Abstract

Objective

To analyze notifications of flu-like syndrome according to the time interval between onset of symptoms and testing for COVID-19.

Methods

This was a cross-sectional study using records of flu-like syndrome cases containing results of COVID-19 diagnostic tests in the Brazilian state capitals and Federal District, held on the e-SUS Notifica system, from March 1^st, 2020 to August 18^th, 2020. The time interval between symptom onset and testing was compared using the ANOVA test, classifying it according to test adequacy/timeliness.

Results

Taking 1,942,514 notifications, average time between symptom onset and testing was 10.2 days (±17.1). Among those tested, females (55.1%), people aged 20-39 years (43.8%), and the Southeast region of Brazil (43.0%) predominated. 58.8% of IgM ELISA tests were performed at an adequate time while 68.0% of rapid antigen tests were not performed at an adequate time.

Conclusion

Inadequacy was found between symptom onset and time taken to test for COVID-19 in the Brazilian regions.

Coronavirus Infections; Laboratory Test; Serologic Tests; Public Health Surveillance; Cross-Sectional Studies

Introduction

COVID-19, a respiratory disease caused by the novel coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), was declared to be a pandemic by the World Health Organization (WHO) at the beginning of March 2020.¹1. McIntosh K. Coronavirus disease 2019 (COVID-19): epidemiology, virology, and prevention [Internet]. [S.l.]: UpToDate; 2020 [cited 2020 Aug 25]. Available from: https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-epidemiology-virology-and-prevention
https://www.uptodate.com/contents/corona...

Due to its high virulence, only a few months after the discovery of the virus, globally the total number of confirmed cases of the disease had reached 23,721,008, with 814,852 deaths as at August 30^th 2020. On the same date, the United States led the global ranking of both confirmed cases, 5,755,002, and deaths, 177,773, while Brazil was in second place with regard to total cases, 3.622.861, and also with regard to total deaths, with 115,309 fatal victims.²2. Johns Hopkins University. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University [Internet]. Baltimore: Johns Hopkins University; 2020 [cited 2020 Aug 30]. Available from: https://coronavirus.jhu.edu/map.html
https://coronavirus.jhu.edu/map.html...

The discovery of the disease and its high virulence has become a huge challenge for health systems around the world. The scientific community has turned its efforts to seeking solutions and strategies to contain the dissemination of the virus, in particular through diagnostic tests and rapid detection, aimed at identifying infected people and taking measures for their isolation, so as to break the disease transmission chain.

However, COVID-19 diagnostic tests are constantly evolving. Reverse transcription polymerase chain reaction (RT-PCR) was considered to be the standard reference method for confirming infection, as it detects the nucleic acid of the SARS-CoV-2 virus in sputum, throat swabs and upper respiratory tract secretion samples in the first seven days of infection.³3. Carvalho ARVS, Cezarotti Filho ML, Azevedo PCP, Silveira Filho RN, Barbosa FT, Rocha TJM, et al. Epidemiology, diagnosis, treatment, and future perspectives concerning SARS-COV-2: a review article. Rev Assoc Med Bras [Internet]. 2020 Mar [cited 2020 Aug 25];66(3):370-4. Available from: https://doi.org/10.1590/1806-9282.66.3.370
https://doi.org/10.1590/1806-9282.66.3.3... In turn, enzyme immunoassays and chromatographic immunoassays detect infection indirectly, by measuring the host’s immune response to infection.⁴4. Sethuraman N, Jeremiah SS, Ryo A. Interpreting diagnostic tests for SARS-CoV-2. JAMA [Internet]. 2020 [cited 2020 Aug 29];323(22):2249-51. Available from: https://doi.org/10.1001/jama.2020.8259
https://doi.org/10.1001/jama.2020.8259...

In general, the sample should be taken with effect from the eighth day following symptom onset, thus ensuring the time needed for the immune system to produce antibodies in a sufficient quantity to be detected. However, test indication, use and interpretation need to be done adequately in order to ensure greater result reliability and avoid wastage and increased costs of the procedure.⁵5. Cerqueira LCN, Garcia KRS, Trugilho FC, Pereira BWS, Gandra RM, Koeppe GBO. Main COVID-19 diagnostic methods: recommendations and perspectives. Saúde Coletiva [Internet]. 2020 [cited 2020 Aug 29];54 Supl 1:2633-8. Available from: https://doi.org/10.36489/saudecoletiva.2020v10i54p2633-2638
https://doi.org/10.36489/saudecoletiva.2... Notwithstanding, there is divergence in the literature as to the best time for diagnostic testing for COVID-19 after symptom onset.

In view of these considerations, the findings of this study can provide information for performing testing in health services within the recommended time limits, thus favoring more reliable results, in addition to enhancing health surveillance actions for COVID-19 detection and control, thereby reducing the number of new cases of the disease and associated costs.

The objective of this study was to analyze flu-like syndrome notifications according to the interval of time elapsing between onset of symptoms and testing for COVID-19.

Methods

This was a cross-sectional study based on records of tests used to diagnose COVID-19 in all the Brazilian state capitals and Federal District.

In March 2020, when COVID-19 began to spread in Brazil, the country began logistic operations to provide supplies and qualified personnel in order to perform diagnostic tests of the disease and, based on the mapping of the results, implement response actions.⁶6. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Plano de contingência nacional para infecção humana pelo novo Coronavírus COVID-19 [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 set 21]. 24 p. Disponível em: https://portalarquivos2.saude.gov.br/images/pdf/2020/fevereiro/13/plano-contingencia-coronavirus-COVID19.pdf
https://portalarquivos2.saude.gov.br/ima... In that context, there was diversity among the laboratory network with regard to timing and type of test used, depending on their availability in the Brazilian states, both in Public Health services and also in Supplementary Health services.

According to the diagnostic test panel available on the Health Ministry website, 15,150,356 tests have been performed in Brazil, of which 7,132,276 (47.1%) were RT-PCR and 8,018,080 (52.9%) were rapid tests, resulting in public expenditure of BRL 384,331,533.78.⁷7. Ministério da Saúde (BR). COVID – 19 testes [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 set 25]. Disponível em: https://viz.saude.gov.br/extensions/DEMAS_C19Insumos_TESTES/DEMAS_C19Insumos_TESTES.html
https://viz.saude.gov.br/extensions/DEMA... It should be noted that it is obligatory to notify the Ministry of Health of all results of all diagnostic tests to detect COVID-19, whether they be performed by public or private laboratories, university laboratories or any other laboratories in the national territory. Notification is compulsory for the results of all diagnostic tests performed, whether they are positive, negative, inconclusive or correlated, regardless of the method used, and notification should be done within 24 hours with effect from the result being ready, by recording and transmitting this information via the National Health Data Network. Notification is the responsibility of health service managers and those in charge of the respective laboratories and is supervised by local health service management. Failure to notify is a breach of health regulations.⁸8. Brasil. Ministério da Saúde. Portaria MS/GM nº 1.792, de 17 de julho de 2020. Altera a Portaria nº 356 GM/MS, de 11 de março de 2020, para dispor sobre a obrigatoriedade de notificação ao Ministério da Saúde de todos os resultados de testes diagnóstico para SARS-CoV-2 realizados por laboratórios da rede pública, rede privada, universitários e quaisquer outros, em todo território nacional. [Internet]. Diário Oficial da União, Brasília (DF), 2020 jul 21 [citado 2020 set 25]; Seção 1:41. Disponível em: https://www.in.gov.br/en/web/dou/-/portaria-n-1.792-de-17-de-julho-de-2020-267730859
https://www.in.gov.br/en/web/dou/-/porta...

This study included notifications of suspected COVID-19 cases in all the Brazilian state capitals and Federal District. Information on the variables listed below was retrieved from these records:

1. Type of COVID-19 test

   Reverse transcription polymerase chain reaction (RT-PCR); rapid test for detecting antibodies (antibody rapid test); rapid test for detecting antigens (antigen rapid test); enzyme immunoassay for detecting IgM antibodies (enzyme immunoassay – IgM ELISA); and electrochemiluminescence immunoassay for detecting IgG antibodies (Electrochemiluminescence immunoassay – IgG ECLIA).

2. Date of symptom onset (day, month and year).

3. Date COVID-19 test performed (day, month and year).

4. Federative Unit of residence, used to classify cases participating in the study by region of residence.

5. Age (in completed years: 0-9; 10-19; 20-39; 40-59; 60 or over).

6. Sex (female; male; undefined).

The data were retrieved from the Health Ministry website on Flu-like Symptom Notifications (https://opendatasus.saude.gov.br/dataset/casos-nacionais),⁹9. Ministério da Saúde (BR). Notificações de síndrome grupal [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 set 22]. Disponível em: https://opendatasus.saude.gov.br/dataset/casos-nacionais
https://opendatasus.saude.gov.br/dataset... the purpose of which is to provide the flu-like syndrome epidemiological database by incorporating the e-SUS Notifica system, which has been in force since March 2020. The data we used were retrieved on August 18^th 2020. All records from March 1^st to August 18^th 2020 were included in the study with no restrictions.

The spreadsheets for each region of Brazil were compiled and stored on a .dta format database. This database was later transferred to the Stata version 15 computer program to clean the data and prepare them for analysis. Missing data resulting from lack of information or failure to fill in fields at the time of notification were not taken into consideration when analyzing the variable corresponding to them, i.e. the measurements of position and dispersion and statistical significance only take into consideration the data available for each variable of interest.

The time elapsed between the date of symptom onset and the date the COVID-19 test was performed was calculated in days, according to the difference between the two dates; later the averages and standard deviations for these data were obtained for the ‘sex’, ‘age range’ and ‘region of the country’ variable categories. A one-factor ANOVA test (F test) was used to investigate the presence of statistically significant average differences between three or more groups.

The time interval between onset of symptoms and the test being performed was classified as adequate or inadequate. An adequate interval was considered to be: 3-7 days for RT-PCR; ≥8 days for the antibody rapid test; 2-7 days for the antigen rapid test; ≥8 days for enzyme immunoassay (IgM ELISA); and ≥8 days for electrochemiluminescence immunoassay (IgG ECLIA).¹⁰10. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Guia de Vigilância Epidemiológica. Emergência de saúde pública de importância nacional pela doença pelo coronavírus 2019: vigilância de síndromes respiratórias agudas COVID-19. [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 ago 29]. 57 p. Disponível em: https://covid19-evidence.paho.org/handle/20.500.12663/2114
https://covid19-evidence.paho.org/handle...

We calculated the adequacy and inadequacy frequencies for each type of COVID-19 test included in the study. Following this, we calculated the average and standard deviation for the intervals of time between symptom onset and the tests being performed according to the adequacy classification. In addition, subgroup analysis was performed for the time elapsed between symptom onset and the COVID-19 tests being performed, taking a maximum interval of 30 days, using a one-factor ANOVA test (F test). The 30-day period was adopted because the majority of COVID-19 tests were found in this interval.

Distribution of COVID-19 testing by region was investigated by calculating adequacy and inadequacy frequencies and analyzed using Pearson’s chi-square test. A 5% significance level was used in all the analyses. The results were organized and presented in tables and graphs.

Results

In the period from March 1^st to August 18^th 2020, 2,420,904 suspected COVID-19 cases were notified on the e-SUS Notifica system for all the state capitals and Federal District. Of these notifications, 1,942,514 (80.2%) had information on the type of COVID-19 test performed, and 1,798,327 (92.6%) of these notifications had a test performance date and a symptom onset date, thus enabling the time interval between the two dates to be calculated.

The time elapsed between onset of symptoms and COVID-19 testing was 10.2 days on average, with ±17.1 standard deviation (SD). Tests were performed predominantly among females (55.1%), people in the 20-39 age range (43.8%) and in the Southeast region (43.0%). Significant differences (p<0.001) were found in the average times between symptom onset and tests being performed, in relation to the ‘sex’, ‘age range’ and ‘region of the country’ variable categories (Table 1).

In Table 2 it can be seen that enzyme immunoassay – IgM ELISA – was the test most performed within an adequate time interval (58.8%), when compared to the other tests. On the other hand, 68.0% of antigen rapid tests were not performed within an adequate time interval, representing the highest frequency of non-conformity with recommended testing periods out of all the types of tests performed.

Figure 1 shows the frequency distribution of tests performed within the 30-day interval between onset of symptoms and testing. The majority of RT-PCRs, antibody rapid tests and enzyme immunoassays – IgM ELISA – can be seen to have been performed within an adequate time interval, although a considerable part of the tests were performed later than recommended. The majority of antigen rapid tests and electrochemiluminescence immunoassays – IgG ECLIA – were not performed within an adequate time interval.

Table 3 shows the average times between appearance of the first symptoms and testing for COVID-19, according to the Brazilian regions. There were statistically significant differences (p<0.001) in the distributions of tests being performed within an adequate time interval between the country’s five regions for all five types of tests recorded on e-SUS Notifica. The average time interval for RT-PCR tests varied between 3.3 and 8.3 days, and the majority of these tests were performed within an adequate time limit, achieving over 50% in the North, Northeast and Midwest regions. With regard to chromatographic immunoassay tests, the average time interval for the antibody rapid test was 6.5 to 18 days, with the Northern region having the highest proportion of this type of test performed in an adequate time interval (65.9%); in turn the average time interval for the antigen rapid test was 5.9 to 13.9 days, with the Northeast having the greatest distribution of adequate time intervals (41.0%). With regard to immunological tests (serology), the most adequate time interval was found in the Southeast region, for both IgM ELISA (75.1%) and for IgG ECLIA (71.8%); the average number of days elapsed between first COVID-19 symptoms and performance of immunobiological tests in all regions of the country varied between 2.7 and 27.3 days for IgM ELISA, and between 4.2 and 32.4 days for IgG ECLIA. It is noteworthy that out of all the tests analyzed, the highest proportion of inadequate time intervals was found in the Southern region (over 65.0%).

Discussion

This study identified that average time between onset of symptoms and testing for COVID-19 in the Brazilian state capitals and Federal District was 10.2 days. The IgM ELISA test was performed within the recommended time for more than half of the cases. On the other hand, the time interval for the antigen rapid was inadequate in the majority of cases, which is possibly prejudicial to its accuracy.

The SARS-CoV-2 tests were performed predominantly on samples from females, young adults and people living in the Southeast region. Two studies of cases notified in China, one covering the period December 11^th 2019 to January 29^th 2020, and the other from December 8^th 2019 to February 10^th 2020, had similar results which found that the majority of confirmed COVID-19 cases were comprised of younger people. Other studies conducted in February 2020 in the large Chinese cities of Wuhan and Shanghai found fewer notifications among children, who tested less, perhaps because schools were closed early and there having been school holidays during this period.¹¹11. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med [Internet]. 2020 Apr [cited 2020 Aug 29];382:1708-20. Available from: https://doi.org/10.1056/NEJMoa2002032
https://doi.org/10.1056/NEJMoa2002032...

According to the e-SUS Notifica records analyzed in this study, RT-PCR and the antibody rapid tests were the tests most performed in Brazil. This fact may have arisen from the Health Ministry’s efforts to comply with the WHO recommendation to increase the number of COVID-19 diagnosis tests.¹⁶16. Ministério da Saúde (BR). Saúde amplia testes para profissionais de saúde e segurança [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 ago 30]. Disponível em: https://www.saude.gov.br/noticias/agencia-saude/46596-saude-amplia-testes-para-profissionais-de-saude-e-seguranca
https://www.saude.gov.br/noticias/agenci... However, only around 50% of each of these tests was performed within an adequate time interval.

According to a study which assessed viral load courses using RT-PCR with samples from mouth and nasopharyngeal swab, sputum, feces, blood and urine samples from nine hospitalized cases discovered on January 27^th 2020 in Munich, Germany, RT-PCR identifies the viral RNA of SARS-CoV-2 through nasopharyngeal secretion samples and should be performed between the third and seventh day of symptoms, in order to ensure greater precision of the method and to reduce false-negative results. This occurs because SARS-CoV-2 infection begins in the lungs and not in the upper respiratory tract.¹⁵15. Cavalcante JR, Cardoso-dos-Santos AC, Bremm JM, Lobo AP, Macário EM, Oliveira WK, et al. COVID-19 in Brazil: evolution of the epidemic up until epidemiological week 20 of 2020. Epidemiol Serv Saúde [Internet]. 2020 [cited 2020 Aug 28];29(4):e2020376. Available from: https://doi.org/10.5123/s1679-49742020000400010
https://doi.org/10.5123/s1679-4974202000...

A study involving 173 people with COVID-19 admitted to the Shenzen Hospital in China between January 11^th and February 9^th 2020, identified that after the seventh day RT-PCR positivity begins to fall, falling as much as 45% between the 15^th and 39^th day after symptom onset.¹⁸18. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J MedVirol [preprint]. 2020 [cited 2020 Apr 30]. Available from: https://doi.org/10.1002/jmv.25727
https://doi.org/10.1002/jmv.25727... In our study we found that RT-PCR tests were performed on approximately half the notified cases within the recommended time period of 3 to 7 days, in particular in the Northeast, North e Midwest regions.

The antigen rapid test can be used for diagnosis in the acute phase of the disease (2^nd to 7^th day following symptom onset) when molecular tests are not available; or when a molecular test result is negative, in the case of incorrect sample collection or collection outside the acute phase.¹⁰10. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Guia de Vigilância Epidemiológica. Emergência de saúde pública de importância nacional pela doença pelo coronavírus 2019: vigilância de síndromes respiratórias agudas COVID-19. [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 ago 29]. 57 p. Disponível em: https://covid19-evidence.paho.org/handle/20.500.12663/2114
https://covid19-evidence.paho.org/handle... In Belgium, between April 6^th and 21^st 2020, an assessment was made of antigen rapid test performance in relation to RT-PCR for 148 nasopharyngeal swabs samples, with 106 positive RT-PCR results – 32 of which were detected by the rapid antigen test, showing overall sensitivity of 30.2%. All the samples detected as being positive for COVID-19 by the antigen rapid test also had positive RT-PCR results.²⁰20. Scohy A, Anantharajah A, Bodéus M, Kabamba-Mukadi B, Verroken A, Rodriguez-Villalobos H. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J Clin Virol [Internet]. 2020 May [cited 2020 Aug 29];129:104455. Available from: https://doi.org/10.1016/j.jcv.2020.104455
https://doi.org/10.1016/j.jcv.2020.10445...

Although the antigen rapid test has several advantages, such as being easy and quick to perform, rapid result, low cost and no requirement for special equipment or skills, when compared with molecular techniques it appears that its low sensitivity means that the rapid antigen test should not be used on its own as a frontline test for COVID-19 diagnosis, given that it can lead to false-negative results.²⁰20. Scohy A, Anantharajah A, Bodéus M, Kabamba-Mukadi B, Verroken A, Rodriguez-Villalobos H. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J Clin Virol [Internet]. 2020 May [cited 2020 Aug 29];129:104455. Available from: https://doi.org/10.1016/j.jcv.2020.104455
https://doi.org/10.1016/j.jcv.2020.10445... In addition, all the Brazilian regions achieved less than 50% in performing the antigen rapid test in an adequate time interval.

With regard to the IgM ELISA, rapid antibody and IgG ECLIA serological tests, these should be used with effect from the eighth day after symptom onset.¹⁰10. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Guia de Vigilância Epidemiológica. Emergência de saúde pública de importância nacional pela doença pelo coronavírus 2019: vigilância de síndromes respiratórias agudas COVID-19. [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 ago 29]. 57 p. Disponível em: https://covid19-evidence.paho.org/handle/20.500.12663/2114
https://covid19-evidence.paho.org/handle... However, a study conducted in China assessed 208 plasma samples from 82 confirmed COVID-19 cases and 58 suspected COVID-19 cases during the initial stage of the epidemic in January 2020, and found that average IgM conversion time was 5 days, while for IgG it was 14 days after symptom onset. That study also showed that combining the IgM ELISA and the RT-PCR test significantly increased COVID-19 detection (98.6%), compared to just testing with RT-PCR (51.8%).²¹21. Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis [Internet]. 2020 Jul [cited 2020 Aug 29];71(15):778-85. Available from: https://doi.org/10.1093/cid/ciaa310
https://doi.org/10.1093/cid/ciaa310... IgM ELISA and IgG ECLIA were performed within an adequate time interval in more than 70% of the Southeast region capital cities.

Furthermore, some studies indicate the need to conduct more research into serological test sensitivity after a period of 33¹⁸18. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J MedVirol [preprint]. 2020 [cited 2020 Apr 30]. Available from: https://doi.org/10.1002/jmv.25727
https://doi.org/10.1002/jmv.25727... and 35²²22. Silva Junior MJ, Mendonça KS, Lima CA, Pires PLS, Calegary T, Oliveira SV. Analysis of the spatial-temporal dynamics of incidence, mortality and test rates (rapid and RT-PCR) of COVID-19 in the state of Minas Gerais, Brazil. Scielo Preprints [preprint]. 2020 [cited 2020 Apr 30]. Available from: https://doi.org/10.1590/SciELOPreprints.1077
https://doi.org/10.1590/SciELOPreprints.... days following the onset of symptoms, based on data produced by the Minas Gerais Health department for the period from March 4^th to June 22^nd 2020. In our study, however, we opted to analyze time with effect from the eighth day as per Ministry of Health recommendations.¹⁰10. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Guia de Vigilância Epidemiológica. Emergência de saúde pública de importância nacional pela doença pelo coronavírus 2019: vigilância de síndromes respiratórias agudas COVID-19. [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 ago 29]. 57 p. Disponível em: https://covid19-evidence.paho.org/handle/20.500.12663/2114
https://covid19-evidence.paho.org/handle...

Antibody rapid tests have become an option for the general population, for screening asymptomatic cases or people with mild to moderate symptoms who do not need to be hospitalized, in order to observe the immunity/recovery of confirmed cases.²³23. Tolia VM, Chan TC, Castillo EM. Preliminary results of initial testing for coronavirus (COVID-19) in the emergency department. West J Emerg Med [Internet]. 2020 Mar [cited 2020 Aug 29];21(3):503-6. Available from: https://doi.org/10.5811/westjem.2020.3.47348
https://doi.org/10.5811/westjem.2020.3.4... Antibody rapid tests are performed on venous or capillary blood or blood plasma samples and allow rapid, straightforward and highly sensitive diagnosis,¹⁸18. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J MedVirol [preprint]. 2020 [cited 2020 Apr 30]. Available from: https://doi.org/10.1002/jmv.25727
https://doi.org/10.1002/jmv.25727... these being important advantages to consider in view of the fact of COVID-19 being a new disease with symptoms very similar to those of influenza,¹⁸18. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J MedVirol [preprint]. 2020 [cited 2020 Apr 30]. Available from: https://doi.org/10.1002/jmv.25727
https://doi.org/10.1002/jmv.25727... as well as available quantities of RT-PCR tests being insufficient, given that they were made available at the beginning of the pandemic in particular for health workers and seriously ill cases.¹⁹19. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis [Internet]. 2020 [cited 2020 Aug 29];28:ciaa344. Available from: https://doi.org/10.1093/cid/ciaa344
https://doi.org/10.1093/cid/ciaa344... This may be why a larger amount of antibody rapid tests have been performed in Brazil.

A variety of different forms of rapid tests have been validated for use in Brazil: some only enable antibody detection with a positive or negative result, without specifying type, while others distinguish between IgM and IgG antibodies.²⁴24. Ministério da Saúde (BR). Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde. Acurácia dos testes diagnósticos registrados na ANVISA para a COVID-19 [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 ago 30]. 34 p. Disponível em: http://portalarquivos2.saude.gov.br/images/pdf/2020/June/02/AcuraciaDiagnostico-COVID19-atualizacaoC.pdf
http://portalarquivos2.saude.gov.br/imag...

It should be noted that serological tests have variable sensitivity and specificity, depending on the manufacturer. In general, the sensitivity of tests approved for use in Brazil is over 85%, while specificity is over 94%. Diagnostic tests with low sensitivity can result in greater probability of detecting false-negatives, thus interfering in the social isolation measures adopted, especially in the case of asymptomatic individuals, thus having a direct influence on virus transmissibility.²⁴24. Ministério da Saúde (BR). Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde. Acurácia dos testes diagnósticos registrados na ANVISA para a COVID-19 [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 ago 30]. 34 p. Disponível em: http://portalarquivos2.saude.gov.br/images/pdf/2020/June/02/AcuraciaDiagnostico-COVID19-atualizacaoC.pdf
http://portalarquivos2.saude.gov.br/imag...

Diagnostic test safety and quality can be threatened by incorrect identification of people and/or samples collected, inadequate or insufficient sample collection, uncertain transportation and sample storage conditions (e.g.: prolonged transportation time and exposure to wounds), presence of interfering substances (e.g.: cell components, due to whole blood freezing and inadequate additives) and problems arising from sample preparation procedures, such as pipetting mistakes during manual preparation of the sample or aliquot, cross contamination or sample incompatibility. This can cause unnecessary investigation and, consequently, increase the financial burden on the health system and result in inadequate and slow health care, according to reviews conducted in Qatar and South Africa.²⁵25. Younes N, Al-Sadeq DW, Al-Jighefee H, Younes S, Al-Jamal O, Daas HI, et al. Challenges in laboratory diagnosis of the novel coronavirus SARS-CoV-2. Viruses [Internet]. 2020 [cited 2020 Aug 31];12(6):582. Available from: https://doi.org/10.3390/v12060582
https://doi.org/10.3390/v12060582...

The limitations of this study relate to recording of dates, in particular uncertainty as to symptom onset, and the high number of incomplete records on the e-SUS Notifica system, resulting in losses in the sample studied. However, we believe that these losses did not interfere in the results found.

Identification of time taken to perform tests can favor the drawing up of emergency plans, Public Health policies and training for health workers to efficiently carry out prevention actions to contain the COVID-19 pandemic. We suggest that future studies analyze the period elapsed between symptom onset and COVID-19 testing using a larger time interval.

References

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