Dataset Information

Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes.

ABSTRACT:

Background

Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, losing sight of the temporal pattern of these changes.

Methods

We conducted a longitudinal analysis on a prospective cohort of COVID-19 patients followed up for >6 months. Neutralizing activity was evaluated using HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. IgG antibody titer was evaluated by ELISA against the S2 subunit, the receptor binding domain (RBD), and the nucleoprotein (NP). Statistical analyses were carried out using mixed-effects models.

Findings

We found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity, which persisted 6 months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a 2-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at 6 months remained higher among hospitalized individuals compared to mild symptomatic. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of anti-RBD, S2, or NP antibody titers, all of them showing a constant decline over the follow-up period.

Conclusions

Our results reinforce the hypothesis that the quality of the neutralizing immune response against SARS-CoV-2 evolves over the post-convalescent stage.

SUBMITTER: Pradenas E

PROVIDER: S-EPMC7847406 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes.

Pradenas Edwards E Trinité Benjamin B Urrea Víctor V Marfil Silvia S Ávila-Nieto Carlos C Rodríguez de la Concepción María Luisa ML Tarrés-Freixas Ferran F Pérez-Yanes Silvia S Rovirosa Carla C Ainsua-Enrich Erola E Rodon Jordi J Vergara-Alert Júlia J Segalés Joaquim J Guallar Victor V Valencia Alfonso A Izquierdo-Useros Nuria N Paredes Roger R Mateu Lourdes L Chamorro Anna A Massanella Marta M Carrillo Jorge J Clotet Bonaventura B Blanco Julià J

Med (New York, N.Y.) 20210131 3

<h4>Background</h4>Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, losing sight of the temporal pattern of these changes.<h4>Methods</h4>We conducted a longitudinal analysis on a prospective cohort of COVID-19 patients followed up for >6 months. Neutralizing activity was evaluated using HIV reporter pseudoviruses expressing SARS-CoV-2 ...[more]

PMID: 33554155

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Project description:BackgroundCalprotectin is an inflammatory marker mainly released by activated neutrophils that is increased in acute severe COVID-19. After initial recovery, some patients have persistent respiratory impairment with reduced diffusion capacity of the lungs for carbon monoxide (DLCO) months after infection. Underlying causes of this persistent impairment are unclear. We aimed to investigate the correlation between circulating calprotectin, persistent lung functional impairment and intensive care unit (ICU) stay after COVID-19 in two university hospital centres in Switzerland.MethodsCalprotectin levels were measured in serum from 124 patients (50% male) from the Bern cohort (post-ICU and non-ICU patients) and 68 (76% male) from the Lausanne cohort (only post-ICU patients) four months after COVID-19. Calprotectin was correlated with clinical parameters. Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models.ResultsOverall, we found that post-ICU patients, compared to non-ICU, were significantly older (age 59.4 ± 13.6 (Bern), 60.5 ± 12.0 (Lausanne) vs. 48.8 ± 13.4 years) and more obese (BMI 28.6 ± 4.5 and 29.1 ± 5.3 vs. 25.2 ± 6.0 kg/m2, respectively). 48% of patients from Lausanne and 44% of the post-ICU Bern cohort had arterial hypertension as a pre-existing comorbidity vs. only 10% in non-ICU patients. Four months after COVID-19 infection, DLCO was lower in post-ICU patients (75.96 ± 19.05% predicted Bern, 71.11 ± 18.50% Lausanne) compared to non-ICU (97.79 ± 21.70% predicted, p < 0.01). The post-ICU cohort in Lausanne had similar calprotectin levels when compared to the cohort in Bern (Bern 2.74 ± 1.15 µg/ml, Lausanne 2.49 ± 1.13 µg/ml vs. non-ICU 1.86 ± 1.02 µg/ml; p-value < 0.01). Calprotectin correlated negatively with DLCO (r= -0.290, p < 0.001) and the forced vital capacity (FVC) (r= -0.311, p < 0.001).ConclusionsSerum calprotectin is elevated in post-ICU patients in two independent cohorts and higher compared to non-ICU patients four months after COVID-19. In addition, there is a negative correlation between calprotectin levels and DLCO or FVC. The relationship between inflammation and lung functional impairment needs further investigations.Trial registrationNCT04581135.

Project description:ImportanceThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The association between clinical characteristics of the virus and neutralizing antibodies (NAbs) against this virus have not been well studied.ObjectiveTo examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19.Design, setting, and participantsIn this cohort study, a total of 175 patients with mild symptoms of COVID-19 who were hospitalized from January 24 to February 26, 2020, were followed up until March 16, 2020, at Shanghai Public Health Clinical Center, Shanghai, China.ExposuresSARS-CoV-2 infections were diagnosed and confirmed by reverse transcriptase-polymerase chain reaction testing of nasopharyngeal samples.Main outcomes and measuresThe primary outcome was SARS-CoV-2-specific NAb titers. Secondary outcomes included spike-binding antibodies, cross-reactivity against SARS-associated CoV, kinetics of NAb development, and clinical information, including age, sex, disease duration, length of stay, lymphocyte counts, and blood C-reactive protein level.ResultsOf the 175 patients with COVID-19, 93 were female (53%); the median age was 50 (interquartile range [IQR], 37-63) years. The median length of hospital stay was 16 (IQR, 13-21) days, and the median disease duration was 22 (IQR, 18-26) days. Variable levels of SARS-CoV-2-specific NAbs were observed at the time of discharge (50% inhibitory dose [ID50], 1076 [IQR, 448-2048]). There were 10 patients whose NAb titers were less than the detectable level of the assay (ID50, <40), and 2 patients who showed very high titers of NAbs, with ID50 levels of 15 989 and 21 567. NAbs were detected in patients from day 4 to 6 and reached peak levels from day 10 to 15 after disease onset. NAbs were unable to cross-react with SARS-associated CoV and NAb titers correlated with the spike-binding antibodies targeting S1 (r = 0.451; 95% CI, 0.320-0.564; P < .001), receptor binding domain (r = 0.484; 95% CI, 0.358-0.592; P < .001), and S2 regions (r = 0.346; 95% CI, 0.204-0.473; P < .001). NAb titers at the time of discharge were significantly higher in the 82 men (1417 [IQR, 541-2253]) than those in the 93 women (905 [IQR, 371-1687]) (median difference, 512; 95% CI, 82-688; P = .01) and at the time of follow-up in 56 male patients (1049 [IQR, 552-2454]) vs 61 female patients (751 [IQR, 216-1301]) (median difference, 298; 95% CI, 86-732; P = .009). Plasma NAb titers were significantly higher in 56 older (1537 [IQR, 877-2427) and 63 middle-aged (1291 [IQR, 504-2126]) patients than in 56 younger patients (459 [IQR, 225-998]) (older vs younger: median difference, 1078; 95% CI, 548-1287; P < .001; middle-aged vs younger: median difference, 832; 95% CI, 284-1013; P < .001). The NAb titers were correlated with plasma C-reactive protein levels (r = 0.508; 95% CI, 0.386-0.614; P < .001) and negatively correlated with lymphocyte counts (r = -0.427; 95% CI, -0.544 to -0.293; P < .001) at the time of admission.Conclusions and relevanceIn this cohort study, among 175 patients who recovered from mild COVID-19 in Shanghai, China, NAb titers to SARS-CoV-2 appeared to vary substantially. Further research is needed to understand the clinical implications of differing NAb titers for protection against future infection.

Dataset Information

Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes.

Background

Methods

Findings

Conclusions

Publications

Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes.

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