Regarding: Masyeni S, Santoso MS, Widyaningsih PD, Wedha Asmara DG, Nainu F, Harapan H, et al. Serological cross-reaction and co-infection of dengue and COVID-19 in Asia: Experience from Indonesia. Int J Infect Dis 2020;102:152-4. https://doi.org/10.1016/j.ijid.2020.10.043.

Dear Editor-in-Chief,

We congratulate the authors of the recently published article in your journal on their efforts to raise public health concern for COVID-19 and dengue detection in countries where both now co-exist.

Three cases were presented. One was described as the first report of dengue-COVID-19 co-infection based on positive results in dengue NS1 and IgM tests, dengue serotyping and detection of SARS-CoV-2 by qRT-PCR. The other two cases were diagnosed as dengue only by the same tests, but COVID-19 negative as SARS-CoV-2 qRT-PCR was negative. Sera from all three cases cross-reacted in COVID-19 rapid tests. For the first case, this was obvious as antibodies to both viruses were present.

The authors concluded that the dengue sera in the last two cases gave “false-positive” results in COVID-19 tests (since they were SARS-CoV-2 negative by qRT-PCR) and explained that this “cross-reactivity” was due to antigenic similarities between these two viruses. However, we think that an alternative and equally plausible explanation could be that both these patients were silently exposed to COVID-19 beforehand, remained asymptomatic during viraemia for about three weeks or so (Zou et al., 2020) and subsequently turned SARS-CoV-2 negative on qRT-PCR testing, due to virus clearance/low abundance (Wajnberg et al., 2020). Meanwhile, they developed COVID-19 antibodies, which are detectable for several months after infection (Ibarrondo et al., 2020). In this phase, if they contracted dengue, the reactivity in COVID-19 rapid tests was not necessarily due to “cross-reacting” dengue antibodies but could also have been due to pre-existing COVID-19 antibodies (Clarke et al., 2020). This is particularly possible for samples collected in the time frame when both diseases are co-existent in the population.

Our same argument holds for the two Singapore case reports (Yan et al., 2020), where in a reverse scenario, sera from COVID-19 RNA-positive patients showed reactivity in dengue rapid antibody tests despite being dengue PCR-negative. Singapore is highly endemic for dengue (Tan et al., 2019). Therefore, it cannot be ruled out that both elderly patients had contracted dengue in the past and had pre-existing dengue antibodies in their serum.

Nevertheless, we concur with the authors that there do appear to be antigenic similarities between SARS-CoV-2 Spike and dengue envelope, as evident from our observation that archived dengue serum samples from 2017, pre-dating the COVID-19 pandemic, cross-reacted in COVID-19 rapid antibody tests (Biswas and Sukla, 2020, Nath et al., 2020, Nath et al., 2021) and later independently confirmed by others (Lustig et al., 2020).

Contribution

SB drafted the letter and critically evaluated the final version. All co-authors have contributed in collecting supporting data and references; writing of the letter and in discussions to arrive at the final version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Funding

This work was supported by a grant from the Council of Scientific and Industrial Research (CSIR), India to SB. Grant number: MLP 130; CSIR Digital Surveillance Vertical for COVID-19 mitigation in India.

Ethical approval

This is a correspondence and does not contain data that require ethical approval.