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Try out PMC Labs and tell us what you think. Learn More. Manaus, located in the Brazilian rainforest, has experienced two health system collapses due to the coronavirus disease COVID pandemic. However, little is known about which groups among the general population have been most affected. A convenience sampling strategy via online advertising recruited adults between 19 August and 2 October Serum anti-severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 nucleocapsid immunoglobulin G antibodies were measured with an enzyme-linked immunosorbent assay.
Prevalence ratios PR were obtained using cluster-corrected and adjusted Poisson's regression models. A crude positivity rate among asymptomatic and symptomatic individuals was estimated at Regression models demonstrated a strong association towards marginalized low-income and vulnerable residents with limited access to health care.
Disproportionate socio-economic disparity was observed among the study participants. The syndemic nature of COVID in the Amazon region needs differential policies and urgent solutions to control the ongoing pandemic. Infectious diseases have a profound impact on humans, particularly vulnerable populations Fauci and Morens, The emergence of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 and a lack of effective treatment and non-pharmaceutical interventions to curb transmission have led to an exponential increase in the burden of coronavirus disease COVID worldwide Hsiang et al.
In Aprilthe Mayor of Manaus declared that the health system had collapsed due to the high volume of severe and critical patients; moreover, the failure in Manaus also meant a state-wide collapse. Since earlyManaus has experienced a reprise of the healthcare collapse of Aprilwith an astounding increase in s of reported COVID cases and deaths. Identifying these factors is important to aid in the formulation of targeted public health measures Aragona et al. This closely monitored cohort will provide a unique opportunity to determine disease attack rates; and to monitor the serological status of residents of Manaus, and the relevance of demographic and socio-economic factors and their association with the prevalence of infection in a setting of high transmission and low non-pharmacological containment measures.
All participants gave oral and written consent prior to enrolment. A convenience sampling strategy was adopted for recruitment, and individuals were recruited between 19 August and 2 October All participants registered online and presented at the blood collection centre Nursing School, Federal University of Amazonaswhere they ed the consent form, filled out an electronic questionnaire and donated a blood sample for testing Figure S1, see online supplementary material.
First, sociodemographic data, including age, sex, occupation and residential address, were collected for each participant. Second, information related to COVID, symptoms since the start of the pandemic, prior diagnosis, preventive self-medication and prescribed medication used to treat symptoms were recorded. Finally, an independent form was used to record the laboratory. Details of blood collection, sample processing and storage are described in the online supplementary material.
The antigen concentration, sample dilution and secondary antibody concentration were determined using a checkerboard method to achieve the optimal al to noise ratio. Antigen lot and interoperator variations were assessed throughout the development of the assay, before the analysis of study samples. Specificity of Further details of the in-house ELISA protocol and performance evaluation are described in the online supplementary material. This study evaluated the cohort baseline data, constituting a cross-sectional analysis.
Crude seroprevalence was further adjusted by ELISA test characteristics Diggle, and antibody decay, defined as the proportion of patients who had a current positive ELISA over the of participants who had any positive serological test at any point before the study, regardless of symptoms or time elapsed. The presence or absence of antibodies to SARS-CoV-2 was the primary dependent variable, and characteristics that were identified in the descriptive analysis were the independent variables. ificant variables were used in a Poisson regression model with robust variance to estimate prevalence ratios.
Variance was corrected per cluster administrative areaand models were adjusted for sex, age, family income, presence of household members with COVID, use of preventive self-medication, and prior COVID diagnosis. Using online advertising, individuals agreed to participate in the study by making an appointment via the study website.
Of these, attended an interview Figure S1, see online supplementary material. In total, Of the individuals included in the cohort, As study participants presented with flu-like symptoms for at least 1 week before recruitment, crude seropositivity was adjusted by the sensitivity and specificity of an ELISA determined for at least 7 days of symptoms.
With sensitivity of In this study, more than two-thirds of the patients with a prior diagnosis of COVID either by PCR or serology were still positive at the cohort baseline, regardless of time since symptom onset. Of the participants who had positive serology before the study, 38 tested negative. Using these data, antibody decay of Scientific literature suggests that the antibody decay rate is higher among asymptomatic patients Yang et al. Given that of the IgG-positive participants were asymptomatic Extrapolating these values, the actual seroprevalence in the study cohort could oscillate between Anti-SARS-CoV-2 antibody levels estimated using RI were elevated in symptomatic patients compared with asymptomatic patients Figure S5, see online supplementary materialand positively correlated with patient age Figure S6, see online supplementary material.
Figure S7 see online supplementary material describes the distribution of COVIDpositive individuals stratified by days since onset of flu-like symptoms, self-declared by the study participants. The prevalence rates were inversely correlated with occupation type and family income. Prevalence was higher among the poorest In general, individuals living in detached or conjugated houses had higher SARS-CoV-2 antibody prevalence compared with individuals living in condo houses and apartment buildings.
Moreover, an increase in the of adults or children in the family household increased the seropositivity rate ificantly. COVID in a distant family member living locally or in another town had no influence on the serological status of the study participant.
Individuals with or without comorbidities had similar antibody prevalence. However, prevalence among individuals taking self-medication of over-the-counter drugs or controlled drugs to prevent SARS-CoV-2 infection was Table 3 summarizes individual symptoms reported by study participants since the start of the pandemic, and access to COVID testing in Manaus.
Around half of the patients diagnosed with COVID reported not taking any over-the-counter or prescribed medicine. All the ificant variables described above were used in a Poisson regression model Table 4. Data were corrected and adjusted for variables that were not controlled experimentally to identify true risk factors Table 4 and Table S2, see online supplementary material. First, men had increased risk compared with women, with an estimated adjusted prevalence rate of 1. Second, individuals with well-paid jobs, good- quality housing and private insurance had a lower prevalence rate, and subsequently had a lower risk of acquiring COVID Moreover, having four or more adults, or three or more children, in the family household ificantly increased the risk of acquiring COVID Most importantly, SARS-CoV-2 infection of a household member increased the risk of acquiring infection among other household members, and had an adjusted prevalence rate of 1.
Furthermore, the prevalence rate increased to 2. Overall, the seroprevalence rate was ificantly higher if the individual had experienced flu-like symptoms since March or had a prior diagnosis of COVID Table 4. The relative frequencies of anti-SARS-CoV-2 nucleocapsid antibodies and associated factors 6 months after the start of the pandemic in Manaus, Brazil were estimated.
The indicate high seropositivity of Furthermore, the analyses showed that the pandemic disproportionately affected low-income families and those with limited access to health care. Additionally, preventive self-medication was associated with higher prevalence of SARS-CoV-2 infection, probably because it is used by people at higher risk of contagion.
Test performance for the in-house assay was similar to other tests reported in other countries and regions Cota et al. The performance of the assay was tested using a wide range of samples, including outpatients and patients with mild symptoms, and inpatients or hospitalized patients with severe disease, to determine the sensibility of the assay. Hence, the approach maximized the range of detection of serum IgG antibody concentrations that can be expected in an exposed heterogeneous population.
The performance of the test improved markedly 14 days after symptom onset Cota et al. Additionally, the specificity analysis included samples that were tested for other tropical diseases and infections to evaluate cross-reactivity.
Pre-pandemic plasma samples positive for dengue, leptospirosis and malaria cross-reacted using the in-house assay Cota et al. However, the authors did not have access to other seasonal coronavirus-positive samples, and could not evaluate cross-reactivity against the nucleocapsid proteins of other coronaviruses. In-house assays with robust validation and good performance can be a viable alternative to commercial assays in low-income countries. The crude seropositivity rate and the rate adjusted by test performance were high. In part, this difference could be due to the inclusion of asymptomatic and oligosymptomatic patients who did not usually seek medical attention or SARS-CoV-2 viral testing, and because of the lower testing rates in Brazil.
The high seroprevalence observed by the present authors and others in areas of Brazil characterized by higher poverty rates is in agreement with the recent evidence that COVID has disproportionately affected marginalized populations, in whom the human development index is lowest Horta et al.
Buss et al. In the present study, Using patient reported data, the antibody decay proportion for the whole cohort can be estimated as The maximum seroprevalence estimate is high, but also suggests that a large proportion of the vulnerable population is still susceptible Aschwanden, Therefore, it is proposed that the high proportion of susceptible individuals may explain, in part, the recent resurgence of SARS-CoV-2 infection in Manaus Ferrante et al. To date, the role of antibodies in controlling disease severity during infection, the duration of serological responses, and the extent to which patient antibody responses may be protective against re-exposure remain to be fully elucidated.
Antibody measurements do not necessarily reflect protection after infection, nor do they fully indicate the efficacy of active immunization Addetia et al. Therefore, inferring immunity or protection from a single biomarker, at individual or population levels, can be misleading. This limitation is acknowledged, and the serological findings and their implications should be interpreted with caution.
Future studies comparing vaccine-induced immune responses with those stimulated by viral infection, and those of individuals who become re-infected, will help to clarify the immunological correlates of protection Anderson et al. It is true that male sex, older age and comorbidities are associated with higher complication rates and mortality; however, their role in acquiring the infection is less clear Giannouchos et al. This study found that male sex was associated with higher seropositivity, which is in agreement with the from other studies Elmore et al.
This could be explained by increased risk of acquiring the infection with age Elmore et al. Additionally, it was noted that seroprevalence was lower among people living in condo houses and apartment buildings, probably because they live in closed communities with strict COVID rules. Marked differences were found between different geographic areas. Seroprevalence in East Manaus, which is the most crowded and poorest area of the city, was up to Access to primary health for economically vulnerable people has always been a limiting factor worldwide; during the ongoing pandemic, this inequality has been even more evident Bambra et al.
A possible solution is to employ centralized isolation in government-sponsored facilities. Additionally, strict follow-up of diagnosed patients, and their family members and contacts, is recommended to reduce virus transmission. This study found that people who self-medicated as prophylaxis had higher seroprevalence of COVID Evidence suggests that most of the drugs used as prophylaxis may not be effective Mega, Moreover, taking a preventive self-medication could produce a false sense of safety and security from the disease, leading to the neglect of other well-established preventive measures.
Additionally, conflicting stances between the state and federal governments in Brazil on strategies to face the pandemic could have played a role in its course Ferrante et al. A convenience sampling strategy was adopted instead of a population approach due to financial and logistical constraints.
Sampling was based on online and university website advertising, which potentially excluded individuals who did not have access to this information; higher education and university employees were oversampled. There was only one collection centre, and this may have excluded individuals who did not have resources to travel to the study centre for recruitment or lived far from the recruitment centre. The recruited cohort may not completely represent the general population of Manaus, and may vary with health seeking and social distancing behaviour, immune response to infection and risk of disease exposure; as such, the prevalence of the study groups and associated risk factors should be interpreted with caution and not extrapolated to the population of Manaus.
Additionally, it is possible that participants enrolled in the study to find out their serological status for COVID, meaning they considered themselves to be at higher risk or to have had a higher percentage of flu-like symptoms since Marchleading to over-reporting.
Therefore, the present seroprevalence estimates should be confirmed and extended by other studies, including serosurveys that use probabilistic sampling to enrol more representative populations. Regarding the in-house assay, it is acknowledged that while the nucleocapsid and spike proteins are expressed abundantly in SARS-CoVinfected cells and tissues, and that antibody responses towards both are highly correlated Jiang et al.
On the contrary, this study and analysis had numerous strengths. The study cohort was representative of both sexes, all age and economic groups, and included individuals from all administrative zones of Manaus. Additionally, clinical, pharmacological and SARS-CoV-2 testing data from both symptomatic and asymptomatic recruits were available. Data collection was performed using electronic forms with internal checks to improve the quality of the data, and there were few missing values.
In addition, a highly specific and sensitive immunoassay was used. The baseline analysis of the DETECTCoV cohort revealed high seroprevalence in Manaus, and demonstrated disproportionate socio-economic disparity among the study participants. Further prospective analyses of the cohort will enable the determination of seroconversion rates over time, behavioural aspects of virus transmission, and the role of declining antibody titres and subsequent re-infection with SARS-CoV In Amazonas and worldwide, socio-economic disparities, as well as inequalities in access to primary health, have amplified the impact of the COVID pandemic.
Governmental policies that do not consider the syndemic nature of COVID will have disproportionate long-term economic, social and health consequences for those who are already disadvantaged. Taken together, mass molecular testing and contact tracing, strict enforcement of voluntary isolation rules, and non-pharmaceutical interventions are needed urgently as part of the community control measures to reduce SARS-CoV-2 transmission and its health and social impact.
All authors revised and approved the final version of this manuscript. In addition, the authors are grateful to Prof. Finally, the authors wish to thank Prof. Bernardo Horta and Prof. Claudio Pannuti for suggestions and diligent proofreading of this paper.
Supplementary material associated with this article can be found, in the online version, at doi National Center for Biotechnology InformationU. Int J Infect Dis. Published online Jul Christian A. Roger V.Manaus seeking man
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