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Studies have shown the opposite with CIVD in that normally most viruses cause lymphocytosis. Sometimes one can get neutropenia with or without lymphocytosis or both. COVID causes lymphopenia or at least a reduced number of lymphocytes which is somewhat unique for viral infections. There is a direct correlation between COVID disease severity and CD8 T cell reductions. There is a diagnostic probability scale with regard to the sensitivity of using the lymphocyte count. Using a 2.0 X10^3 and under cutoff count is where 94% of patients with COVID lie. Most (72%) COVID patients will have a less than 1.1 absolute lymphocyte count. The cutoff for lymphopenia proper is less than 1.0. There are reduced counts but more is going on.
The lymphocytes being depleted are the CD8 T cells vs the CD4 T cells of HIV. It's the reverse with a reverse ratio of CD4/CD8. The suppressor cells are the CD8 cells. The helper cells are the CD4 cells. The imbalance causes dysregulation of the immune cellular system which in turn screws up the humoral antibody system also. One ends up with many autoimmune antibodies that are formed with COVID inclusive of anti-interferon antibodies that suppress the innate immune system of which inteferon is an important part of. The more severe the disease is the more screwed up the immune system becomes and so asymptomatic or mild cases might not have that much screwed up. It functioned well enough to give the person a mild case or no symptoms at all.
So without doing a cytokine panel on you and measuring everything then one would be only guessing if immunity was primed or weakened.
The speculatiion right now is that long COVID might entail an activated immune system because of dysregulation resulting in symptoms or can then lead to latent viruses reactivations or might make the person more susceptible to community acquired viruses out there.
We don't know.
Good summary; can't rep you again yet, but let me put it in a more colloquial form for others--
The immune system is like the square dancers on the Grand Ol' Opry--when everything is going right, it's an intricate, well coordinated thing of beauty, but if one dancer has a broken leg and another is on roller skates, things can get ugly fast and you never know what's gunna happen next.
Good summary; can't rep you again yet, but let me put it in a more colloquial form for others--
The immune system is like the square dancers on the Grand Ol' Opry--when everything is going right, it's an intricate, well coordinated thing of beauty, but if one dancer has a broken leg and another is on roller skates, things can get ugly fast and you never know what's gunna happen next.
Most (if not all) of lymphopenia in Sars-Cov-2 patients can be explained with use of glucocorticoids to treat disease severity as glucocorticoids cause lymphopenia and are prescribed to those with moderate/severe courses of the virus.
Most telling is that people with a normal bout of Sars-CoV-2 don't experience any lymphopenia but lymphocytosis as one would expect. The statistically significance of Sars-CoV-2 infection, lymphopenia, and bad outcomes only realizes during patients classified as 'severe' which are precisely the hospitalized patients given high doses of glucocorticoids to tame the immune system from damaging their lungs [thought to be due to MAST cell excitation and over-release of histamine].
Most (if not all) of lymphopenia in Sars-Cov-2 patients can be explained with use of glucocorticoids to treat disease severity as glucocorticoids cause lymphopenia and are prescribed to those with moderate/severe courses of the virus.
Most telling is that people with a normal bout of Sars-CoV-2 don't experience any lymphopenia but lymphocytosis as one would expect. The statistically significance of Sars-CoV-2 infection, lymphopenia, and bad outcomes only realizes during patients classified as 'severe' which are precisely the hospitalized patients given high doses of glucocorticoids to tame the immune system from damaging their lungs [thought to be due to MAST cell excitation and over-release of histamine].
That is true that steroids can induce lymphopenia and they also can induce neutrophilia and some have postulated that a high neutrophil to lymphocyte ratio in COVID patients has poor outcomes.
The study I cited did just that and they found lymphocyte counts below the general population. Not really lymphopenic but just on the borderline. The ones who ended up with more severe COVID had lower lymphocyte counts.
They proposed using the ER lymphocyte count as a predictor of severity.
"Analysis of absolute lymphocyte count in patients with COVID-19
Am J Emerg Med. 2021
Blood samples for laboratory evaluation were collected at the patient's bedside by ED nurses or physicians while in the ED. Only data from the first blood draw that included ALC was included in our analysis. All patients in our study had a CBC with ALC drawn in the ED; thus, no blood samples acquired upon hospitalization were used in our analysis. CBC samples were assessed by the HFWH laboratory on a UniCel DxH 800 Coulter Cellular Analysis System. The white blood cell (WBC) count was derived using the Coulter Principle. The ALC was then derived from the sample's calculated lymphocyte percentage and WBC count and was expressed in microliters (uL).
Availability and turn-around-time for SARS-CoV-2 PCR testing remain the rate-limiting step in diagnosing COVID-19 in many hospitals and health systems. Our study identified ALC cut-off values with corresponding sensitivities that may be used as a surrogate marker to help identify patients who are unlikely to have COVID-19 upon hospital admission and allow for rapid cohorting of patients.
There are a multitude of variables and disease processes that lead to lymphopenia. These include bacterial and fungal sepsis, corticosteroid use, chemotherapy and radiation therapy, and trauma [10]. Patients in our study may have had factors independent of COVID-19 that contributed to a decreased ALC."
I find it hard to believe that all patients were on steroids as outpatients when the recommendations were predominantly only hospitalized patients were put on steroids. It was considered contraindicated to start patients too early on steriods.
"Lymphopenia in patients affected by SARS-CoV-2 infection is caused by margination of lymphocytes in large bowel: an [18F]FDG PET/CT study
Cytokine dysregulation plays a major role in the development and progression of these diseases [1]. An uncontrolled pro-inflammatory cytokine and chemokine release known as “cytokine storm†[2] is responsible for an initial over-activation of T-cells, enhanced vascular permeability, disseminated intravascular coagulation, ARDS, and other systemic effects known as cytokine released syndrome (CRS). T-cell depletion is also a common finding, frequently observed since the initial phase of COVID-19. A possible explanation is that an up-regulation of pro-inflammatory cytokines may be responsible for T-lymphocytes exhaustion and their depletion from plasma and the accumulation of CD8 + cells in the lungs where they exert their cytotoxic action, thus causing immune-mediated tissue injury [3, 4]. Nevertheless, the reasons for lymphopenia remain unclear.
To the best of our knowledge, no one has yet investigated the biodistribution of [18F]FDG in patients with newly diagnosed COVID-19 aiming at better understanding hypermetabolism of different tissues as a marker of inflammation and correlating the inflammatory status with haematological parameters.
Conclusions
These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel."
"What laboratory abnormalities are commonly seen in patients with COVID-19?
Literature review current through: August 2022. | This topic last updated: September 8, 2022.
Common laboratory abnormalities among hospitalized patients with COVID-19 include:
That is true that steroids can induce lymphopenia and they also can induce neutrophilia and some have postulated that a high neutrophil to lymphocyte ratio in COVID patients has poor outcomes.
The study I cited did just that and they found lymphocyte counts below the general population. Not really lymphopenic but just on the borderline. The ones who ended up with more severe COVID had lower lymphocyte counts.
We shouldn't read too much into that study. It's a fairly small retrospective study, it would have been interesting if it was a prospective study and we knew their ALC before Sars-CoV-2 infection.
As of now, we have to contend with possible confounding factors, including that people with lymphopenia are more at risk of severe COVID19 and not that COVID19 causes their lymphopenia.
One patient in their study had to be removed because they had a pre-diagnosis of chronic lymphocytic leukemia. But it's quite possible many of the adults in their study had other chronic diseases putting their ALC levels slightly below 'normal'. ALC falls rapidly with age after you turn 40, and accelerates after you become 80. The normal values given are that for normal healthy adults, not this demographic.
And while they found a signal between those who died and those who didn't, if we do subgroup analysis we get unexpected results, suggesting profound confounding bias.
For 1, you'd expect "intubation without death" to have higher ALC than "intubation with death", afterall, death is a more severe outcome. But exactly the opposite occurred, those who didn't die but were intubated had lower ALC (0.83, SD = 0.5) vs those who died and were intubated (0.96, SD = 0.83).
An interesting category is "dead without intubation" suggesting they died of something else besides respiratory distress (ARDS, respiratory acidosis, etc). Of course, as the authors mentioned, their patients are hospitalized and included in their study if they tested positive for Sars-CoV-2, but some of these patients were being hospitalized for other reasons entirely and for whatever reason the authors didn't attempt to adjust for this and filter these out, instead they just acknowledged this was a limiting factor of their study.
Finally, when broken down by age, we get an unexpected finding that those above 80 had the highest ALC (1.11, on the bottom of the normal range), those <50 were just a hair under (1.08), while the rest (50-79) seemed to have an ALC between 0.89-0.92. I would have liked the authors to explain those findings.
A larger study was done early on in China. Keep in mind again that cytokine storm is treated with steroids and not everybody is treated with steroids early on. IL-6 levels correlate with lymphocyte depletion and migration of lymphocytes from the peripheral circulation into the lungs and other tissues. The use of steroids causes lymphocyte lysis and not migration into target regions. The following is an observational study not a controlled study but it is large.
"Lymphocyte blood levels that remain low can predict the death of patients with COVID-19
The blood counts of patients during their hospitalization were collected at admission, 25%, 50%, 75% and discharge. The results showed that there were differences in leukocytes, neutrophils and lymphocytes at almost every time point in the three groups (Table 3). Compared with the severe cases and critical recovered cases, the leukocytes and neutrophils of dead patients increased gradually, while their lymphocytes remained at a low level (Fig. 3: A–C). Further analysis found that 70.2% of COVID-19 cases displayed low circulating lymphocyte counts, respectively 64.1% of severe cases and 85.0% of critical cases (75.9% recovered cases, 93.5% deaths). The lymphocyte count in dead patients was significantly lower than that of critical recovered cases, at almost every time point in the critical groups (Fig. 3D)."
The mechanism of lymphopenia and distribution of lymphocytes in steriod use is different.
"Lymphopenia occurs in response to endogenous or exogenous glucocorticoids in animals.1,93,235,424,505 This appears to result in part from the sequestration of lymphocytes in lymphoid organs, including bone marrow.54,459 Glucocorticoids also potentiate apoptosis of sensitive lymphocytes.14"
The fingerprint of steroid use can be seen more implicitly in the differential of white blood cells. One doesn't typically see a left shift or toxic changes in the white blood cells.
"This observation is of consequence especially when infection is suspected, particularly in an immunocompromised host. However, a shift to the left in the peripheral white blood cells, i.e., more than 6 percent band forms, and the appearance of toxic granulation may assist in the differential diagnosis between infection, in which the latter are observed, and corticosteroid-induced leukocytosis, in which they are rare."
What one sees in severely ill COVID patients is a left shift with lymphopenia.
"In addition, patients in the ICU setting had significantly higher WBC counts with associated neutrophilia and left-shifted granulopoiesis (WBC, 9.96 vs 6.00 × 109/L, P = .0009; absolute neutrophil count, 8.32 vs 4.21 × 109/L, P = .001; absolute immature granulocyte [IG] count 2.46 vs 0.64 × 109/L, P = .0212). Importantly, patients in the ICU were more likely to have lymphopenia (ALC, 0.75 vs 1.24 × 109/L, P = .0124) and increased nucleated RBCs (0.24 vs 0.03, × 109/L P = .0462), while there was no statistical difference in monocyte count (AMoC, 0.47 vs 0.40 x 109/L, P = .5820)."
All very interesting minutia-- but is it actionable?... ie- are you going to withhold steroids because a pt presenting in acute distress has a lymphocyte count above some arbitrary level?
Cataloguing these aberrancies is academically important because the history of cellular/molecular biology is full of instances where finding abnormalities led to figuring out normal function. Pure vs applied science. I'm not so sure this stuff is ready for Prime Time yet.
All very interesting minutia-- but is it actionable?... ie- are you going to withhold steroids because a pt presenting in acute distress has a lymphocyte count above some arbitrary level?
Cataloguing these aberrancies is academically important because the history of cellular/molecular biology is full of instances where finding abnormalities led to figuring out normal function. Pure vs applied science. I'm not so sure this stuff is ready for Prime Time yet.
Hospitals were scared because of the number of patients being seen and the limited number of beds available early on in the pandemic. They were looking at ways to predict and triage patients based on severity and the potential of getting worse (predictive value).
They were also suggesting the use of the lymphocyte count as a means of determining who is likely to have COVID (diagnostic value) when PCR testing was taking days or weeks early on or they were getting false negatives with PCR.
The research was problem-based and not solely academic. Now there are a ton of tests to determine disease severity based on the science but early on we had the CBC and everybody was capable of doing CBCs which had a quick turnaround.
I don't think the TLC was ever proposed to selectively screen for candidates of steroid intervention (treatment value).
I had COVID in June and got over it in short order. Last week I got some sort of cold -- sore throat and coughing up phlegm. But, it was such a very mild cold that this had me wondering if fighting off a DIFFERENT virus (COVID) primes your immune system to fight off OTHER viruses (the common cold).
It's possible that you had COVID again. COVID is making it's way through my house right now, and our symptoms are very mild and exactly what you described. My daughter was only sick for maybe 2 days, and then she was fine. Same with me. My husband just started showing symptoms yesterday. All three of us got very clear positive test results. I think one of the strains going around now is pretty mild.
We're all fully vaccinated, and husband also had omicron back in January. I do think the vaccines help reduce severity of infections. Previous infections may as well.
A larger study was done early on in China. Keep in mind again that cytokine storm is treated with steroids and not everybody is treated with steroids early on.
Ok so 2 points.
Many people who are at severe risk of COVID19 outcomes have comorbidities that would be treated with low to even high dose steroids.
For example, one study I saw showed that over 50% of patients who died from COVID19 had either one, two or three APLAbs. And in advanced stages of APLS, patients are treated with high doses of prednisone.
So, I guess what I want to see is a prospective rather than retrospective studies, so we don't confuse cause/effect or chicken/egg.
The Chinese study you linked to is interesting because while it's retrospective, they do take multiple measurements throughout the patient's course of the disease. So that can give us some clue.
An imbalance of Neutrophils to Lymphocytes is measure of body stress, known as NLR. And for whatever reason, some people with chronic conditions have this ratio high to begin with. Chronic kidney or cardiovascular or respiratory (COPD) all result in a high NLR, and some of these people will be at most risk from COVID. Of course COVID will exasperate it, especially due to decreased Oxygen saturation of the blood and activating HIF-1a.
But going back to the Chinese study, they have 5 blood draws (admission, and then in 4 steps to discharge or death). Death from admission usually takes 1-3 weeks. You'd expect to see this NLR to increase in a concomitant way for a worsening condition. Instead looking at their results it was relatively stable, unless they recovered, and last 2 readings showed modest improvement.
So I think we're confusing a lot of chicken and the egg here, we don't have their readings when they're healthy to compare, and while the results of severe patients are high for NLR, they could have been elevated when they were not infected due to perhaps some chronic conditions.
Last edited by AfricanSunset; 09-28-2022 at 04:33 PM..
For me I have had the flu shot for years with no problem,now this year i have from my booster moderna shot have had my femoral artery nerve damaged and with severe aching in lower right leg,my next trip is to a neuroligist.
I went to my vascular surgeon and he checked blood flow and blood pressure and said both legs were ok and said a nerve doctor.neuroligist is next.
Been suffering since Dec.2021
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