Evidence of Leaky Protection Following COVID-19 Vaccination and SARS-CoV-2 Infection in a US Correctional Facility Population (preprint)

Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent ("leaky") protection remains unknown. We examined the effect of prior infection and vaccination on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, unit, and no documented exposures to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection and vaccination reduced the infection risk of residents without a documented exposure (Hazards ratio: infection, 0.36 [0.25-0.54]; vaccination, 0.57 [0.42-0.78]) and with cellblock exposures (infection, 0.61 [0.49-0.75]; vaccination, 0.69 [0.58-0.83]) but not with cell exposures (infection, 0.89 [0.58-1.35]; vaccination, 0.96 [0.64-1.46]). Associations were similar during the Delta period and when analyses were restricted to residents who underwent testing. These findings suggest that SARS-CoV-2 infection and COVID-19 vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in densely crowded settings.

Protection against Omicron conferred by mRNA primary vaccine series, boosters, and prior infection (preprint)

BACKGROUND Prisons and jails are high-risk settings for Covid-19 transmission, morbidity, and mortality. We evaluate protection conferred by prior infection and vaccination against the SARS-CoV-2 Omicron variant within the California state prison system. METHODS We employed a test-negative design to match resident and staff cases during the Omicron wave (December 24, 2021 to April 14, 2022) to controls according to a case's test-week as well as demographic, clinical, and carceral characteristics. We estimated protection against infection using conditional logistic regression, with exposure status defined by vaccination, stratified by number of mRNA doses received, and prior infection, stratified by periods before or during Delta variant predominance. RESULTS We matched 15,783 resident and 8,539 staff cases to 180,169 resident and 90,409 staff controls. Among cases, 29.7% and 2.2% were infected before or during the emergence of the Delta variant, respectively; 30.6% and 36.3% were vaccinated with two or three doses, respectively. Estimated protection from Omicron infection for two and three doses were 14.9% (95% Confidence Interval [CI], 12.3 to 19.7%) and 43.2% (42.2 to 47.4%) for those without known prior infections, 47.8% (95% CI, 46.6 to 52.8%) and 61.3% (95% CI, 60.7 to 64.8%) for those infected before the emergence of Delta, and 73.1% (95% CI, 69.8 to 80.1%) and 86.8% (95% CI, 82.1 to 92.7) for those infected during the period of Delta predominance. CONCLUSION A third mRNA dose provided significant, additional protection over two doses, including among individuals with prior infection. Our findings suggest that vaccination should remain a priority--even in settings with high levels of transmission and prior infection.

Shared within-host SARS-CoV-2 variation in households (preprint)

Background: The limited variation observed among SARS-CoV-2 consensus sequences makes it difficult to reconstruct transmission linkages in outbreak settings. Previous studies have recovered variation within individual SARS-CoV-2 infections but have not yet measured the informativeness of within-host variation for transmission inference. Methods: We performed tiled amplicon sequencing on 307 SARS-CoV-2 samples from four prospective studies and combined sequence data with household membership data, a proxy for transmission linkage. Results: Consensus sequences from households had limited diversity (mean pairwise distance, 3.06 SNPs; range, 0-40). Most (83.1%, 255/307) samples harbored at least one intrahost single nucleotide variant (iSNV; median: 117; IQR: 17-208), when applying a liberal minor allele frequency of 0.5% and prior to filtering. A mean of 15.4% of within-host iSNVs were recovered one day later. Pairs in the same household shared significantly more iSNVs (mean: 1.20 iSNVs; 95% CI: 1.02-1.39) than did pairs in different households infected with the same viral clade (mean: 0.31 iSNVs; 95% CI: 0.28-0.34), a signal that increases with increasingly liberal thresholds. Conclusions: Although only a subset of within-host variation is consistently shared across likely transmission pairs, shared iSNVs may augment the information in consensus sequences for predicting transmission linkages.

Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Infection Caused by the SARS-CoV-2 Omicron Variant in People with a Prior SARS-CoV-2 Infection (preprint)

Importance: The benefit of primary and booster vaccination in people who experienced prior SARS-CoV-2 infection remains unclear. Objective: To estimate the effectiveness of a primary (two-dose) and booster (third dose) vaccination against Omicron infection among previously infection people. Design: Test-negative case-control study. Setting: Yale New Haven Health System facilities serving southern Connecticut communities. Participants: Vaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022. Exposure: COVID-19 mRNA primary and booster vaccination. Main Outcomes and Measures: We conducted two analyses, each with an outcome of Omicron BA.1 variant infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary vaccination during the period before and during booster eligibility (14-149 and [≥]150 days, respectively, after 2nd dose) and of booster vaccination ([≥]14 days after booster dose). To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people. Results: Overall, 10,676 cases and 119,397 controls were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 6.1% and 7.8% had a prior infection. The effectiveness of primary vaccination 14-149 days after 2nd dose was 36.1% (95% CI, 7.1-56.1%) and 28.5% (95% CI, 20.0-36.2%) for people with and without prior infection, respectively. The effectiveness of booster vaccination was 45.8% (95% CI, 20.0-63.2%) and 56.9% (95% CI, 52.1-61.2%) in people with and without prior infection, respectively. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (95% CI, 0.56-1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (95% CI, 0.46-0.56). Conclusions and Relevance: Primary vaccination provided significant but limited protection against Omicron BA.1 infection among people with and without prior infection. While booster vaccination was associated with additional protection in people without prior infection, it was not associated with additional protection among people with prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.

TNFα-producing CD4+ T cells dominate the SARS-CoV-2-specific T cell response in COVID-19 outpatients and are associated with durable antibodies (preprint)

SARS-CoV-2-specific CD4+ T cells are likely important in immunity against COVID-19, but our understanding of CD4+ longitudinal dynamics following infection and specific features that correlate with the maintenance of neutralizing antibodies remains limited. We characterized SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients. The quality of the SARS-CoV-2-specific CD4+ response shifted from cells producing IFN{gamma} to TNF+ from five days to four months post-enrollment, with IFN{gamma}-IL21-TNF+ CD4+ T cells the predominant population detected at later timepoints. Greater percentages of IFN{gamma}-IL21-TNF+ CD4+ T cells on day 28 correlated with SARS-CoV-2 neutralizing antibodies measured seven months post-infection ({rho}=0.4, P=0.01). mRNA vaccination following SARS-CoV-2 infection boosted both IFN{gamma} and TNF producing, spike protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNF-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.

COVID-19 policies in practice and their direct and indirect impacts in Northern California jails (preprint)

Context: Although the increased risk of COVID-19 in carceral facilities is well documented, little is known about the practical barriers to infection control and indirect impacts of pandemic policies in these settings. Evidence in jails is especially scarce. Methods: Between July 8, 2020 and April 30, 2021 we performed SARS-CoV-2 serology testing and administered a questionnaire among residents and staff in four Northern California jails. We analyzed seroprevalence in conjunction with demographic factors and survey responses of self-perceived COVID-19 risk, recent illness, COVID-19 test results, and symptom reporting behaviors. We additionally assessed COVID-19 policies in practice and evaluated their impacts on court dates, mental health, and routine health care. We engaged stakeholder representatives, including incarcerated individuals and their advocates, to guide study design, conduct, and interpretation. Findings: We enrolled 788 incarcerated individuals and 380 staff across four county jails. Most seropositive individuals had not previously tested positive for COVID-19, despite many suspecting prior infection. Among incarcerated participants, we identified deficient access to face masks and prevalent symptom underreporting associated with fears of isolation and perceptions of medical neglect in jail. Incarcerated participants also reported substantial hindrances to court cases and reductions in routine health care due to COVID-19. Incarcerated individuals and staff both cited worsened mental health due to COVID-19, which for incarcerated individuals was largely attributable to further isolation from loved ones and other pandemic restrictions on recreation and programming. Conclusions: Perceptions of inadequate protection from COVID-19 were pervasive among incarcerated individuals. Simultaneously, restrictive measures compounded poor mental health and fostered fears of isolation that undermined effective infection control. Custody officials should work to systematically improve provision of masks, understand and mitigate fears and mistrust, and take proactive steps to minimize the detrimental impacts of restrictive policies on residents' mental health and well-being.

Effectiveness of CoronaVac, ChAdOx1, BNT162b2 and Ad26.COV2.S among individuals with prior SARS-CoV-2 infection in Brazil (preprint)

Background. COVID-19 vaccines have proven highly effective among SARS-CoV-2 naive individuals, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with prior infection is less clear. Methods. Utilizing national COVID-19 notification, hospitalization, and vaccination datasets from Brazil, we performed a case-control study using a test-negative design to assess the effectiveness of four vaccines (CoronaVac, ChAdOx1, Ad26.COV2.S and BNT162b2) among individuals with laboratory-confirmed prior SARS-CoV-2 infection. We matched RT-PCR positive, symptomatic COVID-19 cases with RT-PCR-negative controls presenting with symptomatic illnesses, restricting both groups to tests performed at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity, and the odds of hospitalization or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. Findings. Among individuals with prior SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection [≥] 14 days from vaccine series completion was 39.4% (95% CI 36.1-42.6) for CoronaVac, 56.0% (95% CI 51.4-60.2) for ChAdOx1, 44.0% (95% CI 31.5-54.2) for Ad26.COV2.S, and 64.8% (95% CI 54.9-72.4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose compared with the first dose. Effectiveness against hospitalization or death [≥] 14 days from vaccine series completion was 81.3% (95% CI 75.3-85.8) for CoronaVac, 89.9% (95% CI 83.5-93.8) for ChAdOx1, 57.7% (95% CI -2.6-82.5) for Ad26.COV2.S, and 89.7% (95% CI 54.3-97.7) for BNT162b2.

Change in COVID-19 risk over time following vaccination with CoronaVac: A test-negative case-control study (preprint)

Objective To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech) in Sao Paulo State, Brazil. Design Test negative case-control study. Setting Community testing for covid-19 in Sao Paulo state, Brazil. Participants Adults aged 18-120 years who were residents of Sao Paulo state, without a previous laboratory-confirmed covid-19 infection, who received two doses of CoronaVac, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 30 September 2021. Main outcome measures RT-PCR-confirmed symptomatic covid-19 and associated hospital admissions and deaths. Cases were pair-matched to test-negative controls by age (in 5-year bands), municipality of residence, healthcare worker (HCW) status, and date of RT-PCR test ({+/-}3 days). Conditional logistic regression was adjusted for sex, number of covid-19-associated comorbidities, race, and previous acute respiratory infection. Results From 137,820 eligible individuals, 37,929 cases with symptomatic covid-19 and 25,756 test-negative controls with covid-19 symptoms were formed into 37,929 matched pairs. Adjusted odds ratios of symptomatic covid-19 increased with time since series completion, and this increase was greater in younger individuals, and among HCWs compared to non-HCWs. Adjusted odds ratios of covid-19 hospitalisation or death were significantly increased from 98 days since series completion, compared to individuals vaccinated 14-41 days previously: 1.40 (95% confidence interval 1.09 to 1.79) from 98-125 days, 1.55 (1.16 to 2.07) from 126-153 days, 1.56 (1.12 to 2.18) from 154-181 days, and 2.12 (1.39-3.22) from 182 days. Conclusions In the general population of Sao Paulo state, Brazil, an increase in odds of moderate and severe covid-19 outcomes was observed over time following primary series completion with CoronaVac.

Factors associated with COVID-19 vaccine acceptance and hesitancy among residents of Northern California jails (preprint)

Background: Carceral facilities are high-risk settings for COVID-19 transmission. Understanding of factors associated with COVID-19 vaccine acceptance and hesitancy among incarcerated individuals is incomplete, especially for people living in jails. Methods: We conducted a retrospective review of COVID-19 vaccination data from the electronic health record (EHR) of residents in two Northern California county jails to examine factors associated with vaccine uptake in this population. We additionally administered a survey in four jails to assess reasons for vaccine hesitancy, sources of COVID-19 information, and medical mistrust. We performed multivariate logistic regression to determine associations with vaccine uptake or hesitancy. Results: Of 2,584 jail residents offered a COVID-19 vaccine between March 19, 2021 and June 30, 2021, 1,464 (56.7%) accepted at least one dose. Among vaccinated residents, 538 (36.7%) initially refused the vaccine. Vaccine uptake was higher among older individuals, women, those with recent flu vaccination, and those living in shared cells or open dorms. Leading reasons for vaccine hesitancy included concerns around side effects and suboptimal efficacy. Television and friends/family were the most commonly cited and the most trusted sources of COVID-19 information, respectively. Vaccine acceptance was associated with increased trust in COVID-19 information sources and in medical personnel both in and out of jail. Conclusion: Ongoing evidence-based COVID-19 vaccination efforts are needed in high-risk carceral settings. Effective interventions to improve vaccination rates in this population should utilize accessible and trusted sources of information to address concerns about vaccine side effects and efficacy and foster medical trust.

Uptake of Covid-19 vaccines among frontline workers in California state prisons (preprint)

Background Prisons are high-risk environments for Covid-19. Vaccination levels among prison staff remain troublingly low - lower than levels among residents and members of the surrounding community. The situation is troubling because prison staff are a key vector for Covid-19 transmission. Objective To assess patterns and timing of staff vaccination in California state prisons and identify individual- and community-level factors associated with being unvaccinated. Design We calculated fractions of prison staff and incarcerated residents in California state prisons who remained unvaccinated. Adjusted analyses identified demographic, community, and peer factors associated with vaccination uptake among staff. Setting California Department of Corrections and Rehabilitation prisons. Participants Custody and healthcare staff who worked in direct contact with residents. Main Outcomes and Measures Remaining unvaccinated through June 30, 2021. Results A total of 26 percent of custody staff and 52 percent of healthcare staff took [≥] 1 dose in the first two months of vaccine offer; uptake stagnated thereafter. By June 30, 2021, 61 percent of custody and 37 percent of healthcare staff remained unvaccinated. Remaining unvaccinated was positively associated with younger age, prior Covid-19, residing in a community with relatively low vaccination rates, and sharing shifts with co-workers who had relatively low vaccination rates. Conclusions and Relevance Vaccine uptake among prison staff in California in regular contact with incarcerated residents has plateaued at levels that pose ongoing risks - both of further outbreaks in the prisons and transmission into surrounding communities. Staff decisions to forego vaccination appear to be complex and multifactorial. Achieving safe levels of vaccine protection among frontline staff may necessitate requiring vaccination as condition of employment.

SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19 (preprint)

The COVID-19 pandemic, caused by the viral pathogen SARS-CoV-2, has taken the lives of millions of individuals around the world. Obesity is associated with adverse COVID-19 outcomes, but the underlying mechanism is unknown. In this report, we demonstrate that human adipose tissue from multiple depots is permissive to SARS-CoV-2 infection and that infection elicits an inflammatory response, including the secretion of known inflammatory mediators of severe COVID-19. We identify two cellular targets of SARS-CoV-2 infection in adipose tissue: mature adipocytes and adipose tissue macrophages. Adipose tissue macrophage infection is largely restricted to a highly inflammatory subpopulation of macrophages, present at baseline, that is further activated in response to SARS-CoV-2 infection. Preadipocytes, while not infected, adopt a proinflammatory phenotype. We further demonstrate that SARS-CoV-2 RNA is detectable in adipocytes in COVID-19 autopsy cases and is associated with an inflammatory infiltrate. Collectively, our findings indicate that adipose tissue supports SARS-CoV-2 infection and pathogenic inflammation and may explain the link between obesity and severe COVID-19.

Long Term Accuracy of SARS-CoV-2 Interferon-γ Release Assay and its Application in Household Investigation (preprint)

BackgroundAn immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. MethodsThe performance of a whole blood interferon-gamma (IFN-{gamma}) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific CD4 and CD8 T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. ResultsThe overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-{gamma} response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. ConclusionsThe SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2. Key pointsSARS-CoV-2 immunodiagnostics are needed to identify infected individuals in order to understand the transmission dynamics of emerging variants and to assess vaccine response. Interferon-gamma release assay maintains sensitivity 10 months post-infection in convalescents and detects more household contacts than IgG.

Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19 (preprint)

The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, mild to moderate infections are an important contributor to ongoing transmission. There remains a critical need to identify host immune biomarkers predictive of clinical and virologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial of Peginterferon Lambda for treatment of SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We define early immune signatures, including plasma levels of RIG-I and the CCR2 ligands (MCP1, MCP2 and MCP3), associated with control of oropharyngeal viral load, the degree of symptom severity, and immune memory (including SARS-CoV-2-specific T cell responses and spike (S) protein-binding IgG levels). We found that individuals receiving BNT162b2 (Pfizer-BioNTech) vaccine had similar early immune trajectories to those observed in this natural infection cohort, including the induction of both inflammatory cytokines (e.g. MCP1) and negative immune regulators (e.g. TWEAK). Finally, we demonstrate that machine learning models using 8-10 plasma protein markers measured early within the course of infection are able to accurately predict symptom severity, T cell memory, and the antibody response post-infection.

Effectiveness of COVID-19 Vaccines among Incarcerated People in California State Prisons: A Retrospective Cohort Study (preprint)

BackgroundPrisons and jails are high-risk settings for COVID-19 transmission, morbidity, and mortality. COVID-19 vaccines may substantially reduce these risks, but evidence is needed of their effectiveness for incarcerated people, who are confined in large, risky congregate settings. MethodsWe conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination status, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates that adjusted for resident characteristics and infection rates across prisons. FindingsAmong 60,707 residents in the cohort, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable (74% [95% CI, 62-82%] and 92% [95% CI, 74-98%] from 14 days after first and second doses, respectively), as well as among the subset of residents who received the mRNA-1273 vaccine (71% [95% CI, 58-80%] and 96% [95% CI, 67-99%]). ConclusionsConsistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population. FundingHorowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.

Variation in SARS-CoV-2 bioaerosol production in exhaled breath (preprint)

Using face mask bioaerosol sampling, we found substantial variation between individuals in SARS-CoV-2 copies exhaled over a 15-minute period, which moderately correlated with nasal swab viral load. Talking was associated with a median of 2 log10 greater exhaled viral copies. Exposure varies substantially between individuals but may be risk stratified by nasal swab viral load and whether the exposure involved conversation.

Effectiveness of the ChAdOx1 vaccine in the elderly during SARS-CoV-2 Gamma variant transmission in Brazil (preprint)

BackgroundA two-dose regimen of ChAdOx1 coronavirus disease 19 (Covid-19) vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of severe acute respiratory syndrome 2 (SARS-CoV-2). MethodsWe conducted a test-negative case-control study to estimate the effectiveness of ChAdOx1 vaccine in adults aged 60 years or older during a Gamma-variant-associated epidemic in Sao Paulo state, Brazil, between 17 January and 2 July 2021. Cases and matched test-negative controls were individuals, identified from surveillance databases, who experienced an acute respiratory illness and underwent SARS-CoV-2 RT-PCR testing. We used conditional logistic regression to estimate the effectiveness by dose against RT-PCR-confirmed Covid-19, Covid-19 hospitalization, and Covid-19-related death. Results61,164 individuals were selected into matched case-control pairs. Starting [≥]28 days after the first dose, adjusted effectiveness of a single dose of ChAdOx1 was 33.4% (95% CI, 26.4 to 39.7) against Covid-19, 55.1% (95% CI, 46.6 to 62.2) against hospitalization, and 61.8% (95% CI, 48.9 to 71.4) against death. Starting [≥]14 days after the second dose, the adjusted effectiveness of the two-dose schedule was 77.9% (95% CI, 69.2 to 84.2) against Covid-19, 87.6% (95% CI, 78.2 to 92.9) against hospitalization, and 93.6% (95% CI, 81.9 to 97.7) against death. ConclusionsCompletion of the ChAdOx1 vaccine schedule afforded significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant transmission.

Ventilation and detection of airborne SARS-CoV-2: elucidating high-risk spaces in naturally ventilated healthcare settings (preprint)

Background: In healthcare settings in low- and middle-income countries, which frequently rely upon natural ventilation, the risk of aerosol transmission of SARS-CoV-2 remains poorly understood. We aimed to evaluate the risk of exposure to SARS-CoV-2 in naturally-ventilated hospital settings by measuring parameters of ventilation and comparing these findings with results of bioaerosol sampling. Methods: We measured outdoor and room CO2 to estimate absolute ventilation (liters per second [L/s]) from 9 hospitals in Bangladesh during October 2020 - February 2021. We estimated infectious risk across different spaces using a modified Wells-Riley equation. We collected air samples from these same spaces at 12.5 L/min over 30 minutes and performed RT-qPCR to detect SARS-CoV-2 N-gene. We used multivariable linear regression and calculated elasticity to identify characteristics associated with ventilation. Results: Based on ventilation of 86 patient care areas and COVID-19 case numbers, we found that over a 40-hour exposure period, outpatient departments posed the highest median risk for infection (5.4%), followed by COVID intensive care units (1.8%). We detected SARS-CoV-2 RNA in 18.6% (16/86) of air samples. Ceiling height and total open area of doors and windows were found to have the greatest impact on ventilation. Conclusion: Our findings provide evidence that naturally-ventilated healthcare settings may pose a high risk for exposure to SARS-CoV-2, particularly among non-COVID designated spaces, but improving parameters of ventilation can mitigate this risk.

Effectiveness of the CoronaVac vaccine in the elderly population during a P.1 variant-associated epidemic of COVID-19 in Brazil: A test-negative case-control study (preprint)

ObjectiveTo estimate the effectiveness of the inactivated whole-virus vaccine, CoronaVac, against symptomatic COVID-19 in the elderly population of Sao Paulo State, Brazil during widespread circulation of the Gamma variant. DesignTest negative case-control study. SettingHealth-care facilities in Sao Paulo State, Brazil. Participants43,774 adults aged 70 years or older who were residents of Sao Paulo State and underwent SARS-CoV-2 RT-PCR testing from January 17 to April 29, 2021. 26,433 cases with symptomatic COVID-19 and 17,622 symptomatic, test negative controls were selected into 7,950 matched pairs, according to age, sex, self-reported race, municipality of residence, prior COVID-19 status and date of RT-PCR testing. InterventionVaccination with a two-dose regimen of CoronaVac. Main outcome measuresRT-PCR confirmed symptomatic COVID-19 and COVID-19 associated hospitalizations and deaths. ResultsAdjusted vaccine effectiveness against symptomatic COVID-19 was 18.2% (95% CI, 0.0 to 33.2) in the period 0-13 days after the second dose and 41.6% (95% CI, 26.9 to 53.3) in the period [≥]14 days after the second dose. Adjusted vaccine effectiveness against hospitalisations was 59.0% (95% CI, 44.2 to 69.8) and against deaths was 71.4% (95% CI, 53.7 to 82.3) in the period [≥]14 days after the second dose. Vaccine effectiveness [≥]14 days after the second dose declined with increasing age for the three outcomes, and among individuals aged 70-74 years it was 61.8% (95% CI, 34.8 to 77.7) against symptomatic disease, 80.1% (95% CI, 55.7 to 91.0) against hospitalisations and 86.0% (95% CI, 50.4 to 96.1) against deaths. ConclusionsVaccination with CoronaVac was associated with a reduction in symptomatic COVID-19, hospitalisations and deaths in adults aged 70 years or older in a setting with extensive Gamma variant transmission. However, significant protection was not observed until completion of the two-dose regimen, and vaccine effectiveness declined with increasing age amongst this elderly population. Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSRandomised controlled trials (RCT) have yielded varying estimates (51 to 84%) for the effectiveness of the inactivated whole-virus vaccine, CoronaVac, against symptomatic COVID-19. Current evidence is limited on whether CoronaVac is effective against severe disease or death caused by the SARS-CoV-2 variant of concern, Gamma, or in the setting of extensive Gamma variant circulation. More evidence is needed for the real-world effectiveness of CoronaVac and other inactivated vaccines among elderly individuals, a population that was underrepresented in RCTs of these vaccines. What this study addsA two-dose regimen of CoronaVac provides significant protection against symptomatic COVID-19, hospitalisations and deaths among adults [≥]70 years of age in the setting of widespread Gamma variant transmission. Significant protection did not occur until [≥]14 days after administration of the second dose of CoronaVac. The effectiveness of CoronaVac declines with increasing age in the elderly population.

Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein (preprint)

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.

Outbreaks of Covid-19 Variants in Prisons: A Mathematical Modeling Analysis of Vaccination and Re-Opening Policies (preprint)

Background: Residents of correctional facilities have experienced disproportionately higher rates of SARS-CoV-2 infection and Covid-19-related mortality. To protect against outbreaks, many prisons and jails imposed heavy restrictions on in-person activities, which are now beginning to lift. Uncertainty surrounds the safety of these moves. Methods and Findings: We obtained system-wide resident-day level data for the California state prison system, the nation's third largest. We used the data to develop a transmission-dynamic stochastic microsimulation model that projects the impact of various policy scenarios on risks of SARS-CoV-2 infections and related hospitalization among residents after an initial infection is introduced to a prison. The policy scenarios vary according to levels of vaccine coverage, baseline immunity, resumption of activities, and use of non-pharmaceutical interventions (e.g., masking, physical distancing). The analyses were conducted across 5 types of prisons that differed in their residential layouts, security levels, and resident demographics. If a viral variant is introduced into a prison that has resumed pre-2020 contact levels, has moderate vaccine coverage, and has no baseline immunity, 23-74% of residents are expected to be infected over 200 days. High vaccination coverage coupled with use of non-pharmaceutical measures reduces cumulative infections to 2-54% of residents. In prisons consisting mostly of dormitory housing, even with high vaccine coverage and non-pharmaceutical interventions, resumption of in-person activities is associated with substantial risk, unless there is high baseline immunity (e.g., [≥]50%) from prior outbreaks. In prisons consisting mostly of cell housing, <10% of residents are expected to become infected, even with no baseline immunity. However, hospitalization risks are substantial in prisons that house medically vulnerable populations, even for prisons consisting mostly of cells. Risks of large outbreaks are substantially higher if there is continued introduction of infections into a prison. Some findings may not be transportable to other carceral settings, and our assumptions regarding viral variants will not be accurate for all variants. Conclusions: Balancing the benefits of resuming normal in-person activities against the risks of Covid-19 outbreaks is a difficult challenge for correctional systems. The policy choices are not strictly binary. To protect against viral variants, prisons should focus on achieving both high vaccine coverage and maintaining widespread use of non-pharmaceutical interventions. With both in place, some prisons, especially those with lower room occupancy that have already had large outbreaks, could safely resume in-person activities, while continuing testing and measures to protect the medically-vulnerable.