The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein and the N-protein, as well as the neutralizing activity (NAbs) against SARS-CoV-2 in the blood of moderately afflicted COVID-19 patients, needs further longitudinal investigation. Several new serological methods to examine these parameters were developed, validated and applied in three patients of a family which underwent an ambulatory course of COVID-19 for six months. The virus load had almost completely disappeared after about four weeks. Serum IgA levels to the S1-RBD-protein and, to a lesser extent, to the N-protein, peaked about three weeks after clinical disease onset but declined soon thereafter. IgG levels rose continuously, reaching a plateau at approximately six weeks, and stayed elevated over the observation period. Virus-neutralizing activity reached a peak about 4 weeks after disease onset but dropped slowly. The longitudinal associations of virus neutralization and the serological immune response suggest immunity in patients even after a mild clinical course of COVID-19.

The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination.

Background/Objectives: Early prognostication in critically ill patients with low burden of organ dysfunction (BOD) remains challenging. Progranulin (PGRN), a hypoxia inducible and anti-inflammatory protein, may offer prognostic value. We investigated whether PGRN levels predict mortality in ICU patients stratified by their BOD. Methods: In this secondary analysis of a prospectively recruited ICU cohort (n = 99), patients were categorized into low (Sequential Organ Failure Assessment Score (SOFA) ≤ 8) and high (SOFA > 8) BOD groups. Plasma PGRN concentrations were measured every 8 h for up to 5 days. Initial values and kinetic parameters (maximum, mean, and normalized area score (NAS)) were evaluated. Associations with in-hospital mortality were analyzed by univariate logistic regression and area under the receiver operating characteristic curve (AUROC) comparisons. Results: In patients with low BOD (n = 53), the PGRN kinetics were significantly associated with in-hospital mortality, with odds ratios of 1.086 (95% CI 1.027–1.148), 1.102 (95% CI 1.025–1.184), and 1.093 (95% CI 1.021–1.170) for maximum, mean, and NAS values, respectively. The respective AUROC values were 0.815 (p = 0.001), 0.753 (p = 0.010), and 0.738 (p = 0.016). By contrast, none of the PGRN metrics predicted mortality in patients with high BOD (n = 46; all AUROC values < 0.61, p > 0.25). The respective SOFA and CRP metrics were not predictive in low BOD patients. Maximum PGRN levels predicted death at least 32 h in advance. Conclusions: Serial PGRN measurements offer prognostic information, particularly in ICU patients with low BOD, a group whose deterioration is often difficult to anticipate and may be underestimated by conventional scoring systems such as SOFA. These findings support further investigation of PGRN as a tool for early risk stratification in critical illness.

Summary: Background: Patients infected with SARS-CoV-2 exhibit a highly variable clinical course, varying from barely discernible signs of disease, to moderate flu-like symptoms and, occasionally, with life-threatening pneumonia and/or cytokine storm. The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein and the N-protein as well the neutralizing activity (NAbs) against SARS-CoV-2 in the blood of moderately afflicted COVID-19 patients has not been investigated longitudinally so far. Methods: Several new serological methods to examine these parameters were developed and validated for the longitudinal investigation in three patients of a family which underwent a mild course of COVID-19. Findings: We observed that the virus load had almost completely disappeared after about four weeks, whereas serum antibodies showed a contrasting course. IgA levels to S1-RBD-protein and, to a lesser extent, to the N-protein, peaked about three weeks after clinical disease onset but declined soon thereafter. IgG levels rose continuously, reaching a plateau approximately six weeks after disease onset. NAbs in serum reached a peak about four weeks after disease onset but dropped to a lower level about six weeks later. Interpretation: Our data establishes associations of virus neutralization and a serological immune response foremost against Sars-CoV-2 S1-RDB-protein in a longitudinal manner.