key: cord-0699143-kskh3jxn
authors: Faccini-Martínez, Álvaro A.; Rivero, Ricardo; Garay, Evelin; García, Alejandra; Mattar, Salim; Botero, Yesica; Galeano, Ketty; Miranda, Jorge; Martínez, Caty; Guzmán, Camilo; Arrieta, Germán; Contreras, Hector; Kerguelen, Hugo; Moscote, Maria; Brango, Eimi; Contreras, Veronica
title: Serological cross-reactivity using a SARS-CoV-2 ELISA test in acute Zika virus infection, Colombia
date: 2020-09-28
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.09.1451
sha: 37c56534eb7f59f93f5bf4f92037469223a3ae2b
doc_id: 699143
cord_uid: kskh3jxn

Objectives We investigated seroreactivity, using a commercial SARS-CoV-2 ELISA test, in samples collected from different individuals’ groups, including patients diagnosed as Dengue, Zika, and Chikungunya infection during 2015 and 2019, from an endemic area at the Caribbean Colombian region. Methods A total of 127 sera, obtained from six different groups of individuals, were included in this study: Group A: patients with confirmed SARS-CoV-2 infection; Group B: patients with symptoms suggestive of COVID-19 or asymptomatic contacts of confirmed patients; Group C: patients with acute or recent dengue virus infection; Group D: patients with acute Zika virus infection; Group E: patients with previous Chikungunya virus infection; and Group F: individuals with exposure to spotted fever group rickettsiae. Results Overall, group A, group B, and group D showed seroreactivity to SARS-CoV-2 in 92%, 75%, and 26% of samples, respectively; meanwhile, group C, group E, and group F showed 100% of seronegative. Conclusions We found 26% of serological cross-reactivity in patients with acute Zika virus infection using a commercial SARS-CoV-2 ELISA test. Further studies could evaluate if serological cross-reaction is maintaining along the time in a non-acute patient with previous exposure to the Zika virus and its effect in SARS-CoV-2 serosurveys in endemic areas for this arbovirus.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiological agent of coronavirus disease-2019 , an emerging zoonotic viral disease responsible for an ongoing pandemic (Chams et al., 2020) . The infection has spread across the world, with 31,167,374 confirmed cases and 962,046 related deaths on September 21, 2020 (https://coronavirus.jhu.edu/map.html). Clinically, according to a recent systematic review with meta-analysis, in COVID-19 patients, fever was the most prevalent clinical manifestations (88.7%, 95%CI 84.5-92.9%), following by respiratory symptoms such as cough and dyspnea, which could be presented in less than 60% of the patients (Rodriguez-Morales et al., 2020) . Thus, in tropical areas, have been pointed to included COVID-19 in the differential diagnosis of the acute undifferentiated febrile syndrome (AUFS), along with arboviral diseases, besides, to consider that, nowadays, failure to differentiate common causes of AUFS from COVID-19 could lead to delays in appropriate management and potential overestimate of SARS-CoV-2 epidemiological burden (Nunthavichitra et al., 2020) .

During the 2013-2016 period, Dengue, Chikungunya, and Zika affected more than 1 million people in Colombia, and nowadays, it is considering an endemic country for these arboviruses (Mora-Salamanca et al., 2020) . Meanwhile, Colombia is also part of the SARS-CoV-2 ongoing pandemic, with a total of 765,076 confirmed COVID-19 cases on September 21, 2020 (https://coronavirus.jhu.edu/map.html). With the above, overlapping clinical pictures and co-epidemics of SARS-CoV-2 with other tropical J o u r n a l P r e -p r o o f etiologies, such as arboviral diseases, is a matter for concern in many tropical countries, including Colombia (Nunthavichitra et al., 2020) .

We investigated seroreactivity, using a commercial SARS-CoV-2 ELISA test, in samples collected from different individuals' groups, including patients diagnosed as 

A total of 127 anonymized sera, obtained from six different groups of individuals, were included in this study (Table 1) infection or recent exposure to spotted fever group rickettsiae. Interestingly, through bioinformatics analyses, the referenced Israeli research group identified structure similarities between chains of the SARS-CoV-2 spike protein and chains of the envelope protein of both dengue and Zika, predicting potential cross-reactivity, in addition to dengue, with the Zika virus (Lustig et al., 2020) . Thus, according to this prediction, we found 26% of serological cross-reactivity in patients with acute Zika virus infection. Curiously, although we used a SARS-CoV-2 ELISA test, such as the Israeli group (Lustig et al., 2020) , we do not find cross-reactivity in patients with dengue infection. The used antigen could explain the above in these ELISA tests.

Hence, while the Euroimmun test uses S1 domain of the SARS-CoV-2 spike protein as antigen (Lustig et al., 2020) , the Ingenasa test use nucleocapsid protein (our study).

In any case, this hypothesis must be to confirm. *According assay manufacturers: sensitivity of 100% from day 17 after symptoms onset (85% between days 7 and 16), and specificity of 99,2% (no cross-reactivity with respiratory coronaviruses 229E, NL63, OC43 and HKU1, and other respiratory virus such as Influenza or RSV) (https://www.eurofins-technologies.com/ingezim-covid-19-dr.html). †Serum samples were collected before passed two weeks in 32 patients, and after passed two weeks in 31 patients, since to date of SARS-CoV-2 RT-qPCR-positive collected swab sample. ‡Serum samples of symptomatic patients were collected at the first two weeks of symptoms in 1 patient, and after two weeks symptoms in 5 patients. §Serum samples were collected the same day of dengue-tests (RT-qPCR, NS1 antigen, ELISA IgM) positive samples. ¶Serum samples were collected the same day of Zika-RT-qPCR positive samples. # Serum samples were collected the same day of Chikungunya-ELISA IgG positive samples. **Serum samples were collected the same day of spotted fever group rickettsiae-IFA IgG positive samples.

Evaluation of serological test of Zika in an endemic area of flavivirus in the Colombian Caribbean

COVID-19: A Multidisciplinary Review

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19

Potential antigenic cross-reactivity between SARS-CoV-2 and Dengue viruses

Estimating the burden of arboviral diseases in Colombia between 2013 and 2016

Acute Undifferentiated Febrile Illness-A Tropical World Threat

Zika: the new arbovirus threat for Latin America