ABSTRACT
Background Breakthrough infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has occurred in populations with high vaccination rates. These infections are due to sequence variation in the spike protein leading to a reduction in protection afforded by the current vaccines, which are based on the original Wuhan-Hu-1 strain, or by natural infection with pre-Omicron strains. Methods In a longitudinal cohort study, pre-breakthrough infection sera for Omicron breakthroughs (n=12) were analyzed. Assays utilized include a laboratory-developed solid phase binding assay to recombinant spike protein, a commercial assay to the S1 domain of the spike protein calibrated to the World Health Organization (WHO) standard, and a commercial solid-phase surrogate neutralizing activity (SNA) assay. All assays employed spike protein preparations based on sequences from the Wuhan-Hu-1 strain. Participant demographics and clinical characteristics were captured. Results Pre-breakthrough binding antibody (bAB) titers ranged from 1:800-1:51,200 for the laboratory-developed binding assay, which correlated well and agreed quantitatively with the commercial spike S1 domain WHO calibrated assay. SNA was detected in 10/12 (83%) samples. Conclusions Neither high bAB nor SNA were markers of protection from Omicron infection/re-infection. Laboratory tests with antigen targets based on Wuhan-Hu-1 may not accurately reflect the degree of immune protection from variants with significant spike protein differences. Omicron breakthrough infections are likely due to high sequence variation of the spike protein and reflect incomplete immune protection from previous infection with strains that preceded Omicron or with vaccinations based on the original Wuhan-Hu-1 strain.
Subject(s)
Coronavirus Infections , Breakthrough PainABSTRACT
Herein we measured CD4+ T cell responses against common cold corona (CCC) viruses and SARS-CoV-2 in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC reactive T cells in SARS-CoV-2 seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC reactivity was decreased in SARS-CoV-2 infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.
ABSTRACT
When South Florida became a hotspot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists and administrators, who rapidly built a multi-platform, PCR- and serology-based detection program, established drive-thru facilities and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and to multiple diagnostic laboratory companies and government officials enabled us to implement both FDA authorized and laboratory developed testing (LDT)-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers, to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity, to testing hundreds of healthcare workers and patients daily, within three weeks. We believe our experience can inform the efforts of others, when faced with a crisis situation.