of the COVID-19 pandemic on laboratory diagnosis of tuberculosis in southern

Background and objectives : to understand the impact of the COVID-19 pandemic on tuberculosis (TB) diagnosis in different settings is essential to guide the establishment of appropriate TB control strategies. This study aimed to assess the influence of COVID-19 pandemic in laboratory diagnosis of TB in patients tested and diagnosed for TB. Methods: a data survey was carried out in the database of laboratories that perform TB diagnosis for the public health system in Rio Grande city (Rio Grande do Sul, Brazil). Results: there


RESUMEN
Justificación y objetivos: comprender el impacto de la pandemia Covid-19 en el diagnóstico de tuberculosis (TB) en diferentes lugares es fundamental para orientar el establecimiento de estrategias adecuadas de control de la TB. El objetivo de este estudio fue evaluar la influencia de la pandemia de COVID-19 en el diagnóstico de laboratorio de TB, en términos de pacientes examinados y diagnosticados de TB. Métodos: los datos fueron recolectados de la base de datos de los laboratorios que realizan el diagnóstico de TB para el sistema público de salud en la ciudad de Rio Grande (Rio Grande do Sul, Brasil). Resultados: hubo una reducción de 1.368 a 735 (reducción del 46,3%) en el número de pacientes sometidos a pruebas de TB en los servicios públicos de diagnóstico en 2019 y 2020, respectivamente, y una reducción de 197 a 119 (reducción del 39,6%) en el número de nuevos casos de TB diagnosticados. Por otro lado, la tasa de positividad fue de 14,4% en 2019 y 16,2% en 2020. Además, se observó que el laboratorio que realiza el servicio de diagnóstico para la Atención Primaria de Salud fue el más afectado, en comparación con la Atención Terciaria de Salud. Conclusiones: como consecuencia de las medidas para el control de la propagación del SARS-CoV-2, hubo una reducción en las pruebas de TB y en la detección de nuevos casos, especialmente en la Atención Primaria de Salud, donde se encuentran los pacientes con menor necesidad de hospitalización. INTRODUCTION In January 2020, SARS-CoV-2 virus, the etiologic agent of COVID-19, was first described after being isolated from pneumonia patients in Wuhan, China. 1 Almost two years after, COVID-19 cases reported worldwide exceed 259 million, and more than 5.1 million deaths by the disease have been confirmed. 2 On the other hand, tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis, is an ancient infectious disease that remains as a public health concern worldwide. For several years, TB has been considered the leading cause of death from a single infectious agent, and it is estimated that in 2019 it affected about 10 million individuals and led to 1.4 million deaths. 3 It is recognized that COVID-19 pandemic has been causing health, social and economic impacts since the beginning of 2020. Thus, authorities are engaged in controlling the spread of SARS-CoV-2, and for this, several measures were implemented at the beginning of the pandemic, such as physical distancing, limitation of movement of people, and reallocation of human and financial resources from other diseases to the COVID-19 response. In this context, some of these strategies adopted affected, in general, the routine of health services. In addition to supply and infrastructure reallocation for the COVID-19 response, there were changes in access and admission of patients to health services to support the demand of COVID-19. 3,4 In Europe, diagnostic laboratories already reported a significant decrease in the number of samples received for TB diagnosis, when compared to the pre-pandemic years. 5 This reflect in the reduction of the number of patients tested for TB, and as result, there is an impact in the number of TB cases diagnosed and reported, as described in early 2020 in countries such as Nigeria, 6 Uganda, 7 South Korea, 8 China, 9 Sierra Leone, 10 and Brazil. 11 In a study carried out by Stop TB Partnership, an international agency that works in the fight against TB, it is estimated that the accumulation of undiagnosed and, consequently, not adequately treated TB cases during the COVID-19 pandemic generates a setback of years in the fight against TB, resulting, in the future, in an increase in disease incidence and mortality. 12 Considering that undiagnosed TB cases contribute to the transmission chain of M. tuberculosis, and that monitoring TB cases is important for disease control programs, 3,12 it is emphasized the importance of understanding the impact of the COVID-19 pandemic on TB diagnosis in different settings, in order to guide the establishment of appropriate TB control strategies. In this regard, this study aimed to assess the influence of the COVID-19 pandemic in laboratory diagnosis of TB in a setting with high burden of TB and COVID-19 in patients tested and diagnosed for TB.

Study design
A cross-sectional study was performed at TB diagnosis services in the public

Study setting
Rio Grande is a port city located in the extreme south of Brazil, with an estimated TB incidence of 77.6 new cases per 100,000 inhabitants in 2018. Rio Grande is one of the priority cities for TB control in Rio Grande do Sul, a state with TB incidence rate above the average of Brazil. In 2018, TB incidence for Rio Grande do Sul and for Brazil were 45.4 and 37.2 new cases per 100,000 inhabitants, respectively, and in 2020, incidences were lower (38.9 and 31.6 new cases per 100,000 inhabitants, respectively). 13,14 In relation to Brazil, the country ranks among the 30 countries with a high burden for TB and for TB-HIV co-infection, remaining a priority for disease control by the World Health Organization. 3 COVID-19 cases were first reported in Rio Grande in March 2020, one month after the first confirmed case in Brazil. Throughout 2020, 7805 COVID-19 cases and 170 COVID-19 deaths were reported ( Figure 1). 15 To contain the spread of the SARS-CoV-2 virus, social distancing measures were implemented in the municipality, including restriction of access to public places and non-essential commercial services, at the end of March 2020, after confirmation of the first SARS-CoV-2 cases in Rio Grande, and in early July, with the increase in the number of deaths from COVID-19. Moreover, as a way of limiting the movement of people and avoiding agglomerations, there was also a reduction in the number of public transport available and the suspension of routine medical care in health units. respectively. These laboratories are responsible for diagnosing approximately 80% of TB cases reported in the city. 16 During the COVID-19 pandemic, there were no changes in the workflow of these laboratories and the availability of laboratory supplies and equipment, as they were not relocated for the COVID-19 response. However, the technicians who performed TB diagnoses reported a reduction in the demand for the services provided.

Data collection
The database of the laboratories included in the study were accessed, after authorization by the technicians in charge of TB diagnosis. Data referring to the number of patients tested for TB and new TB cases diagnosed were collected. These are secondary data recorded in the database of these laboratories during the TB diagnosis routine. In this study, patients with at least one sample sent for TB diagnosis, with positive results by microbiological methods (microscopy, culture and/or GeneXpert ® MTB/RIF -Cepheid, USA), were considered new TB cases.

Statistical analysis
The collected data were tabulated in an Excel ® spreadsheet (

RESULTS
The number of patients tested for TB, number of new TB cases diagnosed, diagnostic positivity rate in 2019 and 2020 and percent variation of patients tested and positives for TB in the municipal laboratory, hospital laboratory and both laboratories are represented in Tables 1, 2

Patients tested for tuberculosis
In March 2020, the month when the first COVID-19 case was reported in Rio and 2020, respectively.

DISCUSSION
The first pillar of the END TB Global Strategy comprises "Integrated, peoplecentered care and prevention, aiming at early and universal access to diagnosis and treatment of all forms of TB" 3 . However, health system overload due to COVID-19, as well as restrictions needed to limit SARS-CoV-2 transmission, resulted in severe reductions in the availability and access to health services for detection and treatment of TB cases. 4,17 Challenges in TB management during the pandemic have been observed especially in low-and middle-income countries, such as Brazil. 11 Brazil showed a reduction in the total number of TB reporting in the three levels of health care, with a sharp drop in tertiary care, in 2020 compared to 2019. 13 In addition to already being a country with a high burden of TB, Brazil was considered the epicenter of COVID-19 in 2020. 18 Our results showed a significant reduction in the number of patients tested and positive for TB in 2020, during the COVID-19 pandemic, in comparison to 2019. In opposition to what was observed in Brazil, 13 we reported the highest reduction in the number of TB patients diagnosed in the municipal laboratory, which belongs to Primary Health Care, in relation to the hospital laboratory, which belongs to Tertiary Health Care.
In Brazil, there is great heterogeneity among regions, including socioeconomic heterogeneity, which is reflected in the accessibility of regional health services. 19 Thus, the impact of the COVID-19 pandemic on the health system in each region has been different; therefore, the importance of epidemiological investigation to understand the health situation in different regions of the country stands out.
Regarding the number of patients tested monthly, it was observed that the months of 2020 with the largest variation of patients tested, compared to 2019, were June (-86.9%) and July (-69.6%), in municipal and hospital laboratories, respectively. It is important to emphasize that, during this period, there was an increase in reporting of COVID-19 cases and deaths in Rio Grande, resulting in the adoption of physical distancing strategies and limitation of the movement of people, which difficulted people's access to TB services of diagnosis and treatment. Furthermore, in the absence of severe symptoms, the population was discouraged from seeking health services, to avoid crowding and the social stigma given the similarity of some symptoms of COVID-19 and TB. 3,4 We also observed that in March 2020, when the first COVID-19 case was reported Between 2020 and 2025, health care service disruption worldwide as a consequence of the COVID-19 pandemic could lead to an additional 6.3 million cases and 1.4 million additional TB deaths. 12 Our results showed an overall alarming reduction of 46.2% in the number of patients tested in 2020 compared to 2019. TB cases not diagnosed by the laboratories included in the study due to a reduction in testing, as they do not receive adequate treatment, will negatively impact TB control in southern Brazil.
In view of this, it will be possible to see that the adverse responses of restrictions in health systems to control SARS-CoV-2 transmission will last beyond the COVID-19 pandemic.
Thus, considering that the COVID-19 pandemic is still ongoing and its effects will be visualized in the long term, it is recommended that studies including a longer period of time and assessing different aspects of TB care be carried out. As a limitation, the present study includes an analysis of a relatively short period, as an analysis was carried out only one year before and during the pandemic. Despite this limitation, it is believed that the results obtained will provide immediate answers to guide the adoption of TB control strategies in the studied setting, as well as in other priority settings for TB control.
Finally, it is important highlight that in the laboratories included in the study, there was no interruptions in TB diagnostic services provided during the COVID-19 pandemic, as well as in acquisition of laboratory supplies. In the municipality, there was strategic planning for creating a diagnostic service for COVID-19, including the creation of a laboratory with an appropriate biosafety level focused on molecular diagnosis of this disease only. Thus, no reallocation of staff, supplies and equipment from TB to COVID-19 in terms of laboratory diagnosis. Therefore, it is assumed that the impact of the pandemic on laboratory diagnosis of TB is due to factors external to TB laboratories, such as absence of patients with suspected TB in health facilities.
In conclusion, as a consequence of measures to control the spread of SARS-CoV-2, there was a reduction in TB testing and in detecting of new cases, especially in Primary Health Care, where patients with less need for hospitalization are received. This study was carried out at a setting with high TB burden and high incidence of COVID-19, and showed the negative influence of COVID-19 pandemic in TB diagnosis. Thus, 2020 data, in addition to guiding the necessity of adoption of public policies for TB control, emphasizes the importance of maintaining and strengthening TB services during the pandemic and in the following years, so that missed diagnoses are recovered.