ABSTRACT
Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.
Subject(s)
Antibody Formation , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Vaccines, Synthetic/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , SARS-CoV-2 , VaccinationABSTRACT
The approved Pfizer and Moderna mRNA vaccines are well known to induce serum antibody responses to the SARS-CoV-2 Spike (S)-protein. However, their abilities to elicit mucosal immune responses have not been reported. Saliva antibodies represent mucosal responses that may be relevant to how mRNA vaccines prevent oral and nasal SARS-CoV-2 transmission. Here, we describe the outcome of a cross-sectional study on a healthcare worker cohort (WELCOME-NYPH), in which we assessed whether IgM, IgG, and IgA antibodies to the S-protein and its receptor-binding domain (RBD) were present in serum and saliva samples. Anti-S-protein IgG was detected in 14/31 and 66/66 of saliva samples from uninfected participants after vaccine doses-1 and -2, respectively. IgA antibodies to the S-protein were present in 40/66 saliva samples after dose 2. Anti-S-protein IgG was present in every serum sample from recipients of 2 vaccine doses. Vaccine-induced antibodies against the RBD were also frequently present in saliva and sera. These findings may help our understanding of whether and how vaccines may impede SARS-CoV-2 transmission, including to oral cavity target cells.
ABSTRACT
Importance: The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. Objectives: To develop a simplified mathematical model of tumor growth, control, and new metastases for cancers with varying doubling times and metastatic potential and to estimate tumor control probability (TCP) and metastases risk as a function of treatment delay interval. Design, Setting, and Participants: This decision analytical model describes a quantitative model for 3 tumors (ie, head and neck, colorectal, and non-small cell lung cancers). Using accepted ranges of tumor doubling times and metastatic development from the clinical literature from 2001 to 2020, estimates of tumor growth, TCP, and new metastases were analyzed for various treatment delay intervals. Main Outcomes and Measures: Risk estimates for potential decreases in local TCP and increases in new metastases with each interval of treatment delay. Results: For fast-growing head and neck tumors with a 2-month treatment delay, there was an estimated 4.8% (95% CI, 3.4%-6.4%) increase in local tumor control risk and a 0.49% (0.47%-0.51%) increase in new distal metastases risk. A 6-month delay was associated with an estimated 21.3% (13.4-30.4) increase in local tumor control risk and a 6.0% (5.2-6.8) increase in distal metastases risk. For intermediate-growing colorectal tumors, there was a 2.1% (0.7%-3.5%) increase in local tumor control risk and a 2.7% (2.6%-2.8%) increase in distal metastases risk at 2 months and a 7.6% (2.2%-14.2%) increase in local tumor control risk and a 24.7% (21.9%-27.8%) increase in distal metastases risk at 6 months. For slower-growing lung tumors, there was a 1.2% (0.0%-2.8%) increase in local tumor control risk and a 0.19% (0.18%-0.20%) increase in distal metastases risk at 2 months, and a 4.3% (0.0%-10.6%) increase in local tumor control risk and a 1.9% (1.6%-2.2%) increase in distal metastases risk at 6 months. Conclusions and Relevance: This study proposed a model to quantify the association of treatment delays with local tumor control and risk of new metastases. The detrimental associations were greatest for tumors with faster rates of proliferation and metastasis. The associations were smaller, but still substantial, for slower-growing tumors.
Subject(s)
Decision Support Techniques , Models, Theoretical , Neoplasm Metastasis/diagnosis , Neoplasms/diagnosis , Time-to-Treatment/statistics & numerical data , COVID-19 , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/therapy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Humans , Neoplasms/therapy , Risk Assessment , SARS-CoV-2Subject(s)
Breast Neoplasms/radiotherapy , Coronavirus Infections/radiotherapy , Head and Neck Neoplasms/radiotherapy , Lung Neoplasms/radiotherapy , Pneumonia, Viral/radiotherapy , Breast Neoplasms/complications , Breast Neoplasms/virology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Disease-Free Survival , Female , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/virology , Humans , Lung Neoplasms/complications , Lung Neoplasms/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virologyABSTRACT
The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide. This novel but unconventional use of radiation to treat COVID-19 prompted the National Cancer Institute, National Council on Radiation Protection and Measurements and National Institute of Allergy and Infectious Diseases to convene a workshop involving a diverse group of experts in radiation oncology, radiobiology, virology, immunology, radiation protection and public health policy. The workshop was held to discuss the mechanistic underpinnings, rationale, and preclinical and emerging clinical studies, and to develop a general framework for use in clinical studies. Without refuting or endorsing LDRT as a treatment for COVID-19, the purpose of the workshop and this review is to provide guidance to clinicians and researchers who plan to conduct preclinical and clinical studies, given the limited available evidence on its safety and efficacy.