Assessment of dengue and COVID-19 antibody rapid diagnostic tests cross-reactivity in Indonesia

Abstract

Background The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient’s isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens. Methods We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT. Results We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG. Conclusion Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.

COVID-19 Antibody Detecting Rapid Diagnostic Tests Show High Cross-Reactivity When Challenged with Pre-Pandemic Malaria, Schistosomiasis and Dengue Samples

“…Likewise, previously published clinical observations pointed to the cross-reactivity of dengue infection [44]. Two studies (one from Indonesia, another from Italy) revealed low rates of cross-reactivity (≤1/60 and 1/44 samples) for five and two RDT products tested with dengue positive serum samples [25,45]. Of note, for two products assessed in the Indonesia study (Cellex and Dynamiker), the present study showed 16% and 5% cross-reactivity, respectively.…”

“…The selection of RDT products covered the different antigens used and had various regulatory approvals. Some of them were produced by reputable manufacturers and had been successfully validated in peer-reviewed studies [6,21,25,34,[63][64][65][66] and approved by regulatory authorities (FDA EUA) and independent actors such as FIND [2]. In addition, the laboratory workflow was highly standardized and monitored.…”

“…Adding to the challenges of seroprevalence studies with COVID-19 Ab RDTs is the use of capillary blood (the preferred specimen for seroprevalence studies in LMICs [10]), which needs further study as to its accuracy, particularly when used in field settings [6,8,13]. As to the applications of triage and COVID-19 disease diagnosis in LMICs, the similarity of its early clinical presentations with those of malaria and dengue and the potential co-occurrence of these diseases present additional problems [25,32,40,44,69].…”

“…In low-and middle-income countries (LMICs), COVID-19 Ab RDTs have also been deployed for triage, diagnosis and contact tracing [10][11][12]. Specificity testing of COVID-19 Ab RDTs so far has focused on seasonal coronaviruses (NL63, HKU1, 229E, OC43), SARS-CoV, cytomegalovirus, Epstein-Barr virus, human hepatitis B virus, Mycoplasma pneumoniae and parvovirus infection in addition to interfering conditions (rheumatoid factor, autoimmune pathologies and hyperglobulinemia) [8,[13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Tropical diseases such as malaria, dengue, schistosomiasis and human African trypanosomiasis are well-known for their cross-reactivity with HIV-1 antibody LFA RDTs and malaria antigen RDTs [27][28][29][30].…”

Symptomatic similarity, co-infection and cross-reactivity in dengue and Covid-19 disease

“…It is recommended a conceivable crossreactivity of hostility to dengue and against Covid-19 antibodies in the serological test [35] . The cross-reactivity among dengue and Covid-19 antibodies was evaluated in Indonesia by testing five Covid-19 RDTs (Rapid indicative tests) on 60 RT-PCR affirmed dengue tests and 95 RT-PCR affirmed Covid-19 examples on dengue RDTs [36] . They noticed cross-responses, false-positive outcomes and surprisingly co-infection cases among dengue and Covid-19 disease.…”