Background: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11À13 of 283 days (95% CI 231À349) for anti-N and 725 days (95% CI 623À921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42À1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants.

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Assessment of the kinetics of SARS-CoV-2 antibodies is essential to predict protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCW) including 393 convalescent COVID-19 and 916 COVID-19 negative HCW up to 405 days. From M1 to M7-9 after infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCW in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N antibodies dramatically decreased (half-life: 210 days) while anti-S stabilized (half-life: 630 days) at a median of 2.41 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.11 -2.75). One case of reinfection was recorded in convalescent HCW (0.47 per 100 person-years) versus 50 in COVID-19 negative HCW (10.11 per 100 person-years). Correlation with live-virus neutralization assay revealed that variants D614G and B.1.1.7, but not B.1.351, were sensitive to anti-S antibodies at 2.3 log AU/mL, while IgG ≥ 3 log AU/mL neutralized all three variants. After SARS-CoV-2 vaccination, anti-S levels reached 4 logs regardless of pre-vaccination IgG levels, type of vaccine, and number of doses. Our study demonstrates a long-term persistence of anti-S IgG antibodies that may protect against reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against escape mutants.

Objective Understanding mild to moderate symptoms of coronavirus disease 2019 (Covid-19) is important in order to identify active cases early and thus counteract transmission. Methods In March 2020, Leipzig University Hospital established an outpatient clinic for patients potentially infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Confirmed cases with mild to moderate symptoms self-isolated at home and were followed-up by daily telephone calls for at least 14 days. Symptoms and course of illness of these patients are reported here. Results From March 20 to April 17, 2020, 1460 individuals were tested for SARS-CoV-2 by naso- or oropharyngeal swab for real-time polymerase chain reaction (RT-PCR). Covid-19 was confirmed in 91 (6.2%) patients, of which 87 were included in the final analysis. Patients presented for testing after a mean of 5.9 days (IQR = 2.0–8.5). The median age was 37.0 years (IQR = 28.5–53), and 48 (55.2%) were female. Five (5.7%) patients required hospital admission during the course of illness. Most frequently reported symptoms were fatigue (n = 64, 74%), cough (n = 58, 67%), and hyposmia/hypogeusia (n = 44, 51%). In contrast to previous reports, fever occurred in less than a third of patients (n = 25, 29%). By day 14, more than half of the patients had recovered completely (n = 37/70, 52.9%). Conclusions Fever seems to be less common in patients of relatively young age diagnosed with mild to moderate Covid-19. This suggests that body temperature alone may be an insufficient indicator of SARS-CoV-2 infection.

The breathing patterns of normal subjects monitored with respiratory inductive plethysmography were investigated after mild increases in respiratory resistance provoked by aerosolized methacholine during natural breathing and while breathing on a mouthpiece to a pneumotachograph. First, during natural breathing, comparisons of inspiratory ventilation (VI), tidal volume (VT), frequency (f), inspiratory time (TI), fractional inspiratory time (TI/TT), and mean inspiratory flow (VT/TI) were made before and after aerosolized buffered saline and methacholine in a dose that reduced specific airway conductance (sGaw) by 35% (PD35). There was a significant increase in VT/TI and VI after methacholine, whereas VT, f, TI, and TI/TT were not consistently modified by saline or methacholine. Pretreatment with bronchodilators prevented changes in respiratory resistance (Rrs) as well as in breathing pattern after PD35 methacholine. On another day, Rrs, end-expiratory lung volume level, and breathing pattern during natural breathing were monitored after administration of predetermined doses of methacholine that reduced sGaw by 25% (PD25), PD35, and 55% (PD55). Increases in VT/TI and end-expiratory lung volume level paralleled the increases in Rrs after each dose of methacholine but not with saline control. VI increased along with Rrs at the PD25 and PD35 doses but plateaued at the PD55 dose while Rrs continued to rise. There were no changes in breathing pattern in subjects who breathed on a mouthpiece to a pneumotachograph after PD55 methacholine. Thus alterations of the breathing pattern due to mild-to-moderate degrees of bronchoconstriction are characterized by progressive rises of mean inspiratory flow (an index of respiratory center drive) and end-expiratory lung volume level (a measure of pulmonary hyperinflation), but VI plateaus at the more severe degree of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

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The respiratory inductive plethysmograph is a noninvasive device that has been used to measure tidal volume (VT) in humans from changes in self-inductance of wire coils excited by an oscillator circuit placed about the rib cage and abdomen. We investigated its accuracy in conscious sheep utilizing a new calibration procedure during quiet breathing and breathing associated with bronchospasm provoked by aerosolized carbachol. Seven sheep were intubated with a nasotracheal tube and an esophageal balloon placed for determination of transpulmonary pressure. Base-line mean pulmonary flow resistance (RL) in the sheep was 1.5 +/- 0.7 (SD) cmH2O X l-1 X s. After carbachol inhalation, mean RL increased to a maximum of 8.8 +/- 2.8 cmH2O X l-1 X s (P less than 0.002). AT base line, mean VT estimated by respiratory inductive plethysmography over a 20-s period fell within +/- 6% of spirometry. After carbachol VT in five of the sheep remained close to the initial validation, but in two, it deviated +/- 11% from spirometry. Analysis of the continuous recording of timing and volume components of the breaths revealed that bronchoprovocation did not significantly alter mean VT or frequency. However, there was a slight increase in both parameters resulting in an increase in minute ventilation from 7.6 +/- 2.4 to 9.6 +/- 2.8 l/min (P less than 0.02). Similarly, a slight decline in inspiratory time coupled with the slight rise in VT produced an increase in mean respiratory flow from a base-line value of 0.35 +/- 0.12 to 0.44 +/- 0.17 l/s (P less than 0.05). These results indicate that the respiratory inductive plethysmography accurately monitors breathing pattern in conscious sheep even during severe bronchospasm.

after smoking. Moderate inhalers showed a Key words: breathing pattern, respiratory centre, respiratory inductive plethysmography, cigarette smoking. smoking in six of the subjects. increased mean (~s D ) baseline VT/TI (390 f 39 ml/s) comDared with normal non-smokers and 3* One group Of smokers (n = 4, had a . I another gioup (n = 6) a near normal VT/TI (246 f 36 mlls). The first group (' deep inhalers') LTC cigarettes Vmln (I/min) Deep V , (ml) Deep J, (breathshin) Deep T, (9 Deep TrIT,,,, Deep V,IT, (ml/s) Deep Moderate Moderate Moderate Moderate Moderate Moderate