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IMPORTANCEThe 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. OBJECTIVEDetermine the diagnostic accuracy and robustness of a second generation rapid antigen tests compared to gold-standard, PCR-based diagnostics, for detection of infection with different SARS-CoV-2 Omicron VoC sub lineages in health care workers. DESIGN, SETTING, AND PARTICIPANTSThe study included 428 health care workers from the University Hospital Munich Rechts der Isar of the Technical University of Munich who either reported recent onset of COVID-19 associated symptoms or completed routine diagnostic testing between 24th of May and 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. INTERVENTIONSDuring the first visit, two nasal swabs and one oropharyngeal swab were taken to perform two rapid antigen tests and a SARS-CoV-2 PCR-assay, respectively. A second set of nasal swabs was taken by the participants themselves two days later to repeat the two rapid antigen tests. MAIN OUTCOMES AND MEASURESThe 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. RESULTSIn 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 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 83.7% (95% CI 75.12% - 90.18%), respectively. Increased sensitivity of Test I was also reflected by earlier detection of SARS-CoV-2 infection. The lower test sensitivity of Test II could be compensated for by a repeated test performed two days later. CONCLUSIONS AND RELEVANCEOur study demonstrates that rapid antigen tests are suited to detect 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.
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BackgroundHemodialysis patients are exposed to a markedly increased risk when infected with SARS-CoV-2. To date it is unclear if hemodialysis patients benefit from a fourth vaccination. MethodsA total of 142 hemodialysis patients (median age 72.6 years, 33.8% female) received four COVID-19 vaccinations between December 2020 and March 2022. RDB binding antibody titers were determined in a competitive surrogate neutralization assay. Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC) Delta (B.1.617.2) or Omicron (B.1.1.529, sub lineage BA.1) in a biosafety level 3 laboratory to determine serum infection neutralization capacity before and after vaccination. ResultsAfter the fourth vaccination serum infection neutralization capacity significantly increased from a 50% inhibitory concentration (IC50, serum dilution factor 1:x) of 247.0 (46.3-1560.8) to 2560.0 (1174.0-2560.0) for the Delta VoC, and from 37.5 (20.0-198.8) to 668.5 (182.2-2560.0) for the Omicron VoC (each p<0.001). A significant increase of the neutralization capacity was even observed for patients who had high antibody titers after three vaccinations (p<0.001). Univariate regression analysis indicated immunosuppressive medication (p=0.001) and hepatitis B vaccination non-response (p=0.046), and multivariate analysis immunosuppressive medication as the only factor associated with a reduced effect against Delta (p<0.001). Ten patients with SARS-CoV-2 breakthrough infection before the fourth vaccination had by trend lower prior neutralization capacity for Omicron (p=0.051). ConclusionsOur findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron variant. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients.
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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. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSDue to some rare severe side effects after the administration of the adenoviral vaccine, ChAdOx1 nCoV-19, many countries recommended a heterologous vaccination scheme including mRNA vaccines like BNT162b2 for the second dose. We performed a PubMed search (with no restrictions on time span) using the search terms "SARS-CoV-2" and "heterologous vaccination" and obtained 247 results. Only a fraction of manuscripts included direct comparisons of patient cohorts that received either a heterologous or a homologous vaccination regimen. Of those, the vast majority investigated only short-term immunogenicity after vaccination. Thus, little is known about the long-term maintenance of immunity by heterologous compared to homologous vaccination. Added value of this studyWe add a very comprehensive and comparative study investigating heterologous and homologous vaccination regimens early and late after vaccination. Key features include the number of patients (n = 473), the number of vaccination cohorts (n= 3), the fact that samples were derived from three independent study centers and comparative analyses were performed at two independent study centers, as well as in-depth investigation of humoral and T cellular immunity. Implications of all the available evidenceThe recent data creates a line of evidence that heterologous vaccination, compared to homologous vaccination regimens, results in at least non-inferior maintenance of humoral and cellular immunity. The enhanced understanding of immunity induced by individual vaccination regimens is crucial for further recommendations regarding the necessity, timing and choice of additional vaccinations and public health policies.
