ABSTRACT
Prioritizing Ontarios long-term care home (LTCH) residents for vaccination against severe acute respiratory syndrome coronavirus 2 has drastically reduced their disease burden; however, recent LTCH outbreaks of variants of concern (VOCs) have raised questions regarding their immune responses. In 198 residents, mRNA vaccine dose 1 elicited partial spike and receptor binding domain antibody responses, while the second elicited a response at least equivalent to convalescent individuals in most residents. Residents administered mRNA-1273 (Moderna) mounted stronger total and neutralizing antibody responses than those administered BNT162b2 (Pfizer-BioNTech). Two to four weeks after dose 2, residents (n = 119, median age 88) produced 4.8-6.3-fold fewer neutralizing antibodies than staff (n = 78; median age 47) against wild-type (with D614G) pseudotyped lentivirus, and residents administered BNT162b2 produced 3.89-fold fewer neutralizing antibodies than those who received mRNA-1273. These effects were exacerbated upon serum challenge with pseudotyped VOC spike, with up to 7.94-fold reductions in B.1.351 (Beta) neutralization. Cumulatively, weaker vaccine stimulation, age/comorbidities, and the VOC produced an [~]130-fold reduction in apparent neutralization titers in LTCH residents and 37.9% of BNT162b2-vaccinated residents had undetectable neutralizing antibodies to B.1.351. Continued immune response surveillance and additional vaccine doses may be required in this population with known vulnerabilities.
ABSTRACT
Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated at this site in response to intramuscular COVID-19 vaccination, and whether these Ab protect against subsequent "breakthrough" infections. We collected longitudinal serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines over a 6-month period and measured the relative level of anti-Spike and anti-Receptor Binding Domain (RBD) Ab. We detected anti-Spike/RBD IgG and IgA and associated secretory component in the saliva of most participants receiving 1 dose of mRNA vaccine. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited greatly diminished anti-Spike/RBD IgG and IgA levels concomitant with a reduction in neutralizing activity in the saliva, although the level of secretory component associated anti-Spike was less susceptible to decay. Examining two prospective cohorts of subjects that were monitored for infections post-vaccination, we found that participants who were subsequently infected with SARS-CoV-2 had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data emphasize the importance of developing COVID-19 vaccines that elicit a durable IgA response. One-Sentence SummaryOur study delves into whether intra-muscular mRNA vaccination regimes confer a local IgA response in the oral cavity and whether the IgA response is associated with protection against breakthrough infection.
ABSTRACT
BackgroundThe aim of this prospective cohort study was to determine the burden of SARS-CoV-2 in air and on surfaces in rooms of patients hospitalized with COVID-19, and to identify patient characteristics associated with SARS-CoV-2 environmental contamination. MethodsNasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at six acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 viral RNA and cultured to determine potential infectivity. Whole viral genomes were sequenced from nasopharyngeal and surface samples. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated using a mixed-effects logistic regression model. FindingsSARS-CoV-2 RNA was detected from surfaces (125/474 samples; 42/78 patients) and air (3/146 samples; 3/45 patients) in COVID-19 patient rooms; 17% (6/36) of surface samples from three patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient. Multivariable analysis indicated hypoxia at admission, a PCR-positive nasopharyngeal swab with a cycle threshold of [≤]30 on or after surface sampling date, higher Charlson co-morbidity score, and shorter time from onset of illness to sample date were significantly associated with detection of SARS-CoV-2 RNA in surface samples. InterpretationThe infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited. Surface contamination was greater when patients were earlier in their course of illness and in those with hypoxia, multiple co-morbidities, and higher SARS-CoV-2 RNA concentration in NP swabs. Our results suggest that air and surfaces may pose limited risk a few days after admission to acute care hospitals.
ABSTRACT
BackgroundOn March 29th, 2021, Canadas National Advisory Committee on Immunization (NACI) recommended against using the AstraZeneca COVID-19 vaccine in younger adults pending further review of the risk for Vaccine-Induced Pro-thrombotic Immune Thrombocytopenia (VIPIT). As a result, the province of British Columbia halted its front-line workers vaccination program which used the AstraZeneca vaccine. The province is expected to receive an additional 246,700 doses of AstraZeneca vaccine through US and COVAX until April 11th, enough to provide the first dose of vaccine to all unvaccinated front-line workers. It is unclear whether the alternative, mRNA vaccines can be immediately made available to front-line workers. We evaluated the harms and benefits of delaying vaccination of front-line workers in BC. MethodsWe reviewed the latest available evidence and used compartmental modelling to 1) compare the expected number of deaths due to COVID-19 and VIPIT under the scenarios of immediately continuing vaccination of front-line workers with the AstraZeneca vaccine or delaying it in favour of mRNA vaccines, and 2) compare the individual mortality risk of immediately receiving the AstraZeneca vaccine with waiting to receive an mRNA vaccine later for different age groups. ResultsWe estimate that if British Columbia continues the front-line worker vaccination program with the AstraZeneca vaccine, we expect to see approximately 27,000 fewer cases of COVID-19, 500 fewer hospitalizations, 80 fewer COVID-related deaths, and 1,400 fewer cases of Long COVID from April 1st to October 1st, 2021, for an expected number of VIPIT-related deaths of 0.674 [95% CI 0.414-0.997]. In the same period and in areas of high transmission, the projected excess risk of mortality due to COVID-19 and VIPIT was significantly higher in the delayed vaccination with the mRNA vaccine scenario (3.23 to 4.44 times higher risk) than that of immediate vaccination with the AstraZeneca vaccine for those between 30 and 69 years of age. For those under 30, immediate vaccination with the AstraZeneca vaccine posed a higher risk than delayed vaccination with an mRNA vaccine. ConclusionsThe benefits of immediately continuing immunization of front-line workers with the AstraZeneca vaccine far outweigh the risk both at a societal level and at an individual risk level for those over 40, and those over 30 in high-risk areas.
