Persistent Attenuation of Lymphocyte Subsets After Mass SARS-CoV-2 Infection, 2025, Jiang et al

[Yann04]

Persistent Attenuation of Lymphocyte Subsets After Mass SARS-CoV-2 Infection

Spoiler: Authors

Jiang, Zhengqi; Shan, Tichao; Li, Yucan; Han, Fengjiao; Feng, Baobao; Zhen, Xiaohui; Ni, Heyu; Peng, Jun; Xu, Miao

Abstract
Objectives
Growing evidence suggests that lymphocyte subsets are declined in COVID-19 patients, but it is unclear if these alterations persist after widespread exposure to SARS-CoV-2 or how long they last.
Methods
We analyzed lymphocyte subset data from 40,537 patients across three phases: pre-COVID, mass infection, and post-COVID. The counts of lymphocyte subsets and CD4+/CD8+ ratios were compared using Mann-Whitney U test or Kruskal-Wallis H test. Monthly post-exposure data were compared with pre-exposure data to assess the persistence of impact on lymphocyte subsets by SARS-CoV-2, and subgroup analyses were performed in patients with cardiovascular disease.
Results
During mass infection, T cells, CD4+T cells, CD8+T cells, NK cells, and B cells dropped significantly. Even 20 months post-infection, CD8+ T cells remained 9.9% below baseline. Baseline lymphocyte subsets differed significantly by sex and age. Immune recovery varied by age and sex, with older adults and males showing prolonged lymphopenia. In cardiovascular disease patients, T lymphocytes remained 72.9% below baseline for 20 months post-infection.
Conclusions
Our findings redefine SARS-CoV-2 infection as a condition of long-lasting immune compromise. The sustained subnormal lymphocytes—particularly in cardiovascular disease cohorts—highlight a key immunologic feature of long COVID and underscore the need for personalized care.

Highlights
SARS-CoV-2 causes lasting immune dysregulation for over 20 months.

The impact of SARS-CoV-2 on lymphocytes was especially severe in patients with CVD.

Lymphocyte deficiency is related to long COVID pathogenesis.

Long-term immune dysregulation of long COVID demands tailored treatment.

Graphical Abstract

Web | DOI | International Journal of Infectious Diseases

 

[Utsikt]

Is this clearcut evidence that the immune system doesn’t get stronger from getting infected with covid, it gets weaker instead?

 

[V.R.T.]

The idiocy and cynicism of the corporation/government driven movement to gaslight the public into thinking 'covid is like totally fine now what are you even worried about' never ceases to disgust me.

None of my non ME/LC friends take any precautions anymore. I worry about them - they have been lied to that it is safe. I am cautious by nature but probably would have crumbled under the insane social pressure to pretend it's fine by now if I was well. That or be living in a hut in the woods!

It really goes to show how easily led people are, and how the world is run not based on what is sensible or safe but on what is profitable. Proper covid precautions like air filtration systems in schools hospitals etc would cost a bomb, so its let it rip and false dichotomies about permalockdown vs freedom.

I hope people will see this and wake up, but I think at this point the lie has gotten too big.

 

[Mij]

What 'tailored treatment' are they referring to I wonder. I had mine tested 8 years after post-infectious onset M.E (all way below ref range except NK cells which were normal range) and the virologist rx'd me an immune modulator that caused a relapse and lowered my baseline.

 

[BrightCandle]

What 'tailored treatment' are they referring to I wonder. I had mine tested 8 years after post-infectious onset M.E (all way below ref range except NK cells which were normal range) and the virologist rx'd me an immune modulator that caused a relapse and lowered my baseline.

Whenever they say tailored treatment I just replace it in my head with rehab/exercise and CBT. Its their euphemism for doing the default thing when they have no real treatments but can still get paid for doing something. I might be wrong they might have a real protocol in mind but this is how its usually used in the same way that a multidisciplinary team is a psychologist leading some physiotherapists to do CBT/GET now renamed to whatever gets around the latest guidance. Its not actually what they should be but its what they actually are.

 

[rvallee]

I find the John Snow Project to be generally good so sharing this, although I can't have much opinion on whether it's solid because unlike the biopsychosocial stuff where high school science is more than enough, this stuff is over my head.


SARS-CoV-2 Leaves a Lasting Mark on the Immune System

SARS-CoV-2 Leaves a Lasting Mark on the Immune System

A landmark new study shows COVID-19 isn’t ‘just a cold’: One infection left people with long-lasting immune damage, and those with heart disease lost up to 70% of key immune cells. Reinfections may worsen this. The message is clear: protecting ourselves still matters.

johnsnowproject.org

A landmark new study shows COVID-19 isn’t ‘just a cold’: One infection left people with long-lasting immune damage, and those with heart disease lost up to 70% of key immune cells. Reinfections may worsen this. The message is clear: protecting ourselves still matters.

 

[LPT]

I noticed that the authors didn't adjust average numbers for total cohorts by age, although they provided separate averages for different age groups. Interestingly, they found no difference for the 18-40 cohort. The second thing I noticed is a huge difference in the cardiovascular patient subgroup, but before covid wave, only above 1% of the whole cohort had cardiovascular conditions, while after covid, almost 10% had them. So, it must be some kind of unhealthy selection bias going on there. I suspect that covid infections aggravated chronic cardiovascular conditions in a lot of patients, but it also means that you can't really compare two groups, cause there were very likely different even pre-covid.

Now, the 18-40 groups likely have very few people with cardiovascular conditions. So, I decided to check if there is any difference if I adjust the average numbers by age and then compare the averages only for people without cardiovascular conditions. And as for the 18-40 group, there is pretty much no difference. Basically, while there was a lymphocyte reduction during the wave, it's not possible to conclude that there is a chronic ongoing reduction.

 

[SNT Gatchaman]

Marc Veldhoen wrote a Substack article on this paper. Concluding —

In short, there is no evidence of “a lasting impact on lymphocyte subsets.“ There are suggestions that the pre- and post-Covid cohorts are not similar and the latter is likely undergoing multiple infections compared with the former.

References to T cell “exhaustion” are not relevant or correct, as pointed out above.

Mentioning of “prolonged lymphocyte dysregulation“ also do not hold. Both “exhaustion” and “dysfunction” are not shown.

What the authors do show is the reduction of all lymphocyte subsets assessed in the blood only, they bounce back afterwards. In all three cohorts, the number of lymphocytes remained within physiological levels.

This is in agreement of a lot of studies showing good immunity and immune responses after SARS-CoV-2 infection. There is no “damage”, “dysfuncion” “exhaustion” or “depletion/death/lymphopenia”, SARS-CoV-2 initiates a physiological immune response followed by return to homeostasis.

Persistent Attenuation of Lymphocyte Subsets After Mass SARS-CoV-2 Infection

A paper review

marcveldhoen.substack.com

 

[ME/CFS Science Blog]

Marc Veldhoen wrote a Substack article on this paper.

Seems like a useful commentary. If I understand correctly:

- The groups are independent; this wasn't a longitudinal study following the same people over time
- Although there were differences between groups, they were relatively modest and still within normal limits
- The difference might be explained by the stringent isolation measures in China. Before those measures, people had much fewer infections, and afterwards, a surge of infections (not just COVID-19). That would result in more immune cells moving into the tissue and there being fewer in the blood.