Predictors of Nonseroconversion 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.