Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals

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.

Evolution of antibodies against SARS-CoV-2 over seven months: experience of the Nationwide Seroprevalence ENE-COVID Study in Spain

ObjectivesTo 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). MethodsA 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. ResultsImmunoassays 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). ConclusionsThe 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.

Multicenter evaluation of the Panbio COVID-19 Rapid Antigen-Detection Test for the diagnosis of SARS-CoV-2 infection

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.

SARS-CoV-2 infection fatality risk in a nationwide seroepidemiological study

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.

Establishing the validity of different susceptibility testing methods to evaluate the in vitro activity of amoxicillin-clavulanate against Escherichia coli.

Amoxicillin-clavulanate MICs of 160 Escherichia coli isolates with characterized resistance mechanisms were obtained by 2 MIC gradient strip brands, 3 automated systems, and reference ISO microdilution method using EUCAST (fixed 2µg/mL clavulanate) and CLSI (2:1 ratio) criteria. Discrepancies, mainly obtained with gradient strips, lead to an essential agreement range of 76.2-92.5.

Sequential outbreaks in a Spanish hospital caused by multiresistant OXA-58-producing Acinetobacter baumannii ST92.

The aim of this study was to assess the epidemiology and molecular basis of the infection and dissemination of multidrug-resistant Acinetobacter baumannii (MDRAB) in three sequential outbreaks at the intensive care units (ICUs) of a tertiary university hospital in Granada, Spain, between 2009 and 2011. Strains from all patients infected and/or colonized by MDRAB during outbreak periods were characterized using PFGE and multilocus sequence typing (MLST). The first outbreak appeared in the summer of 2009 involving 38 ICU patients: 25 from a Traumatology-Rehabilitation hospital (TRH) and 13 from a Medical-Surgery hospital (MSH). Between 2010 and 2011, outbreaks were limited to the MSH-ICU, affecting 9 and 11 patients, respectively. Two PFGE types were detected. In the 2009 outbreak, two clones were identified: profile 1 strains were isolated at the TRH, whilst profile 2 was isolated at the MSH. Only one clone was identified in the 2010 and 2011 outbreaks: the profile 2 clone detected at the MSH in 2009. After MLST analysis, a single sequence type (ST92) was identified. This suggested that an endemic strain could evolve and cause localized outbreaks in vulnerable patients. Multiplex PCR for OXA group enzymes yielded a positive result for blaOXA-58-like and blaOXA-51-like genes, and gene sequencing showed the presence of blaOXA-58. However, the absence of ISAba1 upstream of the blaOXA-51-like gene suggested the absence of OXA-51 expression. The susceptibility pattern was not an appropriate method for MDRAB surveillance, as several susceptibility patterns were identified in a single clone. Consequently, molecular methods of characterization are recommended for epidemiological surveillance of MDRAB.

Clinical efficacy of a bleaching system based on hydrogen peroxide with or without light activation.

The objective of the present study was to assess the clinical efficacy of a dental bleaching system based on hydrogen peroxide with or without light activation. This randomized controlled trial evaluated the effect of the light when applied to the hydrogen peroxide by using a split-mouth design with 21 patients, with light activation in one hemi-arch but not in the other. The bleaching agent was QuickWhite 35% hydrogen peroxide and activation was conducted with a diode lamp (Luma Cool). The Classic Vita Guide was used to score tooth shades. Two consecutive applications of hydrogen peroxide were made to one hemi-arch, each light-activated for 10 min. The other hemi-arch was then identically treated but without light activation. After removal of the bleaching agent, the shade was re-scored and the Wilcoxon signed ranks test was used to compare differences in tooth shade values. The bleaching treatment produced significant shade changes (P < 0.01) in both hemi-arches. After treatment, there were no statistically significant differences between light-treated and non-light-treated tooth types (central incisors, lateral incisors, and canines). However, taking central incisor, lateral incisor, and canine as a group, comparison between each hemi-arch showed a significant effect in the hemi-arch with light activation (P < 0.05). The use of diode light with a 35% hydrogen peroxide gel slightly improved the dental bleaching.