-5 Lower Respiratory Infection Mortality: An Ecological Analysis in Ecuador, 1990-2019.

BACKGROUND: Nationwide household transitions to the use of clean-burning cooking fuels are a promising pathway to reducing under-5 lower respiratory infection (LRI) mortality, the leading cause of child mortality globally, but such transitions are rare and evidence supporting an association between increased clean fuel use and improved health is limited. OBJECTIVES: This study aimed to investigate the association between increased primary clean cooking fuel use and under-5 LRI mortality in Ecuador between 1990 and 2019. METHODS: We documented cooking fuel use and cause-coded child mortalities at the canton (county) level in Ecuador from 1990 to 2019 (in four periods, 1988-1992, 1999-2003, 2008-2012, and 2015-2019). We characterized the association between clean fuel use and the rate of under-5 LRI mortalities at the canton level using quasi-Poisson generalized linear and generalized additive models, accounting for potential confounding variables that characterize wealth, urbanization, and child health care and vaccination rates, as well as canton and period fixed effects. We estimated averted under-5 LRI mortalities accrued over 30 y by predicting a counterfactual count of canton-period under-5 LRI mortalities were clean fuel use to not have increased and comparing with predicted canton-period under-5 LRI mortalities from our model and observed data. RESULTS: From 1990 to 2019, the proportion of households primarily using a clean cooking fuel increased from 59% to 95%, and under-5 LRI mortality fell from 28 to 7 per 100,000 under-5 population. Canton-level clean fuel use was negatively associated with under-5 LRI mortalities in linear and nonlinear models. The nonlinear association suggested a threshold at approximately 60% clean fuel use, above which there was a negative association. Increases in clean fuel use between 1990 and 2019 were associated with an estimated 7,300 averted under-5 LRI mortalities (95% confidence interval: 2,600, 12,100), accounting for nearly 20% of the declines in under-5 LRI mortality observed in Ecuador over the study period. DISCUSSION: Our findings suggest that the widespread household transition from using biomass to clean-burning fuels for cooking reduced under-5 LRI mortalities in Ecuador over the last 30 y. https://doi.org/10.1289/EHP11016.

Divergent metabolic phenotypes in two genetic syndromes of low insulin secretion.

AIMS: We examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS). METHODS: Adults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP). RESULTS: Both syndromic cohorts displayed DIS during OGTT. LS subjects had higher serum concentrations of total and HMW adiponectin, and lower levels of IGF-I, IGF-II, and IGF-Binding Protein-3 than individuals in other study groups. Furthermore, they displayed normal glycemic responses during OGTT with the lowest IAPP secretion. In contrast, individuals with GRS had higher levels of protein glycation, deficient glucose control during OGTT, and increased secretion of IAPP. CONCLUSIONS: A distinct metabolic phenotype depending on GH counter-regulatory status, associates with diabetes development and excess glucose-induced IAPP secretion.

Misleading Advertising of Health-Related Products in Ecuador during the COVID-19 Pandemic.

Background Media coverage of the COVID-19 pandemic increased tuning ratings during this time. The aim of this study was to identify misleading advertising of health-related products on Ecuadorian television during the COVID-19 pandemic. Methods Television channels were monitored for 111 h in the months of June and October 2020. Verbal, nonverbal and context content were analyzed from each advertising spot according to ethical standards for the promotion of products for human health Results A total of 667 spots were analyzed. Most, 90%, involved misleading advertising of health-related products. Products for gastrointestinal conditions were the most publicized (17.8%) during the period analyzed. Newscasts most often advertised products intended to improve sexual potency (22.9%) and to a lesser degree those intended to prevent and treat respiratory problems (1.8%); this relationship was reversed when compared to general programming (p < 0.05). Conclusions Most of the health-related products advertised on Ecuadorian television are advertised misleadingly, with news programs having the highest number of such advertisements per hour of programming.

Scientific literacy and preferred resources used by Latin American medical students during the COVID-19 pandemic: A multinational survey.

Background: This study aims to identify the preferred sources for acquiring knowledge about COVID-19 and to evaluate basic knowledge on critical scientific literature appraisal in students from medical schools located in Spanish speaking countries in Latin America.  Methods: We designed an online survey of 15 closed-ended questions related to demographics, preferred resources for COVID-19 training, and items to assess critical appraisal skills. A snowball method was used for sampling. We conducted a descriptive analysis and Chi-squared tests to compare the proportion of correct identification of the concept of a preprint and a predatory journal when considering a) self-perceived level of knowledge, b) public vs private school, c) inclusion of a scientific literature appraisal subject in the curriculum, and d) progress in medical school. Results: Our sample included 770 valid responses, out of which most of the participants included were from Mexico (n=283, 36.8%) and Ecuador (n=229, 29.7%). Participants preferred using evidence-based clinical resources (EBCRs) to learn more about COVID-19 (n=182, 23.6%). The preferred study design was case report/series (n=218, 28.1%). We found that only 265 participants correctly identified the concept of a preprint (34.4%), while 243 students (31.6%) correctly identified the characteristics of a predatory journal. We found no significant differences in the proportion of correct answers regardless of the self-perceived level of knowledge, progress in medical school, or scientific literature critical appraisal classes. Conclusion: This study is novel in its approach of identifying sources of knowledge used by Latin American medical students and provides insights into the need to reinforce training in critical appraisal of scientific literature during medical school.

HIV Rapid Testing in the General Population and the Usefulness of PrEP in Ecuador: A Cost-Utility Analysis.

Introduction: HIV is considered one of the most important chronic transmitted diseases worldwide. The Joint United Nations Program on HIV/AIDS in 2020 proposed the strategy "95-95-95" which goals to achieve a 95% of cases identified, receives ART, and will have achieved suppression of the virus. In Ecuador by 2020, according to the Ministry of Public Health, 45,056 persons are living with HIV, principally men between 15 and 49 years, and a mortality rate of 4.8/100,000 habitats. This study aims to determine the cost-utility of applying an early screening to a sexually active population vs. only a high-risk population and if the use of PrEP is justified depending on different contexts. Methods: For the cost-utility evaluation, it was compared: (a) HIV screening performed only in the high-risk population vs. HIV screening in all population sexually active; and (b) the use of ART only for HIV treatment vs. ART as a treatment in diagnosed cases and the use of PrEP (only at a high-risk population of acquiring HIV). Calculation and weight of DALYs for HIV/SIDA were obtained through WHO guidelines. To generate the Markov model for HIV/AIDS, subjects were classified as symptomatic or asymptomatic, as well as the HIV deaths. Results: Cost-benefit analysis (CUA) showed that ICER for early diagnosis had a negative value which means a saving if the strategy will be implemented as a regular test (-$591, -$4,360) and -108 and -934 DALYs, in the case of ART and PrEP, ICER the $30,541-$59,410, which resulted in more than the GDP's threshold and health years between 2,511 and 10,635 in the general population. With a reduction of 70% in the assigned budget for the early diagnosis, Ecuadorian people could lose between 4 and 6 DALYs, while if the budget reduces more than 50% to ART, it will generate a loss of 10-12 years of healthy life. Conclusion: CUA demonstrates that an early diagnosis in a sexually active population is cost-beneficial. This, combined with ART or PrEP, is ideal to add years of healthy life.

Streamlining breast cancer and colorectal cancer biosimilar regulations to improve treatment access in Latin America: an expert panel perspective.

In a multiday conference, a panel of Latin American experts in biological cancer therapies and health economics were provided with questions to address the barriers restricting access to biosimilars in Latin America, specifically for patients with breast cancer and colorectal cancer, for whom biosimilars can be a path forward to increasing access to care. During the conference, responses were discussed and edited until a consensus was achieved. The regulatory challenges identified in the conference included heterogenous regulations, non-adherence to regulatory pathways, scarcity of market opportunity, inadequate naming of biosimilars by only using international non-proprietary names, imprecise use of interchangeability and substitution, and insufficient traceability and pharmacovigilance. Recommendations were developed to improve the implementation of regulatory pathways and reliable procurement strategies that increase access to these therapies with adequate traceability and outcome measures; efforts from all involved stakeholders will be crucial. These recommendations can serve as a strategy for biosimilar adoption in other countries in a similar situation.

Pathways linking maternal mental health and child health in a dual burden context: Evidence from Galapagos, Ecuador.

Research in low-and-middle income countries links maternal depression to child undernutrition; conversely, maternal depression is a risk factor for child overweight in higher income settings. Less is known about impacts of maternal mental health in dual burden contexts or the environmental and behavioral pathways linking maternal mental health to child health outcomes. Consequently, we examine the association between maternal mental health and the dual burden of undernutrition/infectious disease and overweight/obesity in children and test whether pathogenic, dietary and caregiving exposures mediate this association. Data come from 113 mothers and their 204 children, aged 2 weeks to 15 years, participating in the Healthy Families Study in Galapagos, Ecuador from July 2018 to May 2019, with mental health, anthropometry, diet and household environmental measures. Path analyses were used to test for direct and indirect effects of maternal distress on the likelihood of children experiencing the dual burden. We found that maternal distress is directly associated with a greater risk of having a child in the household with the dual burden with significant indirect paths through the emotional climate of the household and child diet quality. Maternal distress also moderated the impact of exposure to pathogens and diet quality. Our results highlight the need to understand how maternal distress may shape care practices in environments that present challenges for mothers in acquiring adequate resources and support needed to promote healthy child growth.

Financial Incentives, Not Behavioral Nudges, Led to Optimized HIV Testing among Pregnant Women in a High-Burden Urban Population in Ecuador.

Behavioral economic principles are increasingly being used in the fight against HIV, including improving voluntary testing in sub-Saharan Africa and South America. However, behavioral nudges have not been widely tested as a strategy to optimize HIV testing in pregnant women. Here, we assessed whether behavioral nudges or financial incentives were effective in optimizing HIV testing among pregnant women in a high-HIV burden setting. A randomized clinical trial was conducted between May 21 and Oct 5, 2018, to allocate pregnant women in Ecuador into three study arms: information only, soft commitment (i.e., a behavioral nudge), and financial incentives. All participants received an informational flyer, including the address of a testing location. Participants in the soft-commitment arm signed and kept a form on which they committed to get tested for HIV. Those in the financial incentive arm received a $10 incentive when tested for HIV. A stepwise logistic regression analysis estimated the effect of the study arms on HIV testing rate. Participants in the financial-incentive arm had higher odds of getting an HIV test (adjusted odds ratio 17.06, P < 0.001) as compared with information-only participants. Soft-commitment had the opposite effect (adjusted odds ratio 0.14, P = 0.014). Financial incentives might be useful in improving HIV testing among pregnant women, especially among those who might be at higher risk but who have not completed an HIV test.

Social inequalities in healthcare utilization during Ecuadorian healthcare reform (2007-2017): a before-and-after cross-sectional study.

BACKGROUND: Limited research is available about the impact of healthcare reforms on healthcare utilization according to socioeconomic group. Although most health reforms in Latin America have focused on reducing the gap between the most advantaged and disadvantaged groups and improving the quality of health services, the available information has shown limited progress. Therefore, this study assessed whether the recent Ecuadorian healthcare reform (2007-2017) contributed to decreasing the socioeconomic inequalities in healthcare utilization. METHODS: We used data from the National Living Standards Measurement surveys conducted in 2006 and 2014. Unmet healthcare needs (UHCN) were used as the dependent variable and proxy for difficulties in accessing health services. Place of residence, ethnicity, education and wealth were selected as indicators of socioeconomic status. The slope and relative inequality indexes were calculated for adult men and women for each period and socioeconomic variable. A multiplicative interaction term between midpoint scores and time was applied to estimate changes in inequalities over time. Sample weights were applied to all analyses, and 95% confidence intervals were calculated to assess statistical significance in the regression analysis. RESULTS: In 2006, the poor, Indigenous, those living in rural areas and with low education had lower access to health services. In 2014, the overall prevalence of UHCN decreased from 27 to 18% and was higher in women than men. Statistically significant reductions of refraining were observed in absolute and relative terms in all social groups, both in men and women. CONCLUSIONS: Our results showed remarkable and significant decreases in inequalities in all examined socioeconomic groups in absolute and relative terms in this period. Although a new model of healthcare was established to achieve universal health coverage, its performance must be continuously evaluated and monitored with specific indicators. Further studies are also needed to identify the main barriers that contribute to UHCN among socially disadvantaged groups.

Risk Perception and Knowledge, Attitudes, and Practices Against COVID-19 in a Hypertensive Population From a Semi-Urban City of Ecuador.

Background: In an elderly population with hypertension, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a higher incidence of mortality and a protracted course of clinical symptoms. Objective: To assess the perceived risk of infection and complications due to COVID-19 in people with hypertension living in a semi-urban city of Ecuador. Methods: A cross-sectional telephone survey of adult outpatients with a previous diagnosis of hypertension in the semi-urban community of Conocoto in Quito, Ecuador was conducted from August to December 2020. Results: A total of 260 adult outpatients, aged 34-97 years, completed telephone surveys. Of total, 71.5% (n = 186) of respondents were women and 28.5% (n = 74) of respondents were men. Overall, 18.1% believe that their risk of infection is "very high," 55.4% believe that their risk of infection is "high," 21.5% believe that their risk of infection is "low," and 5% believe that their risk of infection is "very low." The perceived risk of complications, if infected by COVID-19, revealed that 21.9% believe that their risk of complication is "very high," 65.0% believe that their risk of complication is "high," 10.4% believe that their risk of complication is "low," and 2.7% believe that their risk of complication is "very low." Conclusion: Patients with hypertension are aware of the risks posed by COVID-19 infection and its impact on their health. However, the health system must educate the population on health practices and behaviors to avoid COVID-19 infection until the majority of the population of Ecuador can be vaccinated.

Effect of altitude on COVID-19 mortality in Ecuador: an ecological study.

BACKGROUND: The SARS-CoV-2/COVID-19 pandemic has claimed nearly 900,000 lives worldwide and infected more than 27 million people. Researchers worldwide are studying ways to decrease SARS-CoV-2 transmission and COVID-19 related deaths. Several studies found altitude having a negative association with both COVID-19 incidence and deaths. Ecuadorian data was used to explore the relationship between altitude and COVID-19. METHODS: This is an ecological study examining province-level data. To explore a relationship between altitude and COVID-19, this study utilized publicly available COVID-19 data and population statistics. ANOVA, correlation statistics, and a multivariate linear model explored the relationship between different Ecuadorian altitudes against incidence, mortality, and case-fatality rates. Population statistics attributed to COVID-19 were included in the linear model to control for confounding factors. RESULTS: Statistically significant differences were observed in the regions of Amazónica, Sierra, Costa of Ecuador for incidence, mortality, and case fatality rates, suggesting an association between altitude and SARS-CoV-2 transmission and COVID-19 disease severity (p-value ≤0.05). In univariate analysis, altitude had a negative association to mortality rate with a 1-unit change in altitude resulting in the decrease of 0.006 units in mortality rate (p-value = 0.03). The multiple linear models adjusted for population statistics showed a statistically significant negative association of altitude with mortality rate (p-value = 0.01) with a 1-unit change in altitude resulting in the decrease in mortality rate by 0.015 units. Overall, the model helped in explaining 50% (R2 = 0.4962) of the variance in mortality rate. CONCLUSION: Altitude may have an effect on COVID-19 mortality rates. However, based on our model and R2 value, the relationship between our variables of interest and COVID-19 mortality may be nonlinear. More research is needed to understand why altitude may have a protective effect against COVID-19 mortality and how this may be applicable in a clinical setting.

Pneumococcal Carriage Among Indigenous Kichwa Children From the Ecuadorian Andes After the 10-Valent Pneumococcal Vaccine Introduction.

BACKGROUND: We assessed nasopharyngeal pneumococcal carriage in Andean Kichwa children, the largest Amerindian indigenous population in the Ecuadorian Andes. All children in our study had been vaccinated with the 10-valent pneumococcal vaccine (PCV10). METHODS: Nasopharyngeal swabs from 63 families, 100 children <10 years old including 38 children under 5 years and 63 adult caregivers, from 5 different communities, were cultivated for Streptococcus pneumoniae and isolates were serotyped and antibiotic susceptibility testing was performed. RESULTS: Respectively, 67% of the 38 children under 5 years old, 49% of the 62 children between 6 and 10 years old and 16% of the 100 adults were colonized with S. pneumoniae. Of these, 30.9% carried a vaccine serotype, 5.4% a serotype shared by the PCV10/13-valent pneumococcal vaccine (PCV13) vaccine and 25.5% a PCV13 serotype or PCV13 vaccine-related serotype, with 19A (10.9%) and 6C (10.9%) as the most prominent. Drug susceptibility testing revealed that 46% of the S. pneumoniae strains were susceptible to 6 tested antibiotics. However, 20.3% of the strains were multidrug-resistant or extensively drug-resistant strains, including 82% of the vaccine (-related) serotype 19A and 6C strains. CONCLUSIONS: Kichwa children, vaccinated with PCV10, were highly colonized with pneumococci and should be considered a high-risk group for pneumococcal disease. Twenty-five percent of the colonizing S. pneumoniae strains were PCV13-only vaccine-targeted serotypes, and in addition to that, most were multidrug-resistant or extensively drug-resistant strains. The vaccine benefits for this population possibly will significantly increase with the introduction of PCV13.

Snake antivenom production in Ecuador: Poor implementation, and an unplanned cessation leads to a call for a renaissance.

Snakebite envenomation is a global health problem. This health problem asymmetrically affects rural populations in developing countries to such an extent that it recently has been listed as a priority neglected tropical disease (NTD). It is estimated that 5.4 million individuals are bitten by snakes each year, causing at least 2.7 million envenomations and more than 100,000 deaths each year. Ecuador has one of the highest snakebite envenomation incidence rates in Latin America, mostly in the coastal and Amazonian provinces. Envenomations in these regions are the result of bites primarily by species of snakes belonging to the Viperidae family. Ecuador was able to locally produce antivenoms, however serious flaws were revealed in the antivenom production process, leading to the decommissioning of the existing facility. In the interest of public health, we have summarized the political and social setbacks experienced by the antivenom serum production plant in Ecuador, while encouraging resuming local production of snake antivenom to improve the responsiveness of the already overburdened health system.

Adapting for the COVID-19 pandemic in Ecuador, a characterization of hospital strategies and patients.

The World Health Organization (WHO) declared coronavirus disease-2019 (COVID-19) a global pandemic on 11 March 2020. In Ecuador, the first case of COVID-19 was recorded on 29 February 2020. Despite efforts to control its spread, SARS-CoV-2 overran the Ecuadorian public health system, which became one of the most affected in Latin America on 24 April 2020. The Hospital General del Sur de Quito (HGSQ) had to transition from a general to a specific COVID-19 health center in a short period of time to fulfill the health demand from patients with respiratory afflictions. Here, we summarized the implementations applied in the HGSQ to become a COVID-19 exclusive hospital, including the rearrangement of hospital rooms and a triage strategy based on a severity score calculated through an artificial intelligence (AI)-assisted chest computed tomography (CT). Moreover, we present clinical, epidemiological, and laboratory data from 75 laboratory tested COVID-19 patients, which represent the first outbreak of Quito city. The majority of patients were male with a median age of 50 years. We found differences in laboratory parameters between intensive care unit (ICU) and non-ICU cases considering C-reactive protein, lactate dehydrogenase, and lymphocytes. Sensitivity and specificity of the AI-assisted chest CT were 21.4% and 66.7%, respectively, when considering a score >70%; regardless, this system became a cornerstone of hospital triage due to the lack of RT-PCR testing and timely results. If health workers act as vectors of SARS-CoV-2 at their domiciles, they can seed outbreaks that might put 1,879,047 people at risk of infection within 15 km around the hospital. Despite our limited sample size, the information presented can be used as a local example that might aid future responses in low and middle-income countries facing respiratory transmitted epidemics.

Cycle Threshold Values in the Context of Multiple RT-PCR Testing for SARS-CoV-2.

PURPOSE: Discharge or follow up of confirmed coronavirus disease 2019 (COVID-19) cases depend on accurate interpretation of RT-PCR. Currently, positive/negative interpretations are based on amplification instead of quantification of cycle threshold (Ct) values, which could be used as proxies of patient infectiousness. Here, we measured Ct values in hospitalized confirmed COVID-19 patients at different times and its implications in diagnosis and follow up. PATIENTS AND METHODS: Observational study between March 17th-May 12th, 2020 using multiple RT-PCR testing. A cohort of 118 Hispanic hospitalized patients with confirmed COVID-19 diagnosis in a reference hospital in Quito, Ecuador. Multiple RT-PCR tests were performed using deep nasal swab samples and the assessment of SARS-CoV-2 genes N, RdRP, and E. RESULTS: Patients' median age was of 49 years (range: 24-91) with a male majority (62.7%). We found increasing levels of Ct values in time, with a mean Ct value of 29.13 (n = 61, standard deviation (sd) = 5.55) for the first test and 34.38 (n = 60, sd = 4), 35.52 (n = 20, sd = 2.85), and 36.12 (n = 6, sd = 3.28), for the second, third, and fourth tests, respectively. Time to RT-PCR lack of amplification for all tests was of 34 days while time to RT-PCR Ct values >33 was of 30 days. CONCLUSION: Cycle thresholds can potentially be used to improve diagnosis, management and control. We found that turnover time for negativity can be large for hospitalized patients and that 11% cases persisted with infectious Ct values for more time than the current isolation recommendations.