Humoral and cellular immune responses and their kinetics vary in dependence of diagnosis and treatment in immunocompromised patients upon COVID-19 mRNA vaccination. (preprint)

Background Knowledge about humoral and cellular immunogenicity and their kinetics following SARS-CoV-2 mRNA vaccinations in immunosuppressed patients is limited. Methods Antibody and cytokine responses were assessed in 263 patients with either solid tumors (SOT, n=63), multiple myeloma (MM, n=70) or inflammatory bowel diseases (IBD, n=130) undergoing various immunosuppressive regimens and from 66 healthy controls before the first and the second, as well as four weeks and 5-6 months after the second mRNA vaccine dose with either BNT162b2 or mRNA-1273. Findings Four weeks after the second dose, seroconversion was lower in cancer than in IBD patients and controls, with the highest non-responder rate in MM patients (17.1%). S1-specific IgG levels correlated with neutralizing antibody titers. While antibody responses correlated with cellular responses in controls and IBD patients, IFN-g; and antibody responses did not in SOT and MM patients. At six months, 19.6% of patients with MM and 7.3% with SOT had become seronegative, while IBD patients and controls remained seropositive in 96.3% and 100%, respectively. Vaccinees receiving mRNA-1273 presented higher antibody levels than those vaccinated with BNT162b2. Interpretation Cancer patients may launch an inadequate seroresponse in the immediate time range following vaccination and up to six months, correlating with vaccine-specific cellular responses. These findings propose antibody testing in immunosuppressed - along with cellular testing - provides guidance for administration of additional vaccine doses, or may indicate the necessity for antibody treatment. IBD patients respond well to the vaccine, but treatment such as with TNF-a; inhibitors may reduce persistence of immune responses.

The kinetic of SARS-CoV-2 antibody (Ab) decline determines the threshold for Ab persistence up to one year (preprint)

Twelve subjects with positive SARS-CoV-2 neutralization test (NT) titers (>1:10) identified in a seroprevalence study with 1655 working adults were followed up for one year. Here we report that 7 of these 12 individuals (58%) still had NT titers [≥]1:50, S1-specific IgG concentrations [≥]50 BAU/ml and [≥]26% ACE2 receptor binding inhibition, measured with surrogate virus NT one year after mild COVID infection. Furthermore, NT_50 titers >1:10 and S1-specific IgG levels >60 BAU/ml present at three months post-infection persisted at detectable levels for 1 year and correlated with circulating S1-specific memory B-cells. Vaccine-induced SARS-CoV2 immune responses decline at similar rates as those after infection; thus the describes threshold of 60 BAU/ml at three months post infection might also be relevant for assessment of Ab persistence after vaccination.

A longitudinal seroprevalence study in a large cohort of working adults reveals that neutralising SARS-CoV-2 RBD-specific antibodies persist for at least six months independent of the severity of symptoms (preprint)

Background In spring 2020, at the beginning of the first pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wave in Europe, we set up an assay system for large-scale testing of virus-specific and protective antibodies including their longevity. Methods We analysed the sera of 1655 adult employees for SARS-CoV-2-specific antibodies using the S1 subunit of the spike protein of SARS-CoV-2. Sera containing S1-reactive antibodies were further evaluated for receptor-binding domain (RBD)- and nucleocapsid protein (NCP)-specific antibodies in relation to the neutralisation test (NT) results at 0, three and six months. Findings We found immunoglobulin G (IgG) and/or IgA antibodies reactive to the S1 protein in 10.15% (n=168) of the participants. In total, 0.97% (n=16) were positive for S1-IgG, 0.91% (n=15) were S1-IgG- borderline and 8.28% (n=137) exhibited only S1-IgA antibodies. Next, we evaluated the 168 S1-reactive sera for RBD- and NCP specificity: 8.33% (n=14) had detectable RBD-specific and 6.55% (n=11) NCP-specific antibodies. The latter correlated with NTs (kappa coefficient = 0.8660) but started to decline already after 3 months. RBD-specific antibodies correlated best with the NT (kappa = 0.9448) and only these antibodies were stable for up to six months. All participants with virus-neutralising antibodies reported symptoms, of which, anosmia and/or dysgeusia correlated best with the detection of virus-neutralising antibodies. Interpretation RBD-specific antibodies were most reliably detected post infection, independent of the number/severity of symptoms, and correlated best with protective neutralising antibodies at least for six months. They thus qualify best for large-scale seroepidemiological evaluation of both seroprevalence and seroprotection.

Significant impact of nationwide SARS-CoV-2 lockdown measures on the circulation of other respiratory virus infections (preprint)

Since the worldwide spread of SARS-CoV-2, different European countries reacted with temporarily nationwide lockdowns with the aim to limit the virus transmission in the population. Also Austria started a lockdown of public life in March. In this study we investigated whether the circulation of different respiratory virus infections in Austria, as assessed by using the established respiratory virus surveillance system, is affected by these measures as well and may reflect the success of the lockdown in limiting respiratory virus transmission. Sentinel data obtained for influenza virus, respiratory syncytial virus, human metapneumovirus and rhinovirus cases were analyzed and compared between the season 2019/ 2020 and the five previous seasons. We observed a rapid and statistically significant reduction of cumulative cases for all these viruses within short time after the lockdown in March 2020, compared to previous seasons (each p<0.001). Also, sentinel screening for SARS-CoV-2 infections was performed and a decrease of SARS-CoV-2 was seen after the lockdown. While for the seasonally occurring viruses as influenza, respiratory syncytial virus or human metapneumovirus the lockdown led to the end of the annual epidemics, a re-increase of rhinovirus infections was observed after liberalization of numerous lockdown measures.  Our data provide evidence that occurrence of different respiratory virus infections reflect not only the efficiency of lockdown measures taken against SARS-CoV-2 but also the effects of their release on respiratory transmission.