ABSTRACT
IMPORTANCE The rapid genetic evolution of SARS-CoV-2 and in particular the highly contagious Omicron variant of concern (VoC) may pose problems for rapid and accurate diagnosis of infection especially in health care workers. OBJECTIVE Determine the diagnostic accuracy and robustness of two rapid antigen tests compared to the golden standard, PCR-based diagnostics, for detection of infection with different SARS-CoV-2 Omicron VoC sub lineages in health care workers. DESIGN, SETTING, AND PARTICIPANTS The study included 428 health care workers from the University Hospital Munich Rechts der Isar who reported recent onset of COVID-19 associated symptoms or completed routine diagnostic testing from 24th of May to 22nd of September 2022. All participants gave written informed consent to participate in this study and completed a questionnaire on infection-associated symptoms, prior SARS-CoV-2 infections and vaccination status. INTERVENTIONS During the first visit, two nasal swabs were taken to perform two rapid antigen tests and one oropharyngeal swab for PCR-based diagnosis of SARS-CoV-2 infection. A second set of nasal swabs was taken by participants two days later for repeated performance of the two rapid antigen tests. MAIN OUTCOMES AND MEASURES The accuracy for detection of infection with different SARS-CoV-2 Omicron VoCs with two rapid antigen tests (Test I and Test II) was determined and compared to quantitative SARS CoV-2 RNA levels detected by PCR. RESULTS In a side-by-side comparison, we found that Test I detected viral nucleocapsids from Omicron VoC (BA.5.2.3) at higher dilutions compared to Test II. In the study, that included a total of 428 health care workers, Test I and Test II detected PCR-confirmed SARS-CoV-2 infection with different Omicron VoCs (BA.2, BA.4, BA.5) with a sensitivity of 89.4% (95% CI 81.9% - 94.6%) and of 83.7% (95% CI 75.12% - 90.18%), respectively. Increased sensitivity by Test I was also reflected by earlier detection of SARS-CoV-2 infection, and lesser test sensitivity by Test II was compensated for by a repeated test performed two days later. CONCLUSIONS AND RELEVANCE The results from the study demonstrate the usefulness of rapid antigen tests for detection of infection with the SARS-CoV-2 Omicron VoC and reveal an advantage of a lower detection limit for earlier detection of infection in health care workers.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Vaccines are the most important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 5 months after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both. Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. T-cell responses showed less waning irrespective of the vaccination regimen. These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent approach to induce long-term humoral and cellular immune protection.
ABSTRACT
Infection-neutralizing antibody responses after SARS-CoV-2 infection or COVID-19 vaccination are an essential part of antiviral immunity. This immune protection is challenged by the occurrence of SARS-CoV-2 variants of concern (VoCs) with immune escape properties, such as omicron (B.1.1.529) that is rapidly spreading worldwide. Here, we report neutralizing antibody dynamics in a longitudinal cohort of COVID-19 convalescent and naïve individuals vaccinated with mRNA BNT162b2 by quantifying anti-SARS-CoV-2-spike antibodies and determining their avidity and neutralization capacity. A superior infection-neutralizing capacity against all VoCs, including omicron, developed by either two vaccinations of convalescents, or a third vaccination or breakthrough infection of twice-vaccinated naïve individuals. These three consecutive spike antigen exposures resulted in an increasing neutralization capacity per anti-spike antibody unit and were paralleled by stepwise increases in antibody avidity. In conclusion, an infection/vaccination-induced hybrid immunity or a triple immunization induces high-quality antibodies resulting in superior neutralization capacity against VoCs, including omicron.
Subject(s)
COVID-19ABSTRACT
Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is controlled by the host´s immune response1-4, but longitudinal follow-up studies of virus-specific immunity to evaluate protection from re-infection are lacking. Here, we report the results from a prospective study that started during the first wave of the COVID-19 pandemic in spring 2020, where we identified 91 convalescents from mild SARS-CoV-2 infection among 4554 health care workers. We followed the dynamics and magnitude of spike-specific immunity in convalescents during the spontaneous course over ≥ 9 months, after SARS-CoV-2 re-exposure and after BNT162b2 mRNA vaccination. Virus-neutralizing antibodies and spike-specific T cell responses with predominance of IL-2-secreting polyfunctional CD4 T cells continuously declined over 9 months, but remained detectable at low levels. After a single vaccination, convalescents simultaneously mounted strong antibody and T cell responses against the SARS-CoV-2 spike proteins. In naïve individuals, a prime vaccination induced preferentially IL-2-secreting CD4 T cells that preceded production of spike-specific virus-neutralizing antibodies after boost vaccination. Response to vaccination, however, was not homogenous. Compared to four individuals among 455 naïve vaccinees (0.9%), we identified 5/82 (6.1%) convalescents with a delayed response to vaccination. These convalescents had originally developed dysfunctional spike-specific immune responses after SARS-CoV-2 infection, and required prime and boost vaccination to develop strong spike-specific immunity. Importantly, during the second wave of the COVID-19 pandemic in fall/winter of 2021 and prior to vaccination we detected a surge of virus-neutralizing antibodies consistent with re-exposure to SARS-CoV-2 in 6 out of 82 convalescents. The selective increase in virus-neutralizing antibodies occurred without systemic re-activation of spike-specific T cell immunity, whereas a single BNT162b2 mRNA vaccination sufficed to induce strong spike-specific antibody and systemic T cell responses in the same individuals. These results support the notion that BNT162b2 mRNA vaccination synchronizes spike-specific immunity in all convalescents of mild SARS-CoV-2 infection and may provide additional protection from re-infection by inducing more rigorous stimulation of spike-specific T cell immunity than re-exposure with SARS-CoV-2.