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1.
Influenza Other Respir Viruses ; 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1927596

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, self-reported COVID-19 vaccination might facilitate rapid evaluations of vaccine effectiveness (VE) when source documentation (e.g., immunization information systems [IIS]) is not readily available. We evaluated the concordance of COVID-19 vaccination status ascertained by self-report versus source documentation and its impact on VE estimates. METHODS: Hospitalized adults (≥18 years) admitted to 18 U.S. medical centers March-June 2021 were enrolled, including COVID-19 cases and SARS-CoV-2 negative controls. Patients were interviewed about COVID-19 vaccination. Abstractors simultaneously searched IIS, medical records, and other sources for vaccination information. To compare vaccination status by self-report and documentation, we estimated percent agreement and unweighted kappa with 95% confidence intervals (CIs). We then calculated VE in preventing COVID-19 hospitalization of full vaccination (2 doses of mRNA product ≥14 days prior to illness onset) independently using data from self-report or source documentation. RESULTS: Of 2520 patients, 594 (24%) did not have self-reported vaccination information to assign vaccination group; these patients tended to be more severely ill. Among 1924 patients with both self-report and source documentation information, 95.0% (95% CI: 93.9-95.9%) agreement was observed, with a kappa of 0.9127 (95% CI: 0.9109-0.9145). VE was 86% (95% CI: 81-90%) by self-report data only and 85% (95% CI: 81-89%) by source documentation data only. CONCLUSIONS: Approximately one-quarter of hospitalized patients could not provide self-report COVID-19 vaccination status. Among patients with self-report information, there was high concordance with source documented status. Self-report may be a reasonable source of COVID-19 vaccination information for timely VE assessment for public health action.

2.
J Med Virol ; 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1925949

ABSTRACT

Compared to adults, the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness in children has been lower and less severe. However, reports comparing SARS-CoV-2 infection among children and adults are limited. As part of our longitudinal cohort study of adults and children with SARS-CoV-2 infection and their household contacts in Nashville, Tennessee, we compared the clinical characteristics and outcomes of SARS-CoV-2 infections between children and adults. Children were more likely to be asymptomatically infected and had a shorter illness duration compared to adults. The differences observed in clinical presentation across ages may inform symptom-specific testing, screening, and management algorithms.

3.
Chest ; 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1914240

ABSTRACT

BACKGROUND: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy. RESEARCH QUESTION: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19? STUDY DESIGN AND METHODS: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for <14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n=487) or placebo (n=473). The primary outcome was clinical status (illness severity) 14 days after study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) <1.0 indicating more favorable outcomes with convalescent plasma than placebo. In secondary analyses, trial participants were stratified by the presence of endogenous anti-SARS-CoV-2 antibodies ("serostatus") at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality. RESULTS: Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR: 1.04; 1/7 support interval (SI): 0.82-1.33), in patients without endogenous antibodies (aOR: 1.15; 1/7 SI: 0.74-1.80), or in patients with endogenous antibodies (aOR: 0.96; 1/7 SI: 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89/482 (18.5%) patients in the convalescent plasma group and 80/465 (17.2%) patients in the placebo group had died (aOR: 1.04, 1/7 SI: 0.69-1.58). INTERPRETATION: Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes.

4.
Clin Infect Dis ; 2022 Jun 08.
Article in English | MEDLINE | ID: covidwho-1890901

ABSTRACT

BACKGROUND: Adults in the United States (US) began receiving the viral vector COVID-19 vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. METHODS: In a multicenter case-control analysis of US adults (≥18 years) hospitalized March 11-December 15, 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. RESULTS: After excluding patients receiving mRNA vaccines, among 3,979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2.229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% CI: 63%-75%) overall, including 55% (29%-72%) among immunocompromised patients, and 72% (64%-77%) among immunocompetent patients, for whom VEs was similar at 14-90 days (73% [59%-82%]), 91-180 days (71% [60%-80%]), and 181-274 days (70% [54%-81%]) post-vaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18%-65%) among immunocompetent patients. CONCLUSIONS: The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months post-vaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.

5.
Blood Rev ; : 100984, 2022 Jun 12.
Article in English | MEDLINE | ID: covidwho-1885637

ABSTRACT

Individuals with hematological malignancies and hematopoietic stem cell transplant (HCT) recipients are immunologically heterogenous groups with varying degrees of immunosuppression at increased risk of severe disease and mortality from SARS-CoV-2 infection. SARS-CoV-2 vaccines are key interventions to preventing severe COVID-19 and its complications. While these individuals were excluded from initial vaccine trials, there is now a growing body of acceptable safety and immunogenicity data among these individuals. A consistent signal for new or worsening graft versus host disease in allogeneic HCT recipients has not been demonstrated post-vaccination. Immunogenicity in these populations is variable depending on disease and treatment factors. However, serological responses may not accurately reflect vaccine protection as correlates of protection within these populations are not yet established. Large-scale studies powered to identify rare serious events, resolve differences in vaccine responses between different vaccination strategies, and identify immune correlates of protection within these populations are needed.

6.
J Infect Dis ; 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1853098

ABSTRACT

BACKGROUND: The study objective was to evaluate 2 and 3 dose COVID-19 mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. METHODS: 21-site case-control analysis of 10,425 adults hospitalized March-December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (SARS-CoV-2 negative). Participants were classified as: SOT recipient (n=440), other immunocompromising condition (n=1684), or immunocompetent (n=8301). VE against COVID-19 associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls. RESULTS: Among SOT recipients, VE was 29% (95% CI: -19 to 58%) for 2 doses and 77% (95% CI: 48 to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI: 64 to 79%) for 2 doses and 92% (95% CI: 85 to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI: 87 to 90%) for 2 doses and 96% (95% CI: 83 to 99%) for 3 doses. CONCLUSION: Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent people and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.

7.
J Infect Dis ; 2022 May 05.
Article in English | MEDLINE | ID: covidwho-1831183

ABSTRACT

We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020--May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2-6 days after symptom onset.

8.
Journal of Clinical and Translational Science ; 6(s1):3, 2022.
Article in English | ProQuest Central | ID: covidwho-1795945

ABSTRACT

OBJECTIVES/GOALS: The spectrum of disease caused by SARS-CoV-2 ranges from asymptomatic detection to severe illness, with varying presentations by age. Therefore, we aimed to compare the clinical characteristics between children and adults with SARS-CoV-2. METHODS/STUDY POPULATION: From March 20, 2020, to August 18, 2021, we conducted SARS-CoV-2 surveillance in individuals from metropolitan Nashville, TN. Children with multisystem inflammatory syndrome were excluded. Analyses were restricted to individuals with SARS-CoV-2 infection confirmed by detection of viral RNA in nasal specimens using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and/or by detection of serum IgG to the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assay (ELISA). Those with negative RT-qPCR results, but a positive ELISA within 4-6 weeks of symptom onset, were classified as SARS-CoV-2 positive. Clinical characteristics between children and adults were compared with Pearson’s chi square. Illness duration was compared using Kaplan Meier estimators. RESULTS/ANTICIPATED RESULTS: Overall, 426/826 (49%) individuals (children: 57 [13%);adults: 369 [87%]) were SARS-CoV-2 positive, with median ages of 12 and 41 years, respectively. Most individuals were female (54%) and white, non-Hispanic (79%). Compared to adults, children were more likely to be asymptomatic (children: 16% vs. adults: 5%;p=0.001). In contrast, symptomatic adults were more likely to report cough (71% vs. 56%), wheezing (21% vs. 8%), shortness of breath (45% vs. 19%), ageusia (67% vs. 23%), and anosmia (64% vs 27%) than symptomatic children (p<0.05). Mean illness duration was shorter in children than adults: 7 days (95% CI: 5.1, 8.9) vs. 14 days (95% CI: 12.4,15.0), respectively. A total of 5% (18/352) of adults reported symptoms lasting ? 4 weeks (range: 31-96 days), whereas all symptoms in children resolved by 31 days. DISCUSSION/SIGNIFICANCE: Overall, children with SARS-CoV-2 present with a shorter and milder disease course compared to adults. Further studies are needed to understand SARS-CoV-2 illness severity across the lifespan.

9.
MMWR Morb Mortal Wkly Rep ; 71(12): 459-465, 2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1761302

ABSTRACT

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).


Subject(s)
2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19/prevention & control , Respiration, Artificial , Vaccine Efficacy , COVID-19/mortality , Hospital Mortality , Humans , United States/epidemiology
10.
BMJ ; 376: e069761, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1736045

ABSTRACT

OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. DESIGN: Case-control study. SETTING: 21 hospitals across the United States. PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). MAIN OUTCOME MEASURES: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression. RESULTS: Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). CONCLUSIONS: mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19/virology , SARS-CoV-2 , Case-Control Studies , Hospitalization , Humans , Immunization Schedule , Prospective Studies , Severity of Illness Index , United States
11.
J Infect Dis ; 225(10): 1694-1700, 2022 05 16.
Article in English | MEDLINE | ID: covidwho-1704377

ABSTRACT

Vaccine effectiveness (VE) against COVID-19 hospitalization was evaluated among immunocompetent adults (≥18 years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was 96% (95% confidence interval [CI], 93%-98%) among patients with no chronic medical conditions and 83% (95% CI, 76%-88%) among patients with ≥ 3 categories of conditions. VE was similar between those aged 18-64 years versus ≥65 years (P > .05). VE against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing comorbidity burden.


Subject(s)
COVID-19 , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Chronic Disease , Hospitalization , Humans , Vaccines, Synthetic , mRNA Vaccines
12.
Pediatrics ; 149(3)2022 03 01.
Article in English | MEDLINE | ID: covidwho-1703643

ABSTRACT

OBJECTIVES: Examine age differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risk from primary cases and infection risk among household contacts and symptoms among those with SARS-CoV-2 infection. METHODS: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower in primary cases age 12 to 17 years than from primary cases 18 to 49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contact pairs age ≥65 years (76%) and 5 to 11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.


Subject(s)
COVID-19/transmission , Contact Tracing , Family Characteristics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Asymptomatic Infections , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prospective Studies , Risk Factors , Tennessee/epidemiology , Wisconsin/epidemiology , Young Adult
13.
Clin Infect Dis ; 2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1700456

ABSTRACT

BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% CI: 80.7 to 91.3%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI: 79.3 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI: 20.8 to 82.6%) than without immunosuppression (91.3%; 95% CI: 85.6 to 94.8%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

14.
Transpl Infect Dis ; 24(1): e13772, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1571110

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased morbidity and mortality in solid organ transplant (SOT) recipients. Despite exclusion from SARS-CoV-2 vaccine clinical trials, these individuals were identified as high-risk and prioritized for vaccination in public health guidelines. METHODS: We prospectively evaluated humoral and cellular immune responses to two doses of the SARS-CoV-2 mRNA vaccine, BNT162b2, in 56 SOT recipients and 26 healthy controls (HCs). Blood specimens collected from participants prior to each dose and following the second dose were tested for SARS-CoV-2-specific antibodies, as well as CD4+ and CD8+ T-cell responses. RESULTS: SOT recipients demonstrated lower mean anti-SARS-CoV-2 antibody levels compared to HCs after each dose, and only 21.6% achieved an antibody response after the second dose within the range of HC responses. Similarly, the percentage of responsive CD4+ and CD8+ T cells in SOT recipients was lower than in HCs. While most HCs showed notable humoral and cellular responses, responses were less concordant in SOT recipients, with some showing evidence of either humoral or cellular response, but not both. CONCLUSION: Humoral and cellular immune responses to the BNT162b2 vaccine are markedly reduced in SOT recipients as compared to HCs, suggesting that SOT recipients may benefit from more tailored regimens such as higher dose and/or additional vaccinations.


Subject(s)
COVID-19 , Organ Transplantation , Antibodies, Viral , COVID-19 Vaccines , Humans , Immunity, Cellular , SARS-CoV-2 , Transplant Recipients , Vaccines, Synthetic
15.
iScience ; 25(1): 103602, 2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1561444

ABSTRACT

The COVID-19 pandemic revealed an urgent need for rapid profiling of neutralizing antibody responses and development of antibody therapeutics. The current Food and Drug Administration-approved serological tests do not measure antibody-mediated viral neutralization, and there is a need for standardized quantitative neutralization assays. We report a high-throughput two-step profiling approach for identifying neutralizing convalescent plasma. Screening and downselection for serum antibody binding to the receptor-binding domain are followed by quantitative neutralization testing using a chimeric vesicular stomatitis virus expressing spike protein of SARS-CoV-2 in a real-time cell analysis assay. This approach enables a predictive screening process for identifying plasma units that neutralize SARS-CoV-2. To calibrate antibody neutralizing activity in serum from convalescent plasma donors, we introduce a neutralizing antibody standard reagent composed of two human antibodies that neutralize SARS-CoV strains, including SARS-CoV-2 variants of concern. Our results provide a framework for establishing a standardized assessment of antibody-based interventions against COVID-19.

16.
JAMA ; 326(20): 2043-2054, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1544165

ABSTRACT

Importance: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. Objective: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. Design, Setting, and Participants: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. Exposures: COVID-19 vaccination. Main Outcomes and Measures: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. Results: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58). Conclusions and Relevance: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.


Subject(s)
COVID-19 , Hospitalization/statistics & numerical data , Adult , Aged , COVID-19/classification , COVID-19/epidemiology , COVID-19/mortality , COVID-19/prevention & control , COVID-19 Vaccines/classification , Case-Control Studies , Disease Progression , Female , Humans , Male , Middle Aged , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Vaccination
17.
JAMA ; 326(20): 2043-2054, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1499190

ABSTRACT

Importance: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. Objective: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. Design, Setting, and Participants: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. Exposures: COVID-19 vaccination. Main Outcomes and Measures: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. Results: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58). Conclusions and Relevance: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.


Subject(s)
COVID-19 , Hospitalization/statistics & numerical data , Adult , Aged , COVID-19/classification , COVID-19/epidemiology , COVID-19/mortality , COVID-19/prevention & control , COVID-19 Vaccines/classification , Case-Control Studies , Disease Progression , Female , Humans , Male , Middle Aged , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Vaccination
18.
Cell Rep ; 37(5): 109929, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1466097

ABSTRACT

Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive ß-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies.


Subject(s)
Antibodies, Viral/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Cell Line , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Cross Reactions , Drug Design , Epitope Mapping , Female , Immunoglobulin G/immunology , Male , Mice , Mice, Inbred BALB C , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Viral Vaccines/immunology
19.
MMWR Morb Mortal Wkly Rep ; 70(38): 1337-1343, 2021 Sep 24.
Article in English | MEDLINE | ID: covidwho-1436415

ABSTRACT

Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Hospitalization/statistics & numerical data , Immunocompromised Host/immunology , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/therapy , COVID-19 Vaccines/administration & dosage , Female , Humans , Male , Middle Aged , United States/epidemiology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Young Adult
20.
MMWR Morb Mortal Wkly Rep ; 70(34): 1156-1162, 2021 Aug 27.
Article in English | MEDLINE | ID: covidwho-1374684

ABSTRACT

Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Hospitalization/statistics & numerical data , Vaccination/statistics & numerical data , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , Humans , Male , Middle Aged , Time Factors , United States/epidemiology , Vaccines, Synthetic , Young Adult
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