With millions of #longCOVID patients, it is becoming better known that even a mild infection can lead to longterm debilitating health problems. SARS-CoV-2 joins the long list of other pathogens that cause post-acute infection syndrome (PAIS). (2/)
What are some common and distinct symptoms associated with PAIS? Strikingly, there are a number of shared symptoms such as excertion intolerance, fatigue, pain, neurological symptoms..etc. Others are more unique to the pathogen that triggered the disease. (3/)
What percentage of people who are infected develop PAIS? Taking an example of mononucleosis associated with Epstein-Barr virus (EBV) infection, #MECFS persisted in ~4% of the participants who continue to experience debilitating symptoms at 2-year follow-up 👇🏽 (4/)
Significant percentages of those infected with #SARSCoV2 report overall #longCOVID (blue) or activity-limiting long COVID (red). Over time, there is some gradual decline but persistence of disease ~6 months since the infection. Source: Office for National Statistics (ONS). (5/)
What could be the possible causes of PAIS? Similar to #longCOVID, we hypothesize a) pathogen reservoir/remnants, b) autoimmunity, c) dysbiosis of microbiome/virome, and d) unrepaired tissue damage. None are mutually exclusive. (6/)
PAIS is an understudied and under-recognized spectrum of infectious diseases. We need more research on the causes, biomarkers and therapeutics to treat PAIS. #PAIS and #MECFS need to be taught at every medical school. We hope this review will help get that started 🙏🏼 (end)
Happy to share our latest work by @YYexin et al. on antibody-mediated control of endogenous retroviruses in mice. In the process, we found “natural antibodies” with broad reactivity against enveloped viruses. Here is how “panviral” antibodies work 🧵(1/)
Endogenous retroviruses (ERV) are remnants of genetic invaders that have integrated into our ancestors' genomes over millions of years. ERVs occupy ~8% of the human genome and are under constant host immune surveillance. (2/) nature.com/articles/nrg31… nature.com/articles/nrmic…
This work started over 7 years ago when @YYexin and @rebecca_treger began to examine why ERVs reactivate in certain mouse strains. Through many genetic crosses, we figured out that secreted IgM recruits complement to suppress infectious ERV from emerging. (3/)
This time, we developed a nasal booster vaccine for influenza viruses. In this preprint, @MiyuMoriyama et al. show that nasal boosters with unadjuvanted hemagglutinin protein induce sterilizing immunity in mice against flu. (1/) biorxiv.org/content/10.110…
This work builds on the Prime and Spike vaccine strategy by @tianyangmao @BenIsraelow et al. against COVID where mRNA vaccine followed by nasal booster with recombinant spike protein established local immunity, ⬇️ infection & transmission in rodents. (2/) science.org/doi/10.1126/sc…
For Prime and HA against flu, @MiyuMoriyama tested several different mRNA IM prime and nasal HA booster doses, followed by a homologous influenza virus challenge. Like Prime and Spike, no adjuvant is needed for the nasal booster due to preexisting immunity from Prime. (3/)
Much-needed data on the genetics of #longCOVID in a new preprint by @23andMeResearch - GWAS of #LongCOVID identified 3 loci pointing to immune and thrombo-inflammatory mechanisms 🔥 @ninaadsc 1) HLA-DQA1–HLA-DQB 2) ABO 3) BPTF–KPAN2–C17orf58
(1/) medrxiv.org/content/10.110…
Among research participants who reported acute SARS-CoV2 infection, 64,384 participants reported to have experienced Long COVID and 178,537 participants did not. Their analytical cohort consisted of 54,390 cases and 124,777 controls 👇🏼 (2/)
The top locus was in the HLA-DQA1–HLA-DQB intergenic region. Further analysis showed that HLA alleles HLA-DRB1*11:04, HLA-C*07:01, HLA-B*08:01, and HLA-DQA1*03:01 were significantly associated with #LongCOVID. In other words, crucial genes for T cell target detection! (3/)
Keynote talk by @MichaelPelusoMD. “#LongCovid is not a mystery anymore. Working with patients, I have optimism that we can figure this out.” #YaleCIISymposium
An excellent framework in thinking about the pathogenesis of #LongCovid
@MichaelPelusoMD
Sharing this scoping review on "Post-Acute sequelae of COVID-19 in pediatric patients within the United States" by @ChrisMillerDO - an amazing @YalePediatrics infectious diseases fellow focused on research and treatment of #longcovidkids (1/)
Key findings:
- Most pediatric LC patients were adolescents.
- ♀>♂️
- 80% of pediatric LC patients started with a mild initial infection.
- Asthma, atopy, allergic rhinitis (type 2 immune diseases), and obesity were frequently reported pre-existing conditions. (2/)
The most frequently reported symptoms in #longcovidkids are listed here (3/)
An important study by F. Eun-Hyung Lee's team shows that long lived plasma cells (the source of long-term circulating antibodies) fail to establish after mRNA vaccination (even combined with SARS-CoV-2 infection). 🧵 (1/) nature.com/articles/s4159…
The longevity of antibody-mediated protection against infectious diseases rely on whether or not the vaccines can establish long lived plasma cells (LLPC) in the bone marrow. They are the source of circulating antibodies for years to decades. (2/) nature.com/articles/s4159…
The study by Nguyen et al examined the long lived and short lived plasma cells in the bone marrow in people who received COVID mRNA vaccines, tetanus and flu vaccines at various time points . They found no LLPC (PopD) specific to COVID but found PopD against tetanus and flu. (3/)