Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants.

Cell-mediated immunity may contribute to providing protection against SARS-CoV-2 and its variants of concern (VOC). We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara (MVA)-based COVID-19 vaccine that stimulated potent spike (S) and nucleocapsid (N) antigen-specific humoral and cellular immunity in a phase 1 clinical trial in healthy adults. Here, we show that individuals vaccinated with COH04S1 or mRNA vaccine BNT162b2 maintain robust cross-reactive cellular immunity for six or more months post-vaccination. Although neutralizing antibodies induced in COH04S1- and BNT162b2-vaccinees showed reduced activity against Delta and Omicron variants compared to ancestral SARS-CoV-2, S-specific T cells elicited in both COH04S1- and BNT162b2-vaccinees and N-specific T cells elicited in COH04S1-vaccinees demonstrated potent and equivalent cross-reactivity against ancestral SARS-CoV-2 and the major VOC. These results suggest that vaccine-induced T cells to S and N antigens may constitute a critical second line of defense to provide long-term protection against SARS-CoV-2 VOC.

Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial.

Background: COH04S1, a synthetic attenuated modified vaccinia virus Ankara vector co-expressing SARS-CoV-2 spike and nucleocapsid antigens, was tested for safety and immunogenicity in healthy adults. Methods: This combined open-label and randomised, phase 1 trial was done at the City of Hope Comprehensive Cancer Center (Duarte, CA, USA). We included participants aged 18-54 years with a negative SARS-CoV-2 antibody and PCR test, normal haematology and chemistry panels, a normal electrocardiogram and troponin concentration, negative pregnancy test if female, body-mass index of 30 kg/m2 or less, and no modified vaccinia virus Ankara or poxvirus vaccine in the past 12 months. In the open-label cohort, 1·0 × 107 plaque-forming units (PFU; low dose), 1·0 × 108 PFU (medium dose), and 2·5 × 108 PFU (high dose) of COH04S1 were administered by intramuscular injection on day 0 and 28 to sentinel participants using a queue-based statistical design to limit risk. In a randomised dose expansion cohort, additional participants were randomly assigned (3:3:1), using block size of seven, to receive two placebo vaccines (placebo group), one low-dose COH04S1 and one placebo vaccine (low-dose COH04S1 plus placebo group), or two low-dose COH04S1 vaccines (low-dose COH04S1 group). The primary outcome was safety and tolerability, with secondary objectives assessing vaccine-specific immunogenicity. The primary immunological outcome was a four times increase (seroconversion) from baseline in spike-specific or nucleocapsid-specific IgG titres within 28 days of the last injection, and seroconversion rates were compared with participants who received placebo using Fisher's exact test. Additional secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ClinicalTrials.gov, NCT046339466. Findings: Between Dec 13, 2020, and May 24, 2021, 56 participants initiated vaccination. On day 0 and 28, 17 participants received low-dose COH04S1, eight received medium-dose COH04S1, nine received high-dose COH04S1, five received placebo, 13 received low-dose COH04S1 followed by placebo, and four discontinued early. Grade 3 fever was observed in one participant who received low-dose COH04S1 and placebo, and grade 2 anxiety or fatigue was seen in one participant who received medium-dose COH04S1. No severe adverse events were reported. Seroconversion was observed in all 34 participants for spike protein and 32 (94%) for nucleocapsid protein (p<0·0001 vs placebo for each comparison). Four times or more increase in SARS-CoV-2 neutralising antibodies within 56 days was measured in nine of 17 participants in the low-dose COH04S1 group, all eight participants in the medium-dose COH04S1 group, and eight of nine participants in the high-dose COH04S1 group (p=0·0035 combined dose levels vs placebo). Post-prime and post-boost four times increase in spike-specific or nucleocapsid-specific T cells secreting interferon-γ was measured in 48 (98%; 95% CI 89-100) of 49 participants who received at least one dose of COH04S1 and provided a sample for immunological analysis. Interpretation: COH04S1 was well tolerated and induced spike-specific and nucleocapsid-specific antibody and T-cell responses. Future evaluation of this COVID-19 vaccine candidate as a primary or boost vaccination is warranted. Funding: The Carol Moss Foundation and City of Hope Integrated Drug Development Venture programme.

Rapid response to COVID-19: health informatics support for outbreak management in an academic health system.

OBJECTIVE: To describe the implementation of technological support important for optimizing clinical management of the COVID-19 pandemic. MATERIALS AND METHODS: Our health system has confirmed prior and current cases of COVID-19. An Incident Command Center was established early in the crisis and helped identify electronic health record (EHR)-based tools to support clinical care. RESULTS: We outline the design and implementation of EHR-based rapid screening processes, laboratory testing, clinical decision support, reporting tools, and patient-facing technology related to COVID-19. DISCUSSION: The EHR is a useful tool to enable rapid deployment of standardized processes. UC San Diego Health built multiple COVID-19-specific tools to support outbreak management, including scripted triaging, electronic check-in, standard ordering and documentation, secure messaging, real-time data analytics, and telemedicine capabilities. Challenges included the need to frequently adjust build to meet rapidly evolving requirements, communication, and adoption, and to coordinate the needs of multiple stakeholders while maintaining high-quality, prepandemic medical care. CONCLUSION: The EHR is an essential tool in supporting the clinical needs of a health system managing the COVID-19 pandemic.

Flight of the COVID-19 patient: experience with a Wuhan evacuee: a case report.

BACKGROUND: Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, was declared a global pandemic by the World Health Organization in March 2020. CASE PRESENTATION: We report a case of a 51-year-old Chinese woman who was evacuated from Wuhan, China and diagnosed with coronavirus disease 2019 infection at a Southern California quarantine facility. Her clinical course was notable for high fevers, night sweats, productive cough, transient leukopenia, lymphopenia, thrombocytopenia, and transaminitis. Evolving hypoxia and infiltrates on chest imaging warranted the trial of an investigational antiviral drug - remdesivir. Our patient recovered and was discharged after 2 weeks of hospitalization. CONCLUSIONS: This case highlights our patient's clinical course, including diagnostic work-up, medical management, and challenges in defining non-infectivity in a relatively unknown disease.