Are Dengue-Antibodies protecting Burmese from COVID-19? |
For me it is very strange, for Burma and China have over 1,000 miles long common border line which is so notoriously porous. When I was in Mandalay just last year, there were so many Chinese who don't speak a single word of Burmese, I felt like I was in China. People don't realise how massive and constant the bilateral movements of goods and animals and humans across that long porous border, and we still do not have a single case of that fatal Wuhan viral disease now called COVID-19?
Now is almost the end of February and if we don't have any Coronavirus cases by the middle of March we will never have a case unless some infected-ones coming back from one of the viral hotspots abroad brought virus into Burma.
What are the reasons the global pandemic not reaching our poor country? I had asked the same question to so many experts, both medical practioners and scientists including the people from WHO, as I want to know more of this strange occurence. But no one could give me the satisfactory answer for my inquiries.
But I have a strong opinion that we Burmese might have some kind of super-antibodies, of which no other people of the world have, and these anti-bodies are giving us the protection or immunity from the fatal and extremely infectious Chinese virus.
Believe it or not we all Burmese fortunately
carry three types of Dengue antibodies that
no other people on earth has. They are namely Ede1-C10, Ede2-A11, and Ede2-B7
antibodies as the results of constant exposure to Dengue-carrying mosquitoes (Striped-Mossies
or Chin-Gyar in Burmese vernacular).
Those Dengue-Mossies carry four types of Dengue viruses, namely DENV-1, DENV-2, DENV-3, and DENV-4. But the Dengue-Antibodies we Burmese have are not known to be giving us immunity from the Wuhan virus or any kind of coronaviruses but somehow, I have a strong feeling that, we are protected.
The strange coincidence between the Dengue virus and Corona virus is that they both are "Single Strand RNA" viruses and they both could have same "Surface Proteins or S Protein" on their cell surfaces.
Who knows, one or all of our three Dengue-Antibodies could be wrongly identifying the Wuhan Virus as one of the Dengue viruses and tagging and destroying them? If we do not get the COVID-19 by mid-March I could be right and my hypothesis should be seriously tested in the advanced virology labs.
Lord Buddha bless and protect us from the made-in-China Wuhan virus and COVID-19 disease!
WARNING! Singapore Study Shows That Covid-19 Patients Could Be Misdiagnosed For Dengue Due To False Positive In Dengue Serological Tests:
Typically, clinical and laboratory features of both Dengue and the Covid-19 disease is quiet identical and difficult to distinguish. To make matters more complicated, it has been reported that Covid-19 patients can produce false-positive results from rapid serological testing for dengue.
Astudy by Singaporean researchers published in The Lancet helps to warn Healthcare professionals around the world of this phenomenon so that wrong diagnosis can be prevented early. The study was lead by Dr Gabriel Yan from the Department Of Medicine, National University of Singapore and was based on the study of two patients in Singapore, one a male and another a female both 57 years of age who were initially misdiagnosed as having Dengue Fever due to serological tests.
Both exhibited thrombocytopenia and also the dengue rapid test was positive for dengue IgM and IgG for both. They were discharged from hospitals after being treated for dengue but readmitted back as their conditions worsened and it was only when further investigations warranted the PCR nucleic acids tests for the SARS-Cov-2 virus, that the test results indicate that both were actually suffering from the Covid-19 disease. Further test also confirmed that they were both not suffering from Dengue at all.
It is also interesting to note that in Thailand, in the case of a 35 year old Thai male who died from the SARS-CoV-2, it was reported in the media that doctors had initially been treating him for Dengue.
Proper diagnostics even in poorer countries with inadequate equipment and test-kits is critical as early detection and treatment of the Covid-19 disease is important to maintain low mortality rates.
For situations where nucleic acid test kits are not available, the usage of CT scans and also chest X-rays with certain biomarkers in blood tests could provide healthcare professionals with sufficient data to make a preliminary assessment to initiate treatment protocols in cases of emergencies.
To date so far the SARS-CoV-2 Coronavirus has infected more than 135,014 individuals worldwide spanning 114 countries and also resulted in about 5,012 deaths. The situation is escalating globally with no respite.
Dengue and coronavirus disease 2019 (COVID-19) are difficult to distinguish because they have shared clinical and laboratory features.
We describe two patients in Singapore with false positive results from rapid serological testing for dengue, who were later confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative virus of COVID-19.
The first case is a 57-year-old man with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 9, 2020, with 3 days of fever and cough. He had thrombocytopenia (platelet count 140 × 10⁹/mL) and a normal chest radiograph.
He was discharged after a negative rapid test for dengue NS1, IgM, and IgG (SD Bioline Dengue Duo Kit; Abbott, South Korea). He returned to a public primary healthcare clinic with persistent fever, worsening thrombocytopenia (89 × 10⁹/mL), and new onset lymphopenia (0·43 × 10⁹/mL).
A repeat dengue rapid test was positive for dengue IgM and IgG (Dengue Combo; Wells Bio, South Korea). He was referred to hospital for dengue with worsening cough and dyspnoea. A chest radiograph led to testing for SARS-CoV-2 by RT-PCR (in-house laboratory-developed test detecting the N and ORF1ab genes) from a nasopharyngeal swab, which returned positive.
The original seropositive sample and additional urine and blood samples tested negative for dengue, chikungunya, and Zika viruses by RT-PCR,3–5 and a repeat dengue rapid test (SD Bioline) was also negative. Thus, the initial dengue seroconversion result was deemed a false positive.
Dengue Virus. |
She returned 2 days later with a persistent fever, worsening thrombocytopenia (65 × 10⁹/mL), and new onset lymphopenia (0·94 × 10⁹/mL). Liver function tests were abnormal (aspartate aminotransferase 69 U/L [reference range 10–30 U/L], alanine aminotransferase 67 U/L [referencerange <55 U/L], total bilirubin 35·8 µmol/L [reference range 4·7–23·2 µmol/L]).
Chest radiography was normal and she was admitted for dengue fever. She remained febrile despite normalisation of her blood counts and developed dyspnoea 3 days after admission. She was found to be positive for SARS-CoV-2 by RT-PCR from a nasopharyngeal swab.
A repeat dengue test (SD Bioline) was negative and an earlier blood sample also tested negative for dengue by RT-PCR.6 The initial dengue IgM result was deemed to be a false positive.
Failing to consider COVID-19 because of a positive dengue rapid test result has serious implications not only for the patient but also for public health. Our cases highlight the importanceof recognising false-positive dengue serology results (with different commercially available assays) inpatients with COVID-19.
We emphasise the urgent need for rapid, sensitive, and accessible diagnostic tests for SARS-CoV-2, which need to be highly accurate to protect public health.
Animal and cell culture studies show evidence that dengue antibodies can both neutralize and enhance Zika, but human investigations have only found protective effects. The mosquito-borne Zika virus that recently spread rapidly throughout the Americas shares many characteristics with another virus: dengue.
Both are flaviviruses, which are enveloped, sphere-shape virions that are typically transmitted by mosquitos and ticks. Due to their structural similarities and because the latest Zika outbreak appeared in dengue-endemic regions, scientists have been investigating whether antibodies against one might be able to react to the other—and whether these interactions could either worsen or buffer against infections.
Researchers had previously demonstrated a phenomenon known as antibody-dependent enhancement (ADE)—where, at certain concentrations, antibodies against one virus can heighten the effects of another—between different types of dengue viruses. This suggested that antibodies against other flaviviruses might possess similar features.
“When the recent Zika outbreak occurred, one of the major questions scientists had was whether or not the enhancement effect could also impact Zika infections,” says Jean Lim, a virologist at the Icahn School of Medicine at Mount Sinai in New York. “Because of the potential for Zika to cause damage during pregnancy, this was—and still is—an important question.”
Early in vitro studies confirmed that dengue antibodies extracted from human blood cross-reacted with Zika, and some suggested that they could strength infection. “There were a lot of people who hypothesized that, perhaps the reason that Zika is causing microcephaly was because you were getting enhancement,” Aubree Gordon, an epidemiologist at the University of Michigan, tells The Scientist. “So there was a lot of interest within the entire field to look at if you see protection or enhancement.”
In animal models, scientists have reported that dengue antibodies can both neutralize and enhance Zika. While the latter observation has raised concerns about heightened Zika infections in regions where dengue is common, the epidemiologic data have been more reassuring.
To date, large, human cohort investigations have only found protective effects against Zika. Still, some scientists say that it is possible that augmentation may occur—and recent experimental studies in human tissues and mice suggest that this may happen in pregnant females.
Earlier this year, two long-term assessments of populations in Central and South America reported that dengue immunity was protective against subsequent Zika infections.
One study, published in Science, examined a cohort of 1,453 residents in Brazil and found that having dengue antibodies prior to the Zika outbreak was tied to a decreased risk for Zika infection and fewer symptoms in those who contracted the disease.
The other, published in PLOS Medicine, followed a group of approximately 3,700 children in Nicaragua, and also discovered that dengue immunity protected against symptoms of Zika, although this study did not find a reduction in total infections.
The fact that we do see protection does make me a bit more concerned, in fact, that enhancement could occur as well, because it verifies that there certainly is an interaction. —Aubree Gordon, University of Michigan.
“We expected that we would see protection,” says Gordon, who is a coauthor of the Nicaragua study. “We thought we might see enhancement at well—but at this point we don’t have any evidence for it.”
Gordon’s anticipation that dengue antibodies might both hurt and help Zika infections came from prior laboratory experiments and epidemiological investigations that found the effects of cross-reactivity are concentration-dependent, at least when it comes to multiple dengue infections. In humans, Gordon and her colleagues have observed that high levels of antibodies against one type of dengue buffers against another, but lower levels actually enhance disease in subsequent exposures.
Zika virus. |
Lim’s group has found evidence that dengue antibodies could enhance Zika infection in mice. But other groups—who have used various different animal models and experimental protocols—have turned up mixed results. “It’s still a very contentious field. Some groups see enhancement effects and other groups do not,” Lim says. “I think everybody is open to the idea that it could happen, but the data is not clear at this point.”
Gordon agrees that it is too early to rule out the possibly that enhancement is happening. “The fact that we do see protection does make me a bit more concerned, in fact, that enhancement could occur as well, because it verifies that there certainly is an interaction.”
Identifying whether ADE occurs is particularly important for current efforts to develop Zika vaccines, notes Albert Ko, a physician and epidemiologist at the Yale School of Public Health and an author of the Brazil cohort study.
“The question is, are the antibodies made by a dengue or Zika vaccine friend or foe” to subsequent infections, he tells The Scientist. “Obviously we have to be cautious, because there are these studies in mice and in vitro that find enhancement, but in humans we don’t see enhancement signals as of yet.”
One of the biggest concerns about Zika is the virus’s ability to cause microcephaly and other severe birth defects. “Zika is a mild disease, but the big public health impact is when pregnant women get affected,” says Ko. “How the prior dengue antibodies influence Zika when a pregnant woman is infected—and how that would influence vertical transmission from the mother to the fetus is an open question.”
Although researchers have yet to find an answer in cohorts of people, recent work in human tissues and animal models provides hints that ADE may indeed influence the spread of Zika from a pregnant mother to her developing fetus. This work may still be preliminary, but “the big picture that’s emerging is that these cross-reactive antibodies look like they’re facilitating Zika virus [transmission] across the placenta,” says Mehul Suthar, an immunologist at Emory University.
We think that Zika, in the presence of dengue antibodies, is really causing damage to the placenta. —Jean Lim, Icahn School of Medicine at Mount Sinai
Several groups, including Suthar’s, have found the Zika virus can infect cells in the placenta, an organ that serves many functions during pregnancy, including providing an immunologic barrier between the mother and her developing fetus.
Last year, Suthar and his colleagues reported in Cell Host & Microbe that dengue antibodies could enhance Zika in human placental tissue and macrophages, the primary cell type infected by the virus. They also found that this process was dependent on Fc receptors, proteins that are involved in transcytosis, the process of trafficking molecules across the placenta.
Two recently published rodent studies also support this theory. One, which appeared in Immunity and was conducted by Lim and her colleagues, found that in pregnant mice, pre-existing dengue antibodies enhanced Zika virus replication in the placenta and caused inflammation and injury to the organ. “We think that Zika, in the presence of dengue antibodies, is really causing damage to the placenta,” Lim says. “And that this is indirectly causing damage to the developing fetus.”
A Zika baby with severe microcephaly. |
Although both rodent studies found enhanced Zika infection in the placenta of dengue-immune mice—and that enhancement effect was dependent on Fc receptors—the Singapore team observed microcephaly-like effects on fetuses while the other group did not.
According to St. John, this is likely because her study used mice that had their immune systems intact and Lim’s used immunocompromised mice (the later model is a common practice when experimenting with Zika and dengue infections because rodents are more resistant to the viruses than humans). However, “fetuses don’t survive Zika infection in the immunocompromised system, so our system allows us to actually study fetal development,” she adds.
Future studies in humans and nonhuman primates will be necessary to verify that this process really occurs. “I do think there is potential for dengue to enhance Zika virus infection,” Lim says. “The real test will be to see whether or not this happens in humans.”
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