THE BURDEN OF DISEASE ATTRIBUTABLE TO COVID-19 IN MARANHÃO

The objective of this study was to estimate the burden of morbidity and mortality of Covid-19 in Maranhão over a 24-month period, between the years 2020 and 2022. For this purpose, the data used were obtained from the bulletins of the State Department of Health of Maranhão, the IBGE portal, and the 2019 Global Burden of Disease Study. Using this information (confirmed cases and deaths, life expectancy


INTRODUCTION
The SARS-CoV-2 virus has caused significant loss of life and human health globally since the beginning of 2020, resulting from the ongoing pandemic, named  https://www.nucleodoconhecimento.com.br18 RC: 148899 Disponible: https://www.nucleodoconhecimento.com.br/health/burden-of-diseaseFollowing its first notification on December 31, 2019, this disease quickly spread worldwide and was declared a pandemic on March 11, 2020, leading to the death of approximately 7.727 million individuals by April 1, 2023, as projected at the beginning of the same year (WHO, 2020;IHME, 2023).Brazil, having reported its first case on February 26, 2020, soon became a major global hotspot for with 363,211 confirmed cases and 22,666 deaths by May 25, 2020 (3 SIMÕES and SILVA et al., 2020).
Maranhão had its first confirmed case on March 20 and the first death by March 29 of the same month.During the first wave of infections (first half of 2020), the state reached 1,396 cases by April 20 and exceeded 30,000 by the end of May, according to data from the State Department of Health of Maranhão (4 SES-MA, 2020).By March 16, 2022, already in the observed third wave of infections, Maranhão had accumulated 420,183 confirmed cases and 10,854 deaths (SES-MA, 2020).
In this context, it is useful to apply a disease burden study to Covid-19.Such studies are systematic efforts to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geography at a specific moment.
The units used to measure human health are Years of Life Lost (YLL), Years Lived with Disability (YLD), and Disability-Adjusted Life Years (DALY), the sum of the two previous factors (CAMPOS et al., 2020).
In general, for an appropriate response to epidemiological emergencies, it is necessary to know the costs of the disease to human health, as well as the burden of such disease on healthcare systems and their clinical protocols.Such measures can assist in the management of medical resources, such as preventive materials, beds, and medicines.Furthermore, for Covid-19, the scientific literature emphasizes the importance of diagnosing and treating the disease as well as preventive measures and post-discharge patient surveillance to prevent lasting sequelae.In summary, these efforts contribute to maximizing the number of total recoveries, as well as organizing health actions in the face of similar diseases in the future.In addition to the diagnostic costs, in the recent past and currently, Covid-19 has been consuming various human and financial resources, making it particularly useful to identify its debilitating potential, an ongoing process.In this context, the aim here is to estimate the burden of Covid-19 for the state of Maranhão, gather epidemiological and demographic information about the disease, and conduct a comparative analysis of the burden of this infection on public health compared to other diseases.

CALCULATION OF YLLs
Careful monitoring of Covid-19-related deaths yielded specific values for the number of deaths at each identified age.This monitoring allows for the verification of deaths by specific ages for both men and women.Thus, the calculation of YLLs in this study https://www.nucleodoconhecimento.com.br20 RC: 148899 Disponible: https://www.nucleodoconhecimento.com.br/health/burden-of-disease could account for individual years of life, using the formula below, where " " it represents the number of deaths for each death at a specific age ("i") in the analyzed gender ("g") (for both men and women), "LE" indicates life expectancy for each analyzed gender, and "I" indicates the age in question, measured in years).
The presented expression is based on an adaptation of the age group formula used by two authors, Vieira et al., (2021) and Mitra et al., (2020).Both in studies of measurement and analysis, respectively, of YLLs in the Life expectancy values were, for practical purposes, approximated to the nearest whole numbers in both calculations.

YLDs CALCULATION
For the calculation of YLDs, a numerical estimate of the severity of Covid-19 and its short-and long-term symptoms (based on incidence) was necessary.This estimate involves applying disability weights (ranging from 0 to 1), where "0" indicates perfect health and "1" indicates death.In essence, the inclusion of weights involves fractionalization of the years lost to account for the loss of quality of life during the specific period.Therefore, the formula for calculating this value is as follows: https://www.nucleodoconhecimento.com.br21 RC: 148899 Disponible: https://www.nucleodoconhecimento.com.br/health/burden-of-diseaseIn the formula above, used under different terms by Rommel et al. (2021), the years lost due to disability (YLD) result from a summation of the products obtained by directly multiplying the incident cases by the average duration of symptoms in years ("D") and the disability weight for the condition regarding the average duration of the symptomatic phase of the disease for each type of manifestation, an average of 14 days was used for mild and moderate cases, 21 days for severe cases, and 32 days for critical cases, with a frequency of 42%, 25%, 27%, 5%, and 1% for asymptomatic, mild, moderate, severe, and critical cases, respectively.These values were extracted from the Covid-19 burden study conducted by Rommel et al. (2021) in Germany, based on data extracted from 1.7 million cases detected throughout 2020.Additionally, the duration values were reinforced based on Ferreira et al. (2022), which determined an average of 15.9 days (or approximately 2 weeks) for the total duration of symptoms in most home cases, as well as the recommendation of a 14-day isolation period issued by the WHO, since the symptomatology of Covid-19 presents a high variability in duration (13 GRENDENE et al., 2021).
As for the long-term effects of Covid-19, a disability weight of 0.006 was determined for cases of post-acute sequelae.This value corresponds to the weight assigned to mild infections, as the symptoms observed in long Covid-19 are similar in terms of severity (MORENO-PÉREZ et al., 2021).The average duration of the post-acute syndrome varies widely, with several studies reporting between 3 to 24 weeks after the acute phase, with an incidence between 4.7% to 80% (CABRERA MARTIMBIANCO et al., 2021).In our study, an average duration of 12 weeks was assumed, with a frequency of 50%

ETHICAL CONSIDERATIONS
This research, involving consultation of publicly available secondary databases where identification of any subjects is not possible, is exempt from submission to the Research Ethics Committee.

RESULTS
According to the epidemiological bulletin of March 16, 2022, from the State Department of Health of Maranhão, there were 420,183 confirmed cases of Covid-19 in the state since the beginning of the count (03/16/2020).During this same period, 10,854 deaths due to the disease were recorded in a territory with 7,153,262 inhabitants (IBGE, 2021).
Furthermore, an average fatality rate of 2.58% (3.52% for men and 1.86% for women) and an average mortality rate of 0.152% (151.73 deaths per 100,000 inhabitants) were recorded in the same interval.
The calculation of YLLs resulted in a total of 95,206 years of life lost for all age groups considered, summing the totals for men and women (with an average of 1,236.441per specific year) (Table 1 and Graph 1).Table 2 shows the preliminary values used and the total amount of Years Lived with Disability -YLDs.The age group with the lowest number of years of life lost per confirmed case was 10 to 19 years (also with the lowest number of deaths), with 0.0506 YLLs per case, while the ages with the highest number were between 60 and 69 years, with 0.5820 YLLs per case.
In the calculation of individual years, it was observed that the specific age most affected was 42 years, with 2,888 YLLs added per 92 registered deaths.It is suggested that such variations in years may be related to the conjunction of random events of contagion in populations of certain ages and the balance between their vulnerability to severe clinical manifestations of Covid-19 and the high number of years of life remaining in the face of average life expectancy.Studies that have explored Covid-19 burden elements by individual years have not been located at this time, so comparisons at this level cannot be made.
Regarding mortality by gender, a total of 46,569 YLLs were observed in men and 48,637 YLLs in women.However, the average years lost per specific age were 674.913 and 631.649 in men and women, respectively.These two comparisons express the higher number of YLLs in women due to their higher life expectancy and the higher average of YLLs in men due to their greater vulnerability to the lethal manifestations of the disease, producing higher lethality.
The population of Maranhão is estimated at 7.15 million in 2021 (IBGE), which yields an average of 0.01331 YLLs per person (or 4.86 days lost), or 1,331 YLLs for every 100,000 inhabitants of the state.This value is considerably below that of other socioeconomically similar regions, such as the 1,998 YLLs per 100,000 inhabitants in Malaysia, according to another study covering 2 years of the pandemic (TAN et al., 2022).It also falls below the DALYs measured in severely affected regions at the beginning of the pandemic and with a high proportion of elderly people in the population, such as Italy, which obtained an average of 2010 DALYs per 100,000 inhabitants (NURCHIS et al., 2020).
The total YLDs obtained constitute 0.0976% of the total DALYs (99.9024%YLLs), and 69% (647.69238YLDs) are represented by the acute phase of Covid-19, within which critical manifestations of the disease were the largest contributors, with 241.1201YLDs, followed by moderate (221.7743YLDs) and severe (160.6395YLDs) phases, respectively.The largest individual contributor to the disability component was the post-acute phase, with 290.695205YLDs in the period (cases that exceeded the end date were considered, provided they originated within the period of interest).
Similar proportions between YLLs and YLDs in this context are seen in various studies, such as Tan et al. (2022), with 99.5% YLLs, and Jo et al. (2020), with 98.2%, respectively.It is worth mentioning that, with the differences in lethality by age group, such proportions vary according to age, as evidenced by Jo et al. (2020) in a study in South Korea at the beginning of the pandemic, in which a variation of 1.8% was observed between YLLs and YLDs between ages 0 and 30 years, and those ages above 80 years (high regional life expectancy).

COMPARISON WITH OTHER DISEASES
For a better understanding of the burden of this disease on public health, the final result was compared to the DALYs per 100,000 inhabitants related to the seven major general causes of morbidity and mortality in Maranhão in 2018 and 2019 (according to GBD 2019 data).These causes were: Ischemic heart diseases, type 2 diabetes mellitus, physical violence by firearms, lower respiratory infections, complications from premature birth, neonatal encephalopathies due to trauma or asphyxia, lower back pain, and anxiety disorders (IHME, 2019).The perspective of studying Covid-19 and its sequelae as a risk factor for future diseases, as well as the psychological burden during the pandemic, is difficult to ascertain at this time.This perspective can be observed in certain national studies such as Ferreira da Mata et al. (2021) andPereira et al. (2021), in literature reviews that highlighted significant impacts of the pandemic on the mental health of young individuals and healthcare professionals, respectively.
The scarcity of Covid-19 disease burden studies (especially in Brazil) posed certain challenges in conducting this project.Notably, the weights used here for calculating YLDs are based on methodological foundations from the last decade and the body of research on this topic since the beginning of the pandemic.Therefore, several assumptions about the behavior of the disease on a large scale had to be made, such as the use of disability weights related to lower respiratory diseases from the latest editions of the GBD for a disease that, in many cases, has a systemic reach.These uncertainties are shared with all available literature at the moment, making the determination of the exact nature of Covid-19 and the magnitude of its long-term sequelae a topic of fundamental importance for future studies in the field.pandemic that shook the world in recent years, the impact of this disease will have long-term repercussions, as its wide range of direct and indirect sequelae will continue to affect the public to some extent, even after the control of the disease and its variants, necessitating proper healthcare preparedness.
It is hoped that this work contributes to the expansion of the available knowledge base regarding the impact of Covid-19 and the behavior of the Sars-Cov-2 virus on a large scale in the state of Maranhão and similar regions.Information useful in the design of future disease burden studies, as well as other epidemiological monitoring actions involving the history of the disease in the North and Northeast regions of Brazil during the early 2020s, was consolidated here.
Covid-19 cases between 16/02/2020 and 16/03/2022 were included, including the number of confirmed cases, deaths due to Covid-19, and their age group.The literature search involved general terms: life expectancy in Maranhão, population of Maranhão, convalescence period of Covid-19, infection weights, and Covid-19related sequelae.Information regarding the progression of the disease in Maranhão was extracted from the available epidemiological bulletins of the State Department of Health of Maranhão (SES-MA).Life expectancies for men and women in the Maranhão population were obtained from IBGE.The values of the weights for the disease and its sequelae were derived from the 2019 Global Burden of Disease study (GBD 2019), whose weight spreadsheet is available on the Global Health Data Exchange (GHDx) portal of IHME.The variables of interest were input into the calculation model to estimate years of life lost due to mortality and morbidity.In total, the disease prevalence, Years of Life Lost (YLL), and Years Lived with Disability (YLD) were estimated.The sum of these last two values allowed the estimation of Disability-Adjusted Life Years (DALY).
context of Covid-19, both following the methodological contributions recommended by WHO.The measurement of YLLs in this study was based on the methodology used for GBD 2010 onwards, thus it does not involve the use of age weights or time discounting.

Graph 1 -
Comparison of YLLs by specific age and by gender, due to Covid-19 in the State of Maranhão, from 2020 to 2022 Source: Authors, 2023.

Figure 7 -
Figure 7 -Comparison between the morbidity and mortality of the most influential communicable diseases in Maranhão between 2018 and 2019, and Covid-19 (by etiological agent), from 3/2020 to 3/2022 https://www.nucleodoconhecimento.com.br32 RC: 148899 Disponible: https://www.nucleodoconhecimento.com.br/health/burden-of-diseaseCONCLUSIONThe observed data attest, in fine detail, to the extremely high clinical significance of Covid-19 for public health in Maranhão during the analyzed period, being the second major general cause of morbidity and mortality, and the most influential communicable disease in the state within the 2020s.Inside and outside the context of the Covid-19 of affected cases, values that approximate those used by Petersen https://www.nucleodoconhecimento.com.br22 RC: 148899 Disponible: https://www.nucleodoconhecimento.com.br/health/burden-of-disease

Table 1 -
YLLs by specific age in men and women in Maranhão between 3/2020 and 3/

Table 2 -
YLDs Estimate due to Covid-19 in Maranhão from 2020 to 2022 https://www.nucleodoconhecimento.com.br26RC:148899Disponible:https://www.nucleodoconhecimento.com.br/health/burden-of-diseaseDISCUSSIONThisstudyaimed to provide an initial estimate of the disease burden of Covid-19 in Maranhão for a broad period of 2 years.To do so, epidemiological and demographic data from the state were aggregated, a comparison was made between the morbidity and mortality of Covid-19 and other diseases, and the current state of research on the global burden of diseases at the national level was assessed.The average YLLs per 10-year age group was 11,900.75(with1,236.44 being the average for each individual year).Additionally, the average years lost for each of the 6,130 deaths considered was 15,531.1.This result is similar to the average of 16 years obtained by Pifaré I Arolas et al. (2021) in a compilation of 81 studies seeking a universal sum of YLLs due to Covid-19 in 2020 and is significantly higher than the 9.6 YLLs per death obtained byRommel et al. (2021).https://www.nucleodoconhecimento.com.br27 RC: 148899 Disponible: https://www.nucleodoconhecimento.com.br/health/burden-of-disease