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Our take —

The study, available as a preprint and thus not yet peer reviewed, compared viral shedding among 78 vaccinated people and 15 unvaccinated people infected with the Delta variant of SARS-CoV-2 incarcerated at a Texas prison in July and August 2021. They found no differences in the duration of SARS-CoV-2 PCR test positivity (13 days) or duration of viable virus shedding between vaccinated and unvaccinated people (5 days). The study included a small sample of unvaccinated individuals which could limit the ability to detect differences between the groups and it is unclear if the participants included in the study are representative of all potential participants eligible for the study. Nonetheless, the study suggests that if someone vaccinated against SARS-CoV-2 is infected with the Delta variant, they will likely have similar viral shedding patterns to unvaccinated individuals. 

Study design

Prospective Cohort

Study population and setting

The study was to identify differences in PCR positivity, Ct value, and virus culture between vaccinated and unvaccinated individuals with SARS-CoV-2 infection during a SARS-CoV-2 outbreak in a Texas prison during July 12 to August 4 2021. The study identified 189 people who tested positive for SARS-CoV-2 infection and 95 (50%) consented to participate. Each participant had a nasal swab collected for 10 days following onset of illness (ascertained by self-report) or date of first positive test. An additional specimen was collected from all participants on August 6, regardless of whether they finished the 10 day testing regimen or not. Specimens were tested by reverse transcriptase-polymerase chain reaction (RT-PCR) and cycle threshold (Ct) were reported. Virus culture was attempted from specimens collected on testing days 0, 3, 5, 7, or 9 days since onset, and whole genome sequencing was attempted for one specimen with Ct <30 per participant. Participants were categorized as fully vaccinated if they had completed all recommended doses more than 14 days before the outbreak start. The researchers compared RT-PCR positivity, Ct values, and viral culture positivity, between vaccinated and unvaccinated groups. They also assessed duration of shedding since onset by the type of vaccine received (Moderna, Pfizer, or Janssen) among those vaccinated.  

Summary of Main Findings

Of the 95 participants, 78 (82%) were fully vaccinated and 15 (16%) were unvaccinated, while 2 (2%) were partially vaccinated and not included in later analyses. Of these participants, 978 specimens were collected. There were no differences between vaccinated and unvaccinated individuals in terms of duration of RT-PCR positivity (median 13 days vs. median 13 days), or viral culture positivity (median: 5 days vs. median 5 days). Among those fully vaccinated, however, individuals who received Moderna had a shorter duration of viral culture positivity than those who received Pfizer or Janssen. Individuals with the Pfizer vaccine completed their vaccine regiment significantly earlier (IQR: 131– 131 days) compared to those who received Moderna (IQR: 81 – 82 days) and Janssen (IQR: 46 – 70 days). All 64 successfully sequenced specimens (100%) were the Delta (B.1.617.2) variant.

Study Strengths

The primary study strength was the consistency of testing conducted, with 10 consecutive days of samples collected for all participants. Additionally, they completed viral cultures in addition to RT-PCR, providing evidence of shedding of infectious virus and not just viral RNA. 

Limitations

The primary limitation of the study was the relatively low consent rate, with only 50% of those approached being included in the study. It is not possible to confirm without further information about people in the housing unit, but there may be some selection bias in forming the study sample. Additionally, they only enrolled a few unvaccinated participants, which may reduce power and bias estimates towards the null. Additionally, symptom onset was self-reported and may be subject to imperfect recall, which could affect estimates, and bias towards the null. While the study looked at differences between the vaccines in duration of disease, individuals who completed the Pfizer vaccine earlier, on average, than those who completed the Moderna, and those who completed the Janssen. Therefore, it is not clear if differences in viral shedding related to vaccine type reflects different biological responses to the vaccine, or potential waning immunity due to vaccine timing. 

Value added

This study shows that vaccinated individuals who become infected with the Delta variant can still shed viable virus and could infect others. 

Our take —

Most SARS-CoV-2 transmission occurs in households. There has been scant high-quality evidence to date about how vaccination status (of both the index case and household contacts) affects household transmission risk since Delta has become the dominant variant. In this community-based study of close contacts of people with COVID-19 in the UK, the authors used daily sampling up to 20 days after initial exposure to estimate differences in the secondary attack rate (the proportion of contacts who become infected) by vaccination status and strain, and to test whether viral loads change differently over time in infected individuals depending on vaccination status and strain. For those contacts exposed to the Delta variant within a household, 25% of fully vaccinated individuals became infected compared to 38% of unvaccinated individuals. Vaccine effectiveness within a household with a delta-infected case was estimated to be 34%. Secondary attack rates were similar regardless of whether the initial case was vaccinated or not. There were no meaningful differences in peak viral load by vaccination status or strain. This study shows that the Delta strain of SARS-CoV-2 can transmit efficiently even within households in which cases and contacts are fully vaccinated; however, vaccinated contacts had a lower secondary attack rate, and this study was not designed to estimate differences in severe disease by vaccination status.

Study design

Prospective Cohort

Study population and setting

This community-based study from the UK was designed to estimate the effect of vaccination status on index case viral load trajectories and close contacts’ risk of infection, particularly with respect to the Delta variant of SARS-CoV-2, between September 13, 2020 and September 15, 2021. The primary aims of the study were: 1) to compare the secondary attack rate (SAR) in households by vaccination status of the infected case and the household contact;, and 2) to compare peak viral load and viral growth/decline rates by vaccination status and variant. Through the UK contact tracing system, 602 close contacts (household and non-household, aged 5 years and older) of 471 people with  COVID-19 were identified; 19 of these index cases were also enrolled in this study. Contacts and the 19 index cases provided 8,145 daily upper respiratory tract samples up to 20 days after exposure, beginning a median of 4 days after exposure. Eligible contacts were identified within 5 days of initial exposure, and agreed to self-swabbing of the upper respiratory tract. Unvaccinated/partially vaccinated/fully vaccinated individuals were defined by having 0/1/2 vaccine doses, respectively, at least 7 days before study enrollment. Log peak viral load, viral growth rates, and viral decline rates were estimated for each group using Bayesian hierarchical models and compared with posterior probabilities of a difference in mean values.

Summary of Main Findings

Of the 621 participants, including the 19 index cases, 163 (26%) had detectable SARS-CoV-2 RNA (55% female, median age 36, 82% white). Of these, 71 (44%) had the Delta variant. All infected participants had non-severe ambulatory illness or were asymptomatic. The secondary attack rate for household contacts exposed to the delta variant was 25% (95% CI: 18% to 33%) for fully vaccinated individuals and 38% (24% to 53%) for unvaccinated individuals. Infected contacts had a longer time period between their second dose and study enrollment relative to uninfected contacts (101 days vs. 64 days). Household secondary attack rates were similar regardless of whether the index case was fully vaccinated. Estimated vaccine effectiveness against the Delta variant within a household was estimated at 34% (-15% to 60%). There were no statistically significant differences by vaccination status or variant in the peak viral load; older age was associated with higher peak viral load. Fully vaccinated individuals with the Delta variant had a faster rate of viral decline (posterior probability >0.75) than unvaccinated individuals with the pre-alpha, alpha, or delta variants. There were 12 cases of transmission of the Delta variant between a fully vaccinated index case and a fully vaccinated household contact (out of 43 such pairs, for an attack rate of 28%).

Study Strengths

This study employed daily sequential testing of individuals for up to 20 days after exposure, permitting a high degree of sensitivity in identifying transmission events and allowing viral load kinetics modeling. Whole genome sequencing allowed comparisons by variant.

Limitations

There were fairly small numbers of individuals in individual strata defined by vaccination status and variant. Only symptomatic index cases were used to identify close contacts; non-symptomatic cases may have different risks of onward transmission. It is possible that in some cases, the defined index case within a household was infected by another household member who was not identified as having been infected. Trajectories of viral load could not be observed for those participants with prevalent infection at study entry. Unvaccinated contacts were younger, on average, than vaccinated contacts (because of the progressive rollout of vaccination in the UK), which may have confounded estimates of peak viral load toward the null, but would have biased SAR estimates only if age is related to susceptibility to infection.

Value added

This study employed well-characterized data on vaccination status, nature of contact, variant type, and longitudinally collected sampling of the upper respiratory tract to provide estimates of household transmission risk by vaccination status for the Delta variant.

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 —

In this preprint study, which has not yet been peer-reviewed, researchers found a relatively low number of in-school transmissions and low secondary attack rate (2.9%) among 70 public K-12 schools in Massachusetts during 2020-2021, prior to the emergence of the delta variant. By using standardized and detailed contact tracing methods in a large number of schools, the study provided important information about in-school exposures. However, there are significant concerns regarding the generalizability of the study, including which interventions were used in the school studied and if the results would hold in the context of potentially more transmissible variants.

Study design

Prospective Cohort

Study population and setting

The study objective was to characterize the secondary attack rate of SARS-CoV-2 in Massachusetts schools and identify risk factors of in-school transmission during the 2020-2021 academic school year. A convenience sample of 25 public K-12 school districts in Massachusetts were invited to participate, of which 8 districts participated and contributed data on 70 schools and >33,000 enrolled students. Each school received a standardized spreadsheet to report de-identified information on SARS-CoV-2 cases and their in-school contacts, including their role in school (e.g., student/staff), case identification method (e.g., asymptomatic or symptomatic testing), location of exposure, mask use during exposure, and number of in-school close contacts. In the primary analysis, the in-school secondary attack rate was calculated as the proportion of in-school contacts that tested positive for SARS-CoV-2 among those that were tested. 

Summary of Main Findings

There were 436 index cases identified with a total of 1,771 school-based contacts. Most school-based contacts were tested for SARS-CoV-2 (n=1327 [75%]), of which 2.9% (39/1327) were positive for SARS-CoV-2. Twenty-nine of the 39 school-based contacts that tested positive for SARS-CoV-2 were considered to reflect possible or probable in-school transmissions, resulting in an in-school secondary attack rate of 2.2% (29/1327). There was evidence of staff-to-staff (n=6), staff-to-student (n=7), student-to-staff (n=3), and student-to-student (n=13) transmissions. A greater in-school secondary attack rate was associated with the index case being a staff member (vs. student), the index case being identified via in-school contact tracing (vs. asymptomatic screening), and when the exposure occurred during lunch (vs. elsewhere). All of the in-school transmission events identified during lunch were among staff. In addition, the in-school secondary attack rate was 7 times higher if both the index case and secondary contact were unmasked as compared to when both individuals were masked. The in-school secondary attack rate did not vary by grade level of the index case or contact.

Study Strengths

A key strength of this study was the use of a standardized contact-tracing tool that collected very detailed information in real-time across a relatively large number of schools. It is also a strength that there was high SARS-CoV-2 testing coverage among in-school contacts. 

Limitations

The schools included were a convenience sample and it is unclear from the study what mitigation policies were implemented during the study period, so it is difficult to know to which settings the results can be generalized.

There may have also been imperfect recall of in-school contacts and the nature of those interactions. Finally, all data were collected prior to the emergence of the delta variant, so these results may not hold for this more transmissible variant.

Value added

This large study provides critical information regarding the risk of SARS-CoV-2 transmission among >33,000 students and staff within 70 K-12 schools.

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 —

As new SARS-CoV-2 variants of concern emerge, the extent to which their severity may diverge from prior strains is a central question for clinical and public health practice. This national-level study from England comparing the hospitalization risk between individuals who tested positive for the SARS-CoV-2 Alpha or Delta variants with whole-genome sequencing between March and May 2021 has provided one of the key pieces of evidence to date that the Delta variant may cause more severe disease than previous strains. The authors estimated that the Delta variant was associated with more than twice the risk of hospitalization within 14 days of testing positive than the Alpha variant. A similarly elevated hospitalization risk with the Delta variant was observed among unvaccinated individuals; however, the small number of vaccinated patients who were hospitalized for COVID-19 limited inferences about differences in variant severity among this group. Though the authors were unable to address confounding by comorbidity status and the reported effect size was surprisingly strongly driven by the adjustment for the period when the specimen was drawn, numerous sensitivity analyses found a consistent elevated hospitalization risk among those with the Delta compared to the Alpha variant during this time period. Relative hospitalization risks of similar magnitude have been reported for the Delta variant in Scotland, Denmark, and Canada. Studies over longer periods will provide more confidence that these early trends continued as Delta became the dominant variant in England and other countries, though challenges remain in measuring severity associated with variants given the changing context of surveillance, population immune protection, and clinical care for COVID-19.

Study design

Prospective Cohort

Study population and setting

This study linked national data sources to compare disease severity by SARS-CoV-2 variant type among 43,338 individuals in England with whole-genome sequencing confirmed Alpha or Delta variant infection between March 29, 2021 and May 23, 2021. Approximately 60% of all positive PCR tests in the national database were successfully sequenced by the second month of the study period. Confirmed Alpha or Delta variant cases were excluded from the study population if they had a prior SARS-CoV-2 infection or if they lacked an associated national health service (NHS) identification number needed to link cases to data on outcomes and covariates. The primary severity outcome was COVID-19-related hospitalization, and a secondary outcome was COVID-19-related hospitalization or emergency department visits, both ascertained through national routine health information systems. Hospitalizations 1-14 days after the positive SARS-CoV-2 specimen collection were defined as COVID-19 related. Hospitalizations which began on the same date as the positive test were only included if the patient’s symptoms began 1-7 days prior to hospitalization, or if the patient died in the hospital and had COVID-19-relevant ICD-10 codes. Emergency department visits were identified as COVID-19 related using the same timeframes relative to specimen collection and additionally excluded visits with ICD-10 codes related to injuries. The following variables that could confound the association between variant type and risk of hospitalization were identified by linking each sequenced case to additional data sources with their NHS identification number: age, sex, area or residency, level of socioeconomic status as measured by the index of multiple deprivation (IMD), ethnicity, international travel within 14 days of specimen collection, and date of specimen collection. The relationship between the variant type and hospital admission/emergency care visit was assessed using Cox proportional hazard regression models, adjusted and stratified for these confounders. An interaction term with vaccination status was included in the model to determine whether an association between the Delta variant and hospitalization differed between vaccinated and unvaccinated groups.

Summary of Main Findings

A total of 43,338 cases were included in the study; 34,656 (80%) had the Alpha variant and 8,682 (20%) had the Delta variant. Over the eight-week study period, the prevalence of the Alpha variant dropped from 99% to 35% of weekly cases. Patients with the Delta variant were younger (median age 29 vs 31 years old) and were more likely to be Asian and live in London or the northwest England. Individuals with the Delta variant had a higher risk of hospitalization than those with the Alpha variant, with an adjusted hazard ratio (aHR) of 2.26; 95%CI 1.32-3.89. The risk of the combined endpoint of hospitalization or an emergency department visit was also higher among those with the Delta compared to the Alpha variant (aHR of 1.45; 95%CI 1.08-1.95). These inferences were robust to a series of sensitivity analyses that varied the definitions of outcomes and covariates and used alternative analytic approaches. Among unvaccinated patients and those less than 21 days from their first vaccinated dose, Delta variant was associated with a higher risk for hospitalization with an adjusted HR of 2.32; 95%CI 1.29-4.16. Among individuals with at least partial vaccination, the risk of hospital admission was higher among patients with Delta variant compared to those with Alpha variant (aHR 1.94, 95%CI 0.47-8.05); however, the estimate was not statistically significant with low precision due to the small number of vaccinated individuals who were hospitalized.

Study Strengths

Whereas other studies of Delta variant severity inferred the variant type based on S-gene target detection, a strength of this study was the measurement of variant type by whole-genome sequencing during a period when the national coverage was relatively high in England (60% of all PCR-confirmed cases were successfully sequenced by the second month of the study). The analysis accounted for most strong confounders through stratification and regression adjustment. Several sensitivity analyses were done to reduce the possibility of a spurious association between the Delta variant and hospitalization risk.

Limitations

Since the study covered only the first few weeks that the Delta variant accounted for a significant proportion of COVID-19 cases, it is possible that infections with faster durations or more severe courses are over-represented among the Delta cases and under-represented among the Alpha cases, overestimating the hazard ratios. Studies over longer periods will provide more confidence that these early trends continued as Delta became the dominant variant in England and other countries. Second, the use of whole-genome sequencing, while the gold standard for variant measurement, may not be possible on PCR test results with lower viral loads, thus the sample likely underrepresents individuals with milder cases. An additional 11% of cases with genomic sequencing were excluded from the analysis due to lacking NHS number to link to the other data sources, and this was more likely to be missing for Delta cases, and for Black or Asian individuals or those who travelled internationally. Finally, the Cox regression analysis was described as being stratified on several variables simultaneously, but the paper was unclear as to how the authors arrived on the single hazard ratio reported for hospitalization risk by variant. While sensitivity analyses suggested that the Delta hospitalization risk associated with the Delta variant was robust to more standard multivariable regression methods and varying definitions, the study was not able to account for confounding by comorbidity status, a strong predictor of hospitalization.

Value added

This study was among the first and largest to establish a link between the Delta variant and disease severity with variants confirmed by whole-genome sequencing.

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.