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1.
PLoS Med ; 19(5): e1003991, 2022 05.
Article in English | MEDLINE | ID: covidwho-1846918

ABSTRACT

BACKGROUND: Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants. METHODS AND FINDINGS: In a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231-556] and 214 [95% CI 153-299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11-30] and 14 [95% CI 8-25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02-0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data. CONCLUSIONS: Overall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cohort Studies , Health Personnel , Humans , Netherlands/epidemiology , Prospective Studies , SARS-CoV-2/genetics
2.
Cell Rep Med ; 3(1): 100486, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1569129

ABSTRACT

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , /immunology , COVID-19/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Vaccination/methods , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/virology , Female , Follow-Up Studies , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Neutralization Tests , Prospective Studies , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome
3.
Elife ; 102021 11 23.
Article in English | MEDLINE | ID: covidwho-1529013

ABSTRACT

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.


Subject(s)
COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Viral/blood , Coronavirus/immunology , Cross Reactions/immunology , Healthy Volunteers , Humans , Immunoglobulin G/immunology , Macaca , Middle East Respiratory Syndrome Coronavirus/immunology , Principal Component Analysis , Protein Domains/immunology , Serum/immunology , Serum/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Tetanus Toxoid/immunology , /immunology
4.
EBioMedicine ; 72: 103589, 2021 10.
Article in English | MEDLINE | ID: covidwho-1433161

ABSTRACT

BACKGROUND: To optimise the use of available SARS-CoV-2 vaccines, some advocate delaying second vaccination for individuals infected within six months. We studied whether post-vaccination immune response is equally potent in individuals infected over six months prior to vaccination. METHODS: We tested serum IgG binding to SARS-CoV-2 spike protein and neutralising capacity in 110 healthcare workers, before and after both BNT162b2 messenger RNA (mRNA) vaccinations. We compared outcomes between participants with more recent infection (n = 18, median two months, IQR 2-3), with infection-vaccination interval over six months (n = 19, median nine months, IQR 9-10), and to those not previously infected (n = 73). FINDINGS: Both recently and earlier infected participants showed comparable humoral immune responses after a single mRNA vaccination, while exceeding those of previously uninfected persons after two vaccinations with 2.5 fold (p = 0.003) and 3.4 fold (p < 0.001) for binding antibody levels, and 6.4 and 7.2 fold for neutralisation titres, respectively (both p < 0.001). The second vaccine dose yielded no further substantial improvement of the humoral response in the previously infected participants (0.97 fold, p = 0.92), while it was associated with a 4 fold increase in antibody binding levels and 18 fold increase in neutralisation titres in previously uninfected participants (both p < 0.001). Adjustment for potential confounding of sex and age did not affect these findings. INTERPRETATION: Delaying the second vaccination in individuals infected up to ten months prior may constitute a more efficient use of limited vaccine supplies. FUNDING: Netherlands Organization for Health Research and Development ZonMw; Corona Research Fund Amsterdam UMC; Bill & Melinda Gates Foundation.


Subject(s)
Antibodies, Viral/blood , Antibody Formation , COVID-19 Vaccines/pharmacology , COVID-19 , SARS-CoV-2/immunology , Adult , COVID-19 Vaccines/therapeutic use , Female , Health Personnel , Humans , Immunity, Humoral , Immunoglobulin G/blood , Male , Middle Aged , Netherlands , Prospective Studies , Time Factors , Treatment Outcome
5.
Sci Adv ; 7(36): eabj5365, 2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1403006

ABSTRACT

Emerging SARS-CoV-2 variants of concern (VOCs) pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three VOCs (B.1.1.7, B.1.351, and P.1) in cohorts of COVID-19 convalescent patients (n = 69) and Pfizer-BioNTech vaccine recipients (n = 50). Spike binding and neutralization against all three VOCs were substantially reduced in most individuals, with the largest four- to sevenfold reduction in neutralization being observed against B.1.351. While hospitalized patients with COVID-19 and vaccinees maintained sufficient neutralizing titers against all three VOCs, 39% of nonhospitalized patients exhibited no detectable neutralization against B.1.351. Moreover, monoclonal neutralizing antibodies show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1 but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOCs and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOCs.

6.
JAMA Netw Open ; 4(7): e2118554, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1328587

ABSTRACT

Importance: It is unclear when, where, and by whom health care workers (HCWs) working in hospitals are infected with SARS-CoV-2. Objective: To determine how often and in what manner nosocomial SARS-CoV-2 infection occurs in HCW groups with varying exposure to patients with COVID-19. Design, Setting, and Participants: This cohort study comprised 4 weekly measurements of SARS-CoV-2-specific antibodies and collection of questionnaires from March 23 to June 25, 2020, combined with phylogenetic and epidemiologic transmission analyses at 2 university hospitals in the Netherlands. Included individuals were HCWs working in patient care for those with COVID-19, HCWs working in patient care for those without COVID-19, and HCWs not working in patient care. Data were analyzed from August through December 2020. Exposures: Varying work-related exposure to patients infected with SARS-CoV-2. Main Outcomes and Measures: The cumulative incidence of and time to SARS-CoV-2 infection, defined as the presence of SARS-CoV-2-specific antibodies in blood samples, were measured. Results: Among 801 HCWs, there were 439 HCWs working in patient care for those with COVID-19, 164 HCWs working in patient care for those without COVID-19, and 198 HCWs not working in patient care. There were 580 (72.4%) women, and the median (interquartile range) age was 36 (29-50) years. The incidence of SARS-CoV-2 was increased among HCWs working in patient care for those with COVID-19 (54 HCWs [13.2%; 95% CI, 9.9%-16.4%]) compared with HCWs working in patient care for those without COVID-19 (11 HCWs [6.7%; 95% CI, 2.8%-10.5%]; hazard ratio [HR], 2.25; 95% CI, 1.17-4.30) and HCWs not working in patient care (7 HCWs [3.6%; 95% CI, 0.9%-6.1%]; HR, 3.92; 95% CI, 1.79-8.62). Among HCWs caring for patients with COVID-19, SARS-CoV-2 cumulative incidence was increased among HCWs working on COVID-19 wards (32 of 134 HCWs [25.7%; 95% CI, 17.6%-33.1%]) compared with HCWs working on intensive care units (13 of 186 HCWs [7.1%; 95% CI, 3.3%-10.7%]; HR, 3.64; 95% CI, 1.91-6.94), and HCWs working in emergency departments (7 of 102 HCWs [8.0%; 95% CI, 2.5%-13.1%]; HR, 3.29; 95% CI, 1.52-7.14). Epidemiologic data combined with phylogenetic analyses on COVID-19 wards identified 3 potential HCW-to-HCW transmission clusters. No patient-to-HCW transmission clusters could be identified in transmission analyses. Conclusions and Relevance: This study found that HCWs working on COVID-19 wards were at increased risk for nosocomial SARS-CoV-2 infection with an important role for HCW-to-HCW transmission. These findings suggest that infection among HCWs deserves more consideration in infection prevention practice.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , COVID-19/genetics , Personnel, Hospital , Phylogeny , Population Surveillance , SARS-CoV-2/immunology , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Serological Testing , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged
8.
Clin Microbiol Infect ; 27(2): 264-268, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-932986

ABSTRACT

OBJECTIVE: To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. METHODS: We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. RESULTS: Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81-1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24-2.02) in the full model. CONCLUSIONS: After adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in hospitalised patients with COVID-19.


Subject(s)
COVID-19/drug therapy , Chloroquine/therapeutic use , Hospitals/standards , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/pathology , Female , Hospital Mortality , Hospitals/statistics & numerical data , Humans , Hydroxychloroquine/therapeutic use , Male , Middle Aged , Netherlands/epidemiology , SARS-CoV-2 , Standard of Care
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