Persistent humoral and CD4+ TH cell immunity after mild SARS-COV-2 infection-The CoNAN long-term study.

Understanding persistent cellular and humoral immune responses to SARS-CoV-2 will be of major importance to terminate the ongoing pandemic. Here, we assessed long-term immunity in individuals with mild COVID-19 up to 1 year after a localized SARS-CoV-2 outbreak. CoNAN was a longitudinal population-based cohort study performed 1.5 months, 6 months, and 12 months after a SARS-CoV-2 outbreak in a rural German community. We performed a time series of five different IgG immunoassays assessing SARS-CoV-2 antibody responses on serum samples from individuals that had been tested positive after a SARS-CoV-2 outbreak and in control individuals who had a negative PCR result. These analyses were complemented with the determination of spike-antigen specific TH cell responses in the same individuals. All infected participants were presented as asymptomatic or mild cases. Participants initially tested positive for SARS-CoV-2 infection either with PCR, antibody testing, or both had a rapid initial decline in the serum antibody levels in all serological tests but showed a persisting TH cell immunity as assessed by the detection of SARS-CoV-2 specificity of TH cells for up to 1 year after infection. Our data support the notion of a persistent T-cell immunity in mild and asymptomatic cases of SARS-CoV-2 up to 1 year after infection. We show that antibody titers decline over 1 year, but considering several test results, complete seroreversion is rare. Trial registration: German Clinical Trials Register DRKS00022416.

Non-patient-related SARS-CoV-2 exposure from colleagues and household members poses the highest infection risk for hospital employees in a German university hospital: follow-up of the prospective Co-HCW seroprevalence study.

PURPOSE: The Co-HCW study is a prospective, longitudinal, single-center observational study that aims to assess the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany. METHODS: This follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each of the three voluntary study visits, participants filled out a questionnaire regarding their SARS-CoV-2 exposure and provided serum samples to detect specific SARS-CoV-2 antibodies. Participants who were tested positive for antibodies against nucleocapsid and/or spike protein without previous vaccination and/or reported a positive SARS-CoV-2 PCR test were regarded to have been infected with SARS-CoV-2. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants. RESULTS: Out of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for the final analysis as their COVID-19 risk area (high-risk n = 76; intermediate-risk n = 198; low-risk n = 132) did not change during the study. Forty-four participants [10.8%, 95% confidence interval (95%CI) 8.0-14.3%] had evidence of a current or past SARS-CoV-2 infection detected by serology (n = 40) and/or PCR (n = 28). No association between SARS-CoV-2 infection and the COVID-19 risk group according to working place was detected. However, exposure to a SARS-CoV-2 positive household member [adjusted OR (AOR) 4.46, 95% CI 2.06-9.65] or colleague (AOR 2.30, 95%CI 1.10-4.79) was found to significantly increase the risk of a SARS-CoV-2 infection. CONCLUSION: Our results demonstrate that non-patient-related SARS-CoV-2 exposure posed the highest infection risk for hospital staff members of JUH.

Immunoadsorption to treat patients with severe post-COVID syndrome.

INTRODUCTION: Following SARS-CoV-2-infection up to 21% of patients will develop post-COVID-syndrome. Autoantibodies (AAbs) targeting neuronal-ß-adrenergic and muscarinic receptors may provide crucial contributions to the pathophysiology of this condition. Immunoadsorption (IA) has been identified as an effective means of removing AAbs and has resulted in clinical improvements of other autoantibody-associated diseases. METHODS: We determined AAb-levels (anti-ß1/ß2 and anti-M3/M4 receptor) in 178 patients diagnosed with post-COVID-syndrome and described the clinical courses of two patients with elevated AAb-levels that underwent IA-treatment. RESULTS: AAbs were detected in 57% (101/178) of patients diagnosed with post-COVID-syndrome. Substantial reductions in AAb-levels and clinical remission were achieved in one of two patients who was treated with IA. However, this patient relapsed within 6 weeks with a concomitant increase in AAb-levels. CONCLUSION: Collectively, AAbs may play a pathophysiologic role in post-COVID and their removal provide transient benefits in some patients. However, these findings should be further investigated in randomized-controlled-trials.

Prospective surveillance study in a 1,400-bed university hospital: COVID-19 exposure at home was the main risk factor for SARS-CoV-2 point seroprevalence among hospital staff.

The Co-HCW study is a prospective cohort study among hospital staff, including healthcare workers (HCWs) and administration staff, at the Jena University Hospital (JUH), Germany. The objectives of this study were to assess SARS-CoV-2 IgG seroprevalence, individual exposure risk factors and compliance of HCWs to wear personal protective equipment (PPE). After the first nosocomial COVID-19 outbreak at JUH, mandatory masking was implemented on 20th March 2020. We evaluated point seroprevalence using two IgG detecting immunoassays and issued a questionnaire to assess COVID-19 exposure, clinical symptoms and compliance to wear PPE. Antibody retesting was offered to participants with a divergent result of both immunoassays 5-10 weeks after the first test. Between 19th May and 19th June 2020, we analysed 660 participants [out of 3,228; 20.4%]. Among them, 212 participants (32.1%) had received a previous COVID-19 test. Four of them (1.9%) reported a positive test result. After recruitment, 18 participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Overall, 21 participants (3.2%) had any evidence of a past or current SARS-CoV-2 infection. Among them, 13 (61.9%) were not aware of direct COVID-19 exposure and 9 (42.9%) did not report any clinical symptoms. COVID-19 exposure at home (adjusted OR (aOR) with 95% CI: 47.82 (5.49, 416.62)) was associated with SARS-CoV-2 seroprevalence. We observed no evidence for an association between seroprevalence and exposure at work (aOR 0.48 (0.13, 1.70)) or with COVID-19 risk area according to the working place (aOR for intermediate-risk vs. high-risk: 1.97 (0.42, 9.22), aOR for low-risk versus high-risk: 2.10 (0.40, 11.06); p = .655). Reported compliance of HCWs to wear PPE differed (p < .001) between working in high-risk (98.3%) and in intermediate-risk areas (69.8%). In conclusion, compared to administration staff, we observed no additional risk to acquire SARS-CoV-2 infections by patient care, probably due to high compliance to wear PPE.

Antibody response using six different serological assays in a completely PCR-tested community after a coronavirus disease 2019 outbreak-the CoNAN study.

OBJECTIVES: Due to a substantial proportion of asymptomatic and mild courses, many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed to determine and characterize the rate of SARS-CoV-2 infections and the resulting seroprevalence in a defined population. The primary objective of the study was to assess SARS-CoV-2 antibody seroprevalence using six different IgG-detecting immunoassays. Secondary objectives of the study were: (a) to determine potential risk factors for symptomatic versus asymptomatic coronavirus disease 2019 courses, and (b) to investigate the rate of virus RNA-persistence. METHODS: CoNAN is a population-based cohort study performed in the community Neustadt am Rennsteig, Germany, which was quarantined from 22 March to 5 April after six SARS-CoV-2 cases were detected in the village's population. The SARS-CoV-2 outbreak comprised 51 cases and 3 deaths. The CoNAN study was performed from 13 May to 22 May 2020, 6 weeks after a SARS-CoV-2 outbreak. RESULTS: We enrolled a total of 626 participants (71% of the community population) for PCR and antibody testing in the study. All actual SARS-CoV-2 PCR tests were negative. Fifty-two out of 620 (8.4%) participants had antibodies against SARS-CoV-2 in at least two different assays. There were 38 participants with previously PCR-confirmed SARS-CoV-2 infection. Of those, only 19 (50%) displayed anti-SARS-CoV-2 antibodies. We also show that antibody-positive participants with symptoms compatible with a respiratory tract infection had significantly higher antibody levels then asymptomatic participants (EU-assay: median 2.9 versus 7.2 IgG-index, p 0.002; DS-assay: median 45.2 versus 143 AU/mL, p 0.002). Persisting viral replication was not detected. CONCLUSIONS: Our data question the relevance and reliability of IgG antibody testing to detect past SARS-CoV-2 infections 6 weeks after an outbreak. We conclude that assessing immunity for SARS-CoV-2 infection should not rely on antibody tests alone.

SARS-CoV-2 antibody testing-questions to be asked.

Severe acute respiratory syndrome coronavirus 2 infection and development of coronavirus disease 2019 presents a major health care challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against severe acute respiratory syndrome coronavirus 2, presents a major cornerstone in handling the pandemic. Currently, there is an increase in demand for antibody testing and a large number of tests are already marketed or are in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity, the diagnostic value of antibodies of different isotypes, and the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article, the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues on the basis of currently available data sets in this rapidly moving field.