Антител у болевших тяжело было в 2 раза больше, чем у болевших средне, и высокие титры появлялись, в среднем, через 11 дней (у болевших средне- через 22 дня). Ранний и сильный гуморальный ответ коррелировал с тяжестью заболевания.
In this study, we describe IgG antibody responses in 47 patients during and after severe and mild COVID-19. Patients with severe disease seroconverted earlier and had higher maximum concentrations of anti-viral IgG than those with mild disease. Whilst all of the patients with severe symptoms seroconverted, three (9.4%) of the 32 patients with mild disease failed to produce levels of IgG detectable with commercial assays, even more than 90 days PSO. However, NAbs against SARS-CoV-2 were detected in all of these three patients.
Among the 15 patients with severe symptoms, seroconversion was observed after in median 11 (range 7–20) days PSO (Fig 1A). Among the 29/32 patient with mild symptoms that were considered IgG positive, seroconversion was observed after median 22 (range 14–79) days PSO (Fig 1B) Furthermore, we found significantly higher concentrations of IgG antibodies in patients with severe symptoms (mean 107 AU/ml) than in patients with mild symptoms (mean 65 AU/ml) within 35 days PSO (P = 0.004; Fig 1C). Within both groups, antibody concentrations did not change significantly in patients >75 days, hence the differences between the groups remained
Our results confirm previous findings that clinical severity of disease is associated with higher SARS-CoV-2-specific serum-IgG antibodies [18–21]. Studies comparing time to seroconversion between these groups are still lacking and we show that clinical severity is also associated with significantly earlier seroconversion. Due to the long follow-up period of this study, we were also able to observe that all seroconverted patients with both mild and severe symptoms still have detectable IgG levels after more than 75 days. Long et al reported that 97% of 37 patients with mild COVID-19 had decreased levels of IgG 2–3 months PSO , while another study with 34 hospitalized patients with COVID-19 presented increased levels of IgG until 5 weeks PSO, followed by consistent levels up to 7 weeks PSO . Interestingly, our study shows that several patients with both mild and severe symptoms had increased in IgG concentrations over time. Wajnberg et al have shown that S-protein IgG levels could increase up to mean 82 days PSO in patients whose antibody levels were low initially . The discrepancies between the results may at least partly be explained by different target antigens used in antibody detection in the different studies.
In this study, we found that almost 10% of patients with mild COVID-19 did not develop detectable anti-SARS-CoV-2 IgG in serum as evaluated by assays used in clinical practice. Previous studies have similarly failed to detect IgG antibodies in patients with mild disease [24–26], but due to short follow-up (less than 25–50 days) no conclusions regarding the proportion of patients who do not seroconvert have been made in the belief that antibody levels become detectable later in time. We show that despite 90 days or more PSO, not all patients develop detectable levels of IgG in these assays. However, using a virus neutralization assay, considered the golden standard of serology testing, all patients with undetectable IgG using commercial methods had NAbs
interestingly, the patients with detectable IgG also had detectable anti-RBD-IgA >75 days PSO, with no difference in IgA levels between mild and severe cases. Other studies have found serum-IgA after mild COVID-19 to be transient and undetectable after only one month post recovery [18, 28], again highlighting the sensitivity of our in-house RBD-ELISA. It is unsurprising that the validated SARS-CoV-2 antibody assays used in clinical practice miss a proportion of positive samples which other assays may detect.
Еще статья, где обнаружили, что раннее появление IgG к шипику было только у тех, кто госпитализирован (тяжелое течение), но не при ковиде средней и легкой тяжести.
IgM reactive toward S1 and E proteins increased early regardless of disease severity, but IgG increased early only in hospitalized participants with severe COVID-19.
А вот, ситуация слегка отличная, в другом исследовании, опубликованном примерно в то же самое время. При том, что антител все равно больше у тех, кто тяжелее болеет, и кто старее (в 4 раза), зато у тех, кто болел тяжело- выработка антител начиналась позже на неделю, по сравнению с теми, кто болел умеренно:
Here we analyze the laboratoryfind-ings of 1,850 patients to describe the dynamic changes of the total antibody, spike protein(S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M(IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-,RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levelsare 4-fold higher in older patients than in younger patients during hospitalization. In addition,the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgGlevels are associated with a lower lymphocyte percentage, higher neutrophil percentage, anda longer duration of viral shedding. Patients with low antibody levels on discharge mightthereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery
Так же, у тех, у кого было меньше антител, был слабее и клеточный ответ, и зачастую, при том, что они "выздоровели", они продолжали выделять вирус.