What is the relevance of viral load in #COVID19 disease severity? A very talented @YaleMSTP student @SilvaJ_C found that saliva viral load to be a better predictor of disease than nasopharyngeal viral load. Here is a thread to explain the findings. (1/n)

I preface by saying that numerous fantastic studies by many have demonstrated nasopharyngeal viral load to correlate with disease severity and mortality, while others do not find such correlation. Here are some of these studies. (2/n)
Being at @yale, the birthplace of #SalivaDirect and everything saliva bc of awesome colleagues like @awyllie13 @NathanGrubaugh @VogelsChantal et al, we had access to both saliva and nasopharyngeal (NP) samples from the same patients to do direct comparisons. (3/n)
We already knew that saliva is an easy and reliable way to detect viral load in patients, thanks to the great work of colleagues here @YaleSPH @YaleMed. @awyllie13 et al. (4/n)

What about saliva’s ability to predict #COVID19 disease? @SlivaJ_C compared first whether saliva and NP viral load correlates with risk factors, age, sex. Saliva (top panels) but not NP (btm panels) viral load correlated with all of these. (5/n)
Next, @silvaJ_C examined whether viral loads correlate with severity of #COVID19. Saliva (top panels) but not NP (btm panels) viral load was elevated in hospitalized, severe and deceased patients. (6/n)
Moreover, saliva viral load (top) and NP viral load (btm) declined over time in patients that survived #COVID19 but not those who died (purple). Patients with lethal disease maintained v. high viral load over the course of disease. (7/n)
What associates with saliva viral load? Most influential predictors of saliva viral load was assessed by running a non-linear iterative
partial least squares (NIPALS) analysis of all factors and then assessing for variable importance with Variable Importance Plot (VIP). (8/n)
Positive correlation with saliva load: the usual suspects-chemokine, cytokines, IFNs.
Negative correlation with saliva load: antiviral antibodies and platelets.
We know early antibody kinetics is key to survival @carolilucas @sneakyvirus1 et al. (9/n)

Patients with high saliva viral load developed antiviral antibodies with significantly delayed kinetics than those who had low viral load. (10/n)
Time spent in the high, medium, and low saliva viral
load brackets was compared. Deceased
patients spent longest time in the high saliva viral load bracket, while non-hospitalized spent shortest time with high viral load. Moderate/severe in between. (11/n)
Why is saliva viral load a better correlate of disease than NP load? We think that NP only reflects upper respiratory tract (URT) viral replication, while saliva represents both URT and lower respiratory tract. Mucociliary clearance propels virus from LRT to oral cavity. (12/n)
URT virus is key to transmission, but LRT is key to severe #COVID19. Saliva appears to be better at capturing the critical viral source driving severe disease.
This was once again an amazing collaboration with the Yale IMPACT team 🙏🏼 Led by @SilvaJ_C 💪🏼 (end)

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More from @VirusesImmunity

1 Jan
My first tweet of 2021 is going to be about 1 dose vs. 2 dose vaccine. I have tweeted in the past of the immunological advantages of a 2 dose vaccine. However, given the enhanced transmission variants on the rise, we need a modified strategy. (1/n)

We typically give vaccines in more than one dose to increase 1) quantity, 2) quality, 3) longevity of antibody responses. This holds true for most vaccines including mRNA vaccines. Here is what I tweeted about this before. (2/n)

However, the 2 dose vaccine with limited number of vaccine means only half the people getting vaccinated at this time. If the virus is spreading slowly, we want to do the right thing and give the most vulnerable 2 doses and others to wait. (3/n)
Read 11 tweets
30 Dec 20
Inspired by this tweet by @TheMenacheryLab, I reached out to the wonderful colleagues at the @serimmune to see if the other mutations found in the B.1.1.7 variant would evade antibody responses generated by the wild type #SARSCOV2. (1/n)
According to this report, B.1.1.7 harbors non-synonymous mutations in the following viral genes, resulting in truncation, deletions and amino acid changes. Would these mutations result in evasion from antibodies generated by wild type virus? (2/n)

To probe this possibility, @serimmune used their technology platform based on bacterial display peptide libraries, next generation sequencing & machine learning to reveal antibody reactivity against WT and B.1.1.7 viral antigens. (3/n)

Read 11 tweets
26 Dec 20
What aspects of antibody responses determine the outcome of #COVID19? In this new preprint by @carolilucas @sneakyvirus1 et al., we found that the early timing of antibody response (before 14 days of symptom) in infected person is key to recovery. (1/n)

As others have shown, we found that antibody levels from COVID patients correlated with disease severity.


However, patients with lethal COVID did not have the highest level of anti-S or anti-RBD antibodies. What’s going on? (2/n)
To understand better the features of antibody responses in patients who died vs. survived, we compared their time course. We found a delay in antibody responses in lethal disease. We also noted patients with very high neutralizing Ab (HN) with very early antiviral Abs. (3/n)
Read 11 tweets
12 Dec 20
New exciting collaboration work with @Aaronmring lab reveals diverse and functional autoantibodies in #COVID patients.

Our findings provide clues for why COVID affects many organs, induce range of symptoms that are long lasting.

Thread (1/n)

How do we look for autoantibodies against a wide range of self antigens? The @aaronmring lab developed a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) against 2,770 extracellular and secreted proteins "exoproteome" 💪🏼 (2/n)
A large fraction of #COVID patients had autoantibodies to multiple self antigens. The more severe the disease, more autoantibodies they had.(3/n)
Read 14 tweets
5 Dec 20
Here is a thread to explain the findings of this study, that used computational tools to predict T cell reactive sequences in #SARSCOV2 subunit vaccines.

The bottom line: there is no cause for alarm.

Here is why (1/n)
Our adaptive immune system has 2 types of white blood cells known as lymphocytes. T cells and B cells. These lymphocytes give us protection from wide variety of pathogens. Each lymphocyte has unique receptor that detect specific features of a pathogen. (2/n)
B cells detect pathogens structures through antibodies. T cells cannot detect pathogens on their own. They can only “see” pathogen when tiny pieces of viral proteins (peptides) are presented by molecules called major histocompatibility complex (MHC). (3/n)
Read 12 tweets
7 Nov 20
Do some people have cross-reactive antibodies to #SARSCoV2? If so, who are they? And are these cross-reactive Abs protective against #COVID19? A fascinating study by @KevinWNg et al provides answers. Thread. (1/n)

Do some people have cross-reactive antibodies? The answer is yes. SARS-CoV-2 Spike-reactive IgG was detected in 5 of 34 SARS-CoV-2-uninfected individuals with RT-qPCR-confirmed HCoV infection, as well as in 1 of 31 individuals without recent HCoV infection. (2/n)
Who has cross-reactive anti-spike antibodies? Mostly children and adolescents. The prevalence of SARS-CoV-2 S-reactive IgG antibodies peaked at 62% between 6 and 16 years of age. This age group is also the one in which antibodies to seasonal coronaviruses peak.(3/n)
Read 8 tweets

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