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2.
preprints.org; 2022.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202209.0200.v1

ABSTRACT

Background: COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being described. Objective: To describe the findings of a current systematic review of the long-term effects related to post-COVID-19 sequelae. Design: A systematic review was carried out in which cohort studies, case series, clinical case reports were included, and the PubMed, Scielo, SCOPUS and Web of Science databases were ex-tracted. Information published 2020 to June 1, 2022, was sought. Results: We reviewed 300 manuscripts during the first step of the literature review process. Then 260 abstracts were analyzed. In the end, we included 32 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 9 for neurological and psychiatric, and 8 for cutaneous sequelae. Conclusion: Studies show that the most common sequelae are those linked to the lungs, followed by skin, cutaneous and psychiatric alterations. Women report a higher incidence of the sequelae, as well as those with comorbidities and severer COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its apparition but has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems and further burden healthcare systems around the world.


Subject(s)
COVID-19
4.
preprints.org; 2022.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202208.0376.v1

ABSTRACT

Background: Some patients who have recovered from COVID-19 have experienced a range of persistent symptoms or the appearance of new ones after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (< 2,500 m) and high altitude (>2,500 m).Results: Overall, 1100 (52.3%) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by women (64.0%), the most affected group was young adults (68.5%), and the majority of long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of persisting symptoms was observed among those who received an incomplete vaccine scheme.Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 20-40, are more likely to describe sequalae associated with post-COVID. We also found that living at a high altitude was associated with earlier onset and longer symptom duration. Finally, we found a greater risk to report long lasting symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.


Subject(s)
COVID-19
5.
preprints.org; 2022.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202205.0243.v1

ABSTRACT

The COVID-19 pandemic has put a lot of pressure on health systems worldwide. Mass vaccination against SARS-CoV-2 has reduced morbidity and mortality worldwide. Despite their safety profiles, vaccines like any other medical product can cause adverse events. Yet, in countries with poor epidemiological surveillance and monitoring systems, reporting vaccine-related adverse events is scarce. The objective of this study was to describe self-reported vaccine adverse events after receiving one of the available COVID-19 vaccine schemes in Ecuador. A cross-sectional analysis based on an online self-reporting 32-questionnaire was conducted in Ecuador from April 1st to July 15th, 2021. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 6,654 participants were included in this study. A 38.2% of the participants reported having at least one comorbidity. Patients received AstraZeneca, Pfizer, and Sinovac vaccines, and these were distributed 38.4%, 31.1%, and 30.5%, respectively. Pain, inflammation at the injection site (20,01%), and headache (16,91%) were the most reported adverse events. Women addressed ESAVIs (64%), more often than men (36%). After receiving the first dose of any available COVID-19 vaccine, a total of 19,481 self-reported ESAVIs were informed (86.9% were mild, 11.6% moderate and 1.5% severe). In terms of vaccine type and brand, the most reactogenic vaccine was AstraZeneca with 57.8%, followed by Pfizer (24.9%) and Sinovac (17, 3 %). After the second dose, 6,757 self-reported ESAVIs were reported (87.0% mild, 10.9% moderate, and 2.1% severe). AstraZeneca vaccine users reported a higher proportion of ESAVIs (72.2%) in comparison to Pfizer/BioNTech (15.9%) and Sinovac Vaccine (11.9%). Swelling at the injection site, headache, muscle pain, and fatigue were the most common ESAVIs for the first as well as second dose. In conclusion, most ESAVIs were mild. AstraZeneca users were more likely to report adverse events. Participants without a history of COVID-19 infection, as well as those who receive the first dose, were more prone to report ESAVIs.


Subject(s)
COVID-19
6.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1059337.v1

ABSTRACT

Background: SARS-CoV-2 has spread throughout the world, including areas located at high or very high altitudes. There is a debate about the role of high altitude hypoxia on viral transmission, incidence, and COVID-19 related mortality. This is the first comparison of SARS-CoV-2 viral load across elevations ranging from 0 to 4,300 m. Objective: To describe the SARS-CoV-2 viral load across samples coming from 62 cities located at low, moderate, high, and very high altitudes in Ecuador. Method: ology: An observational analysis of viral loads among nasopharyngeal swap samples coming from a cohort of 4,929 patients with a RT-qPCR test positive for SARS-CoV-2. Results: : The relationship between high and low altitude only considering our sample of 4,929 persons is equal in both cases and not significative (p-value 0.19). In the case of low altitude, adding the gender variable to the analysis, it was possible to find a significative difference between female and male gender (p-value 0.068). Considering initially gender and then altitude, it was possible to find a significative difference between high and low altitude for male gender (p-value 0.065). There is not enough evidence to state that viral load is affected directly by altitude range but adding a new variable as sex in the analysis shows that the presence of new variables influences the relationship of altitude range and viral load. Conclusions: : There is no evidence that viral load differs at altitude level when we consider only one measure. Using as reference the variable gender is possible to note that at low altitude there is a difference between female and male gender. There is not difference between gender at high altitude level. In the case of considering gender as reference variable, it was possible to find that high and low altitude are different for male gender an equal for female gender. Viral load not only depends on altitude range; it also is affected by other variables like sex.


Subject(s)
COVID-19 , Hypoxia
7.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-808746.v1

ABSTRACT

There is pressing urgency to identify drugs that allow treating COVID-19 patients effectively. Respiratory failure is the leading cause of death in patients with severe COVID-19, and the host inflammatory response at the lungs remains poorly understood. Therefore, we retrieved data from postmortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, functional enrichment, and shortest pathways to cancer hallmark phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials. Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were: inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, thymic stromal lymphopoietin, blood coagulation, IL-1 and megakaryocytes in obesity, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF- κ B, TNF, oncostatin M, AGE-RAGE signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis. Lastly, we propose five small molecules involved in advanced-stage COVID-19 clinical trials: baricitinib, pacritinib, and ruxolitinib are tyrosine-protein kinase JAK2 inhibitors, losmapimod is a MAP kinase p38 alpha inhibitor, and eritoran is a TLR4/MD-2 antagonist. After being thoroughly analyzed in COVID-19 clinical trials, these drugs can be considered for treating severe COVID-19 patients.


Subject(s)
Neoplasms , Obesity , COVID-19
8.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-739011.v1

ABSTRACT

Background: Latin America is the most affected region by the COVID-19 pandemic in terms of excessive mortality. Diagnostic and health care capabilities are limited in this region, deficiencies resulting in poor contact tracing, insufficient medical treatment and an unprecedented number of deaths. One of the key issues to estimate the pandemic's actual impact is to track deaths as one of the most reliable indicators when SARS-CoV-2 under-diagnosis is evident. Objective: This study's objective was to estimate the number of deaths attributed to COVID-19 based on excess mortality data in Ecuador. Method: ology: An ecological study of all-cause mortality recorded in Ecuador during the year 2020. In order to calculate the total excess death relative to the historical average for the same dates in 2017, 2018 and 2019, a Poisson fitting analysis was used to identify trends on officially recorded all-caused deaths and those attributed to COVID-19. A bootstrapping technique based on central tendency measures was used to emulate the sampling distribution of our expected deaths estimator μ deaths by simulating the data generation and model fitting processes. Results: : In Ecuador, during the first year of the pandemic, at least 115,070 deaths were recorded. At least 42,453 of those were catalogued as excessive mortality when comparing with the last 3-years average (2017-2019). Ecuador is the country with the highest recorded excess mortality in the world with 6 / 100,000 deaths per capita in one single day while Peru had 2 / 100,000. This value represents an additional 408% of the expected fatalities. The province with the highest number of excess deaths was Santa Elena on Ecuador's coast, with more than 154% increment versus previous years. Conclusions: : Adjusting for population size and time, the hardest-hit country due to the COVID-19 pandemic was Ecuador. The mortality excess rate shows that the SARS-CoV-2 virus spread rapidly in the country, especially in the coastal province of Santa Elena and Guayas. Our results and the new proposed methodology could help to address the actual death toll situation during the early phase of the pandemic in Ecuador.


Subject(s)
COVID-19 , Deficiency Diseases
9.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.06.17.21259078

ABSTRACT

Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings We develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.


Subject(s)
COVID-19
10.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3817420

ABSTRACT

Background: The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of current and proposed treatments, and consequently research and procurement priorities, have not been clear. Methods: First, we used a model of SARS-CoV-2 transmission, COVID-19 disease and clinical care pathways to explore the potential impact of dexamethasone - the main treatment currently for hospitalised COVID-19 patients - under scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) the efficacy of dexamethasone in the absence of supportive care. We then fit the model to the observed epidemic trajectory to-date in 165 countries and analysed the potential future impact of dexamethasone in different countries, regions, and country-income strata. Finally, we constructed hypothetical profiles of novel therapeutics based on current trials, and compared the potential impact of each under different circumstances. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. Findings: We find the potential benefit dexamethasone is severely limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). However, therapeutics for different patient populations (in particular, those not in hospital and early in the course of infection) and types of benefit (in particular, reducing disease severity or infectiousness) could have much greater benefits. Such therapeutics would have particular value in resource-poor settings facing large epidemics, even if the efficacy or achievable coverage of such therapeutics is lower in comparison to other types. Interpretation: People in low-income countries will benefit the least from advances in the treatment of COVID-19 to date, which have focussed on hospitalised-patients with adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have much greater impact. Such therapeutics may be feasible and research into their efficacy and means of delivery should be a priority. Funding: None to declare. Declaration of Interest: None to declare.


Subject(s)
COVID-19
11.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-315954.v1

ABSTRACT

BackgroundSince its molecular isolation on January 7, 2020, the novel coronavirus SARS-CoV-2 has spread rapidly, taking governments worldwide off-guard. The virus arrived in low and middle-income countries violently, especially in Latin America. Ecuador received the worst outbreak in the world if we count excess mortality per capita. Although one study has reported the epidemiological impact of COVID-19 in Ecuador, there is no clinical course or outcome data among intensive care patients with COVID-19 in Ecuador. This study describes the clinical, epidemiological, and therapeutical features of 89 patients hospitalized in a secondary-level hospital in Quito, Ecuador.MethodsWe did a retrospective cohort study. We collected health records data from adult patients with severe COVID-19 admitted to the intensive care unit (ICU) in Quito, Ecuador, during the first five months of the SARS-CoV-2 outbreak in Ecuador. All patients had a confirmed SARS-CoV-2 RNA infection diagnostic, a positive real-time RT-PCR, and pulmonary imaging suggesting COVID-19. We used the Chi-square test or a Fisher's exact statistic to analyze risk and associations between survivors and non-survivors due to COVID-19. We used the ROC curve analysis to predict mortality, determining cut-off points for the parameters related to mechanical, analytical, and cytometry ventilation. At the multivariate level, we used the Wald test to evaluate model categorical predictors during the regression analysis.Results89 patients with COVID-19 were recruited during the study. The average age of the patients was 54.72 years. Man represented 68.54% (n = 61) and women 31,46% (n = 28). Significant differences were observed in terms of mortality (men 40.98% vs. women 17.76%). Serological parameters demonstrated that LDH and IL-6 at 24 hours were higher among non-survivors when compared with survivors. Persistent hypercapnia ( > > 45 mmHg), a PaFiO2 ratio of less than 140 mmHg, and a positive end-expiratory pressure (PEEP) titration greater than nine mmHg were also associated with higher mortality.ConclusionsIncreased levels of LDH at 24 hours, IL-6, the lymphocyte and platelet count at 48 hours, the neutrophil count at 48 hours, and the INL are factors associated with higher motility, increased risk of failed extubation and reintubation


Subject(s)
COVID-19
12.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3756820

ABSTRACT

Background: The novel human coronavirus, SARS-CoV-2, has affected at least 218 countries worldwide. Some geographical and environmental factors are positively associated with a better or worse prognosis concerning COVID-19 disease and with lower or higher SARS-CoV-2 transmission. High altitude exposure has been associated with lower SARS-CoV-2 attack rates; nevertheless, the role of chronic high-altitude exposure on the clinical outcome of critically ill COVID-19 patients has not been studied.Objective: To compare the clinical course and outcomes of critically ill patients with COVID-19 hospitalized in two intensive care units (ICU) located at low and high altitude.Exposure and Outcome: To explore the effect of two different elevations (10 m vs 2,850 m above sea level) on COVID-19 clinical outcome and survival.Methods: A prospective cohort, two-center study in confirmed COVID-19 adult patients admitted to a low altitude (Sea level) and high altitude (2,850 m) ICU units in Ecuador was conducted. Two hundred and thirty confirmed COVID-19 patients were enrolled from March 15th to July 15th, 2020. Sociodemographic, clinical, laboratory and imaging parameters including supportive therapies, pharmacological treatments and medical complications were reported and compared between the low and high-altitude groups.Results: The median age of all the patients was 60 years, 64.8% were men and 35.2% were women. A total of 105 (45.7%) patients had at least one underlying comorbidity, the most frequent being chronic diseases, such as hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale at 72 hours was especially higher in the low-altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the group of high altitude. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group. Conclusion: There has been a substantial improvement in survival amongst people admitted to the high-altitude critical care unit. Low altitude living was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours and reported better respiratory and ventilatory profiles than the low altitude group.Funding Statement: This work did not receive a formal grant: however, it received financial support associated with the publication fee from the University of the Americas in Quito, Ecuador.Declaration of Interests: The authors have no conflict of interest to declare.Ethics Approval Statement: This work was approved by the hospital's internal bioethical review committee (ID: IESS-HG-SQ-CIE-2020-2656-M).


Subject(s)
COVID-19 , Kidney Failure, Chronic , Hypertension
13.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.01.22.21249811

ABSTRACT

Background The novel human coronavirus, SARS-CoV-2, has affected at least 218 countries worldwide. Some geographical and environmental factors are positively associated with a better or worse prognosis concerning COVID-19 disease and with lower or higher SARS-CoV-2 transmission. High altitude exposure has been associated with lower SARS-CoV-2 attack rates; nevertheless, the role of chronic high-altitude exposure on the clinical outcome of critically ill COVID-19 patients has not been studied. Objective To compare the clinical course and outcomes of critically ill patients with COVID-19 hospitalized in two intensive care units (ICU) located at low and high altitude. Exposure and Outcome To explore the effect of two different elevations (10 m vs 2,850 m above sea level) on COVID-19 clinical outcome and survival. Methods A prospective cohort, two-center study in confirmed COVID-19 adult patients admitted to a low altitude (Sea level) and high altitude (2,850 m) ICU units in Ecuador was conducted. Two hundred and thirty confirmed COVID-19 patients were enrolled from March 15 th to July 15 th , 2020. Sociodemographic, clinical, laboratory and imaging parameters including supportive therapies, pharmacological treatments and medical complications were reported and compared between the low and high-altitude groups. Results The median age of all the patients was 60 years, 64.8% were men and 35.2% were women. A total of 105 (45.7%) patients had at least one underlying comorbidity, the most frequent being chronic diseases, such as hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale at 72 hours was especially higher in the low-altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the group of high altitude. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group. Conclusion There has been a substantial improvement in survival amongst people admitted to the high-altitude critical care unit. High altitude living was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours and reported better respiratory and ventilatory profiles than the low altitude group.


Subject(s)
COVID-19 , Kidney Failure, Chronic , Hypertension
14.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-147689.v1

ABSTRACT

BackgroundSince its molecular isolation on January 7, 2020, the novel coronavirus SARS-CoV-2 has spread rapidly, taking governments worldwide off-guard. The virus arrived in low and middle-income countries violently, especially in Latin America. Ecuador received the worst outbreak in the world if we count excess mortality per capita. Although one study has reported the epidemiological impact of COVID-19 in Ecuador, there is no clinical course or outcome data among intensive care patients with COVID-19 in Ecuador. This study describes the clinical, epidemiological, and therapeutical features of 89 patients hospitalized in a secondary-level hospital in Quito, Ecuador.MethodsWe did a retrospective cohort study. We collected health records data from adult patients with severe COVID-19 admitted to the intensive care unit (ICU) in Quito, Ecuador, during the first five months of the SARS-CoV-2 outbreak in Ecuador. All patients had a confirmed SARS-CoV-2 RNA infection diagnostic, a positive real-time RT-PCR, and pulmonary imaging suggesting COVID-19. We used the Chi-square test or a Fisher's exact statistic to analyze risk and associations between survivors and non-survivors due to COVID-19. We used the ROC curve analysis to predict mortality, determining cut-off points for the parameters related to mechanical, analytical, and cytometry ventilation. At the multivariate level, we used the Wald test to evaluate model categorical predictors during the regression analysis.Results89 patients with COVID-19 were recruited during the study. The average age of the patients was 54.72 years. Man represented 68.54% (n = 61) and women 31,46% (n = 28). Significant differences were observed in terms of mortality (men 40.98% vs. women 17.76%). Serological parameters demonstrated that LDH and IL-6 at 24 hours were higher among non-survivors when compared with survivors. Persistent hypercapnia ( > > 45 mmHg), a PaFiO2 ratio of less than 140 mmHg, and a positive end-expiratory pressure (PEEP) titration greater than nine mmHg were also associated with higher mortality.ConclusionsIncreased levels of LDH at 24 hours, IL-6, the lymphocyte and platelet count at 48 hours, the neutrophil count at 48 hours, and the INL are factors associated with higher motility, increased risk of failed extubation and reintubation


Subject(s)
COVID-19 , Hypercapnia
15.
preprints.org; 2020.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202006.0045.v1

ABSTRACT

Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.


Subject(s)
Coronavirus Infections , Respiratory Distress Syndrome , COVID-19 , Inflammation , Respiratory Insufficiency
16.
chemrxiv; 2020.
Preprint in English | PREPRINT-CHEMRXIV | ID: ppzbmed-10.26434.chemrxiv.12408074.v1

ABSTRACT

There is pressing urgency to better understand the immunological underpinnings of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) in order to identify potential therapeutic targets and drugs that allow treating patients effectively. To fill in this gap, we performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19. As results, the high-confidence protein interactome network was conformed by 1,588 nodes between immune system proteins and human proteins physically associated with SARS-CoV-2. Subsequently, we screened all these nodes in ACE2 and TMPRSS2 co-expressing cells according to the Alexandria Project, finding 75 potential therapeutic targets significantly overexpressed (Z score > 2) in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs for 25 of the 75 aforementioned proteins. On one hand, we obtained 45 approved drugs, 16 compounds under investigation, and 35 experimental compounds with the highest area under the receiver operating characteristic (AUROCs) for 15 immune system proteins. On the other hand, we obtained 4 approved drugs, 9 compounds under investigation, and 16 experimental compounds with the highest multi-target affinities for 9 immune system proteins. In conclusion, computational structure-based drug discovery focused on immune system proteins is imperative to select potential drugs that, after being effectively analyzed in cell lines and clinical trials, these can be considered for treatment of complex symptoms of COVID-19 patients, and for co-therapies with drugs directly targeting SARS-CoV-2.


Subject(s)
Coronavirus Infections , Lung Diseases , COVID-19
17.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.05.08.20095943

ABSTRACT

Background: The SARS-CoV-2 virus has spread rapidly around the globe. Nevertheless, there is limited information describing the characteristics and outcomes of COVID-19 patients in Latin America. Methods: We conducted a cross-sectional analysis of 9,468 confirmed COVID-19 cases reported in Ecuador. We calculated overall incidence, mortality, case fatality rates, disability adjusted life years, attack and crude mortality rates, as well as relative risk and relative odds of death, adjusted for age, sex and presence of comorbidities. Results: A total of 9,468 positive COVID-19 cases and 474 deaths were included in the analysis. Men accounted for 55.4% (n = 5, 247) of cases and women for 44.6% (n = 4, 221). We found the presence of comorbidities, being male and older than 65 years were important determinants of mortality. Coastal regions were most affected by COVID-19, with higher mortality rates than the highlands. Fatigue was reported in 53.2% of the patients, followed by headache (43%), dry cough (41.7%), ageusia (37.1%) and anosmia (36.1%). Conclusion: We present the first analysis of the burden of COVID-19 in Ecuador. Our findings show that men are at higher risk of dying from COVID-19 than women, and risk increases with age and the presence of comorbidities. We also found that blue-collar workers and the unemployed are at greater risk of dying. These early observations offer clinical insights for the medical community to help improve patient care and for public health officials to strengthen Ecuador s response to the outbreak. Keywords: COVID-19; SARS-CoV-2; Ecuador; Epidemiology; Latin America


Subject(s)
Headache , Cough , Olfaction Disorders , Death , COVID-19 , Ageusia
18.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.04.25.20079863

ABSTRACT

Background: The relentless advance of the SARS-CoV-2 virus pandemic has resulted in a significant burden on countries, regardless of their socio-economic conditions. The virus has infected more than 2.5 million people worldwide, causing to date more than 150,000 deaths in over 210 countries. Objective: The aim of this study was to describe the trends in cases, tests and deaths related to novel coronavirus disease (COVID-19) in Latin American and Caribbean (LAC) countries. Methodology: Data were retrieved from the WHO-Coronavirus Disease (COVID-2019) situation reports and the Center for Systems Science and Engineering (CSSE) databases from Johns Hopkins University. Descriptive statistics including death rates, cumulative mortality and incidence rates, as well as testing rates per population at risk were performed. A comparison analysis among countries with [≥]50 confirmed cases was performed from February 26th, 2020 to April 8th, 2020. Results: Brazil had the greatest number of cases and deaths in the region. Panama experienced a rapid increase in the number of confirmed cases with Trinidad and Tobago, Bolivia and Honduras having the highest case fatality rates. Panama and Chile conducted more tests per million inhabitants and more tests per day per million inhabitants, followed by Uruguay and El Salvador. Dominican Republic, Bolivia, Ecuador and Brazil had the highest positive test rates. Conclusions: The COVID-19 disease pandemic caused by the SARS-CoV-2 virus has progressed rapidly in LAC countries. Some countries have been affected more severely than others, with some adopting similar disease control methods to help slow down the spread of the virus. With limited testing and other resources, social distancing is needed to help alleviate the strain on already stretched health systems.


Subject(s)
COVID-19 , Coronavirus Infections , Death
19.
preprints.org; 2020.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202004.0283.v1

ABSTRACT

Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms, while others that infect animals can evolve and become infectious to humans. Three recent examples of this viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19).COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 14 April 2020 show more than 2 million people had been infected with the virus, causing more than 120,000 deaths in over 210 countries worldwide. The large amount of information we receive every day concerning this new disease is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).


Subject(s)
Coronavirus Infections , Respiratory Tract Diseases , Infections , Severe Acute Respiratory Syndrome , Respiratory Tract Infections , COVID-19
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