COVID-19 virus infection and transmission are observably less in highly Dengue-endemic countries: Can Dengue vaccines be “repurposed” to prevent COVID-19?

We observed that global severity maps of ongoing dengue epidemic and COVID-19 pandemic do not overlap. Countries where dengue is highly endemic (>1.5 million cases/year) appear to be less hit by COVID-19 pandemic in terms of infection and transmission. Other evidences also support our proposition that pre-exposure to other wide-spread/highly endemic viral infections like dengue may thwart the spread of the COVID-19 pandemic.


Introduction
Dengue is caused by an arbovirus i.e. the dengue virus (DENV) (genus: Flavivirus, Family: The human race is currently going through the scourge of COVID-19 pandemic, caused by despite higher population density, lower average longevity and relatively poor healthcare systems ( Table 1). The high DENV-endemic regions recorded an increase from 5 to 12 SARS-CoV-2 infections per million population while the low endemic/sporadic DENV prevalent countries recorded a rise from 200 to 400 infections/million population over a week (Table 1). Mortality is 2-3% of the infections in DENV-endemic versus 5-6% in low DENV reporting countries (Table 1)

Current understanding on effect of weather and climate on COVID-19
One may argue that the high DENV endemic regions are relatively warmer than the regions worst affected by COVID-19 pandemic, but from overall consensus from past and current data, it appears that SARS-CoV-2 can be transmitted in hot and humid weather as well. 5,6 Pre-exposure to Dengue protects against COVID-19?
From the above observations, it is highly probable that DENV sero-conversion in people in DENV endemic countries might provide cross-protection to SARS-CoV-2 infection, rendering it less severe in the regions where DENV infections occur rampantly.

Our proposition is supported by a recent publication from Singapore in Lancet Infectious
Diseases, 7 where an elderly man and a woman (both 57 years) were originally COVID-19 virus-positive but found false-positive in serological tests for dengue, including DENV-IgM and/or IgG. Both patients were confirmed DENV RNA-negative by qRT-PCR. So, it is probable that SARS-CoV-2 shares antigenic similarity with DENV and may cross-react with DENV-specific antibodies used in the DENV serological tests. Furthermore, the original seropositive sample as well as additional urine and blood samples from the aforesaid male patient were also found negative for DENV, Chikungunya, and Zika viruses by RT-PCR.
We are of opinion that pre-existing immunological memory to DENV exposure, in the form of DENV antibodies and memory B and T cells, may have a negative impact on transmission, severity and pathogenesis of COVID-19 infections. Regular exposure to DENV is also likely to cue the innate immunity in people in the highly endemic regions towards ready response to other exotic viral infections (viral interference).

Dengue anti-sera and dengue vaccines may be effective against COVID-19 spread?
If DENV sero-positivity acts against COVID-19 spread and severity, convalescent human sera with proven high DENV-IgG titres may be useful in treating severe COVID-19 cases in the non-DENV endemic parts of the world, where the COVID-19 pandemic has hit hard.
Based on the anecdotal evidence that SARS-CoV-2 may cross react with DENV antibodies, 7 another vital question is whether immunization of susceptible population/population at risk (eg. people in the United States at present) with live attenuated dengue vaccines (eg. CYD-TDV or DENVax/ Tak-003) 9 will cue the anti-viral immune response to bring down SARS-CoV-2 replication and severity? The risk of developing post-vaccination "Antibodydependent Enhancement (ADE)" in subsequent exposure to DENV is low as dengue is not endemic in the countries, where COVID-19 is currently rampant and spreading like bushfire.

Childhood BCG vaccination and COVID-19
Countries where BCG vaccination is recommended (in early childhood) 10 Table 1).

Conclusion
There appears to be a stark contrast in COVID-19 spread and severity between countries in the tropical and sub-tropical regions and those in the temperate regions. In general, China, Western Europe, and USA showed more vulnerability to COVID-19 compared to some of the less developed parts of the world like the Indian subcontinent, South-East Asia, Latin America and Africa. But current understandings suggest that temperature and climate do not appear to significantly influence the transmission and survival of SARS-CoV-2 in the environment.
The aforesaid tropical and sub-tropical countries record DENV epidemics on a regular basis.
Therefore, it appears that populations exposed to regular dengue virus epidemics are relatively resistant to COVID-19 transmission and pathogenesis.
Incidentally, many of the highly dengue endemic countries also overlap with those where universal BCG vaccination is recommended at early childhood against tuberculosis. So, it is also thought that BCG vaccination may have a protective role against COVID-19. This may be true as BCG vaccination boosts cell mediated immunity and likely to augment antiviral response. But one may also observe several important exceptions such as China and Iran.
BCG vaccination is still carried out in these countries but they were heavily affected by COVID-19 in terms of transmission, severity and mortality. Interestingly, DENV incidences are low/sporadic in these two countries, supporting our proposition.
However, all the above observations and speculations are from anecdotal evidences and historical perspectives and presently at hypothesis levels. They need rigorous validation by proper experiments and epidemiological studies.