Association of Polymorphisms of IL-6 Pathway Genes (IL6, IL6R and IL6ST) with COVID-19 Severity in an Amazonian Population.

Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects.

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies.

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19.

Introduction: Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19. Methods: Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively. Results: The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed. Discussion: The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.

Antibody Response to the SARS-CoV-2 Spike and Nucleocapsid Proteins in Patients with Different COVID-19 Clinical Profiles.

The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19.

Thrombophilia and Immune-Related Genetic Markers in Long COVID.

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development.

Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome.

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included;cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Strengths, Weaknesses, Opportunities and Threats (SWOT) Analysis of the Implementation of Public Health Policies on HTLV-1 in Brazil.

Human T lymphotropic virus 1 (HTLV-1) is a public health issue for most countries and imposes important consequences on patients' health and socioeconomic status. Brazil is one of the global leaders of the public health response to these viruses. The country has challenges to overcome to implement meaningful policies aiming to eliminate HTLV-1/2. An analysis of strengths, weaknesses, opportunities, and threats (SWOT) for the implementation of public health policies on HTLV-1/2 was performed. The strengths identified were the Brazilian Unified Health System (SUS); Brazilian expertise in public health programs successfully implemented; currently available policies targeting HTLV; and strong collaboration with researchers and patient's representative. Lack of awareness about HTLV, insufficient epidemiological data, lack of reference centers for patient care, insufficient availability of confirmatory tests, lack of universal antenatal screening, and absence of cost-effectiveness studies were identified as weaknesses. Some interesting opportunities included the increased interest from international organizations on HTLV, possibility of integrating HTLV into other programs, external funding for research, available online platforms, opportunity to acquire data from HTLV-1/2 surveillance to gather epidemiological information, and HTLV policies that were implemented independently by states and municipalities. In addition to the COVID-19 pandemic, existing demands from different diseases, the country's demography and its marked sociocultural diversity and the volatility of the technical team working with HTLV-1/2 at the Brazilian Ministry of Health are threats to the implementation of public policies on HTLV-1/2. This SWOT analysis will facilitate strategic planning to allow continuous progress of the Brazilian response to HTLV-1/2 infection.

Retrospective epidemiology of the SARS-CoV-2 (and COVID-19) epidemic among 27 Brazilian cities.

Background: Most of the countries facing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic are still trying to understand the dynamics of the behavior of the virus and dissemination of the new agent. Objectives: A retrospective descriptive epidemiological study of the 26 state capitals of Brazil and its capital, Brasilia, was performed to investigate the behavior of the infection and disease caused by SARS-CoV-2. Study design: The data presented were obtained from the State Health Departments and the Brazilian Ministry of Health. Seven epidemiological markers (including the incidence, mortality and case fatality rates and the growth of the epidemic measured by the ratios observed on days 30, 60 and 90) were compared for the initial 90 days of the epidemic for each city. Results: The epidemic spread to the country within 25 days, and deaths occurred as early as nine days from initiation. The incidence and mortality rates ranged from 70 to almost 1,599/100,000 and less than 1 to 1,171/1,000,000, respectively, at the end of the 90-day period of observation. The CFR was less than two up to 12.31%. The magnitude of each marker clustered the cities in different groups. The epidemic was managed differently in each city, with differences in qualified medical services and medical preparedness to face the emergency situation. Conclusions: Although modeling the epidemic has been a constant task, epidemiological data should be pursued to define actual information, such as the prevalence and incidence rates, to understand the unpredictable nature of this emerging infection, including the present policy of vaccination campaigns.

COVID-PA Bulletin: reports on artificial intelligence-based forecasting in coping with COVID-19 pandemic in the state of Pará, Brazil. / Boletim COVID-PA: relatos sobre projeções baseadas em inteligência artificial no enfrentamento da pandemia de COVID-19 no estado do Pará.

OBJECTIVE: To report the university extension research result entitled 'The COVID-PA Bulletin', which presented forecasts on the behavior of the pandemic in the state of Pará, Brazil. METHODS: The artificial intelligence technique also known as 'artificial neural networks' was used to generate 13 bulletins with short-term forecasts based on historical data from the State Department of Public Health information system. RESULTS: After eight months of predictions, the technique generated reliable results, with an average accuracy of 97% (observed for147 days) for confirmed cases, 96% (observed for 161 days) for deaths and 86% (observed for 72 days) for Intensive Care Unit bed occupancy. CONCLUSION: These bulletins have become a useful decision-making tool for public managers, assisting in the reallocation of hospital resources and optimization of COVID-19 control strategies in various regions of the state of Pará.

Assessment of Anti-SARS-CoV-2 Antibodies Post-Coronavac Vaccination in the Amazon Region of Brazil.

The present study evaluated the frequency of seropositivity for anti-SARS-CoV-2 (S1 and S2) total antibodies and anti-SARS-CoV-2 (receptor binding domain-RBD-S1) neutralizing antibodies in individuals vaccinated with the immunizing agent Coronavac. This was a cross-sectional study involving 358 individuals divided into two groups. Group 1 consisted of 205 volunteers who were tested for anti-SARS-CoV-2 total antibodies; group 2 consisted of 153 individuals tested for the presence of anti-SARS-CoV-2 neutralizing antibodies. Seropositivity was greater than 70% in both groups, although 17.6% and 20.9% of individuals showed no neutralizing or total antibody reactivity, respectively. The frequency of anti-SARS-CoV-2 total antibodies displayed a significantly different distribution between the sexes but not according to age. The frequency of anti-SARS-CoV-2 neutralizing antibodies was 93.3% (95% CI 68.1-99.8) in the age group from 21 to 40 years but significantly decreased with advancing age, and was 76.2% (95% CI 52.8-91.8) for 41 to 60 years, 72.5% (95% CI 62.8-80.9) for 61 to 80 years, and 46.7% (95% CI 21.3-73.4) for >80 years. Our results reveal a high prevalence of anti-SARS-CoV-2 total antibodies and anti-SARS-CoV-2 neutralizing antibodies in individuals who received both doses of the Coronavac vaccine, suggesting a lower effectiveness of the humoral immune response among those older than 60 years of age, which might be associated with senescence of the immune system.

Migration in times of pandemic: SARS-CoV-2 infection among the Warao indigenous refugees in Belém, Pará, Amazonia, Brazil.

BACKGROUND: The emergence of the new causative agent of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the city of Wuhan, China, in December 2019, and its spread worldwide, led the World Health Organization (WHO) to declare a pandemic. The disease has caused high mortality among traditional populations and the most socially vulnerable groups such indigenous and refugees. The present study aims to investigate the prevalence of anti-SARS-CoV-2 IgG antibodies in the population of Venezuelan indigenous Warao refugees residing in private and public shelters in the city of Belem, capital of Para State, in the Brazilian Amazon. METHODS: One hundred one individuals of both sexes (43 men and 58 women) with ages varying from 18 to 77 years (average of 36 years) were investigated. Whole blood samples were collected and subsequently separated into plasma and leukocytes. Serological analysis was performed using an enzyme-linked immunosorbent assay - ELISA (Anti-SARS-COV-2 S1 IgG, EUROIMMUN, USA). RESULTS: The results indicate a positive serum prevalence of 83.2% (84), of which 77.6% (45/58) were females and 90.7% (39/43) were males. An indeterminate profile was observed in 6.9% (7), where it was not possible to confirm the presence of antibodies, and 9.9% (10) individuals were negative for IgG antibodies. CONCLUSIONS: The finding of the high seroprevalence of IgG anti-SARS-CoV-2 antibodies reveals a high exposure of the Warao population in Belem to infection with the new coronavirus. These results underscore the importance of maintaining epidemiological surveillance with testing in traditional populations due to the high possibility of spreading the virus, especially among the most socioeconomically vulnerable groups, which depend exclusively on the Unified Health System (SUS), such as refugees and indigenous people.

Dynamics of anti-SARS-CoV-2 IgG antibodies post-COVID-19 in a Brazilian Amazon population.

BACKGROUND: In this study, the prevalence and persistence of anti-SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) IgG was evaluated in volunteers 90 days after COVID-19 (coronavirus disease 2019) diagnosis by correlating response dynamics with clinical conditions, epidemiological characteristics, and disease severity. METHODS: The study recruited 200 volunteers aged 18 years or older of both sexes diagnosed with COVID-19. Of the 200 volunteers initially selected, the 135 individuals who underwent serological testing for anti-SARS-CoV-2 antibodies on the first visit to the laboratory, were invited to return, after 90 days, and provide a new blood sample for a second assessment of the presence of anti-SARS-CoV-2 IgG antibody. Disease severity and longevity of symptoms were evaluated for each individual and associated with the serological profile. RESULTS: Among the 135 individuals who underwent a previous serological test for anti-SARS-CoV-2 antibody, 125 showed reactivity to IgG (92.6%). Of the 125 individuals with detectable IgG in the first test, 87 (69.6%) showed persistence of this antibody after 90 days and 38 (30.4%) lost IgG reactivity in the second evaluation. The frequency of all reported symptoms was higher in individuals who maintained IgG persistence after 90 days of symptoms. Symptom manifestations lasted ≥21 days in the group with a persistent IgG response (39.6%) and ≤ 7 days in the group with a nonpersistent IgG response (50.0%). The length of hospital stay and supplemental oxygen use were higher in individuals with a persistent IgG response. CONCLUSIONS: The results of the present study show a high frequency of loss of anti-SARS-CoV-2 IgG antibodies within 3 months after COVID-19 diagnosis in the Brazilian Amazon.

Artificial neural networks for short-term forecasting of cases, deaths, and hospital beds occupancy in the COVID-19 pandemic at the Brazilian Amazon.

The first case of the novel coronavirus in Brazil was notified on February 26, 2020. After 21 days, the first case was reported in the second largest State of the Brazilian Amazon. The State of Pará presented difficulties in combating the pandemic, ranging from underreporting and a low number of tests to a large territorial distance between cities with installed hospital capacity. Due to these factors, mathematical data-driven short-term forecasting models can be a promising initiative to assist government officials in more agile and reliable actions. This study presents an approach based on artificial neural networks for the daily and cumulative forecasts of cases and deaths caused by COVID-19, and the forecast of demand for hospital beds. Six scenarios with different periods were used to identify the quality of the generated forecasting and the period in which they start to deteriorate. Results indicated that the computational model adapted capably to the training period and was able to make consistent short-term forecasts, especially for the cumulative variables and for demand hospital beds.

High prevalence of anti-SARS-CoV-2 IgG antibody in the Xikrin of Bacajá (Kayapó) indigenous population in the brazilian Amazon.

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reached the Brazilian Amazon and spread among indigenous populations. In the present study, we demonstrate a high prevalence of infection among the Xikrin of Bacajá people (Kayapó). A sample of 100 individuals of both sexes (51 men and 49 women) with ages ranging from 2 to 82 years were clinically evaluated and tested for the presence of anti-SARS-CoV-2 IgG antibody. Among all investigated individuals, 58 were IgG-reactive (58 %) by a rapid test, and 73 (73 %) were reactive in an enzyme-linked immunosorbent assay, with no difference between sexes. Oxygen saturation ranged from 82 to 99 %, with the lowest value observed in a two-year-old girl. The results show that as expected, SARS-CoV-2 infection rapidly reached more than 70 % of the population, most likely because of the difficulties of maintaining social distance due to cultural characteristics. These results highlight the importance of indigenous health policies as a means of minimizing the impact of the pandemic on these communities.

Effects of temperature and humidity on the spread of COVID-19: A systematic review.

BACKGROUND: Faced with the global pandemic of COVID-19, declared by World Health Organization (WHO) on March 11th 2020, and the need to better understand the seasonal behavior of the virus, our team conducted this systematic review to describe current knowledge about the emergence and replicability of the virus and its connection with different weather factors such as temperature and relative humidity. METHODS: The review was registered with the PROSPERO database. The electronic databases PubMed, Scopus, Web of Science, Cochrane Library, LILACS, OpenGrey and Google Scholar were examined with the searches restricted to the years 2019 and 2020. Risk of bias assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist tool. The GRADE tool was used to assess the certainty of the evidence. RESULTS: The initial screening identified 517 articles. After examination of the full texts, seventeen studies met the review's eligibility criteria. Great homogeneity was observed in the findings regarding the effect of temperature and humidity on the seasonal viability and transmissibility of COVID-19. Cold and dry conditions were potentiating factors on the spread of the virus. After quality assessment, two studies had a high risk of bias, eleven studies were scored as moderate risk of bias, and four studies were classified as low risk of bias. The certainty of evidence was graded as low for both outcomes evaluated. CONCLUSION: Considering the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. However, these variables alone could not explain most of the variability in disease transmission. Therefore, the countries most affected by the disease should focus on health policies, even with climates less favorable to the virus. Although the certainty of the evidence generated was classified as low, there was homogeneity between the results reported by the included studies.

The challenges of COVID-19 in the Brazilian Amazonian communities and the importance of seroepidemiological surveillance studies.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has alarmed the world with its high rate of transmission and the ability to cause severe and fatal disease. The impact of this pandemic may be even greater in populations where the absence of health services is a chronic aspect, as reported with populations living in the Brazilian Amazon. In this article, we address the perspective of possible impacts of the pandemic on these populations and the importance of conducting seroepidemiological surveillance studies.