Harvard’s Humoral Immune Profiling Study Discovers That Immunity To Non-COVID-19 Endemic Coronaviruses May Play A Role In Who Develops Long COVID!

A study by Harvard researchers involving humoral immune profiling has discovered that immunity to non-COVID-19 endemic coronaviruses may play a role in who develops PASC (Post-Acute Sequelae of COVID-19) commonly known as Long COVID!
 


The study team comprised scientists from Ragon Institute of MGH, MIT, and Harvard-USA, Brigham and Women’s Hospital-Boston, Massachusetts General Hospital-Boston and Massachusetts Institute of Technology-Boston.
 
Utilizing high dimensional humoral immune profiling, the study team uncovered the potential importance of previous common coronavirus imprinting as a novel marker and potential mechanism of an endotype of PASC or Long COVID.
 
Aside from the unpredictable acute illness caused by SARS-CoV-2, one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection.
 
Detailed insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) or Long COVID will be critical for the prevention and clinical management of long-term complications of COVID-19.
 
Numerous hypotheses have been proposed that may account for the development of Long COVID, including persistence of virus or the dysregulation of immunity.
 
Interestingly, among the immunological changes noted in Long COVID, alterations in humoral immunity have been observed in some patient subsets.
 
In order to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in Long COVID, the study team performed comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens using Systems Serology in a cohort of patients with pre-existing rheumatic disease who either developed or did not develop Long COVID.
 
Importantly, a distinct humoral immune response was observed in individuals with Long COVID.
 
It was found that uniquely, individuals with Long COVID harbored less inflamed and weaker Fcγ receptor binding anti-SARS-CoV-2 antibodies and a significantly expanded and more inflamed antibody response against endemic Coronavirus OC43.
 
Also, people with Long COVID further, generated more avid IgM responses and developed an expanded inflammatory OC43 S2-specific Fc-receptor binding response, linked to cross reactivity across SARS-CoV-2 and common coronaviruses.
 
The study findings implicate previous common Coronavirus imprinting as a marker for the development of Long COVID.
 
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.medrxiv.org/content/10.1101/2022.09.25.22280335v1
 
In simple terms, the study findings imply that individuals who develop Long COVID may be responding more strongly to a non–SARS -CoV-2 virus they encountered in the past than to SARS-CoV-2.
 
It has been found that Long COVID causes various symptoms that persist at least 4 weeks after the initial SARS-CoV-2 infection and in some in can linger on for a very long time.
 
The study findings give perspectives into possible mechanisms of Long COVID.
 
Co-lead author, Dr Jonathan D. Herman, MD, PhD, from Ragon Institute of MGH, MIT, and Harvard said, "Immunity to non-COVID endemic coronaviruses may play a role in who develops Long COVID. There's still so much more we need to understand, but it is striking that back-boosting of immune responses to coronavirus OC43 was uniquely enriched in individuals with PASC."
 
Co-senior author Dr Galit Alter, PhD, also from Ragon Institute of MGH, MIT, and Harvard added, "In our research, we found that individuals with Long COVID preferentially generated stronger responses to previously encountered cold-causing coronaviruses. Instead of generating strong SARS-CoV-2 immunity, they bolstered a response to a different coronavirus, potentially making their response less effective in clearing SARS-CoV-2. Surprisingly, most of the individuals had been vaccinated and yet they still maintained this unusual antibody response.”
 
The study team said that the research findings pave the way to new therapeutic pathways to treat Long COVID with humoral immunity providing a clue to Long-COVID origins.”
 
The study team noted that up to one-fifth of COVID-19 patients progress to Long COVID, but which patients develop Long COVID and why are not well understood.
 
Dr Alter added, "Antibodies represent powerful biomarkers that have been used for decades to diagnose disease. However, antibodies also provide a powerful source of information on previous infections. The use of antibody profiling, here, pointed to the presence of incomplete antibody responses to SARS-CoV-2 in individuals with Long COVID."
 
The study team reviewed the medical records of patients in the Mass General Brigham health care system in Boston, including referrals from rheumatologists of participants diagnosed with COVID-19 outside the MGB system, starting on March 1, 2020.
 
The study team focused on patients with systemic autoimmune rheumatic diseases (SARDs) because their tendency toward inflammation and autoantibody production may make them more susceptible to Long COVID and enrich for specific inflammatory-driven endotypes.
 
In all, a total of 43 participants who had COVID-19 without hospital admission and SARDs (Systemic autoimmune rheumatic diseases) were included in the study. All patients who were treated only for fibromyalgia, osteoarthritis, mechanical back pain, gout, or pseudogout without a SARD were excluded from the study.
 
A total of 79% of participants were female, 35% had rheumatoid arthritis, 19% had psoriatic arthritis, and 95% had received a COVID-19 vaccine.
 
The study team utilized used systems serology to perform comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens.
 
Interestingly the study findings showed that Long-COVID patients had a distinct immune response.
 
It was found that 17 patients developed Long COVID and 26 did not, and in those with Long COVID, these individuals were found to have a distinct humoral immune response.
 
The individuals with Long COVID:
 
-harbored less inflamed and weaker Fc-gamma receptor–binding anti–SARS-CoV-2 antibodies;
 
-showed a significantly expanded and more inflamed antibody response against endemic coronavirus OC43; and
 
-mounted more avid IgM responses and developed expanded inflammatory OC43 S2–specific Fc-receptor–binding responses, which were linked to cross reactivity across SARS-CoV-2 and common coronaviruses.
 
Co-senior author Dr Jeffrey A. Sparks, MD, MMSc from the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women’s Hospital commented, "Strengths of the research include the detailed phenotypes of cases after COVID-19, particularly to classify Long COVID presence or absence, as well as the depth and breadth of antibody profiling. This allowed us to identify a humoral immune signature of Long COVID."
 
He further added, “The study was however limited in its size to investigate different types of Long COVID conditions such as fatigue or lung symptoms, that may have biologic differences. Also, it was noted that all patients in the study had a preexisting pre-existing rheumatic disease.”
 
The study team also said that a substantial portion of patients with COVID-19 will develop Long COVID, which can have substantial impact on health and quality of life. Given the higher risk of COVID-19 in many patients with rheumatic disease, it is important to understand the etiology of Long COVID in this vulnerable population, to enable future diagnostic and therapeutic advances.
 
The study team are still pursuing further research in to Long COVID.
 
Dr Mark Cameron, PhD, associate professor in the department of population and quantitative health sciences at Case Western Reserve University, Cleveland who was not involved in the study commented, "In this initial study, the study team  focused on individuals who had rheumatic disease before getting COVID-19, knowing they are at higher risk for lasting complications and hopefully are more immunologically similar when diagnosed with Long COVID…this is a single 'endotype' or group of patients with similar clinical symptoms and background.”
 
He added, "Our immune system's memory sometimes fails to effectively fight a new virus that looks too much like a virus it saw before. This ineffective immune response can set up various problems, including the poor recoveries we see in people with long COVID. OC43 probably emerged in the late 1800s and probably caused a pandemic of severe respiratory illness between 1889 and 1890, previously thought to be a flu. OC43 is still around as an endemic coronavirus, usually causing mild or moderate upper-respiratory infections."
 
He further added, “COVID-19 immunity is complex and previous SARS-CoV-2 infection doesn't guarantee protection, especially now as many new variants and sub-lineages have emerged. These study findings may help us better comprehend the risks and possible mechanisms associated with COVID-19 and Long COVID in the face of previous coronavirus infections. It may also help guide future COVID-19 therapies and vaccines."
 
For more on Long COVID, keep on logging to Thailand Medical News.
 
Read Also: https://www.thailandmedical.news/news/german-study-shockingly-discovers-pre-existing-immunity-to-seasonal-coronaviruses-increases-sars-cov-2-susceptibility-and-covid-19-severity