Reasons for no antibodies after SARS-CoV-2 Infection (Liu et al., Sept. 2021)

Pyrrhus

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Interestingly, many patients with Long Covid report that they never tested positive on any antibody tests.

The following CDC study tried to determine why some people don't seem to develop antibodies after a SARS-CoV-2 infection, even though they tested positive on a PCR test. (a phenomenon called non-seroconversion) Apparently, this phenomenon might be much more prevalent than imagined, calling into question some key assumptions of some key studies...


Predictors of Nonseroconversion after SARS-CoV-2 Infection (Liu et al., Sept. 2021)
https://wwwnc.cdc.gov/eid/article/27/9/21-1042_article
Excerpt:
Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2–specific antibodies. [...] Initial serosurveys identified antibodies in nearly 100% of persons with [PCR]–confirmed SARS-CoV-2 infection (5). However, more recent studies have shown that seroconversion rates are surprisingly variable (610). For example, a multicenter study from Israel reported that 5% of participants remained seronegative despite a positive [PCR] test result on a nasal swab specimen (6). In contrast, a seroprevalence study from New York found that 20% of persons with a positive [PCR] test result did not seroconvert (8). Another study from Germany reported that 85% of confirmed infected COVID-19 contacts failed to develop antibodies (9).
:monocle:?
 

Pyrrhus

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A new paper that emphasizes that people with mild coronavirus infections are much less likely to develop antibodies than those with severe infections:

Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection (Van Elslande et al., 2021)
https://doi.org/10.1016/j.jcv.2021.104765
Excerpt:
A retrospective multi-center study was performed using 652 samples of 236 PCR-confirmed SARS-CoV-2 infected patients from 2 Belgian University hospitals. Patients were included if at least two samples were available (range 2–7 samples); including at least one sample collected 30 days or later after first positive PCR (range 0–240 days). Of those 236 patients, 19.1 % were classified as mild/asymptomatic (mild) and 80.9 % as moderate to critical (severe).
[...]
22.2 % of mild and 2.6 % of severe COVID-19 cases never seroconverted (p < 0.001).
 

Learner1

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Very interesting @Pyrrhus

I had almost all negative antibodies for Epstein Barr but a positive PCR, almost 40 years after having mono. Several doctors missed it because they were looking for antibodies. My specialist said "I've never seen anyone with this combination of labs, but you definitely have EBV." Testing it helped a lot.

Thank you for pointing this out.
 

Pyrrhus

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I had almost all negative antibodies for Epstein Barr but a positive PCR, almost 40 years after having mono.
When I was a child, I used to have cold sores all the time, which are caused by Herpes Simplex Virus 1 (HSV1). It is generally thought that once you get infected with HSV1, you are infected for life.

So I was somewhat surprised last year when I learned that I have no antibodies to HSV1.

Maybe I don't have antibodies because I was infected before 6 months of age, before the immune system has developed enough to be able to distinguish between "self" and "foreign" molecules. My mother apparently had a bad attack of cold sores while she was pregnant with me, so I might have been infected in utero.

Or there could be another perfectly good explanation...
 

Pyrrhus

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Are people with Long Covid more or less likely to have generated antibodies from a coronavirus infection?


Here is a small study that failed to find a significant correlation:

The Association Between Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Post–COVID-19 Syndrome in Healthcare Workers (Pereira et al., 2021)
https://doi.org/10.1093/infdis/jiab120
This longitudinal study includes healthcare staff who tested positive for SARS-CoV-2 between March and April 2020, with follow-up of their antibody titers and symptoms. More than half (21 of 38) had PCS after 7–8 months. There was no statistically significant difference between initial reverse-transcription polymerase chain reaction titers or serial antibody levels between those who did and those who did not develop PCS.

Here is a larger study that found that people with lower antibody levels might be slightly more likely to develop Long Covid:

Antibody Response to SARS-CoV-2 is Associated with Long-term Clinical Outcome in Patients with COVID-19: a Longitudinal Study (Garcia-Abellan et al., 2021)
https://link.springer.com/article/10.1007/s10875-021-01083-7
We aimed to characterize the medium and long-term clinical, virological, and serological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID. [...] Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2, and 6 months post-discharge. [...] Patients filled out a COVID-19 symptom questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized.
[...]
Of 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2 months and 6 months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. [...] Adjusted 2-month predictors of the highest CSQ scores were lower peak [antibodies] (0.80 [0.66–0.94]) and higher WHO severity score; 6-month predictors were lower peak [antibodies] (0.89 [0.79–0.99]) and female sex.

EDIT: Here is a study that found that low levels of anti-coronavirus antibodies might predispose someone to developing Long Covid, and that one explanation is because the low levels of antibodies allows the coronavirus to persist longer:

Serum Level of Anti-Nucleocapsid, but Not Anti-Spike Antibody, Is Associated with Improvement of Long COVID Symptoms (Varnai et al, 2022)
https://forums.phoenixrising.me/thr...-long-covid-symptoms-varnai-et-al-2022.86920/
[Nucleocapid antibody (NC-Ig)] level above median was as an independent predictor for complete remission at follow-up. The difference in NC-Ig levels in subgroup analyses (severe fatigue vs. non-severe fatigue; complete remission vs. incomplete remission or progression) was found to be significant only in patients who received vaccination.
[...]
The patients who have low levels of antibodies at the time of hospital discharge may have a high risk of developing redetectable SARS-CoV-2 RNA on RT-PCR testing after recovery. These findings indicate the important role of these antibodies in viral clearance.
[...]
An inadequate humoral immune response (against nucleocapsid antigen) may indirectly promote further viral replication and lead to further partial persistence of symptoms.
 
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Pyrrhus

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What if someone had a coronavirus infection, without generating antibodies, and then got a vaccination?

If someone happens to have a "silent" coronavirus infection, without antibodies, is it possible for them to develop COVID-like symptoms when they simultaneously receive a coronavirus vaccination? In this case, the vaccination might spur their immune system into action, finally attacking the silent coronavirus infection and producing COVID-like symptoms. Understandably, the person might then blame the vaccine for the COVID-like symptoms.

And what about Long Covid? If someone has a "silent" coronavirus infection, without antibodies, is it possible for them to develop Long Covid symptoms when they simultaneously receive a coronavirus vaccination? The journal Science just published the following article:

In rare cases, coronavirus vaccines may cause Long Covid–like symptoms
https://www.science.org/content/art...avirus-vaccines-may-cause-long-covid-symptoms
In late 2020, Brianne Dressen began to spend hours in online communities for people with Long Covid, a chronic, disabling syndrome that can follow a bout with the virus. “For months, I just lurked there,” says Dressen, a former preschool teacher in Saratoga Springs, Utah, “reviewing post after post of symptoms that were just like my own.”

Dressen had never had COVID-19. But that November, she’d received a dose of AstraZeneca’s vaccine as a volunteer in a clinical trial. By that evening, her vision blurred and sound became distorted—“I felt like I had two seashells on my ears,” she says. Her symptoms rapidly worsened and multiplied, ultimately including heart rate fluctuations, severe muscle weakness, and what she describes as debilitating internal electric shocks.
[...]
By January 2021, researchers at the National Institutes of Health (NIH) began to hear about such reports and sought to learn more, bringing Brianne Dressen and other affected people to the agency’s headquarters for testing and sometimes treatment.

The research was small in scale and drew no conclusions about whether or how vaccines may have caused rare, lasting health problems. The patients had “temporal associations” between vaccination and their faltering health, says Avindra Nath, clinical director at the National Institute of Neurological Disorders and Stroke (NINDS), who has been leading the NIH efforts. But “an etiological association? I don’t know.” In other words, he does not know whether vaccination directly caused the subsequent health problems.
 

SWAlexander

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If someone happens to have a "silent" coronavirus infection, without antibodies, is it possible for them to develop COVID-like symptoms when they simultaneously receive a coronavirus vaccination? In this case, the vaccination might spur their immune system into action, finally attacking the silent coronavirus infection and producing COVID-like symptoms.
Suspecting this was my case.
 
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So quick question then in light of this and indeed other developments occurring in this area, had a debate with Joshua Leisk around covid testing - still don't really understand it all.

My question is, even if you had a negative test from IMD labs for say an entereoviral infection like coxsackie b4 or quite frankly any of the main suspects, cmv, hhv6, ebv antibodies. That wouldn't necessarily mean you didn't have those things and that they didn't need to be treated? I might be reading too much into it to be honest, would welcome thoughts.
 
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Also wonder whether ME patients with little to no immune response to anything, which seems semi common in more severe patients, could they end up with covid being silently active as you say @Pyrrhus ? Again probably not but thought I'd ask.
 

BrightCandle

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Its certainly possible since by and large the way we find infections in the body is by looking at the immune response and not the actual virus material. If we aren't producing the right defense against a virus we have, maybe due to something that or another virus has done to coopt our immune system that would certainly explain the ill feeling all the time. They keep finding virus RNA in the bodies of dead ME and long haulers so its pretty likely there is still active virus roaming around and its not being beaten to nothing like it ought to.