COVID-19 Infection and Transmission are Observably Less in Highly Dengue-endemic Countries

Comment: Copy of Report sent to
Vandine@online.com.kh
orvandine@hotmail.com

Excellency
Dr Or Vandine
Secretary of State /Ministry of Health /Phnom Penh Cambodia

Subject : low covid-19 infection report in Cambodia. Partial Cross heterologous Immunity.

I worked in Cambodia with the NGO (MSF-F) from 1992 to 1998 at the Battambang Provincial Referral hospital.
Since that period I have been visiting regularly this hospital. My last visit was during the last two months. (February 4th to March 20th).
During my recent 6 weeks’ visit, I have been working with my Cambodian Collegues in charge of the Emergency Room, Medical Intensive Care Unit and other medical wards (with the agreement of Dr Kak Seila, Provincial Referral Hospital director).
The referral hospital was very active during that period with a large number of patients referred by district hospitals and other private hospitals in Battambang Town.
The laboratory department of this hospital is particularly active and efficient, helping clinical diagnosis especially thanks to the microbiological unit (Ms Chiek Sivhour)
All the medical staff were particularly aware of the Covid Pandemic and perferctly informed about suspect case definition provided by your Ministry (MOH)
During the last few months, they didn’t observe an increase number of patients with Acute Respiratory distress Syndrome.
As you know, following your surveillance network, by mid March, they sent to Phnom Penh some specimens (Nasal and Throat Swabs). The first positive patients were Cambodian adults returning from a pilgrimage in Malaysia. These patients came spontaneously to the hospital without symptoms but worrying about a possible Covid infection (history of previous positive contact).
So far, a large proportion of positive covid patients in Cambodia (total around 100) are foreigners.
Cambodia is a country highly visited by tourists from all Asia and Europe. As an rapidly developing country this explains the presence of a large expatriate community.

Many Epidemiolgical experts have recently published reports questionning the actual low incidence of covid-19 infections in South-East Asia. (Lipstick et Al) Until early February, Cambodia has been visited by thousands of people from China.
Epidemiology data available in Battambang doesn’t indicate any significant change concerning patients admitted with ARDS or Unexplained Fever.
Malaria incidence is very low all over Cambodia. Dengue epidemics have been a recurrent and major Public health concern for the last 25 years in many Provinces of this country (amongst them Battambang)
The last epidemic was severe in September 2019. In many Provinces, Dengue epidemics occur annualy with different subtypes.
Previous Seroprevalence studies have showed that more than 80% of the adult population have a positive serology for Dengue.
During the last few months, since the beginning of Covid Outbreak in China and until now, Cambodia has been exposed to the virus. So far, about one hundred cases has been confirmed in Cambodia. So far, local transmission of covid-19 is apparently very low.

Hypothesis of (partial)cross heterologous immunity Dengue virus

In the last few months, in Singapore and Thailand, case reports have been published of covid patients misdiagnosed as Dengue by transient positive Dengue serology.
Dengue has been ruled out by pcr and these patients have had no history of past Dengue infections.

As you know better than my personal clinical experience, Dengue infection is a fascinating subject of research in the field of immunomical response to viral infection, antibody dependant enhancement…
Development of Dengue Vaccine is particularly difficult in regard to this complex immunological response. (Dengvaxia , Tak-003 phase III recently published in NEJM) Shibadas.biswal@takeda.com

During dengue epidemic, often asymptomatic, many not initially severe patients can deteriorate quickly to lethal conditions (DSS/Dhf). The immunologic storm of these patients is similar on many points to covid.
Cross immunity is described amongst viral diseases.(in vitro or in vivo) Given the complexity of the immune response to viral infection, there are many possible targets where « immunity even partial » to one virus can interact with another viral infection (with theoretical positive or negative effect, innate immune system through Tool-like-receptor TLC, activation or suppression of different T cells subpopulations and interleukines productions…)
A lot has been published about dengue virus sequential infection by its different serotypes.
A lot has been published about dengue vaccine protective AND harmful effects.

With your experience in the field of Dengue and the existing technical support available in Phnom Penh and Internationaly , do you consider that this theoretical explanation could be investigated in your population.
Laos, south of Vietnam and many parts of Thailand and Malaysia are also hyper endemic areas for Dengue. These countries or regions are also reporting less than expected covid infection cases.
Besides theoretical, other explanations (genetic, climatic…) partial cross immunity with Dengue could explain the unexpected lower spread of this covid epidemic or the very low incidence of severe presentation in the Cambodian population. If this « protective » interaction exists, it could open new fields of investigations.
Previous immunity to dengue (some subtype) could be a theoretical explanation to a different immunological response to covid infection. (less covid infected patients with severe evolution)

So far, there is no publihed data about dengue /covid except clinical reports on false positive dengue serological tests and difficulties regarding differential diagnosis in populations affected by two outbreaks (mayotte, reunion island)

Comment: Dear sirs/madams,
Is it not possible that corvus is going undiagnosed in these countries whilst positive dengue diagnosis grows? It is now clear that corvid produces a false positive dengue result.
Thank you for your consideration

Comment: I had come across the same observation here in Brazil. Cities with a history of Dengue epidemies had a slower covid increase.
Add-ons to the false positive Dengue results occurred on Singapore, I believe there might be a crossaction of the antibodies of one desease with the other.

Comment: Dear Readers,

Please see version 3 of our article (link: given above) for more data and updates on our observations.

Since there is evidence of cross-reaction of antibodies between the two viruses, the two viruses i.e. SARS-CoV-2 and dengue virus must share antigenic similarity.

Based on observations of "non-overlap"between dengue and COVID-19 global maps & serological cross-reactions between the two viruses, we believe that already available (licensed & safe) live attenuated dengue vaccines may be the best choice we have" right now" to immunize people in Europe, USA, Iran and China and save thousands of lives in the coming days before safe and tested SARS-CoV-2 vaccines and antivirals become available.

"Antibody-dependent enhancement" should not be a big problem in the post-vaccinated individuals as dengue is not endemic in the above COVID-19-worst hit countries.

Our proposition can be easily tested in animal models by vaccinating experimental animals like monkeys with live dengue vaccines and then infecting them with SARS-CoV-2 and comparing protection with respect to infected but non-vaccinated controls.

Best wishes,
Authors.

Comment: Further computational modeling based approach was perceived to validate this hypothesis.
Please find the preprint link of the research article:
https://osf.io/dutx4/