ABSTRACT
The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naïve individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naïve individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. Here we characterized, SARS-CoV-2 spike-specific humoral and cellular immunity in naïve and previously infected individuals during and after two-doses of BNT162b2 vaccination. Our results demonstrate that, while the second dose increases both the humoral and cellular immunity in naïve individuals, COVID-19 recovered individuals reach their peak of immunity after the first dose. These results suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.Funding: Research reported in this publication was supported in part by National Cancer Institute of the NIH (5R01HD102614-02; R01CA249204 and R01CA248984) and ISMMS seed fund to EG. The authors gratefully acknowledge use of the services and facilities of the Tisch Cancer Institute supported by the NCI Cancer Center Support Grant (P30 CA196521). MS was supported by a NCI training grant (T32CA078207). This work was supported by ISMMS seed fund to JO; Instituto de Salud Carlos III, COV20-00668 to RCR; Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181) co-financed by European Development Regional Fund “A way to achieve Europe” to EP; Instituto de Salud Carlos III, Spain (COV20/00170); Government of Cantabria, Spain (2020UIC22-PUB 0019) to MLH; Instituto de Salud Carlos III (PI16CIII/00012) to PP; Fondo Social Europeo e Iniciativa de Empleo Juvenil YEI (Grant PEJ2018-004557-A) to MPE; REDInREN 016/009/009 ISCIII; This project has received funding from the European Union’s Horizon 2020 research and innovation programme VACCELERATE under grant agreement No [101037867] to JO.Conflict of Interest: AB declares the filling of a patent application relating to the use of peptide pools in whole blood for detection of SARS-CoV-2 T cells (pending). The other authors declare no competing interests.Ethical Approval: The study protocols for the collection of clinical specimens from individuals with and without SARS-CoV-2 infection were reviewed and approved by Hospital La Paz, Hospital 12 de Octubre, Hospital Gregorio Marañón, IIS-Fundación Jimenez Díaz, Hospital Universitario Marqués de Valdecilla-IDIVAL and Hospital Puerta de Hierro Clinical Research Ethics Committee (CEIm), and Mount Sinai Hospital Institutional Review Board (IRB).
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , Multiple Sclerosis , Cross Infection , Neoplasms , COVID-19ABSTRACT
The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has been questioned. Here we characterized SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naive individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
Abstract Objectives: To analyse temporal trends in SARS-CoV-2 anti-nucleocapsid IgG throughout the four rounds of the nationwide seroepidemiologic study ENE-COVID (April-November 2020), and to compare the fourth-round results of two immunoassays detecting antibodies against nucleocapsid and to S protein receptor-binding domain (RBD). Methods: A chemiluminescent microparticle immunoassay (CMIA) was offered to all participants in the first three rounds (Abbott; anti-nucleocapsid IgG). In the fourth round we offered this test and a chemiluminescence immunoassay (CLIA) (Beckman; anti-RBD IgG) to i) a randomly selected sub-cohort, ii) participants who were IgG-positive in any of the three first rounds; and iii) participants who were IgG-positive in the fourth round by point-of-care immunochromatography. Results: Immunoassays involving 10,153 participants (82.2% of people invited to donate samples) were performed in the fourth round. A total of 2595 participants (35.1% of participants with immunoassay results in the four rounds) were positive for anti-nucleocapsid IgG in at least one round. Anti-nucleocapsid IgG became undetectable in 43.3% of participants with positive first-round results. Pneumonia was more frequent in participants with anti-nucleocapsid IgG in all four rounds (11.2%) than those in which IgG became undetectable (2.4%). In fourth round, anti-nucleocapsid and anti-RBD IgG were detected in 5.5% and 5.4% participants of the randomly selected sub-cohort, and in 26.6% and 25.9% participants with at least one previous positive result, respectively. Agreement between techniques was 90.3% (kappa: 0.72). Conclusions: The response of IgG to SARS-CoV-2 is heterogeneous and conditioned by infection severity. A substantial proportion of the SARS-CoV-2 infected population may have negative serologic results in the post-infection months.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
The standard RT-PCR assay for COVID-19 is laborious and time-consuming, limiting the availability of testing. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the reliability of the PanbioTM COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) for SARS-CoV-2 in nasopharyngeal swab specimens. This was a prospective multicenter study in ten Spanish university hospitals of patients from hospital units with clinical symptoms or epidemiological criteria for COVID-19. Patients whose onset of symptoms or exposure was more than 7 days earlier were excluded. Two nasopharyngeal exudate samples were taken to perform the PanbioRT and a diagnostic RT-PCR test. Among the 958 patients studied, 359 (37.5%) were positive by RT-PCR and 325 (33.9%) were also positive by the PanbioRT. Agreement was 95.7% (kappa score: 0.90). All 34 false-negative PanbioRT results were in symptomatic patients, with 23.5% of them at 6-7 days since the onset of symptoms and 58.8% presenting CT >30 values for RT-PCR, indicating a low viral load. Overall sensitivity and specificity for the PanbioRT were 90.5% and 98.8%, respectively. The PanbioRT provides good clinical performance as a point-of-care test, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. While this study has had a direct impact on the national diagnostic strategy for COVID-19 in Spain, the results must be interpreted based on the local epidemiological context.
Subject(s)
COVID-19ABSTRACT
ObjectiveTo estimate the range of the age- and sex-specific infection fatality risk (IFR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on confirmed coronavirus disease 2019 (COVID-19) deaths and excess all-cause deaths. DesignNationwide population-based seroepidemiological study combined with two national surveillance systems. Setting and participantsNon-institutionalized Spanish population of all ages. Main outcome measuresThe range of IFR was calculated as the observed number of COVID-19 deaths and excess deaths divided by the estimated number of SARS-CoV-2 infections in the non-institutionalized Spanish population. Laboratory-confirmed COVID-19 deaths were obtained from the National Epidemiological Surveillance Network (RENAVE) and excess all-cause deaths from the Monitoring Mortality System (MoMo) up to July 15, 2020. SARS-CoV-2 infections were derived from the estimated seroprevalence by a chemiluminiscent microparticle immunoassay for IgG antibodies in 61,092 participants in the ENE-COVID nationwide serosurvey between April 27 and June 22, 2020. ResultsThe overall IFR (95% confidence interval) was 0.8% (0.8% to 0.9%) for confirmed COVID-19 deaths and 1.1% (1.0% to 1.2%) for excess deaths. The IFR ranged between 1.1% (1.0% to 1.2%) and 1.4% (1.3% to 1.5%) in men and between 0.6% (0.5% to 0.6%) and 0.8% (0.7% to 0.8%) in women. The IFR increased sharply after age 50, ranging between 11.6% (8.1% to 16.5%) and 16.4% (11.4% to 23.2%) in men [≥]80 years and between 4.6% (3.4% to 6.3%) and 6.5% (4.7% to 8.8%) in women [≥]80 years. ConclusionThe sharp increase in SARS-CoV-2 IFR after age 50 was more marked in men than in women. Fatality from COVID-19 is substantially greater than that reported for other common respiratory diseases such as seasonal influenza. WHAT IS ALREADY KNOWN ON THIS TOPICInfection fatality risk (IFR) for SARS-CoV-2 is a key indicator for policy decision making, but its magnitude remains under debate. Case fatality risk, which accounts for deaths among confirmed COVID-19 cases, overestimates SARS-CoV-2 fatality as it excludes a large proportion of asymptomatic and mild-symptomatic infections. Population-based seroepidemiological studies are a valuable tool to properly estimate the number of infected individuals, regardless of symptoms. Also, because ascertainment of deaths due to COVID-19 is often incomplete, the calculation of the IFR should be complemented with data on excess all-cause mortality. In addition, data on age- and sex-specific IFR are scarce, even though age and sex are well known modifiers of the clinical evolution of COVID-19. WHAT THIS STUDY ADDSUsing the ENE-COVID nationwide serosurvey and two national surveillance systems in Spain, this study provides a range of age- and sex-specific IFR estimates for SARS-CoV-2 based on laboratory-confirmed COVID-19 deaths and excess all-cause deaths. The risk of death was very low among infected individuals younger than 50 years, but it increased sharply with age, particularly among men. In the oldest age group ([≥]80 years), it was estimated that 12% to 16% of infected men and 5% to 6% of infected women died during the first epidemic wave.