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2.
Infect Control Hosp Epidemiol ; 42(11): 1340-1344, 2021 11.
Article in English | MEDLINE | ID: covidwho-1574695

ABSTRACT

BACKGROUND: Widespread testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) is necessary to curb the spread of coronavirus disease 2019 (COVID-19), but testing is undermined when the only option is a nasopharyngeal swab. Self-collected swab techniques can overcome many of the disadvantages of a nasopharyngeal swab, but they require evaluation. METHODS: Three self-collected non-nasopharyngeal swab techniques (saline gargle, oral swab and combined oral-anterior nasal swab) were compared to a nasopharyngeal swab for SARS-CoV-2 detection at multiple COVID-19 assessment centers in Toronto, Canada. The performance characteristics of each test were assessed. RESULTS: The adjusted sensitivity of the saline gargle was 0.90 (95% CI 0.86-0.94), the oral swab was 0.82 (95% CI, 0.72-0.89) and the combined oral-anterior nasal swab was 0.87 (95% CI, 0.77-0.93) compared to a nasopharyngeal swab, which demonstrated a sensitivity of ˜90% when all positive tests were the reference standard. The median cycle threshold values for the SARS-CoV-2 E-gene for concordant and discordant saline gargle specimens were 17 and 31 (P < .001), for the oral swabs these values were 17 and 28 (P < .001), and for oral-anterior nasal swabs these values were 18 and 31 (P = .007). CONCLUSIONS: Self-collected saline gargle and an oral-anterior nasal swab have a similar sensitivity to a nasopharyngeal swab for the detection of SARS-CoV-2. These alternative collection techniques are cheap and can eliminate barriers to testing, particularly in underserved populations.


Subject(s)
COVID-19 , Outpatients , Humans , Nasopharynx , SARS-CoV-2 , Saliva , Specimen Handling
3.
J Immunol ; 208(2): 429-443, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1572737

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces T cell, B cell, and Ab responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. In this study, we followed T cell and Ab responses in 24 mainly nonhospitalized human subjects who had recovered from PCR-confirmed SARS-CoV-2 infection at two time points (median of 45 and 145 d after symptom onset). Ab responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-spike (anti-S) and anti-receptor binding domain IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. T cell responses to SARS-CoV-2 peptides were determined using intracellular cytokine staining, activation markers, proliferation, and cytokine secretion. All study subjects had a T cell response to at least one SARS-CoV-2 Ag based on at least one T cell assay. CD4+ responses were largely of the Th1 phenotype, but with a lower ratio of IFN-γ- to IL-2-producing cells and a lower frequency of CD8+:CD4+ T cells than in influenza A virus (IAV)-specific memory responses within the same subjects. Analysis of secreted molecules also revealed a lower ratio of IFN-γ to IL-2 and an altered cytotoxic profile for SARS-CoV-2 S- and nucleocapsid-specific responses compared with IAV-specific responses. These data suggest that the memory T cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxicity profile compared with long-term memory to whole IAV within the same subjects.


Subject(s)
Antibody Formation , COVID-19/immunology , Immunity, Cellular , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Th1 Cells/immunology , Adult , Aged , Female , Humans , Male , Middle Aged , Time Factors
4.
PLoS One ; 16(12): e0261003, 2021.
Article in English | MEDLINE | ID: covidwho-1556871

ABSTRACT

The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada's public health policy in response to COVID-19.

5.
Preprint in English | EuropePMC | ID: ppcovidwho-296078

ABSTRACT

Background The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed. Methods Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed;in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence. Results Of 3’334 HCW (median 41 years;80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73% vs .52%, p<0.001);seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16% vs .6%, p<0.001) and hair loss (17% vs .10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago;anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores. Conclusions Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19. summary In this prospective healthcare worker cohort, participants with SARS-CoV-2-positive nasopharyngeal swab were most likely to report long-COVID symptoms, whereas seropositive participants without positive swab were only mildly affected. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue.

6.
Preprint in English | Other preprints | ID: ppcovidwho-295180

ABSTRACT

ABSTRACT Objectives In a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus. Methods Baseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with Coronavirus Disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies. Results A total of 4’818 HCW participated, whereof 144 (3%) were seropositive at baseline. We analysed 107’820 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs . 23 per person, P=0.83) between those with and without positive baseline serology. Among 2’713 HCW with ≥1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2646 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22;95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95%-CI: 0.15-0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95%-CI: 0.39-0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95%-CI: 0.49-0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results. Conclusions Having SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least eight months.

7.
Preprint in English | Other preprints | ID: ppcovidwho-294881

ABSTRACT

ABSTRACT Background There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. We analysed the impact of filtering facepiece class 2 (FFP2) vs . surgical masks on the risk of SARS-CoV-2 acquisition among Swiss healthcare workers (HCW). Methods Our prospective multicentre cohort enrolled patient-facing HCWs from June to August 2020. Participants were asked about COVID-19 risk exposures/behaviours, including preferred mask type when caring for COVID-19 patients outside of aerosol-generating procedures (AGP). For those performing AGPs, we asked whether they used FFP2 irrespective of the patient’s COVID-19 status (i.e. universal use). The impact of FFP2 on i) self-reported SARS-CoV-2-positive nasopharyngeal PCR/rapid antigen tests captured during weekly surveys, and ii) SARS-CoV-2 seroconversion between baseline and January/February 2021 was assessed. Results We enrolled 3’259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2 respirators. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users (median follow-up 242 days);seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was non-significantly associated with a decreased risk for SARS-CoV-2-positive swab (adjusted hazard ratio [aHR] 0·8, 95% CI 0·6-1·0, p=0·052) and seroconversion (adjusted odds ratio [aOR] 0·7, 95% CI 0·5-1·0, p=0·053);household exposure was the strongest risk factor (aHR for positive swab 10·1, p<0·001;aOR for seroconversion 5·0, p<0·001). In subgroup analysis, FFP2 use was clearly protective among those with frequent (>20 patients) COVID-19 exposure (aHR 0·7, p<0·001;aOR 0·6, p=0·035). Universal FFP2 use during AGPs showed no protective effect (aHR 1·1, p=0·7;aOR 0·9, p=0·53). Conclusion Respirators compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients. Funding Swiss National Sciences Foundation, Federal Office of Public Health, Cantonal Health Department St.Gallen

8.
Nat Med ; 27(11): 2012-2024, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526091

ABSTRACT

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

9.
Microbiol Spectr ; : e0088621, 2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1522922

ABSTRACT

The evaluation of humoral protective immunity against SARS-CoV-2 remains crucial in understanding both natural immunity and protective immunity conferred by the several vaccines implemented in the fight against COVID-19. The reference standard for the quantification of antibodies capable of neutralizing SARS-CoV-2 is the plaque-reduction neutralization test (PRNT). However, given that it is a laboratory-developed assay, validation is crucial in order to ensure sufficient specificity and intra- and interassay precision. In addition, a multitude of other serological assays have been developed, including enzyme-linked immunosorbent assay (ELISA), flow cytometry-based assays, luciferase-based lentiviral pseudotype assays, and commercially available human ACE2 receptor-blocking antibody tests, which offer practical advantages in the evaluation of the protective humoral response against SARS-CoV-2. In this study, we validated a SARS-CoV-2 PRNT to assess both 50% and 90% neutralization of SARS-CoV-2 according to guidelines outlined by the World Health Organization. Upon validation, the reference-standard PRNT demonstrated excellent specificity and both intra- and interassay precision. Using the validated assay as a reference standard, we characterized the neutralizing antibody response in specimens from patients with laboratory-confirmed COVID-19. Finally, we conducted a small-scale multilaboratory comparison of alternate SARS-CoV-2 PRNTs and surrogate neutralization tests. These assays demonstrated substantial to perfect interrater agreement with the reference-standard PRNT and offer useful alternatives to assess humoral immunity against SARS-CoV-2. IMPORTANCE SARS-CoV-2, the causal agent of COVID-19, has infected over 246 million people and led to over 5 million deaths as of October 2021. With the approval of several efficacious COVID-19 vaccines, methods to evaluate protective immune responses will be crucial for the understanding of long-term immunity in the rapidly growing vaccinated population. The PRNT, which quantifies SARS-CoV-2-neutralizing antibodies, is used widely as a reference standard to validate new platforms but has not undergone substantial validation to ensure excellent inter- and intraassay precision and specificity. Our work is significant, as it describes the thorough validation of a PRNT, which we then used as a reference standard for the comparison of several alternative serological methods to measure SARS-CoV-2-neutralizing antibodies. These assays demonstrated excellent agreement with the reference-standard PRNT and include high-throughput platforms, which can greatly enhance capacity to assess both natural and vaccine-induced protective immunity against SARS-CoV-2.

10.
Clin Infect Dis ; 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1522160

ABSTRACT

BACKGROUND: Since its emergence in late 2019, SARS-CoV-2 continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions like coughing and care activities like aerosol-generating procedures likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. OBJECTIVE: Develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known COVID-19. METHODS: IDSA formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. RESULTS: The IDSA guideline panel agreed on eight recommendations, including two updated recommendations and one new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included. CONCLUSIONS: Using a combination of direct and indirect evidence, the panel was able to provide recommendations for eight specific questions on the use of PPE for HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2 and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies.

11.
Viruses ; 13(11)2021 11 08.
Article in English | MEDLINE | ID: covidwho-1512696

ABSTRACT

Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n = 22), compared to those that had recovered from other mild respiratory infections (n = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections.

12.
BMC Med ; 19(1): 270, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1496171

ABSTRACT

BACKGROUND: In a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus. METHODS: Baseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with coronavirus disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies. RESULTS: A total of 4812 HCW participated, wherein 144 (3%) were seropositive at baseline. We analyzed 107,807 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P = 0.83) between those with and without positive baseline serology. Among 2712 HCW with ≥ 1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2645 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95% CI 0.15-0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95% CI 0.39-0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95% CI 0.49-0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results. CONCLUSIONS: Having SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least 8 months.


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , Health Personnel , Humans , Prospective Studies , Sentinel Surveillance
13.
Infect Control Hosp Epidemiol ; 41(5): 499-504, 2020 05.
Article in English | MEDLINE | ID: covidwho-1452452

ABSTRACT

OBJECTIVE: Older adults often have atypical presentation of illness and are particularly vulnerable to influenza and its sequelae, making the validity of influenza case definitions particularly relevant. We sought to assess the performance of influenza-like illness (ILI) and severe acute respiratory illness (SARI) criteria in hospitalized older adults. DESIGN: Prospective cohort study. SETTING: The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network undertakes active surveillance for influenza among hospitalized adults. METHODS: Data were pooled from 3 influenza seasons: 2011/12, 2012/13, and 2013/14. The ILI and SARI criteria were defined clinically, and influenza was laboratory confirmed. Frailty was measured using a validated frailty index. RESULTS: Of 11,379 adult inpatients (7,254 aged ≥65 years), 4,942 (2,948 aged ≥65 years) had laboratory-confirmed influenza. Their median age was 72 years (interquartile range [IQR], 58-82) and 52.6% were women. The sensitivity of ILI criteria was 51.1% (95% confidence interval [CI], 49.6-52.6) for younger adults versus 44.6% (95% CI, 43.6-45.8) for older adults. SARI criteria were met by 64.1% (95% CI, 62.7-65.6) of younger adults versus 57.1% (95% CI, 55.9-58.2) of older adults with laboratory-confirmed influenza. Patients with influenza who were prefrail or frail were less likely to meet ILI and SARI case definitions. CONCLUSIONS: A substantial proportion of older adults, particularly those who are frail, are missed by standard ILI and SARI case definitions. Surveillance using these case definitions is biased toward identifying younger cases, and does not capture the true burden of influenza. Because of the substantial fraction of cases missed, surveillance definitions should not be used to guide diagnosis and clinical management of influenza.


Subject(s)
Influenza, Human/diagnosis , Influenza, Human/epidemiology , Aged , Aged, 80 and over , Bias , Canada/epidemiology , Female , Frail Elderly , Hospitalization , Humans , Immunization , Laboratories, Hospital , Male , Prospective Studies , Research , Sensitivity and Specificity , Sentinel Surveillance
14.
CMAJ Open ; 9(4): E929-E939, 2021.
Article in English | MEDLINE | ID: covidwho-1468744

ABSTRACT

BACKGROUND: Health care workers have a critical role in the pandemic response to COVID-19 and may be at increased risk of infection. The objective of this study was to assess the seroprevalence of SARS-CoV-2 immunoglobulin G (IgG) antibodies among health care workers during and after the first wave of the pandemic. METHODS: We conducted a prospective multicentre cohort study involving health care workers in Ontario, Canada, to detect IgG antibodies against SARS-CoV-2. Blood samples and self-reported questionnaires were obtained at enrolment, at 6 weeks and at 12 weeks. A community hospital, tertiary care pediatric hospital and a combined adult-pediatric academic health centre enrolled participants from Apr. 1 to Nov. 13, 2020. Predictors of seropositivity were evaluated using a multivariable logistic regression, adjusted for clustering by hospital site. RESULTS: Among the 1062 health care workers participating, the median age was 40 years, and 834 (78.5%) were female. Overall, 57 (5.4%) were seropositive at any time point (2.5% when participants with prior infection confirmed by polymerase chain reaction testing were excluded). Seroprevalence was higher among those who had a known unprotected exposure to a patient with COVID-19 (p < 0.001) and those who had been contacted by public health because of a nonhospital exposure (p = 0.003). Providing direct care to patients with COVID-19 or working on a unit with a COVID-19 outbreak was not associated with higher seroprevalence. In multivariable logistic regression, presence of symptomatic contacts in the household was the strongest predictor of seropositivity (adjusted odds ratio 7.15, 95% confidence interval 5.42-9.41). INTERPRETATION: Health care workers exposed to household risk factors were more likely to be seropositive than those not exposed, highlighting the need to emphasize the importance of public health measures both inside and outside of the hospital.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/transmission , Cohort Studies , Female , Humans , Immunoglobulin G/blood , Logistic Models , Male , Middle Aged , Occupational Exposure/statistics & numerical data , Ontario/epidemiology , Prospective Studies , Risk Factors , SARS-CoV-2/genetics , Seroepidemiologic Studies , Tertiary Care Centers
15.
BMJ Open ; 11(9): e052842, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1448019

ABSTRACT

INTRODUCTION: There is considerable variability in symptoms and severity of COVID-19 among patients infected by the SARS-CoV-2 virus. Linking host and virus genome sequence information to antibody response and biological information may identify patient or viral characteristics associated with poor and favourable outcomes. This study aims to (1) identify characteristics of the antibody response that result in maintained immune response and better outcomes, (2) determine the impact of genetic differences on infection severity and immune response, (3) determine the impact of viral lineage on antibody response and patient outcomes and (4) evaluate patient-reported outcomes of receiving host genome, antibody and viral lineage results. METHODS AND ANALYSIS: A prospective, observational cohort study is being conducted among adult patients with COVID-19 in the Greater Toronto Area. Blood samples are collected at baseline (during infection) and 1, 6 and 12 months after diagnosis. Serial antibody titres, isotype, antigen target and viral neutralisation will be assessed. Clinical data will be collected from chart reviews and patient surveys. Host genomes and T-cell and B-cell receptors will be sequenced. Viral genomes will be sequenced to identify viral lineage. Regression models will be used to test associations between antibody response, physiological response, genetic markers and patient outcomes. Pathogenic genomic variants related to disease severity, or negative outcomes will be identified and genome wide association will be conducted. Immune repertoire diversity during infection will be correlated with severity of COVID-19 symptoms and human leucocyte antigen-type associated with SARS-CoV-2 infection. Participants can learn their genome sequencing, antibody and viral sequencing results; patient-reported outcomes of receiving this information will be assessed through surveys and qualitative interviews. ETHICS AND DISSEMINATION: This study was approved by Clinical Trials Ontario Streamlined Ethics Review System (CTO Project ID: 3302) and the research ethics boards at participating hospitals. Study findings will be disseminated through peer-reviewed publications, conference presentations and end-users.


Subject(s)
COVID-19 , Genome-Wide Association Study , Humans , Observational Studies as Topic , Prospective Studies , SARS-CoV-2 , Severity of Illness Index
16.
Nat Med ; 27(11): 2012-2024, 2021 11.
Article in English | MEDLINE | ID: covidwho-1402107

ABSTRACT

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

17.
JAMA Netw Open ; 4(9): e2123622, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1391523

ABSTRACT

Importance: Patients undergoing hemodialysis have a high mortality rate associated with COVID-19, and this patient population often has a poor response to vaccinations. Randomized clinical trials for COVID-19 vaccines included few patients with kidney disease; therefore, vaccine immunogenicity is uncertain in this population. Objective: To evaluate the SARS-CoV-2 antibody response in patients undergoing chronic hemodialysis following 1 vs 2 doses of BNT162b2 COVID-19 vaccination compared with health care workers serving as controls and convalescent serum. Design, Setting, and Participants: A prospective, single-center cohort study was conducted between February 2 and April 17, 2021, in Toronto, Ontario, Canada. Participants included 142 patients receiving in-center hemodialysis and 35 health care worker controls. Exposures: BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Main Outcomes and Measures: SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP). Results: Among the 142 participants undergoing maintenance hemodialysis, 94 (66%) were men; median age was 72 (interquartile range, 62-79) years. SARS-CoV-2 IgG antibodies were measured in 66 patients receiving 1 vaccine dose following a public health policy change, 76 patients receiving 2 vaccine doses, and 35 health care workers receiving 2 vaccine doses. Detectable anti-NP suggestive of natural SARS-CoV-2 infection was detected in 15 of 142 (11%) patients at baseline, and only 3 patients had prior COVID-19 confirmed by reverse transcriptase polymerase chain reaction testing. Two additional patients contracted COVID-19 after receiving 2 doses of vaccine. In 66 patients receiving a single BNT162b2 dose, seroconversion occurred in 53 (80%) for anti-spike and 36 (55%) for anti-RBD by 28 days postdose, but a robust response, defined by reaching the median levels of antibodies in convalescent serum from COVID-19 survivors, was noted in only 15 patients (23%) for anti-spike and 4 (6%) for anti-RBD in convalescent serum from COVID-19 survivors. In patients receiving 2 doses of BNT162b2 vaccine, seroconversion occurred in 69 of 72 (96%) for anti-spike and 63 of 72 (88%) for anti-RBD by 2 weeks following the second dose and median convalescent serum levels were reached in 52 of 72 patients (72%) for anti-spike and 43 of 72 (60%) for anti-RBD. In contrast, all 35 health care workers exceeded the median level of anti-spike and anti-RBD found in convalescent serum 2 to 4 weeks after the second dose. Conclusions and Relevance: This study suggests poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in the hemodialysis population, supporting adherence to recommended vaccination schedules and avoiding delay of the second dose in these at-risk individuals.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Aged , Aged, 80 and over , COVID-19/epidemiology , Case-Control Studies , Dose-Response Relationship, Immunologic , Female , Humans , Immunoglobulin G/biosynthesis , Male , Pandemics , Prospective Studies , Renal Dialysis , Spike Glycoprotein, Coronavirus/immunology
18.
Infect Control Hosp Epidemiol ; 42(5): 604-608, 2021 05.
Article in English | MEDLINE | ID: covidwho-1387086

ABSTRACT

In this prospective cohort of 1,012 Swiss hospital employees, 3 different assays were used to screen serum for SARS-CoV-2 antibodies. Seropositivity was 1%; the positive predictive values of the lateral-flow immunoassay were 64% (IgG) and 13% (IgM). History of fever and myalgia most effectively differentiated seropositive and seronegative participants.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Immunoglobulin G/blood , Immunoglobulin M/blood , Personnel, Hospital/statistics & numerical data , Adolescent , Adult , COVID-19/blood , COVID-19/virology , Female , Humans , Immunoassay , Male , Middle Aged , Prevalence , Prospective Studies , SARS-CoV-2 , Seroepidemiologic Studies , Switzerland/epidemiology , Young Adult
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