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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.
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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.
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BackgroundPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. MethodsWe conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. ResultsThe trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. ConclusionsConvalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).
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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.
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ObjectivesSARS-CoV-2 whole-genome analysis has identified three large clades spreading worldwide, designated G, V and S. This study aims to analyze the diffusion of SARS-CoV-2 in Spain/Europe. MethodsMaximum likelihood phylogenetic and Bayesian phylodynamic analyses have been performed to estimate the most probable temporal and geographic origin of different phylogenetic clusters and the diffusion pathways of SARS-CoV-2. ResultsPhylogenetic analyses of the first 28 SARS-CoV-2 whole genome sequences obtained from patients in Spain revealed that most of them are distributed in G and S clades (13 sequences in each) with the remaining two sequences branching in the V clade. Eleven of the Spanish viruses of the S clade and six of the G clade grouped in two different monophyletic clusters (S-Spain and G-Spain, respectively), with the S-Spain cluster also comprising 8 sequences from 6 other countries from Europe and the Americas. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated in the city of Wuhan, China, around November 24, 2019, with a 95% highest posterior density (HPD) interval from October 30-December 17, 2019. The origin of S-Spain and G-Spain clusters were estimated in Spain around February 14 and 18, 2020, respectively, with a possible ancestry of S-Spain in Shanghai. ConclusionsMultiple SARS-CoV-2 introductions have been detected in Spain and at least two resulted in the emergence of locally transmitted clusters, with further dissemination of one of them to at least 6 other countries. These results highlight the extraordinary potential of SARS-CoV-2 for rapid and widespread geographic dissemination.
