Cross-reactivity: Do flu shots confer 'bystander immunity' against COVID-19?

FOCUS ON IMMUNITY: Our immune system is the swarm of biological soldiers that fight viruses and bacteria when they invade the body. Defenders called B-cells swarm into affected areas, unleashing antibody molecules that seek to destroy the invaders.

CREATION OF ANTIBODIES: For many years now, researchers had been exploring how our immune systems create antibodies. Immunologists have mapped how the human body produces antibodies (protective proteins that fight antigens, or disease-causing viruses/bacteria/germs). Experts say that the reported cases show different severity of symptoms, ranging from mild to severe, and in some cases, no symptoms. Antigen is the common term used to describe an invading microbe (a.k.a. "pathogen").

VARYING SEVERITY: Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is a highly infectious and rapidly-evolving disease. Due to fast-spreading mortality rates within a rather short time – it has so far killed 1 million since January 2020 – it needs rapid intervention. More than 33.5 million had been infected worldwide as of September 30, 2020. Photo is a high-power magnification image that shows the structure and density of SARS-CoV-2 virions (red) produced by human airway epithelia.

LIMITED RESEARCH ON IMMUNE RESPONSE: COVID-19 is generally a mild disease in children, including infants, according to a study published in The Lancet in June [https://bit.ly/2HEdroJ]. But there’s been little extensive research conducted on the immune responses toward COVID-19, according to immunology experts. However, a recent study conducted by a team at the Peter Doherty Institute for Infection and Immunity in Australia assessed the immune responses in the blood from a patient with COVID-19 disease with mild severity in what is called a “longitudinal” study. [https://pubmed.ncbi.nlm.nih.gov/32284614/]

RESPONSES AT SET TIME POINTS: The researchers looked at the cellular and humoral immune responses at different time points during the COVID-19 infection — before, during and after resolution of the disease, and recovery of the patient. Their longitudinal analysis showed a robust immune response across different cell types associated with clinical recovery.

COVID-19 'SIMILAR' TO FLU: The results, the researchers said, were similar to what the same group had reported before in patients with influenza infection.

LINK BETWEEN IMMUNITY AND RECOVERY FROM COVID-19: A team led by Dr. Mohamed Labib Salem of the Immunology and Biotechnology Unit, Department of Zoology, Faculty of Science, Tanta University, Egypt, suggested a link between the quality of the immunity and recovery from COVID-19, at least in part, in patients with mild symptoms. The study results were published by Elsevier. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194943/]

VARYING SUSCEPTIBILITIES: Different susceptibilities to COVID-19 disease were observed between different age groups. Children showed lower rate of infection than adults and elderly. Among the small proportion of children that develop severe disease requiring ICU admission and prolonged ventilation, fatal outcome is overall rare.

ONE POSSIBLE EXPLANATION: The mechanism behind these differences in infection severity and susceptibility is not clear yet to medical science. But one possible explanation, as advanced by Dr Mohamed Salem’s team, “could be the difference in the quality and quantity of the immune performance that is shaped by the history of recent infections and/or vaccinations." Anyone above the age of six months is advised to get a flu shot.

CROSS-REACTIVITY HYPOTHESIS: Dr Mohamed Salem of Egypt’s Tanta University presented the hypothesis that the “resultant immunity against prior influenza infection would, at least in part, foster immunity against SARS-CoV-2.” They backed this by what they see as a “similarity” in the quality of immunity toward both viruses (SARS-CoV-2 and Influenza), and by the previous studies showing “cross reactivity” of immunity between flu and coronavirus — due to the similarity in their structures.

WHAT IS BYSTANDER IMMUNITY? Besides the cross reactivity effect, the anti-Flu immune responses can induce “bystander immunity”, according to researchers citing a previous study in the journal "Cell", titled “Memory B cell activation, broad anti-influenza antibodies, and bystander activation revealed by single-cell transcriptomics”, published in January 2020. They also hypothesized that cross-reactivity could augment immunity, though “non-specifically”, against other viral infection, such as SARS-CoV-2.

ANTIBODY MEMORY: Among immunology experts, it’s a well-understood fact that antibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies. However, the ways these aspects of the response are coordinated in the human body remains little understood.

PROFILE OF ANTIBODY RESPONSE: The team led by Felix Horns, a biophysicist at Stanford University in California, published their work in the journal "Cell" in January 2020. They profiled the molecular and cellular features of the antibody response to influenza vaccination. They did this by integrating what they called "single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements.” Single-cell transcriptional profiling reveals a program of memory B cell activation characterised by CD11c and T-bet expression associated with clonal expansion and differentiation toward effector function.

ONE EFFECT OF FLU VACCINATION: Vaccination elicits an antibody “clone”. These clones rapidly acquire broad high-affinity hemagglutinin binding during affinity maturation. A team of researchers led by Stanford University’s Felix Horns unexpectedly found that many antibody clones elicited by vaccination do not bind vaccine. This, they say, demonstrates non-specific activation of “bystander antibodies” by a flu shot. The results offer insights into how molecular recognition, transcriptional programs, and clonal proliferation are coordinated in the human B cell repertoire during memory recall. [https://pubmed.ncbi.nlm.nih.gov/31968262/]

SUSTAINED IMMUNITY: Dr Mohamed Salem’s team then hypothesised that influenza vaccination itself would generate sustained immunity that overall enhance immunity against SARS-CoV-2. "This would explain,” they stated, “why the rate of SARS-CoV-2 in children is low since they catch flu more than adults do”. As such, it is expected that children’s immune systems be often alarmed against influenza, generating “bystander immunity” that harness the immune responses against related viral infection. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194943/]

HUGE DEMAND: There's been a huge demand for the seasonal flu vaccine, according to health officials. A new four-strain flu vaccine (quadrivalent) is expected next week. The UAE Ministry of Health and Prevention has launched an awareness campaign about the new flu jab, which is seen give better protection against seasonal influenza this 2020-2021 flu season. [https://gulfnews.com/uae/health/huge-demand-for-flu-vaccine-in-the-uae-1.74189403]