BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

SARS-CoV-2 antibody response eight months after vaccination with mRNA vaccines. Influence of prior SARS-CoV-2 exposure

BackgroundLimited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age.MethodsUsing data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan–Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups.ResultsAmong 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, −2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age).ConclusionsOur findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.)

BackgroundVaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines.MethodsWe used a test-negative case–control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants.ResultsVaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults.ConclusionsWe observed limited waning in vaccine effectiveness against Covid-19–related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.

COVID-19 severity, rather than sex or age, predicts SARS-CoV-2 kinetics, and SARS-CoV-2 viral load from lower respiratory tract specimens may predict severe disease days before clinical deterioration for COVID-19 patients.

BackgroundWith large waves of infection driven by the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose.MethodsTo evaluate the early effectiveness of a fourth dose of the BNT162b2 vaccine for the prevention of Covid-19–related outcomes, we analyzed data recorded by the largest health care organization in Israel from January 3 to February 18, 2022. We evaluated the relative effectiveness of a fourth vaccine dose as compared with that of a third dose given at least 4 months earlier among persons 60 years of age or older. We compared outcomes in persons who had received a fourth dose with those in persons who had not, individually matching persons from these two groups with respect to multiple sociodemographic and clinical variables. A sensitivity analysis was performed with the use of parametric Poisson regression.ResultsThe primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction–confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19–related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19–related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19–related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19. In sensitivity analyses, estimates of relative effectiveness against documented infection were similar to those in the primary analysis.ConclusionsA fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19–related outcomes among persons who had received a third dose at least 4 months earlier. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)

The common severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has infected approximately 600 million people across 228 countries worldwide, leaving behind natural immunity.1 Acute COVID-19 infection can cause a cytokine storm that leads to acute respiratory failure (ARDS) and death,2 while severe inflammatory disease can result in chronic polymyositis syndrome in children (PIMS).3 Almost half (44.8%) of symptomatic infections in children and adults manifest as varied symptoms related to chronic infection, in the form of long-COVID/post-COVID clinical syndrome, cognitive and physical deficits, pulmonary fibrosis, myocarditis, or neurological deficits.4, 5 The findings so far show that to acquire antiviral immunity to SARS-CoV-2, one does not need to come into contact with the virus and become infected.6 Being around immunized people can provide a cellular and humoral response. To what extent is it active and provides self-immunity? How to check if we have acquired the appropriate antivirus response, or only had contact with it? When should a booster be given? The situation applies to everyone, including the healthy, those sick with a viral disease in any stage, those with impaired immunity, and young people. The data we collected show that it is necessary to measure the concentration of IgG-specific antibodies after the onset of SARS-CoV-2 and to measure the concentration of post-vaccine IgG (anti-S, anti-RBD, and S-RBD).6 IgM and IgG antibody levels (SARS-CoV-2-specific) may indicate early- or late-phase infection.7 Administration of antibody response acquisition during the early phase has only demonstrated therapeutic implications for symptomatic COVID-19 cases,8 and vaccination of people with a history of SARS-CoV-2 without knowledge of their humoral response is considered safe.9 In our hospital, most medical staff and patients underwent vaccinations without knowing that they had acquired a humoral response beforehand.10 The decline in humoral immunity over time following coronavirus infection, including SARS-CoV-2, is typical in mild cases.11-16 Then, do all infections require antibody monitoring? Barrière et al.17 found that after administering a second dose of the vaccine (complete vaccination) in cancer patients, the individual humoral anti-S antibody response level could be determined after three to four weeks. It has been proven that the level of S-RBD antibodies is correlated with protection against symptomatic SARS-CoV-2 infection,18, 19 and not asymptomatic infection.20 Thus, after the third dose and subsequent boosters, does the level of only anti-S antibodies determine immunity? In a selected population of healthy people, the level of the humoral response can last up to 13 months.19 During our study, the Delta strain of SARS-CoV-2 accounted for over 95% of infections in Poland. At that time, rapid neutralization by current vaccines of the new Delta virus20, 21 was reported after complete inoculation with BNT162b2. We asked whether, during the next wave of infections in Europe with the different Omicron virus types, the administration of a booster in healthy people would stimulate the immune system again,22, 23 or if it would only cause an increase in the S-RBD in response to the vaccine? The description of five different courses of SARS-CoV-2 infection until the administration of subsequent doses of the Comirnaty vaccine shows that a specific immune response expires approximately 1 year after the onset of the disease and is not induced after subsequent artificial immunization.10 We call this effect vanishing antibodies. Another illness with a new variant of the SARS-CoV-2 virus can stimulate a new response to a different level.24-26 We call this a new set-up. In other data, currently unpublished, article focused on a year-long case observation of the COVID-19 humoral response, we saw that an early double infection (without or after vaccination), rather than a third booster, raises antibodies to a higher “protective” IgG level. Before vaccines were introduced in 2021, the natural immunity in the SARS-CoV-2 pandemic was investigated by analyzing antibody concentrations. Antibody measurements were analyzed routinely for oncology patients and hospital staff for medical purposes during the COVID-19 pandemic. Retrospectively, we decided to follow five previously selected people for approximately 24 months—with most measurements taken monthly (timeline). (Supplementary Table). The complete characteristics of the antibody collection in five subjects (Case #1,2,3,4,5) in months (samples timeline). Event: SARS—SARS-CoV-2 infection time (positive PCR or antigen test); Com1, Com2, Com3, Com4—vaccination time (Comirnaty). Three patients (#2, #4, #5) and two hospital staff persons (#1, #3) were chosen. Case #2 was chosen because of their rapid response to SARS-CoV-2 infection (hyper-responder with SARS-CoV-2 IgG > 2000 AU/mL in less than 14 days), providing an excellent case of early seroconversion relevant to acute viral infection. The other two persons were selected as the controls, one being COVID-19 convalescent (#3) and one lacking a SARS-CoV-2 history (#1). The other two patients passed COVID-19 twice with mild (#4) and severe (#5) respiratory problems. Case #3 stayed at the hospital and was cured against COVID-19 using remdesivir (Veklury) for five days. Case #1 patient was chosen because of a lack of a history of COVID-19, but analyses of his seroconversion proved past SARS-CoV-2 infection (IgG cut-off > 0.2 AU/mL). Case #4 stayed and cured COVID-19 at home. Case #5 remained at the hospital because of bilateral pneumonia and was given steroids and early plasma antibodies. All five were vaccinated with BNT162b2 messenger RNA (mRNA) (Comirnaty) according to the manufacturer's schedules and took booster vaccines at different times (gray arrows in figures; Com1, Com2, Com3, Com4). Chest CTs for Cases #2, #3, and #5 showed no post-COVID changes 3 months after treatment. Our study materials were blood specimens taken through venipuncture sampling. The concentration of antibodies was evaluated 4 hours after blood collection. If an immediate assessment was impossible, the serum was collected and stored at –80°C. Due to the fact that most of the data (2021) are in AU/mL, the results of measurements in BAU/mL in 2022 were converted into AU/mL. The antibody concentrations were detected by the chemiluminescent immunoassay CLIA (MAGLUMI; Snibe Diagnostic). Per the manufacturer's protocol, results greater or equal to 1.0 AU/mL of SARS-CoV-2 IgG, IgM, and S-RBD were considered reactive and positive. The maximum limits of the antibody measurements were assumed: 2000 AU/mL of S-RBD (initially, it was 100 AU/mL), with the upper limit of the SARS-CoV-2 antibody measurements being 2000 AU/mL. According to our earlier observations in this population, the cut-off value for SARS-CoV-2 IgG should be >0.2 AU/mL for a positive test result. Antibody tests were ordered by a hospital doctor at different times, from vaccination to illness. The results are presented in a table depending on the time of the test (timeline). The patients provided their written consent for performing humoral immunity tests and for participating in this study. The Bioethics Commission of the Medical University provided consent for our research. SARS-CoV-2 IgM with IgG; SARS-CoV-2 IgG with S-RBD IgG; (A‘) or (B‘) and (B“) is a part of the diagram (A) or (B), respectively, to explain the dynamic changes of humoral response; (C) All three antibody concentrations are time-related in the logarithmic chart. Figures 1-5 presents the humoral response of each person after infection and vaccination in time. The legend in the figures shows arrows indicating systemic vaccinations (Com1, Com2, Com3, and Com4) and the symbol of the virus pointing to SARS infections. Figure 1. Case #1: (A) All IgG and IgM antibodies (measurements 1–24). A retrospective case study showed that the person had had SARS-CoV-2 infection in October 2020 without clinical symptoms, so we present (A‘) an additional diagram with only 1–20 measurements separately to point out this phenomenon. There is a typical seroconversion, seen as an increase in IgM and IgG, assumed as positive results (cut-offs: IgM > 1.0 AU/mL and IgG > 0.2 AU/mL). The results should be considered clinically asymptomatic of previous SARS-CoV-2 infection. As hospital staff, he was routinely vaccinated in January 2021 with two doses of BNT162b2 (Comirnaty) on a schedule over 28 days (see arrows). (B) Postvaccination effects are seen as S-RBD gains and triple antibody resynthesis in SARS-CoV-2 infection and vaccination ([A‘] The three peaks of IgM and IgG mean three seroconversions in a row). (C) Logarithmic representation of the three antibody concentrations. Notable here is a conversion to higher SARS-CoV-2 IgG concentrations than baseline before SARS-CoV-2 infection at the beginning of the diagram. A booster was given 8 months after the second dose of Comirnaty (see arrow) due to another wave of illness (autumn) for medical personnel (only increased S-RBD). On the contrary, at that time, the second vaccination did not work—(B) only increased S-RBD after the booster, but together with COVID-19 (raised S-RBD with SARS-CoV-2 IgG). This phenomenon is called enhanced humoral response without classical seroconversion (fast release IgG-specific antibodies). (C) After a few months, he passed SARS-CoV-2 asymptomatically, which provided a new set-up of humoral response (in the red frame). Case #2: (A) Perspective case analysis; the person, had symptomatic COVID-19 infection in March 2021, with a sore throat and muscles, a fever, and the chills. (A) Antibody collection for assays was routinely scheduled (considered a hyper-responder) as a hospital-monitored oncology patient, vaccinated in July 2021 with two doses of BNT162b2 (Comirnaty) on a schedule over 28 days (see arrows). A booster was given after half a year delay, as an auto-immunologic person. (C) A logarithmic representation of the three antibody concentrations. (B) Postvaccination effects, shown as an increase in S-RBD extended to 6 months and no resynthesis of antibodies in the vaccine prompt. (B, C) No fluctuations in the IgM and IgG concentrations. The conversion to higher IgG concentrations before SARS-CoV-2 infection and the exceptional smooth/stable course of the immune antibody curves are noteworthy. (C) A new set-up of antibodies can be seen in the red frame. Case #3: (A) Retrospective case analysis. The person had symptomatic COVID-19 infection in December 2020, including a sore throat, a cough, a fever, and dyspnea. Routinely, antibodies were collected for assay; (A‘) during inpatient treatment, remdesivir (Veklury) was administered for 5 days while being monitored by medical personnel in the hospital, and vaccinations occurred in January and in May 2021 with two doses of BNT162b2 (Comirnaty) because this patient underwent an urgent spine operation in March. A booster was given 5 months after the second dose of Comirnaty because of lost antibodies—SARS-CoV-2 IgG of 0.26 AU/mL and S-RBD IgG of 32.40 AU/mL (see arrows). (B) Here, we can see the postvaccination effects, shown as an increase in both S-RBD and SARS-CoV-2 IgG extended to over 3 months, as well as a decrease in IgG antibodies in the prompt for SARS-CoV-2 (IgG = 0.22 AU/mL and IgM = 0.05 AU/mL) and vaccination (S-RBD IgG = 63.56 AU/mL) after 5 months. Case #4: (A) Retrospective case analysis. Delayed humoral response. She past twice SARS-CoV-2 with mild symptoms (COVID-19). She is an out-patient at the breast unit. In Figure 4 (A) and (A’), we see a crossing-line dynamic of all antibodies with little correlation with vaccination (Com3; timeline 24). Figure 4. (B), (B‘), and (C) present delayed effects in time SARS-CoV-2 infection (ending “old” SARS-CoV-2 IgG and replacing them with “new”). Now all three antibodies are in response. Building a new humoral strategy: seroconversion (IgM), humoral response (S-RBD), immunity (SARS-CoV-2 IgG). That is also an example of a new set-up raise of IgG-specific antibodies at the end of observation. That person is still a riddle. That is why she did not yet decide on vaccination (Com4). Case #5: Figure 5 (A) Retrospective case analysis (measurement 2−39). The selected patient underwent COVID-19 with pneumonia and was administered steroids for respiratory failure and convalescent plasma with antibodies. Another “reinfection” of SARS-CoV-2 may have been due to the long-standing genetic material of the virus (RT-PCR positive) before urological surgery (no clinical correlation). Figure 5 (A), (A’), (B), and (C) are the only evidence of correlation with vaccinations (Com1 and Com2). As you can see, stable levels of the three classes of antibodies are maintained in cancer patients after surgery and prostate cancer hormone therapy (Com3 and Com4 vaccinations). This is evidence that COVID-19 in some immunosuppressed patients is well tolerated. Due to the significant decrease in immunity, the antibodies reduction, and the patient's clinical condition, a third dose of the vaccine was used (Figure 3A',B). After a few months, he passed into mild symptomatic COVID-19, cured after five days by molnupiravir (Lagevrio), which provided a new set-up of humoral responses (Figure 3C in the red frame). A logarithmic representation of all three antibody concentrations can be seen in Figures 1C, 2C, 3C, 4C, and 5C. The effect of the new increasing level of IgG antibodies was obtained. Conversion to higher IgG concentrations was noticeable (after disease and after complete vaccination) initially after infection with SARS-CoV-2 and a symmetrical course of S-RBD IgG curves of immune antibodies in the time immediately after the third dose of Comirnaty. There was a difference in antibody surge after COVID-19 getting sick with the boosted vaccine (third dose) between a symptomatic patient (Figure 3B) and SARS-CoV-2 asymptomatic patient (Figure 1B). The symptom convalescent patient had a higher IgG-specific level. Following autoimmunity (Case #2), the antibody response after disease and inoculation was stable. Significantly, it was strengthened by administering the first mRNA vaccine, respectively, after 3 months. The results indicate that the active autoimmune disease stabilized the level of specific IgG after systemic mRNA vaccination for at least half a year. Looking at all cases of vaccinated convalescents, we believe a booster dose should be given later than 28 days after SARS-CoV-2 infection. Then, we can observe fluctuations in antibodies, suggesting a change in response to the subsequent immunization, depending on the patient's condition. We expected a longer duration of neutralizing antibodies after vaccination. The level of postvaccine IgG antibodies decreased when vaccination was performed within 3 months after disease onset, depending on the patient's condition. We can change this by appropriately tracking S-RBD IgG and SARS-CoV-2 IgG antibodies 1 month after the disease.17 According to observations, raising IgG-specific antibodies will better occur by administering the vaccine's second (next) dose 3 months after the first. The administered booster dose (third dose) only increased the concentration of S-RBD antibodies. Despite the decrease in specific IgG, their level was higher than before disease and vaccination. Declining IgG-specific antibodies were observed. S-RBD IgG levels are not correlated with SARS-CoV-2 IgG levels in vaccinated convalescents,10 but they are related to symptomatic ones.16 Surprisingly, there was no apparent spike in IgG antibody levels after the third dose of the vaccine after 6 months, despite a persistently elevated level. Based on the collected data, we suggest that monitoring S-RBD antibodies is sensitive, but not equivalent to a specific humoral response for SARS-CoV-2 IgG. The observations of the five presented cases show that the measurement of S-RBD correlates with specific IgG only in the period from 1 to 3 months following disease and inoculation, but not for the booster doses given in the 6 months after the initiation of vaccination. Many clinical data indicate that vaccination with a third dose of Comirnaty is useful in immunocompromised people,10, 11 the chronically ill,12 or people undergoing oncological treatment.13, 14 An analysis of specific antibody concentration charts at a cut-off for SARS-CoV-2 of >0.2 AU/mL was used,10 allowing us to observe asymptomatic COVID-19 and the natural course of the disease.15 Patterns of antibody seroconversion in response to SARS-CoV-2 infection and the BNT162b2 mRNA vaccine were apparent in the five separate cases. In the case of Case #3, it turned out to be effective. Currently, a wave of infection with the SARS-CoV-2 virus strain Omicron is going through Europe and the USA, as the BNT162b2 vaccine is effective against this strain. The ideal past seroconversion is when IgG antibodies are formed after stimulation and are maintained for longer. For Case #1, Comirnaty vaccination needed to be postponed one more month after getting sick; for Case #2, double vaccination did not show/change anything (excess antibodies); for Case #3, in terms of the vaccination, the third dose significantly improved the initial level of antibodies, indicating that it is safe and advisable, and similarly to Case #1, the first dose of the Comirnaty vaccine was taken too early. Analyzing a new set-up in these five cases shows that in Case #2, subsequent infection was not needed to reach a stable level of IgG antibodies. To sum up, administration of the vaccine too early in the case of people with excess antibodies (e.g., Case #2) does not produce the expected effect, as too early an administration (Cases #1 and #3) does not allow to hit the serological window after falling ill. Following readministration (Case #3) after 5 months from the administration of the first dose, based on individual indications for vaccination, the level of antibodies responds correctly. The analysis of these five cases of antibody changes over time during the COVID-19 pandemic provides students training material and allows them to observe and control the effects of treatment—including when to administer the third or subsequent dose of the vaccine at the appropriate time for the natural course of the disease.25, 26 Persistently elevated levels of specific IgG after vaccination, even at low levels, after COVID-19 infection suggests that SARS-CoV-2 IgG-specific antibodies help in monitoring humoral immunity for a long time.26 Crucially, however, they provide a new humoral response re-build up, observed twice following infection. Moreover, we have to add that in the five cases, we primarily saw good SARS-CoV-2 response seroconversion (IgM and IgG) after mild infection and some different responses after vaccination. A lack of a humoral-specific response for complete BNT162b2 vaccination and a booster (Case #2) does not mean seroconversion (S-RBD response). The mechanism of poor, late seroconversion is supposed to be involved in a substantial primary SARS-CoV-2 response (early responder). Moreover, a poor humoral response (seroconversion of IgG and IgM) was observed for the second and subsequent booster vaccinations in healthy SARS-CoV-2 asymptomatic cases (Case #1 and #3), not only for immunocompromised people.27, 28 A preprint has previously been published.29 Piotr Kosiorek, Samuel Stróż, and Anna Stasiak-Barmuta analyzed the data and drafted the manuscript. Robert Milewski, Dorota Elżbieta Kazberuk, Anna Hryniewicz, and Klaudia Bartoszewicz participated in data analysis and extensively reviewed the manuscript. Piotr Kosiorek, Samuel Stróż, Magdalena J. Borkowska, and Anna Stasiak-Barmuta contributed to the clinical and laboratory data acquisition and reviewed the manuscript. All authors read and agreed to the published version of the manuscript. The authors thank all of the healthcare workers involved in the examinations at the Maria Sklodowska-Curie Bialystok Oncology Center in Bialystok, Poland. All of the individuals included in this work consented to the acknowledgments. This research did not receive specific funding but was performed as part of the work of the authors at Maria Sklodowska-Curie Bialystok Oncology Centre, Poland. The authors declare no conflict of interest. The Bioethics Commission of the Medical University approved this research. Approval code: APK.002.267.2021; approval date: 29 April 2021. Written informed consent was obtained from the patient(s) to publish this paper. The lead author (Piotr Kosiorek) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

SARS-CoV-2 Transmission Risk to Household and Family Contacts by Vaccinated Healthcare Workers.

The effectiveness and safety of mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines among individuals with chronic kidney diseases

The intersection of genetics and COVID-19 in 2021: preview of the 2021 Rodney Howell Symposium

BackgroundSince it was first identified in early November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread quickly and replaced the B.1.617.2 (delta) variant as the dominant variant in many countries. Data on the real-world effectiveness of vaccines against the omicron variant in children are lacking.MethodsIn a study conducted from January 21, 2022, through April 8, 2022, when the omicron variant was spreading rapidly, we analyzed data on children in Singapore who were 5 to 11 years of age. We assessed the incidences of all reported SARS-CoV-2 infections (confirmed on polymerase-chain-reaction [PCR] assay, rapid antigen testing, or both), SARS-CoV-2 infections confirmed on PCR assay, and coronavirus disease 2019 (Covid-19)–related hospitalizations among unvaccinated, partially vaccinated (≥1 day after the first dose of vaccine and up to 6 days after the second dose), and fully vaccinated children (≥7 days after the second dose). Poisson regression was used to estimate vaccine effectiveness from the incidence rate ratio of outcomes.ResultsA total of 255,936 children were included in the analysis. Among unvaccinated children, the crude incidence rates of all reported SARS-CoV-2 infections, PCR-confirmed SARS-CoV-2 infections, and Covid-19–related hospitalizations were 3303.5, 473.8, and 30.0 per 1 million person-days, respectively. Among partially vaccinated children, vaccine effectiveness was 13.6% (95% confidence interval [CI], 11.7 to 15.5) against all SARS-CoV-2 infections, 24.3% (95% CI, 19.5 to 28.9) against PCR-confirmed SARS-CoV-2 infection, and 42.3% (95% CI, 24.9 to 55.7) against Covid-19–related hospitalization; in fully vaccinated children, vaccine effectiveness was 36.8% (95% CI, 35.3 to 38.2), 65.3% (95% CI, 62.0 to 68.3), and 82.7% (95% CI, 74.8 to 88.2), respectively.ConclusionsDuring a period when the omicron variant was predominant, BNT162b2 vaccination reduced the risks of SARS-CoV-2 infection and Covid-19–related hospitalization among children 5 to 11 years of age.

Pre-Existing Pancreatitis and Elevated Risks of COVID-19 Severity and Mortality

In December 2019, a novel coronavirus was identified in Wuhan City, Hubei Province, China and later the disease was named coronavirus disease 2019 (COVID-19). On March 11, 2020, the World Health Organization (WHO) officially announced that COVID-19 had reached global pandemic status. This article summarized the understanding of the etiology, pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and prevention and control measures of COVID-19 based on the available data and anti-epidemic experience in China.

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BackgroundWaning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear.MethodsWe conducted two matched retrospective cohort studies to assess the effectiveness of booster vaccination, as compared with that of a two-dose primary series alone, against symptomatic SARS-CoV-2 infection and Covid-19–related hospitalization and death during a large wave of omicron infections from December 19, 2021, through January 26, 2022. The association of booster status with infection was estimated with the use of Cox proportional-hazards regression models.ResultsIn a population of 2,239,193 persons who had received at least two doses of BNT162b2 or mRNA-1273 vaccine, those who had also received a booster were matched with persons who had not received a booster. Among the BNT162b2-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 2.4% (95% confidence interval [CI], 2.3 to 2.5) in the booster cohort and 4.5% (95% CI, 4.3 to 4.6) in the nonbooster cohort after 35 days of follow-up. Booster effectiveness against symptomatic omicron infection, as compared with that of the primary series, was 49.4% (95% CI, 47.1 to 51.6). Booster effectiveness against Covid-19–related hospitalization and death due to omicron infection, as compared with the primary series, was 76.5% (95% CI, 55.9 to 87.5). BNT162b2 booster effectiveness against symptomatic infection with the delta (or B.1.617.2) variant, as compared with the primary series, was 86.1% (95% CI, 67.3 to 94.1). Among the mRNA-1273–vaccinated persons, the cumulative incidence of symptomatic omicron infection was 1.0% (95% CI, 0.9 to 1.2) in the booster cohort and 1.9% (95% CI, 1.8 to 2.1) in the nonbooster cohort after 35 days; booster effectiveness against symptomatic omicron infection, as compared with the primary series, was 47.3% (95% CI, 40.7 to 53.3). Few severe Covid-19 cases were noted in the mRNA-1273–vaccinated cohorts.ConclusionsThe messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19–related hospitalization and death. (Funded by Weill Cornell Medicine–Qatar and others.)

Background and Aims Previous vaccine effectiveness studies in the hemodialysis population have mainly focused on the Alpha and Delta variant periods, demonstrating that two doses of mRNA COVID-19 vaccines provide substantial protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes. However, evidence regarding the effectiveness of a boosting mRNA vaccine dose in hemodialysis patients during the Omicron era remains limited. Method We conducted a retrospective cohort study of maintenance hemodialysis patients in South Korea who received either two or three doses of mRNA COVID-19 vaccines between January 16, 2022, and April 16, 2022. Data regarding vaccination status, SARS-CoV-2 infection, and COVID-19–related hospitalizations and deaths were identified through the National Health Insurance Service. The RT-PCR–confirmed SARS-CoV-2 infection, hospitalization, and death were evaluated as outcomes. A Cox proportional hazards model was used to estimate hazard ratios (HR) after adjustment for age, sex, region, insurance status, and Charlson Comorbidity Index. Results A total of 66,654 individuals (mean age 65.7 ± 12.8 years; 60.5% male) were included. At baseline, 11,314 (17%) had completed two vaccine doses, whereas 55,340 (83%) had received three doses. Compared with two-dose recipients, those who received three doses had a 10% lower risk of SARS-CoV-2 infection (HR 0.90, 95% confidence interval [CI] 0.86–0.93), a 20% reduction in COVID-19–related hospitalization (HR 0.80, 95% CI 0.68–0.93), and a 56% reduction in 30-day mortality following infection (Hr = 0.44, 95% CI 0.37–0.51, Fig. 1). Both BNT162b2 and mRNA-1273, when administered as a third dose, significantly decreased the risks of SARS-CoV-2 infection, COVID-19-related hospitalization, and death. Conclusion During the Omicron period, three-dose mRNA COVID-19 vaccination was associated with lower rates of SARS-CoV-2 infection and severe COVID-19 outcomes among maintenance hemodialysis patients compared with two-dose regimens. Our results highlight the importance of ongoing booster strategies in hemodialysis patients to further reduce COVID-19–related morbidity and mortality.