Three Studies Link High IgG4 to Severe COVID-19

Previously, I published Pfizer mRNA shots Switch Antibodies to Non-Neutralizing IgG4. It featured research from Germany that showed that the IgG4 is produced by the memory B cells after two doses of Pfizer mRNA injection.

Immunoglobulin G4 is an antibody and is a subclass of IgG. IgGs are typically known to be active in fighting inflammation. But not so with IgG4. It is more anti or even non-inflammatory.

The IgG4 does not show up right away, but after 180 days, it comprises about 20% of the neutralizing antibodies against SARS-CoV-2. That means that not all neutralizing antibodies in Pfizer-“fully-vaccinated” may be effective in blocking the spike protein of the SARS-Cov-2 from attaching to human cells.

In that regard, I looked around to see if any clinical evidence shows that high IgG4 leads to poor COVID-19 outcomes.

This article features three studies that showed the negative association between high levels of IgG4 and COVID-19 mortality. All are peer-reviewed.

The first is a prospective study published in the European Journal of Internal Medicine. One hundred twenty-eight patients (41 females, 31.3 %) with COVID-19 were followed between June and December 2020 at the San Raffaele Hospital in Milan, Italy.[1]

Using multivariate analysis, they found that age, C-Reactive protein (CRP) levels, and the IgG4/IgG1 ratio are independent predictors of 30-day mortality.

CRP is a measure of inflammation in the body. So its elevation in severe COVID-19 makes sense due to multi-organ involvement.

IgG1 is a subclass of immunoglobulin G or IgG. IgG1 activates the immune system and is needed to get rid of viral infections. IgG3 does the same, as you will see later.

Thus, a high IgG4/IgG1 ratio indicates that an environment more permissive to infection is ongoing, which explains the poor outcome.

In particular, the level of IgG4 and the ratio of IgG4 and IgG1 are the most significant.

Specifically, a concentration of serum IgG4 > 700 mg/dl and an IgG4/IgG1 ratio > 0.05 were associated with a significantly increased mortality at 30-days.

The figure below shows that those with IgG4 levels of > 700 mg/ml have a lower survival rate with time.[1]

Source: Serum IgG4 level predicts COVID-19-related mortality. Eur J Intern Med. 2021 Nov; 93:107-109

The second study is from Brazil and was published in Scientific Reports.

Forty-seven symptomatic patients positive for SARS-CoV-2 infection and admitted at the Emilio Ribas Institute of Infectology in São Paulo, Brazil, between March and June 2020 were included.[2]

The levels of the different IgG subclasses that attach to the receptor-binding domain (RBD) of the SARS-CoV-2 virus were measured and correlated with survival.

Their result showed that those who survived COVID-19 had high IgG1 and IgG3 but had no IgG4 to SARS-CoV-2.

In contrast, patients who died during the second and third weeks had higher anti-RBD (receptor-binding domain) IgG4 levels than the recovered patients.

In our analysis, more than half (of the) serum samples of patients who progressed to death showed positivity to RBD-specific IgG4 antibodies, whereas most patients who recovered from COVID-19 were IgG4 negative to SARS-CoV-2 RBD in the same window of time.[2]

The authors explain that the increase in the IgG4 could be related to the rise in interleukin-10, which is known as an anti-inflammatory cytokine.

The third is a European multinational study published in Rheumatology of Oxford Academic.[3]

The third research is a bit different. This time it looked at the outcomes of COVID-19 in people diagnosed with IgG4-related disease.[3]

The IgG4-related disease is a chronic inflammatory condition where lymphocytes and IgG4-secreting plasma cells infiltrate the organs. The cause is unknown.

A total of 305 patients (87 women) with a median age of 64 (54–74) years were enrolled.

Thirty-two out of 305 patients with IgG4-related disease (10%) had COVID-19 between February and December 2020.

29 out of 32 patients with COVID-19 (91%) were symptomatic. Fever (69%), dry cough (63%), and shortness of breath (51%) were the most common manifestations.

Eleven out of 32 patients (34%) were hospitalized; two (6%) required intensive care unit admission, and four (13%) died.

All deceased patients were men with a history of IgG4-RD for more than three years and had multiple comorbidities.

The 13% mortality indicates that people with IgG4-related disease are at increased risk for poor COVID-19 outcomes.[3]

To sum it up, there are published, peer-reviewed pieces of evidence that show that high IgG4 can lead to poor outcomes. This is especially relevant to the ones who had the Pfizer shots.

In that regard, during this time when many new circulating SARS-CoV-2 variants are resistant to antibodies, thanks to molnupiravir, staying healthy by optimizing the immune system and access to effective antivirals (not Paxlovid) should be available to all.

Truth heals. Lies kill. Don’t Get Sick!

Knowledge about Covid-19 is rapidly evolving. Stay current by subscribing. Feel free to share and like.

Please consider donating to show your support if you find value in this website.

Follow me on Gettr, Truth Social, Gab, Twitter, and Facebook.

Related:

References:

Della-Torre E, Lanzillotta M, Strollo M, Ramirez GA, Dagna L, Tresoldi M; COVID-BioB study group. Serum IgG4 level predicts COVID-19 related mortality. Eur J Intern Med. 2021 Nov;93:107-109. doi: 10.1016/j.ejim.2021.09.012. Epub 2021 Sep 24. PMID: 34598853; PMCID: PMC8461218.
Moura AD et al. Assessment of avidity related to IgG subclasses in SARS-CoV-2 Brazilian infected patients. Sci Rep. 2021 Sep 3;11(1):17642. doi: 10.1038/s41598-021-95045-z. PMID: 34480056; PMCID: PMC8417219.
Ramirez GA et al. Clinical features and outcomes of COVID-19 in patients with IgG4-related disease: a European multi-centre study. Rheumatology (Oxford). 2022 May 5;61(5):e109-e111. doi: 10.1093/rheumatology/keab930. PMID: 34919665; PMCID: PMC9383139.

As an Amazon Associate, I earn from qualifying purchases.