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Our take —

Data on the durability of protection offered by SARS-CoV-2 vaccines has been limited. This study demonstrated a significant decline in the humoral (antibody) response in the six months following administration of the second dose of the BNT162b2 vaccine (Pfizer BioNTech). This reduction was more pronounced among men, older participants, and those who were immune suppressed. Despite waning antibody levels, breakthrough infection was identified in only 25 (0.5%) study participants, demonstrating that vaccines remain highly effective. The host immune response to viral infection is incredibly complex, and antibodies are only one component of this response. In addition, the minimum antibody levels required to prevent infection have not yet been established, making it difficult to contextualize the data presented here. However, a cautious interpretation supports the use of an additional vaccine dose to boost humoral responses in high-risk individuals, including the elderly and those with immunosuppression.

Study design

Prospective Cohort

Study population and setting

Global vaccination against SARS-CoV-2 continues to progress at a rapid pace, but few data have been reported on the durability of protection. This prospective study assessed the dynamics of the humoral (antibody-based) immune response to SARS-CoV-2 in the six months following receipt of the second dose of the BNT162b2 vaccine (Pfizer BioNTech), using samples collected from Israeli healthcare workers (n= 4,868) between December 2020 and July 2021. All participants were seronegative at study enrollment, prior to receipt of the first vaccine dose. Anti-spike IgG antibody levels and neutralizing antibody titers were measured prior to vaccine receipt and monthly for six months. PCR testing and anti-N (nucleocapsid) IgG antibody screening was used to rule out breakthrough SARS-CoV-2 infection among symptomatic participants and/or those with substantial increases in antibody titers between visits. Demographic data was collected for study participants using a computer-based survey. Linear mixed models were used to examine the kinetics of the antibody response to vaccination and to identify factors associated with lower antibody levels six months after vaccine receipt.

Summary of Main Findings

The highest antibody responses were observed in the first thirty days post vaccination. These levels consistently decreased by a factor of 18.3 over the next six months. Titers of neutralizing antibody also decreased rapidly for the first three months (factor of 3.9), but this decay slowed between months three and six (factor of 1.2). IgG antibody levels and neutralizing antibody titers were highly correlated, but this relationship was dependent on the time since vaccine administration. At the end of the study period, neutralizing antibody titers were significantly lower among men, participants older than 65 years, and those with a history of immunosuppression. During the study period, 20/4,868 (0.4%) participants were diagnosed with breakthrough SARS-CoV-2 infection via PCR testing, and 5 participants developed anti-N antibody reactivity, also indicating vaccine breakthrough.

Study Strengths

This study represents the first large-scale effort to assess the durability of the humoral immune response to SARS-CoV-2 following full vaccination with the Pfizer BioNTech vaccine (BNT162b2). The size of the study allowed for stratified analyses based on demographic characteristics and comorbidities. While neutralization assays were only completed for a subset of the study population, this segment of the cohort was enriched to include higher proportions of older participants and those with underlying comorbidities, to represent the general population more accurately.

Limitations

The study population was composed solely of healthcare workers, who may not be demographically representative the general population. Participants who failed to complete the computer-based survey (n= 1,060, 22%) were excluded from the mixed-model analysis, although this behavior may not have been entirely random. Neutralizing antibody titers were measured using a pseudovirus-based assay rather than one using live virus. Neutralization assays were only completed for a subset of the study population (n=1,269, 26%). All neutralization assays were completed in the absence of other important components of the immune system (i.e., complement, T-cells) whose effector functions may remain intact despite reductions in antibody levels. Threshold titers required to prevent breakthrough infection have not yet been defined, and levels reported here may still be sufficient for protection. Researchers failed to assess the relationship between lower antibody levels/neutralization titers and breakthrough infection during the study.

Value added

This study provides a first look at the long-term durability of antibody responses after two doses of the Pfizer BioNTech SARS-CoV-2 vaccine (BNT162b2), using longitudinal samples collected from a large population of healthcare workers in Israel up to six months following vaccination.

Our take —

This observational study compared myocarditis incidence rates among US adults (aged 18 years and older) between those who received a SARS-CoV-2 mRNA vaccine December 2020 to July 2021 and two control groups: 1) these same individuals one year prior to vaccination; and 2) unvaccinated adults temporally matched to vaccinated adults. The study used data from approximately 3.9 million adults in the Kaiser Permanente Southern California health care system. Though myocarditis incidence 10 days after vaccination was extremely low (5.8 cases per 1 million vaccinated individuals) and primarily occurred among young males, myocarditis rates following the second mRNA vaccine dose were elevated relative to unvaccinated individuals (2.7 times higher) and to themselves in the previous year (3.3 times higher) in an unadjusted analysis. Similar to recent studies, all 15 cases of myocarditis (among 2.4 million vaccinated individuals) after vaccination in this large and ethnically diverse sample in the US were mild and self-limited. These results add to existing evidence that while risk of myocarditis appears elevated following vaccination, is remains rare and generally mild.

Study design

Prospective Cohort

Study population and setting

This observational study assessed myocarditis rates following SARS-CoV-2 vaccination with mRNA vaccines among Kaiser Permanente Southern California (KPSC) members aged 18 years or older between December 14, 2020 and July 20, 2021. Two cardiologists adjudicated all hospitalizations with myocarditis listed as the discharge diagnosis within 10 days of vaccine administration to identify cases. Clinical characteristics associated with each case were presented. The study compared incidence rates during the 10-day period after each individual’s first and second mRNA vaccine dose to myocarditis rates among unvaccinated individuals between December 14, 2020 and July 20, 2021 and to myocarditis rates among vaccinated individuals during the 10-day period 1 year prior to vaccination.

Summary of Main Findings

Pfizer and Moderna vaccines were administered in equal proportions among the 2.4 million KPSC members with at least 1 dose of the vaccine (93.5% received 2 doses). More than half (54%) of vaccinated members were female, 37.8% identified as Hispanic, 31.2% as White, 14.3% as Asian, and 6.7% as Black. Vaccinated members had a median age of 49 years (interquartile range [IQR] 34, 64 years) Of the 1.6 million unvaccinated individuals, 49.1% were female, 39.2% identified as Hispanic, 29.7% as White, 8.8% as Black, and 6.6% as Asian. Unvaccinated individuals had a median age of 39 years (IQR 28-53 years). The authors identified 15 cases of myocarditis (2 after dose 1, 13 after dose 2 among vaccinated individuals and 75 cases of myocarditis among unvaccinated individuals. Vaccinated individuals were all male and had a median age of 25 years (IQR 20, 32 years) compared to unvaccinated individuals, who were 52% male and had a median age of 52 years (IQR 32, 59 years). Vaccinated individuals with myocarditis did not have prior heart disease and only two of 15 had evidence of cardiac dysfunction on echocardiogram (1 of whom recovered after discharge).

Unvaccinated individuals had 2.2 cases of myocarditis over a 10-day observation period per 1 million individuals. After the first mRNA vaccination dose, there were 0.8 cases over 10 days per 1 million individuals (incidence rate ratio [IRR] 0.38, 95% confidence interval [CI] 0.05, 1.40 compared to unvaccinated individuals and IRR 1.0, 95% CI 0.1, 13.8 compared to the same vaccinated individuals a year before vaccination). After the second mRNA vaccination dose, there was an incidence of 5.8 cases over 10 days per 1 million individuals (incidence rate ratio [IRR] 2.7, 95% confidence interval [CI] 1.4, 4.8 compared to unvaccinated individuals and IRR 3.3, 95% CI 1.0, 13.7 compared to vaccinated individuals a year before vaccination).

Study Strengths

This study included careful adjudication of myocarditis cases in a large, diverse cohort of individuals who did and did not receive mRNA-based SARS-CoV-2 vaccinations. It was also able to compare myocarditis incidence among vaccinated individuals to themselves the year before the vaccine became available, given that vaccinated and unvaccinated individuals had different demographic characteristics.

Limitations

Due to the rare incidence of myocarditis, there were not enough events to assess myocarditis incidence by age or sex. The study also excluded adolescents under 18 years old. This is particularly important because other studies have found higher rates of myocarditis in young males relative to other age/sex subgroups. The small number of events also limited confounder adjustment, increasing the likelihood of confounding biasing the incidence rate ratio estimates. Additionally, choosing a 10-day observation period may have undercounted myocarditis cases, underestimating the reported incidence. Relying on myocarditis being listed as a discharge diagnosis or reported by clinicians may have undercounted cases of myocarditis, although this is unlikely to be differential across groups.

Value added

This study adds to the evidence that myocarditis after mRNA-based SARS-CoV-2 vaccines, while extremely rare, is more common in young males. It also adds to the evidence that post-vaccination myocarditis cases, when they happen, are likely to be mild and self-limited in adults.

Our take —

This study directly examined the effect of utilizing airborne infection isolation room (AIIR) to treat COVID-19 patients on incidence of SARS-CoV-2 infections among healthcare staff at two major US hospitals in Boston with otherwise identical infection control protocols during March – August 2020. At one hospital 22% of COVID-19 patient days were spent in AIIRs, while at the other hospital, 96% of patient days were spent in AIIRs. Despite this, only 2% of patient-facing staff at each hospital was diagnosed with SARS-CoV-2 infection over the study time period. Also, the study found no differences in COVID-19 incidence rates between staff in patient-facing vs. non-patient-facing roles. While the study is unable to determine which infections were acquired from exposures at work versus in the community, this study suggests that using AIIRs resulted in no decrease in infection risk to staff, above and beyond the protection provided by other infection control practices.

Study design

Prospective Cohort

Study population and setting

The study objective was to measure the difference in healthcare worker SARS-CoV-2 infection rates in settings where there is high utilization of airborne infection isolation rooms (AIIR) compared to low utilization. The study was conducted at two hospitals in Boston, Massachusetts from March 1st to August 21st 2020: Massachusetts General Hospital, which has a limited number of AIIRs, and Brigham and Women’s hospital, which has multiple negative pressure wards for COVID-19. The two hospitals had identical infection control policies, given they are part of the same hospital center (Mass General Brigham), so the only differences were their use of AIIR. Universal masking was in place since March 22, and on April 10, both hospitals began recommending N95 respirators for all COVID-19 care, regardless of whether aerosol generating procedures were being conducted or not. The study calculated the ratio of hospitalization days for patients with confirmed COVID-19 in AIIRs versus standard pressure rooms for each hospital. The study then calculated weekly incidence rates among patient-facing vs. non-patient-facing roles, and fit an interrupted time series model to compare the incidence rates. Testing was available for any symptomatic staff, and beginning in early May, for any staff who experienced any unprotected exposures regardless of symptoms.

Summary of Main Findings

In total, 1,938 COVID-19 patients were admitted for 16,821 patient-days to MGH, and 1,142 patients were admitted for 8,529 patient-days to BWH. Patients at MGH spent 3,626 patient-days (22%) in AIIRs, and patients at BWH spent 8,157 (96%) patient-days in AIIRs. Of the 15,592 patient-facing employees at MGH, 2% (N=313) became infected with SARS-CoV-2, compared to 2% of 8,076 non-patient-facing employees (N=165). Of the 9,393 patient-facing BWH employees, 2% became infected (N=189), compared to 1.5% of non-patient-facing employees (108 cases among 7,251 employees). There were no statistically significant differences between the weekly infection rates at either hospital, and between patient-facing and non-patient-facing roles. Implementation of the N95 respirator policy on April 10 was not associated with any change in incidence of infection.

Study Strengths

They used two hospitals with identical infection control policies, which improved the ability of authors to make inferences about the contributions of airborne infection isolation rooms to infection control. In addition, the easy access that staff had to testing at these hospitals meant that is is unlikely that many infections among health care workers went unreported.

Limitations

The study noted that many hospital staff were already using N95 respirators before the April 10 policy, which will reduce any differences in infection incidence before vs. after its implementation.

Value added

This study directly examines the impact of airborne infection isolation rooms on incidence of SARS-CoV-2 infections among healthcare workers at two hospitals who otherwise have identical infection control policies.

Our take —

This study investigated an outbreak in a federal prison facility in Texas from July to August 2021. They found, among 233 people in the unit, 79% were fully vaccinated, and 74% became ill with either symptomatic or asymptomatic COVID-19. Vaccinated people had an attack rate of 70%, compared to an attack rate of 93% for unvaccinated people. Individuals vaccinated greater than 4 months ago also had a significantly higher attack rate compared to people vaccinated between 2 weeks and 2 months ago. Genomic sequencing determined all specimens had the Delta variant strain. This study highlights the importance of continued COVID-19 precautions and testing following vaccination among people currently incarcerated, especially given the rise in the Delta variant.

Study design

Prospective Cohort

Study population and setting

Beginning on July 12, 2021, 18 people incarcerated in federal prison in Texas reported COVID-19 symptoms and received positive rapid antigen tests for SARS-CoV-2 infection. Following this, between July 12 and August 14, 2021, antigen testing was conducted on 233 people in the two interconnected units. Testing was conducted on July 12 to 13, July 14, July 19, July 22, August 2, and August 10 with a combination of rapid antigen and reverse transcriptase-polymerase chain reaction (RT-PCR) testing. Testing was also offered to staff members on a voluntary basis. A subset of 70 people who were incarcerated in the units consented to a secondary investigation with daily symptom reports and nasal swabs for up to 20 days after symptom onset. Viral culture was performed for RT-PCR-positive specimens among a subset of participants, and genomic sequencing was conducted for one specimen from each participant. Staff members were vaccinated only voluntarily and vaccination received outside of the correctional clinic was not recorded by the Federal Bureau of Prisons (BOP). BOP also collected vaccination status, demographic characteristics, and medical condition history from the electronic medical records (EMRs) of the 233 incarcerated people. Descriptive statistics were calculated, including the attack rate.

Summary of Main Findings

Of the 233 people living in the unit, 185 (79%) were fully vaccinated, 42 were unvaccinated (18%) and 6 (3%) were partially vaccinated at the time of data collection. Overall, there were 172 cases, with an attack rate of 74%. By vaccination status, of the 185 vaccinated people, the attack rate was 70% (129 cases), and for the 42 unvaccinated people, the attack rate was 93% (39 cases), which was a statistically significant difference in the attack rates. Four (2%) of these cases were hospitalized, with 3 of them unvaccinated and 1 fully vaccinated. Of those fully vaccinated with Moderna (N=50), the attack rate was 40% (20 cases), compared to 122 people vaccinated with Pfizer, who had an attack rate of 81% (99 cases), and 13 people with the Janssen vaccine who had an attack rate of 77% (10 cases), though it was not clear if these related to specific differences in vaccination or timing since vaccination, where Pfizer was offered first to participantsl. There was a statistically significant difference between these attack rates as well. Also, comparing the times since their full vaccination to the outbreak, among the fully vaccinated, the attack rate for those vaccinated between 2 weeks and 2 months ago was 61% (19 cases among 31 people), while for those vaccinated 4 to 6 months ago, the attack rate was 89% (83 cases among 93 individuals). Of the 275 staff members, 9 reported a positive SARS-CoV-2 test (3%). Genomic sequencing identified the Delta variant in 58 specimens from 58 people sequenced.

Study Strengths

The study had electronic medical records for all incarcerated people, which allowed for ascertainment of not only vaccination status, but the date and product used, as well as underlying conditions. This granularity adds strength to the study in assessing the different factors potentially related to the attack rates. Their testing strategy across multiple timepoints also likely allowed them to identify many newer infections soon after those individuals became infected, which aided in correctly classifying new cases and determining time since vaccination and symptoms.

Limitations

The study used a mix of rapid antigen tests and RT-PCR tests, which have varying sensitivities and specificities, as well as turnaround times. Therefore, ascertainment of a case may be delayed for an RT-PCR test or subject to a false negative on the rapid antigen test especially for asymptomatic cases, and it is not clear how this potential misclassification may have impacted the attack rate. One limitation was the lack of consistent testing for the staff. Staff members had to self-report tests outside of the correctional setting to the BOP, which likely reduced the number of tests actually reported. Additionally, it is not clear that the differences between vaccine product reflect actual differences in their effectiveness—particularly because individuals vaccinated greater than 4 months ago had a higher attack rate, and most of those vaccinated at that point were done so with the Pfizer vaccine because it was the first available in the correctional setting. Therefore, there may be confounding in the estimated difference in attack rate between these products.

Value added

This is one of the first studies examining the risk of infection among vaccinated people in prison since the proliferation of the Delta variant.

Our take —

This study evaluated the effectiveness of the at-home direct antigen rapid test (DART) for COVID-19 to compare performance with qRT-PCR on self-collected nasal specimens among employees within the Cambridge and Boston areas over a 6 month period. Surveillance using twice weekly testing with DART was 96.2% sensitive in identifying individuals positive for COVID-19 between 0-3 days of symptoms, compared to self-collected swabs that were tested by qRT-PCR. Although only laboratory affiliated persons were recruited and results may differ from within the general population as they may be better at self-swabbing, twice-weekly DART testing was able to identity positive participants before reported symptoms of COVID-19. This study shows real-world application to workplace surveillance to prevent in-person transmission in social environments.

Study design

Prospective Cohort

Study population and setting

Within a 6-month period (NB: exact dates of study recruitment and enrollment were not provided in the manuscript), 257 employees (age 21-72 years ) working at 3 laboratories in Cambridge and Boston, Massachusetts self-collected 2 nasal swab specimens twice weekly. Swabs were tested by direct antigen rapid tests (DARTs) and the gold standard qRT-PCR and results were compared. The DART cassette contains a monoclonal antibody/nanoparticle conjugate that detects the nucleocapsid protein in SARS-Co-V-2, displaying visible lines for positive and negative results. The DART test was completed at home, where the swab was mixed with an extraction buffer, then 100ul were measured and placed into the DART cartridge, before waiting 15 minutes before reading. The second swab was sent to the laboratory for qRT-PCR testing.

Summary of Main Findings

During the study period, 15 participants contracted COVID-19 as determined by self-swab qRT-PCR testing, and the twice weekly self-swabs tested by DART detected 100% of these infections. Between 0-12 days of symptom onset, as compared to qRT-PCR, the sensitivity of DART was 78.9% (95% CI, 69.1%-88.8%) and the specificity was 97.1% (95% CI 96.3-97.8%).  DART sensitivity for SARS-CoV-2 nucleocapsid and RNA detection for individual infections was 96.2% (95% CI 88.8%-100.0%) within 0-3 days of symptom onset.

Study Strengths

This was a prospective study where large number of samples were collected from a small cohort overtime. Paired self-collected nasal swabs were tested by DART and qRT-PCR. 

Limitations

Those enrolled in this study were affiliated with one of three laboratories, and no one from the general population was included. The ability of these participants to complete the DART test, which required pipetting reagents and sample, therefore, may have differed from that of the general population.

Value added

This study  validated effectiveness of at-home DART testing. This was the first time a direct comparison of self-collected rapid testing compared to self-collected swabs for qRT-PCR testing used in workplace surveillance.

Our take —

This descriptive study characterized the symptom duration and burden of 1,734 symptomatic children with a positive SARS-CoV-2 test and matched controls in the UK between September 1, 2020 and January 24, 2021. Among this self-selected sample of children with symptomatic COVID-19, long-term symptoms reported by adult proxy via mobile phone app were relatively rare (4.4% at 28 days and 1.8% at 56 days). Children who tested negative for SARS-CoV-2 were less likely to have long-term symptoms (0.9% at 28 days) than those with COVID-19, though it is possible that the latter were more likely to perceive symptoms given media reports of long-term sequelae of COVID-19. Although the self-selected participation in this study might limit its generalizability, the findings add to a small but growing evidence base suggesting that long term persistence of COVID-19 symptoms among children is rare.

Study design

Prospective Cohort

Study population and setting

This prospective cohort study included children aged 5-17 years in the United Kingdom with COVID-19 symptoms, whose data was reported by an adult proxy to the mobile-phone based COVID-Symptom Study. This analysis included children who were symptomatic and completed SARS-CoV-2 testing (PCR or lateral flow antigen testing)  between September 1, 2020 (when school started in the UK) and January 24, 2021. Participation in the study was voluntary and all data was self-reported by adult proxy; after enrollment participants received daily prompts to report symptoms and SARS-CoV-2 testing and results throughout the study period. Illness duration was calculated from the first reported symptom until recovery or reporting ceased. Symptom burden was the number of different reported symptoms over the first week, first 28 days, and the entire illness duration. Children with positive SARS-CoV-2 tests were compared to children who reported symptoms but tested negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing. The study compared illness duration and symptom burden based on SARS-CoV-2 test positivity and among younger (5-11 years old) versus older (12-17 years old) children.

Summary of Main Findings

Of the 258,790 UK children aged 5-17 years with proxy-reported symptoms between March 24, 2020 and February 22,2021, 6,975 reported positive SARS-CoV-2 test results, 1,912 of whom met the criteria to calculate illness duration. The analytic sample, limited to children tested between September 1, 2020 and January 24, 2021, included 1,734 children, 588 aged 5-11 years and 1,146 aged 12-17 years. COVID-19 symptoms lasted a median of 6 days (interquartile range [IQR] 3,11 days) compared to a median 3 days (IQR 2, 7 days) of symptoms in matched SARS-CoV-2 negative controls. The older group had a slightly longer symptom duration than the younger children (median 7 days, IQR 3, 12 days versus median 5 days, IQR 2, 9 days). Overall, the most common reported symptoms among children with COVID-19 were headache (n=1,079, 62.2%) and fatigue (n=954, 55%). Younger children were more likely to report fever (n=257, 43.7%), sore throat (n=213, 36.2%), or abdominal pain (n=163, 27.7%), whereas older children were more likely to report sore throat (585, 51%), loss of smell (n=554, 48.3%), and fever (n=396, 34.6%). Overall, 77 children with COVID-19 (4.4%, 95% CI 3.5%, 5.5%) had proxy-reported symptoms that lasted 28 or more days (5.1% among older children and 3.1% among younger children), compared with 15 children in the symptomatic group that tested negative (0.9%). Among the children with COVID-19 symptoms lasting 28 days or more, fatigue (n=65, 84.%), headache (n=60, 77.9%), loss of smell (n=60, 77.9%), and sore throat (n=57, 74%) were the most common symptoms over the course of the disease. Fatigue was also the most common symptom among matched proxy-reported children who tested negative for SARS-CoV-2. Only 25 of the 1379 with follow-up time through 56 days had COVID-19 persistent symptoms by that time (1.8%, 95% CI 1.2%, 2.7%).These results did not change when they further excluded children (n=183, 10.5%) who tested positive and reported COVID-19 symptoms but did not have a reported asymptomatic day (e.g., reporting stopped and the authors assumed the child was asymptomatic for the primary analysis).

Study Strengths

This study measured COVID-19 symptom duration in children, a population for whom there is relatively little data on post-acute sequelae of COVID-19. Symptoms were reported prospectively, reducing recall bias. Children with similar symptoms who had tested negative for SARS-CoV-2 were matched to cases on key variables to serve as a control group.

Limitations

It is difficult to assess how representative children with proxy-reported symptoms in a mobile application are to other children in the United Kingdom or children who live elsewhere. It is likely that their proxy is more health conscious than the proxies of children who did not report symptoms, for both children with and without diagnosed SARS-CoV-2 infections. It is also unclear how accurate proxy-reported symptoms may be for potentially more subtle symptoms such as fatigue or headache, or how proxy-symptom reporting could vary based on a child’s age. Although the control group is very helpful in making a comparison, these factors make it difficult to assess how symptom misclassification may bias the symptom duration estimates, especially if symptom reporting changes after a SARS-CoV-2 diagnosis. If a SARS-CoV-2 diagnosis makes proxies more attuned to a child’s symptoms, for example, the difference in symptom duration may overestimate the difference between the duration of COVID-19 compared to infections with similar symptoms.

Value added

This study provides information about COVID-19 symptom duration in children aged 5-17 years and compares COVID-19 symptoms and their duration to other illnesses that cause similar symptoms.

Our take —

A cohort study among healthcare workers at a hospital in Israel was conducted to understand the impact of the BNT162b2 vaccine (Pfizer) on susceptibility to infection, regardless of symptoms, and infectiousness through measurement of viral shedding. It was found that those who were vaccinated were less likely to become infected and, among those who did, experienced a significant reduction in viral shedding compared with their unvaccinated counterparts. This study suggests that the vaccine is effective in this population, but that: 1) breakthrough infections do happen; and 2) infectiousness among those with breakthrough infections is reduced. These data were collected before the Delta variant was in high circulation, and implications may differ in contexts of high Delta circulation or with subsequent variants.

Study design

Prospective Cohort

Study population and setting

A cohort study of healthcare workers at Sheba Medical Center in Israel was conducted between December 19, 2020 and March 14, 2021 to understand the effectiveness of vaccination (BNT162b2 – Pfizer-BioNTech) in reducing infectiousness among SARS-CoV-2 cases. The start of the study corresponded to the start of vaccine roll-out, and during the study period 7794/9347 (83%) of eligible HCW received at least one dose, and 7324/9347 (78%) received two doses. Those who had previously been infected with SARS-CoV-2 were not eligible for vaccination. The authors estimated prevalence of SARS-CoV-2 in exposed individuals using RT-PCR (susceptibility to infection) and viral shedding using (cycle threshold) Ct values. HCWs experiencing an exposure (at work, home, etc.) was required to undergo PCR testing.

Summary of Main Findings

Fully vaccinated healthcare workers experienced a reduced prevalence of SARS-CoV-2 infection compared with those who were unvaccinated (1.8% vs. 5.2%). Mean Ct values for unvaccinated versus vaccinated healthcare workers were 22.2 +/- 1.0 and 27.3 +/- 2.2, suggesting a significant mean difference (5.09, 95% CI: 2.8-7.4) or a significant reduction in viral shedding among those vaccinated.

Study Strengths

This study estimates prevalence of infection among those who were exposed, regardless of symptoms, providing an estimate of the vaccine’s impact on susceptibility to infection.

Limitations

The study sample was made up of primarily younger women, and the results presented here may not be generalizable to other populations.

Value added

This study shows that in a real-world setting the vaccine was effective at preventing infections following exposure, and that Ct values were significantly higher (i.e., which is an imperfect proxy measure for viral load being lower) in people who were vaccinated compared with those who were unvaccinated.

Our take —

This analysis examined factors associated with mortality among hospitalized persons with COVID-19 in South Africa during the first two pandemic waves (July 2020 and January 2021). The respective peaks of the first and second waves of the pandemic were in July 2020 and January 2021. The second wave was more severe, as evidenced by higher rates of cases, admissions, and deaths. The authors hypothesized that the severity of the second wave could be due to the predominance of the new Beta lineage of the virus. Using comprehensive national surveillance data, authors demonstrated that characteristics differed across patients hospitalized across waves, with Black individuals making up a higher percentage in the first vs second wave (78.6% vs. 68.1%). A major limitation of the paper is that while measures of disease frequency (e.g., odds) were reported separately for waves 1 and 2, measures of association (e.g., odds ratios) were only presented for wave 2, making it difficult to clearly decipher how associations between patient characteristics and clinical outcomes might have differed between the waves. Furthermore, some measures of frequency may be underestimates as people without access to care or who died outside of hospitals were not captured in the surveillance data. Notwithstanding, this paper presents important information on the dynamics of COVID-19 in South Africa, demonstrating a more severe second wave compared to the first and an overall high case-fatality risk among hospitalized patients.

Study design

Prospective Cohort

Study population and setting

This study examined characteristics and risk factors for mortality among patients hospitalized with COVID-19 in South Africa from March 5, 2020, to March 27, 2021 (the first two waves of the pandemic). Five distinct periods were defined: pre-wave 1 (March-June 6, 2020), wave 1 (June 7-Aug 22, 2020), post-wave 1 (Aug 23-Nov 14, 2020), wave 2 (Nov 15, 2020-Feb 6, 2021), and post-wave 2 (Feb 7-March 27, 2021). National active surveillance data of persons with SARS-CoV-2 positive RT-PCR or antigen test with hospital stay of at least one day was analyzed, regardless of a patient’s age or reason for hospitalization. Information on patients’ socio-demographic, occupational factors, and comorbidity was collected using a modified WHO COVID-19 case reporting tool. Odds ratios were obtained using multivariable logistic regression (with a random effect on admission facility). Incomplete or missing data were handled through imputation.

Summary of Main Findings

A total of 1,545,431 SARS-CoV-2 cases and 227,932 COVID-19 hospital admissions were reported within the period. Of 219,565 COVID-19 patients with information on in-hospital outcome (96.3%), 51,037 died (case fatality risk: 23.28%). The second wave was more severe than the first wave as evidenced by higher peak case fatality risk (29.34% vs. 21.80%, p < 0.0001), in-hospital deaths (8.3 deaths/100,000 people vs 3.6 deaths/100,000 people), admissions (27.9 admissions/100,000 people vs 16.1 admissions/100,000 people), average weekly growth rate of admissions (43% vs. 20%), and cases (240.4 cases/100,000 people vs 136.0 cases /100,000 people). Black individuals made up a higher proportion of COVID-19 hospitalizations in the first wave vs. the second (78.6% vs. 68.1%), while the reverse was true for individuals who identified as mixed race (7.1% vs. 13.6%); percentages were as follows for white individuals (9.2% vs. 11.6%) and Indian individuals (5.2% vs. 6.8%). Comorbidities were more common among admitted patients in the first wave compared to the second (60.7% vs. 55.0%). Compared to those < 40 years, risk of mortality was higher for those aged 40-64 years (OR: 3.17, 95% CI: 3.05-3.30) and those 65+ (OR: 7.89, 95% CI: 7.58-8.22) during the period. Overall, being male was associated with a 30% increased risk of mortality, while being Black, Mixed race, and of Indian race were respectively associated with 18%, 16%, 30% significantly increased risk of mortality compared to being white.

Study Strengths

Data came from a comprehensive national surveillance system that captured information from all South African hospitals that admitted COVID-19 patients and covered the entirety of the first and second waves of the pandemic in the country. In addition, the authors performed robust analyses that included adjustment for covariates and imputation for missing or incomplete data.

Limitations

The reported measures of frequency are likely to be underestimates as information on persons without access to care or who died outside the hospital system were not captured, potentially leading to some bias in the findings. While the authors presented measures of disease frequency (e.g., odds of admission for the respective waves, comparisons of measures of association (odds ratios) across individuals were only presented for wave 2, making it difficult to unequivocally decipher how adjusted relationships between patient characteristics and the clinical outcomes differed across the waves. Obesity, and some other important factors could not be adjusted for, due to incomplete capturing of these data within the surveillance system. Despite these limitations, the use of national surveillance system data from all South African hospitals with COVID-19 patients provides, overall, a complete picture of changes in severity and mortality across waves.

Value added

This study improves understanding about changing dynamics of COVID-19 hospitalizations and death in South Africa, which currently has the highest number of recorded COVID-19 cases and deaths within sub-Saharan Africa.

Our take —

This study, available as a preprint and thus not yet peer-reviewed, sought to estimate the risk of infection among Italian healthcare workers before and after vaccination. Among 3,810 total workers, 2.7% tested positive among those with prior infection from the first pandemic wave, compared to 6.5% among those without prior infection. After vaccination, 0.4% of previously infected participants and 1% of previously uninfected participants tested positive for infection. Overall, the estimated protective effect was 87% across all groups. Household transmission amongst breakthrough infections was low (2/33). Notably, there was no unvaccinated control group to directly compare the risk of infection following vaccination and no pre-vaccination estimates of household transmission amongst cases, however this paper provides evidence of the real-world protection offered by vaccines. These data precede the emergence of the Delta variant; results related to breakthrough infections and onward transmission may be different in areas in which the Delta variant is predominant.

Study design

Prospective Cohort

Study population and setting

The study objective was to assess the risk of infection among vaccinated healthcare workers. Healthcare workers from Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, were tested for active infection and antibodies to indicate prior SARS-CoV-2 infection from April 29 to June 30, 2020. During the second wave of the pandemic from September 1 to November 30, 2020, they were tested again for SARS-CoV-2 infection and the 3-month cumulative incidence was estimated. Current infection was determined via the presence of SARS-CoV-2 RNA determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Healthcare workers began to be vaccinated in December with the BNT162b2 (Pfizer/BioNTech) vaccine, with second doses for full immunity being given from January 18 to March 31, 2021. The study compared the incidence of SARS-CoV-2 infection in the second wave among previously uninfected individuals compared to previously infected individuals. They also estimated the 3-month cumulative incidence of SARS-CoV-2 infection following vaccination, as well as stratified by prior infection before vaccination. Symptom data was available for a subset of participants and was also described. They also completed genotyping on the samples collected to determine the potential variant. Contact tracing among family and coworkers was conducted for vaccinated subjects who tested positive.

Summary of Main Findings

In the initial testing from April 29 to June 30, 2020, 3810 healthcare workers were tested. 336 (8.8%) participants were found to have prior infection, compared to 3474 without prior infection of SARS-CoV-2. Participants were tested for antibodies via chemiluminescent assay for anti-S1 and anti-S2 IgG. Among these two strata, in the second wave from September 1 to November 30, 9 individuals with prior infection tested positive (2.7%) compared to 225 in those without prior infection (6.5%). This reflected a statistically significant difference in the 3-month cumulative incidence among previously infected vs. previously uninfected groups. Of these, 1 of the 4 (25%) subjects had mild symptoms among those with prior infection, compared to 85 of 108 (79%) of those without prior infection. Of those initially enrolled, 3268 participants’ serostatus could be determined from both the first and second pandemic wave. Infection was determined in 33 vaccinated subjects: 2 among the 507 previously infected with follow-up (0.4%), compared to 24 among the 2,761 previously uninfected individuals (0.9%), and 7 among 452 individuals with unknown or indeterminate serostatus (1.5%). The odds of developing SARS-CoV-2 infection after vaccination compared to subjects before vaccination was 0.13 (95% CI: 0.08 to 0.19), with an estimated protective effect of 87%. They determined that all analyzed patients were infected by the B.1.1.7 (alpha) variant. Of the 33 infections post-vaccination, only 2 were transmitted to family members (6.1%); comparable data were not available pre-vaccination.

Study Strengths

The study had prior infection data available throughout multiple waves of the pandemic, as well as vaccination status information available. Healthcare workers, particularly in Italy, which was hard hit in the pandemic, are at increased risk for SARS-CoV-2 infection. Therefore, this gives insight into the vaccine protection conferred to individuals who are most likely to be exposed. They also genotyped the samples, which is important to consider given the proliferation of new variants. They also conducted contact tracing, allowing them to measure potential transmission due to infected individuals even post-vaccination.

Limitations

There was no prospective unvaccinated control group available to compare the risk of infection to properly estimate vaccine effectiveness in this sample, but rather the comparison was to the same prior to vaccination. This offers a potential estimate of protective effect but not of specific vaccine efficacy or variant-specific vaccine efficacy. Similarly, there were few individuals testing positive post-vaccination and no transmission estimates from pre-vaccination, therefore while they show few transmitted infections from vaccinated people, it is not possible to extrapolate if that is due to their vaccination in this study.

Value added

This study examines breakthrough cases among a cohort of healthcare workers at high risk of infection, including potential transmission to others.

Our take —

This was a prospective cohort study conducted in Germany. Researchers compared the immunological responses as well as local and systematic reactions between two groups: the homologous group (i.e., two doses, three weeks apart, of the same vaccine formulation [BNT162b2 by Pfizer-BioNTech]) and the heterologous group (i.e., two doses of different vaccine formulations 10-12 weeks apart [first ChAdOx1 by AstraZeneca and then BNT162b2]). As shown in other studies, participants’ B-cell immune responses were significantly higher after the 1st dose with BNT162b2 compared to ChAdOx1. However, following the second dose of BNT162b2, the heterologous group had comparable B-cell immune responses and slightly higher T-cell immune responses, versus the homologous group. Both groups experienced similar local reactions after their first and second doses. Systemic reactions were more common after the first dose of ChAdOx1 vs. BNT162b2 but less common in the heterologous group after the second dose with BNT162b2. This study highlights the laboratory evidence of efficacy and safety assurance of heterologous immunization with ChAdOx1 followed 10-12 weeks later by BNT162b2, especially for females who are more likely to have rare thromboembolic adverse event following two doses with ChAdOx1. These results are limited by a relatively small sample size and lacked an evaluation of the clinical effectiveness of heterologous immunization.

Study design

Prospective Cohort

Study population and setting

This was a prospective cohort study conducted in Germany that included healthcare workers who received either (1) homologous immunization with two doses, three weeks apart, of BNT162b2 (Pfizer-BioNTech) vaccine or (2) heterologous immunization with an initial dose of ChAdOx1-nCoV19 (AstraZeneca) vaccine followed 10-12 weeks later by BNT162B2. Baseline demographic data were collected at the study enrollment. Anti-nucleocapsid antigen was measured at enrollment to exclude participants with prior infection with SARS-CoV-2. B-Cell immunity against SARS-CoV-2 was quantified by measuring anti-receptor binding domain and anti-S1 antibodies using enzyme-linked immunosorbent assay (ELISA), and T-cell immunity by measuring INF-Gamma induced by S1 peptide antigen. High serum antibody avidity was defined as antibodies with more than 60% avidity. These B-cell and T-cell responses were compared between subsets of both groups, who were matched on age and sex. The proportion of participants who had local and systemic reactions after 1st (prime) and 2nd (booster) doses were captured by asking the participants to fill electric questionnaires on days 1, 3, 5, and 7 after every vaccination.

Summary of Main Findings

One hundred eighty-nine participants received two doses of BNT162B2 vaccine, three weeks apart (homologous boost group), and 110 participants received heterologous immunization with ChAdOx1 vaccine followed by BNT162B2 vaccine with a median time of 71 days between doses (heterologous boost group). The median ages of the groups were 35 and 38 years, respectively. The homologous group was 55% women vs. 78% in the heterologous group.

After vaccination with the first dose, 67% (95% CI: 57 – 76%) of those who received BNT162B2 had anti-S1 antibodies compared to 28% (95% CI: 18 – 40%) in the ChAdOx1 group, with a statistically significant difference. However, after the second dose with BNT162b2, all patients had anti-SARS-COV-2 S1 antibodies. Similarly, after the first dose, 95% of the homologous group had neutralizing antibodies compared to 84% in the heterologous group, with a statistically significant difference, but 100% and 99% had neutralizing antibodies after the second dose, respectively.

High serum antibody avidity was not detected after the first dose of vaccine in either group. Avidity is the overall strength of connection between an antibody and its attachment site on a disease-causing microbe. After the second dose, high serum antibody avidity was detected in 100% (95% CI: 94 – 100%) of participants in the heterologous group and 90% (95% CI 74 – 97%) in the homologous group. The median level for the interferon gamma assay was statistically higher in the heterologous group (2.25 AU) than the homologous group (1.67 AU). Across groups, there were no noticeable differences in local reactions to either the first or second dose of vaccine. However, systemic reactions were more common after the first dose of ChAdOx1 in the heterologous group vs. the first dose of BNT162b2 in the homologous group, but less common after the second dose in the heterologous group.

Study Strengths

B-cell and T-cell immune response were measured in subsets in both groups who were matched on age and sex and at comparable intervals following vaccine administration in both groups, which strengthen the comparability between the study groups. Also, data were collected prospectively which minimized the chance of information or recall bias.

Limitations

Only subsets of both cohorts had serum testing for B-cell and T-cell immune responses, and matching between both cohorts were based only on age and sex. This could have resulted in selection bias if subjects in both groups were different in a way that that could affect their immune response to the vaccine (e.g., being immunocompromised). Also, local and systemic reactions were measured by soliciting response through direct questionnaires instead of observation. Since the study was unmasked as well, participants might have been influenced to be more or less observant to their reactions, based on their prior knowledge of their specific vaccine’s side effects. Furthermore, there was not a comparison group consisting of heterologous immunization with a 3-week interval between doses, which makes it difficult to discern whether the heterologous immunization or difference in timing was responsible for these results.

Value added

This is the first study to examine B-cell and T-cell immune responses as well as local and systematic reactions between heterologous (ChAdOx1 then BNT162b2) and homologous (BNT162b2 for both doses) immunization groups. Since females have been reported to be more prone to rare but serious thromboembolic events following ChAdOx1 vaccination, this study provides strong laboratory data for the efficacy and safety of heterologous immunization, at least at the short run.