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)
In this study, @MiyuMoriyama et al investigate how well SARS-CoV-2 variants of concern (VOC) suppress MHC I needed for recognition by cytotoxic T cells. This question is important to understand how well the virus limits CD8 killing 🧵(1/) @biorxivpreprint biorxiv.org/content/10.110…
CD8 T cells help fight off viral infection by detecting and killing infected cells. CD8 T cells detect MHC I + viral peptide on infected cells. One of the common tricks viruses use to avoid killing is to inhibit MHC I expression and presentation. (2/)
SARS-CoV-2 is no exception. A previous study showed that SARS-CoV-2 (ancestral) induced MHC I down-regulation in infected cells. They found a key role of ORF8 in this process. (3/)
A Phase 2 clinical trial of oral camostat mesylate during early phase of COVID-19 in outpatients reduced illness course (including fatigue) and prevented loss of smell and taste!
Work of fantastic colleagues at @YaleMed. (1/)
This randomized double-blind placebo-controlled phase 2 trial gave patients (within 3 days of testing PCR+) either oral camostat mesylate or placebo pills, 4x/day for 7 days. Note the lower smell/taste scores (meaning better ability to smell and taste) in camostat group (2/)
Camostat mesylate blocks TMPRSS2, which cleaves the spike protein allowing the virus to fuse with the cell and start to replicate. However, there was no differences in detectable viral RNA levels in patients treated with camostat vs. placebo in nasopharyngeal swab or saliva. (3/)
This new preprint by Stadler et al. integrated data from 37 randomized controlled trials to ask how the timing and dose of passive antibodies (monoclonal Ab & convalescent plasma) predict protection from SARS-CoV-2 disease. A short 🧵 (1/)
Timing: the study found that the earlier the patients were treated with monoclonal antibodies (mAb) or convalescent plasma (CP), the more effective the passive antibodies were in preventing the clinical outcome measured (indicated by right end of line). #TheEarlierTheBetter (2/)
These data are reminiscent of endogenously induced antibody responses against SARS-CoV-2. In patients with fatal COVID, the onset of antiviral antibodies was significantly delayed compared to those who survived COVID. @carolilucas@sneakyvirus1 (3/)
What immune cell features are most predictive of COVID outcomes? @mkuchroo@JcsHuang Patrick Wong et al used ML algorithm Multiscale PHATE to assign each immune cell type in COVID patients a mortality-likelihood score. Latest from @KrishnaswamyLab 💪🏼 (1/) go.nature.com/3K0QCqi
Based on the flow cytometry data on 54 million cells from COVID 168 patients, the low density granulocytes (neutrophils and eosinophils) were the most enriched cell types in patients who had fatal COVID, followed by inflammatory monocytes and certain B cell subsets. (2/)
In contrast, T cells (most of them; see below), NK cells and dendritic cells were associated with the lowest mortality likelihood scores. They are likely protecting the host from lethal disease. (3/)
“COVID toes” are swollen discolored toes (and fingers) that were seen in areas with high incidence of COVID-19, but the cause is unknown. This new study by @JeffGehlhausen et al shows lack of association between covid toes and SARS-CoV-2 infection. 🧵(1/)
We enrolled 23 pandemic chilblains (PC) patients. While there is an association with community COVID cases (blue line) and PC (red bars), only 2 PC patients had evidence of infection by PCR or antibodies. We wondered if people may have missed the time window for testing +ve. (2/)
PCR testing was difficult to access at the time of initial wave (2020). Thus, we employed two distinct measures of antibodies - ELISA and @serimmune SERA assays - against SARS-CoV-2 S, RBD and N. Only 2 of the 23 patients (who were also PCR +ve) had consistent antiviral Abs. (3/)
Vaccines that reduce infection & disease are needed to combat the pandemic. Here, @tianyangmao@BenIsraelow et al. describe our new mucosal booster strategy, Prime and Spike, to induce such immunity via nasal delivery of unadjuvanted spike vaccine 🧵 (1/)
Current COVID vaccines are given intramuscularly. This induces robust circulating antibodies and systemic T & B cell responses that block viral spread and disease. However, to better block infection, immunity has to be established at mucosal surfaces. (2/) annualreviews.org/doi/10.1146/an…
To elicit mucosal immunity from scratch, live attenuated vaccines are often necessary, due to the need to introduce sufficient antigen and innate immune signals needed for priming via mucosal surfaces. Live vaccines are not safe for immunocompromised. (3/) nature.com/articles/s4157…