Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection.

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. 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 diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants 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 suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. Our study finds that a local secretory component-associated IgA response is induced by COVID-19 mRNA vaccination that persists in some, but not all participants. The serum and saliva IgA response modestly correlate at 2-4 weeks post-dose 2. Of note, levels of anti-Spike serum IgA (but not IgG) at this timepoint are lower in participants who subsequently become infected with SARS-CoV-2. As new surges of SARS-CoV-2 variants arise, developing COVID-19 booster shots that provoke high levels of IgA has the potential to reduce person-to-person transmission.

Surface and Air Contamination With Severe Acute Respiratory Syndrome Coronavirus 2 From Hospitalized Coronavirus Disease 2019 Patients in Toronto, Canada, March-May 2020.

BACKGROUND: We determined the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in air and on surfaces in rooms of patients hospitalized with coronavirus disease 2019 (COVID-19) and investigated patient characteristics associated with SARS-CoV-2 environmental contamination. METHODS: Nasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at 6 acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 ribonucleic acid (RNA), cultured to determine potential infectivity, and whole viral genomes were sequenced. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated. RESULTS: Severe acute respiratory syndrome coronavirus 2 RNA was detected from surfaces (125 of 474 samples; 42 of 78 patients) and air (3 of 146 samples; 3 of 45 patients); 17% (6 of 36) of surface samples from 3 patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient. Multivariable analysis indicated hypoxia at admission, polymerase chain reaction-positive nasopharyngeal swab (cycle threshold of ≤30) on or after surface sampling date, higher Charlson comorbidity score, and shorter time from onset of illness to sampling date were significantly associated with detection of SARS-CoV-2 RNA in surface samples. CONCLUSIONS: The 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.

Genomic Epidemiology of Carbapenemase-Producing Enterobacterales at a Hospital System in Toronto, Ontario, Canada, 2007 to 2018.

At a hospital system (H1) in Ontario, Canada, we investigated whether whole-genome sequencing (WGS) altered initial epidemiological interpretation of carbapenemase-producing Enterobacterales (CPE) transmission. We included patients with CPE colonization/infection identified by population-based surveillance from October 2007 to August 2018 who received health care at H1 in the year before/after CPE detection. H1 reported epidemiological transmission clusters. We combined single nucleotide variant (SNV) analysis, plasmid characterization, and epidemiological data. Eighty-five patients were included. H1 identified 7 epidemiological transmission clusters, namely, A to G, involving 24/85 (28%) patients. SNV analysis confirmed transmission clusters C, D, and G and identified two additional cases belonging to cluster A. One was a travel-related case that was the likely index case (0 to 6 SNVs from other isolates); this case stayed on the same unit as the initially presumed index case 4 months prior to detection of the initially presumed index case on another unit. The second additional case occupied a room previously occupied by 5 cluster A cases. Plasmid sequence analysis excluded a case from cluster A and identified clusters E and F as possibly two parts of a single cluster. SNV analysis also identified a case without direct epidemiologic links that was 18 to 21 SNVs away from cluster B, suggesting possible undetected interhospital transmission. SNV and plasmid sequence analysis identified cases belonging to transmission clusters that conventional epidemiology missed and excluded other cases. Implementation of routine WGS to complement epidemiological transmission investigations has the potential to improve prevention and control of CPE in hospitals.

Are Sink Drainage Systems a Reservoir for Hospital-Acquired Gammaproteobacteria Colonization and Infection? A Systematic Review.

Increasing rates of antimicrobial-resistant organisms have focused attention on sink drainage systems as reservoirs for hospital-acquired Gammaproteobacteria colonization and infection. We aimed to assess the quality of evidence for transmission from this reservoir. We searched 8 databases and identified 52 studies implicating sink drainage systems in acute care hospitals as a reservoir for Gammaproteobacterial colonization/infection. We used a causality tool to summarize the quality of evidence. Included studies provided evidence of co-occurrence of contaminated sink drainage systems and colonization/infection, temporal sequencing compatible with sink drainage reservoirs, some steps in potential causal pathways, and relatedness between bacteria from sink drainage systems and patients. Some studies provided convincing evidence of reduced risk of organism acquisition following interventions. No single study provided convincing evidence across all causality domains, and the attributable fraction of infections related to sink drainage systems remains unknown. These results may help to guide conduct and reporting in future studies.

Standard versus combined chemical, mechanical, and heat decontamination of hospital drains harboring carbapenemase-producing organisms (CPOs): A randomized controlled trial.

We sought to determine whether combined chemical, mechanical, and heat cleaning was superior to standard cleaning for the decontamination of 32 sink and shower drains harboring carbapenemase-producing organisms (CPOs). Of 16 intervention drains, 10 (63%) were decontaminated until day 7 versus 1 (5%) of 16 comparator drains (P = .002). Intensive cleaning may be useful if administered repeatedly in drain-associated CPO outbreaks.

Sensitivity of Nasopharyngeal Swabs and Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2.

We enrolled 91 consecutive inpatients with COVID-19 at 6 hospitals in Toronto, Canada, and tested 1 nasopharyngeal swab/saliva sample pair from each patient using real-time RT-PCR for severe acute respiratory syndrome coronavirus 2. Sensitivity was 89% for nasopharyngeal swabs and 72% for saliva (P = .02). Difference in sensitivity was greatest for sample pairs collected later in illness.

Household Transmission of Carbapenemase-producing Enterobacterales in Ontario, Canada.

BACKGROUND: Data on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada. METHODS: We enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations. RESULTS: Ninety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case's spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05-36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92-25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52-27.40). CONCLUSIONS: Nine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.

Sensitivity of midturbinate versus nasopharyngeal swabs for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

To compare sensitivity of specimens for COVID-19 diagnosis, we tested 151 nasopharyngeal/midturbinate swab pairs from 117 COVID-19 inpatients using reverse-transcriptase polymerase chain reaction (RT-PCR). Sensitivity was 94% for nasopharyngeal and 75% for midturbinate swabs (P = .0001). In 88 nasopharyngeal/midturbinate pairs with matched saliva, sensitivity was 86% for nasopharyngeal swabs and 88% for combined midturbinate swabs/saliva.

Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients.

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Longitudinal analysis revealed that anti-SARS-CoV-2 IgA and IgM antibodies rapidly decayed, while IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

Development of a tool to assess evidence for causality in studies implicating sink drains as a reservoir for hospital-acquired gammaproteobacterial infection.

BACKGROUND: Decades of studies document an association between Gammaproteobacteria in sink drains and hospital-acquired infections, but the evidence for causality is unclear. AIM: We aimed to develop a tool to assess the quality of evidence for causality in research studies that implicate sink drains as reservoirs for hospital-acquired Gammaproteobacterial infections. METHODS: We used a modified Delphi process with recruited experts in hospital epidemiology to develop this tool from a pre-existing causal assessment application. FINDINGS: Through four rounds of feedback and revision we developed the 'Modified CADDIS Tool for Causality Assessment of Sink Drains as a Reservoir for Hospital-Acquired Gammaproteobacterial Infection or Colonization'. In tests of tool application to published literature during development, mean percent agreement ranged from 46.7% to 87.5%, and the Gwet's AC1 statistic (adjusting for chance agreement) ranged from 0.13 to 1.0 (median 68.1). Areas of disagreement were felt to result from lack of a priori knowledge of causal pathways from sink drains to patients and uncertain influence of co-interventions to prevent organism acquisition. Modifications were made until consensus was achieved that further iterations would not improve the tool. When the tool was applied to 44 articles by two independent reviewers in an ongoing systematic review, percent agreement ranged from 93% to 98%, and the Gwet's AC1 statistic was 0.91-0.97. CONCLUSION: The modified causality tool was useful for evaluating studies that implicate sink drains as reservoirs for hospital-acquired infections and may help guide the conduct and reporting of future research.

Infection prevention and control practices related to carbapenemase-producing Enterobacteriaceae (CPE) in acute-care hospitals in Ontario, Canada.

OBJECTIVE: To determine infection prevention and control (IPAC) practices for carbapenemase-producing Enterobacteriaceae (CPE), an emerging threat, at acute-care hospitals in Ontario, Canada. DESIGN: A descriptive cross-sectional survey. METHODS: We surveyed IPAC directors and managers at all acute-care hospitals in Ontario, Canada, to gather information on IPAC practices related to CPE, including admission screening, other patient screening, environmental testing, use of precautions to prevent transmission, and outbreak management. RESULTS: Of 116 acute-care hospitals, 105 (91%) responded. Admission screening included patients previously colonized or infected with CPE (n = 64, 61%), patients recently hospitalized outside of Canada (Indian subcontinent, n = 62, 59%; other countries, n = 56, 53%), and patients recently hospitalized in Canada (n = 22, 21%). Fifty-one hospitals (49%) screened patients for colonization during an outbreak. Almost all hospitals (n = 101, 96%) used precautions to prevent transmission from patients with CPE colonization or infection; most hospitals (n = 54, 53%) continued precautions indefinitely. Few hospitals (n = 19, 18%) performed environmental cultures. Eight hospitals (8%) reported at least 1 outbreak, and 6 hospitals (6%) reported transmission from sink or shower drains to patients. CONCLUSIONS: Variability in practices may result from lack of evidence and challenges in updating guidelines as evidence emerges. A coordinated approach to slow the emergence of CPE should be considered in our population.

Incidence and characteristics of needlestick injuries among medical trainees at a community teaching hospital: A cross-sectional study.

OBJECTIVES: This field study aimed to determine the incidence and distribution of needlestick injuries among medical trainees at a community teaching hospital in Toronto, Canada. METHODS: The study was performed during the 2013-2015 academic years at Toronto East General Hospital (TEGH), a University of Toronto-affiliated community-teaching hospital during the 2013-2015 academic years. Eight-hundred and forty trainees, including medical students, residents, and post-graduate fellows, were identified and invited via email to participate in an anonymous online fluidsurveys.com survey of 16 qualitative and quantitative questions. RESULTS: Three-hundred and fifty trainees responded (42% response rate). Eighty-eight (25%) respondents reported experiencing at least one injury at TEGH. In total, our survey identified 195 total injuries. Surgical trainees were significantly more likely to incur injuries than non-surgical trainees (IRR = 3.03, 95% CI 1.80-5.10). Orthopaedic surgery trainees had the highest risk of a needlestick injury, being over 12 times more likely to be injured than emergency medicine trainees (IRR = 12.4, 95% CI 2.11-72.32). Only 28 of the 88 most recent needlestick injuries were reported to occupational health. Trainees reported a perception of insignificant risk, lack of resources and support for reporting, and injury stigmatization as reasons for not reporting needlestick injuries. CONCLUSIONS: Needlestick injuries were a common underreported risk to medical trainees at TEGH. Future research should investigate strategies to reduce injury and improve reporting among the high-risk and reporting-averse trainees.

Simkania negevensis and acute cellular rejection in lung transplant recipients.

Simkania negevensis infection has been hypothesized to play a role in lung transplant rejection. The incidence of S. negevensis infection and its association with acute cellular rejection (ACR) were determined in a prospective cohort study of 78 lung transplant recipients (LTRs) in Toronto, Canada, and Pittsburgh, USA, from July 2007 to January 2010. Simkania negevensis testing was detected by quantitative polymerase chain reaction (PCR) on bronchoalveolar lavage fluid. The relationship between S. negevensis and ACR was examined using Cox proportional hazards models and generalized linear and latent mixed models. Cumulative incidence estimates for time-to-ACR in S. negevensis PCR-positive vs. PCR-negative LTRs were 52.7% vs. 31.1% at six months and 68.9% vs. 44.6% at one yr, respectively. Although not statistically significant, there was a trend toward a higher risk of ACR among S. negevensis PCR-positive vs. PCR-negative LTRs in all statistical models.

Risk factors for late-onset cytomegalovirus infection or disease in kidney transplant recipients.

BACKGROUND: CMV-D+/R- serostatus is the only well-established risk factor for late-onset cytomegalovirus (CMV) infection/disease (i.e., incident CMV infection/disease after cessation of prophylactic antiviral therapy). This study aimed to explore other potential risk factors for late-onset CMV infection/disease in kidney transplant recipients. METHODS: We conducted a retrospective cohort study of 641 kidney transplant recipients in Toronto, Canada, from January 1, 2003, to December 31, 2010. The cumulative incidence of late-onset CMV infection/disease was assessed using the Kaplan-Meier product-limit method. Potential risk factors for late-onset CMV infection/disease were examined using Cox proportional hazards regression models. RESULTS: Cumulative incidence estimates for CMV infection/disease after prophylaxis cessation in D+/R- versus D+/R+ versus D-/R+ patients were 26.2% versus 7.4% versus 3.1% at 6 months and 30.0% versus 7.7% versus 3.7% at 1 year, respectively. D+/R- serostatus (vs. R+ serostatus) and an estimated glomerular filtration rate of less than 45 mL/min (vs. ≥ 60 mL/min) at prophylaxis cessation were independently associated with late-onset CMV infection/disease (hazard ratio, 4.04 [95% confidence interval, 2.39-6.83]; and hazard ratio, 2.03 [95% confidence interval, 1.07-3.88], respectively). CONCLUSIONS: Patients with lower estimated glomerular filtration rate at prophylaxis cessation may be at an increased risk of late-onset CMV infection/disease and should be considered for more intensive CMV viral load monitoring, particularly within the first year after prophylaxis cessation.