Durability of protection from original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes among adults in the United States -- September 2022-August 2023 (preprint)

ObjectiveTo evaluate the durability of protection provided by original monovalent and bivalent COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes. DesignMulticenter case-control design with prospective enrollment Setting26 hospitals in 20 US states ParticipantsAdults aged [≥]18 years admitted to hospital with COVID-19-like illness from 8 September 2022 to 31 August 2023 Main outcome measuresThe main outcomes were absolute and relative vaccine effectiveness of original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes, including advanced respiratory support (defined as receipt of high-flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation [IMV]) and IMV or death. Vaccine effectiveness was estimated using multivariable logistic regression, in which the odds of vaccination (versus being unvaccinated or receiving original monovalent vaccination only) were compared between COVID-19 case patients and control-patients. Bivalent vaccine effectiveness analyses were stratified by time since dose receipt. ResultsAmong 7028 adults without immunocompromising conditions, 2924 (41.6%) were COVID-19 case patients and 4104 (58.4%) were control patients. Compared to unvaccinated patients, absolute vaccine effectiveness against COVID-19-associated hospitalization was 6% (-7% to 17%) for original monovalent doses only (median time since last dose [IQR] = 421 days [304-571]), 52% (39% to 61%) for a bivalent dose received 7-89 days earlier, and 13% (-10% to 31%) for a bivalent dose received 90-179 days earlier. Absolute vaccine effectiveness against COVID-19-associated advanced respiratory support was 31% (15% to 45%) for original monovalent doses only, 66% (47% to 78%) for a bivalent dose received 7-89 days earlier, and 33% (-1% to 55%) for a bivalent dose received 90-179 days earlier. Absolute vaccine effectiveness against COVID-19-associated IMV or death was 51% (34% to 63%) for original monovalent doses only, 61% (35% to 77%) for a bivalent dose received 7-89 days earlier, and 50% (11% to 71%) for a bivalent dose received 90-179 days earlier. ConclusionWhen compared to original monovalent vaccination only, bivalent COVID-19 vaccination provided additional protection against COVID-19-associated hospitalization and certain severe in-hospital outcomes within 3 months of dose receipt. By 3-6 months, protection from a bivalent dose declined to a level similar to that remaining from original monovalent vaccination only. Although no protection remained from original monovalent vaccination against COVID-19-associated hospitalization, it provided durable protection against severe in-hospital outcomes >1 year after receipt of the last dose, particularly against IMV or death. SUMMARY BOX What is already known on this topic- On September 1, 2022, bivalent mRNA COVID-19 vaccination was recommended for US adults who had completed at least an original monovalent COVID-19 primary series. - Early estimates of bivalent vaccine effectiveness are available for the period soon after dose receipt; however fewer data exist on their durability of protection and effectiveness against severe outcomes. What this study adds- When compared to original monovalent vaccination only, bivalent mRNA COVID-19 vaccination provided additional protection against COVID-19-associated hospitalization and certain severe in-hospital outcomes within 3 months of dose receipt. By 3-6 months, protection from a bivalent dose declined to a level similar to that remaining from original monovalent vaccination only. - Although no protection remained from original monovalent vaccination against COVID-19-associated hospitalization, it provided durable protection against severe in-hospital outcomes >1 year after receipt of the last dose, particularly against invasive mechanical ventilation or death.

Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022.

INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. CONCLUSIONS: Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.

Update to the study protocol for an implementation-effectiveness trial comparing two education strategies for improving the uptake of noninvasive ventilation in patients with severe COPD exacerbation.

BACKGROUND: There is strong evidence that noninvasive ventilation (NIV) improves the outcomes of patients hospitalized with severe COPD exacerbation, and NIV is recommended as the first-line therapy for these patients. Yet, several studies have demonstrated substantial variation in NIV use across hospitals, leading to preventable morbidity and mortality. In addition, prior studies suggested that efforts to increase NIV use in COPD need to account for the complex and interdisciplinary nature of NIV delivery and the need for team coordination. Therefore, our initial project aimed to compare two educational strategies: online education (OLE) and interprofessional education (IPE), which targets complex team-based care in NIV delivery. Due to the impact of the COVID-19 pandemic on recruitment and planned intervention, we had made several changes in the study design, statistical analysis, and implementation strategies delivery as outlined in the methods. METHODS: We originally proposed a two-arm, pragmatic, cluster, randomized hybrid implementation-effectiveness trial comparing two education strategies to improve NIV uptake in patients with severe COPD exacerbation in 20 hospitals with a low baseline rate of NIV use. Due to logistical constrains and slow recruitment, we changed the study design to an opened cohort stepped-wedge design with three steps which will allow the institutions to enroll when they are ready to participate. Only the IPE strategy will be implemented, and the education will be provided in an online virtual format. Our primary outcome will be the hospital-level risk-standardized NIV proportion for the period post-IPE training, along with the change in rate from the period prior to training. Aim 1 will compare the change over time of NIV use among patients with COPD in the step-wedged design. Aim 2 will explore the mediators' role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and effectiveness. Finally, in Aim 3, through interviews with providers, we will assess the acceptability and feasibility of the educational training. CONCLUSION: The changes in study design will result in several limitation. Most importantly, the hospitals in the three cohorts are not randomized as they enroll based on their readiness. Second, the delivery of the IPE is virtual, and it is not known if remote education is conducive to team building. However, this study will be among the first to test the impact of IPE in the inpatient setting carefully and may generalize to other interventions directed to seriously ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04206735 . Registered on December 20, 2019.

Comparison of mRNA vaccine effectiveness against COVID-19-associated hospitalization by vaccination source: Immunization information systems, electronic medical records, and self-report-IVY Network, February 1-August 31, 2022.

BACKGROUND: Accurate determination of COVID-19 vaccination status is necessary to produce reliable COVID-19 vaccine effectiveness (VE) estimates. Data comparing differences in COVID-19 VE by vaccination sources (i.e., immunization information systems [IIS], electronic medical records [EMR], and self-report) are limited. We compared the number of mRNA COVID-19 vaccine doses identified by each of these sources to assess agreement as well as differences in VE estimates using vaccination data from each individual source and vaccination data adjudicated from all sources combined. METHODS: Adults aged ≥18 years who were hospitalized with COVID-like illness at 21 hospitals in 18 U.S. states participating in the IVY Network during February 1-August 31, 2022, were enrolled. Numbers of COVID-19 vaccine doses identified by IIS, EMR, and self-report were compared in kappa agreement analyses. Effectiveness of mRNA COVID-19 vaccines against COVID-19-associated hospitalization was estimated using multivariable logistic regression models to compare the odds of COVID-19 vaccination between SARS-CoV-2-positive case-patients and SARS-CoV-2-negative control-patients. VE was estimated using each source of vaccination data separately and all sources combined. RESULTS: A total of 4499 patients were included. Patients with ≥1 mRNA COVID-19 vaccine dose were identified most frequently by self-report (n = 3570, 79 %), followed by IIS (n = 3272, 73 %) and EMR (n = 3057, 68 %). Agreement was highest between IIS and self-report for 4 doses with a kappa of 0.77 (95 % CI = 0.73-0.81). VE point estimates of 3 doses against COVID-19 hospitalization were substantially lower when using vaccination data from EMR only (VE = 31 %, 95 % CI = 16 %-43 %) than when using all sources combined (VE = 53 %, 95 % CI = 41 %-62%). CONCLUSION: Vaccination data from EMR only may substantially underestimate COVID-19 VE.

Uncovering the Effects of COVID-19 Mask Wearing on Bird Flight Initiation Distance in Urbanized Areas in the Southern Philippines.

The COVID-19 pandemic has caused significant changes in public and human activities worldwide, including using masks and reducing human interaction. These changes have also affected wildlife behavior, especially in urban areas. However, there is limited understanding of the impact of COVID-19-related human activities, mainly mask wearing, on the behavior of urban bird species. This case is intriguing in the Philippines, where COVID-19 restrictions and mask wearing have been more prolonged than in other countries. We studied two common urban bird species (Geopelia striata and Passer montanus) in Southcentral Mindanao, Philippines, to assess their response to mask wearing by examining their alert distance (AD) and flight initiation distance (FID). We found that birds had a reduced FID to mask wearing, but only significantly in G. striata (Zebra Doves) and not in P. montanus (Eurasian tree sparrow). The effect of the variables related to urbanization on FID was contrasting. For example, ambient noise increased bird vigilance while proximity to roads reduced bird FID in urbanized areas, but their effects were weaker compared to mask wearing. We conclude that mask wearing during the COVID-19 pandemic is a significant environmental element that alters bird escape responses in urban areas, and the effects may be species-specific.

Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023.

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

A Review of ST-Elevation Myocardial Infarction in Patients with COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

Total and subgenomic RNA viral load in patients infected with SARS-CoV-2 Alpha, Delta, and Omicron variants.

BACKGROUND: SARS-CoV-2 genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear. METHODS: Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by RT-qPCR in specimens from 3,204 individuals hospitalized with COVID-19 at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression. RESULTS: Ct values at presentation for N (mean ±standard deviation) were 24.14±4.53 for non-variants of concern, 25.15±4.33 for Alpha, 25.31±4.50 for Delta, and 26.26±4.42 for Omicron. N and sgN RNA levels varied with time since symptom onset and infecting variant but not with age, comorbidity, immune status, or vaccination. When normalized to total N RNA, sgN levels were similar across all variants. CONCLUSIONS: RNA viral loads were similar among hospitalized adults, irrespective of infecting variant and known risk factors for severe COVID-19. Total N and subgenomic RNA N viral loads were highly correlated, suggesting that subgenomic RNA measurements adds little information for the purposes of estimating infectivity.

Vaccine effectiveness against influenza A(H3N2)-associated hospitalized illness, United States, 2022.

BACKGROUND: The COVID-19 pandemic was associated with historically low influenza circulation during the 2020-2021 season, followed by increase in influenza circulation during the 2021-2022 US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain. METHODS: To understand the effectiveness of the 2021-2022 vaccine against hospitalized influenza illness, a multi-state sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness (ARI) and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative controls, adjusting for confounders. A separate analysis was performed to illustrate bias introduced by including SARS-CoV-2 positive controls. RESULTS: A total of 2334 patients, including 295 influenza cases (47% vaccinated), 1175 influenza- and SARS-CoV-2 negative controls (53% vaccinated), and 864 influenza-negative and SARS-CoV-2 positive controls (49% vaccinated), were analyzed. Influenza VE was 26% (95%CI: -14 to 52%) among adults aged 18-64 years, -3% (95%CI: -54 to 31%) among adults aged ≥65 years, and 50% (95%CI: 15 to 71%) among adults 18-64 years without immunocompromising conditions. Estimated VE decreased with inclusion of SARS-CoV-2-positive controls. CONCLUSIONS: During a season where influenza A(H3N2) was antigenically different from the vaccine virus, vaccination was associated with a reduced risk of influenza hospitalization in younger immunocompetent adults. However, vaccination did not provide protection in adults ≥65 years of age. Improvements in vaccines, antivirals, and prevention strategies are warranted.

Antibody Correlates of Protection for COVID-19 Convalescent Plasma Associated with Reduced Outpatient Hospitalizations (preprint)

SARS-CoV-2 antibody levels associated with reduced hospitalization risk remain undefined. Our outpatient COVID-19 convalescent plasma (CCP), placebo-controlled trial observed SARS-CoV-2 antibody levels decreasing 22-fold from matched donor units into post-transfusion seronegative recipients. Unvaccinated recipients were jointly stratified by a) early or late transfusion (< 5 or >5 days from symptom onset) and b) high or low post-transfusion SARS-CoV-2 antibody levels (< or > geometric mean). Early treatment with high post-transfusion antibody levels reduced hospitalization risk-0/102 (0%) compared to all other CCP recipients-17/370 (4.6%; Fisher exact-p-0.03) and to all control plasma recipients-35/461 (7.6%; Fisher exact p-0.001). A similar donor upper/lower half antibody level and early late transfusion stratified analyses indicated significant hospital risk reduction. Pre-transfusion nasal viral loads were similar in CCP and control recipients regardless of hospitalization outcome. Therapeutic CCP should comprise the upper 30% of donor antibody levels to provide effective outpatient use for immunocompromised and immunocompetent outpatients.

Diagnosis of COVID-19 Using Artificial Intelligence Techniques

Artificial intelligence is being used in a variety of ways by those trying to address variants and for data management. AI, on the other hand, not only uses historical data, it makes assumptions about the data without applying a defined set of rules. This allows the software to learn and adapt to information patterns in more real time. Numerous sources of medical images (e.g., X-ray, CT, and MRI) make deep learning a great technique to combat the COVID-19 outbreak. Motivated by this fact, a large number of research works have been proposed and developed. Chest CT is an emergency diagnostic tool to identify lung disease. Artificial intelligence (AI) gives big guidance in the rapid analysis of CT scans to differentiate variants of COVID-19 findings. This work focuses on the recent advances of COVID-19 drug and vaccine development using artificial intelligence and the potential of intelligent training for the discovery of COVID-19 therapeutics. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Mechanical Circulatory Support in Patients With COVID-19 Presenting With Myocardial Infarction.

ST-segment elevation myocardial infarction (STEMI) complicating COVID-19 is associated with an increased risk of cardiogenic shock and mortality. However, little is known about the frequency of use and clinical impact of mechanical circulatory support (MCS) in these patients. We sought to define patterns of MCS utilization, patient characteristics, and outcomes in patients with COVID-19 with STEMI. The NACMI (North American COVID-19 Myocardial Infarction) is an ongoing prospective, observational registry of patients with COVID-19 positive (COVID-19+) with STEMI with a contemporary control group of persons under investigation who subsequently tested negative for COVID-19 (COVID-19-). We compared the baseline characteristics and in-hospital outcomes of COVID-19+ and patients with COVID-19- according to the use of MCS. The primary outcome was a composite of in-hospital mortality, stroke, recurrent MI, and repeat unplanned revascularization. A total of 1,379 patients (586 COVID-19+ and 793 COVID-19-) enrolled in the NACMI registry between January 2020 and November 2021 were included in this analysis; overall, MCS use was 12.3% (12.1% [n = 71] COVID-19+/MCS positive [MCS+] vs 12.4% [n = 98] COVID-19-/MCS+). Baseline characteristics were similar between the 2 groups. The use of percutaneous coronary intervention was similar between the groups (84% vs 78%; p = 0.404). Intra-aortic balloon pump was the most frequently used MCS device in both groups (53% in COVID-19+/MCS+ and 75% in COVID-19-/MCS+). The primary outcome was significantly higher in COVID-19+/MCS+ patients (60% vs 30%; p = 0.001) because of very high in-hospital mortality (59% vs 28%; p = 0.001). In conclusion, patients with COVID-19+ with STEMI requiring MCS have very high in-hospital mortality, likely related to the significantly higher pulmonary involvement compared with patients with COVID-19- with STEMI requiring MCS.

A brief primer on conducting regression-based causal mediation analysis.

OBJECTIVE: We provide an overview of regression-based causal mediation analysis in the field of traumatic stress and guidance on how to conduct mediation analysis using our R package regmedint. METHOD: We discuss the causal interpretations of the quantities that causal mediation analysis estimates, including total, direct, and indirect effects, especially when the interaction between exposure and mediator is permitted. We discuss the assumptions that must be fulfilled for mediation analyses to validly estimate these causal quantities, discuss suitable study designs for assessing mediation, and describe how causal mediation analysis differs from traditional methods of mediation. To illustrate how to conduct and interpret mediation analysis using our R package regmedint, we use data from a published longitudinal study to assess the extent to which children's externalizing behavior mediates changes in parental negative feelings during the COVID-19 lockdown. We compare the results to those obtained using traditional methods, thus illustrating the importance of accounting for exposure-mediator interaction when an interaction may be present. RESULTS: When the exposure and the mediator interact, traditional methods can provide estimates of direct and indirect effects that differ from those provided by more flexible causal mediation methods. When the exposure and the mediator do not interact, traditional methods and causal mediation method may estimate similar direct and indirect effects depending on the model specification. CONCLUSIONS: In contrast to traditional methods of mediation analysis, regression-based causal mediation methods seek to estimate specific interventional quantities, not mere associations, and the causal methods explicitly allow for exposure-mediator interactions. We recommend using these methods by default rather than using more restrictive traditional methods. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Protection of mRNA vaccines against hospitalized COVID-19 in adults over the first year following authorization in the United States.

BACKGROUND: COVID-19 mRNA vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization. METHODS: Case control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states March 11 - December 15, 2021, including COVID-19 case patients and RT-PCR-negative controls. We included adults who were unvaccinated or vaccinated with two doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (<180 vs ≥180 days since dose two) and continuous time modeled using restricted cubic splines. RESULTS: 10,078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (IQR 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE <180 days was 90% (95%CI: 88-91) vs 82% (95%CI: 79-85) at ≥180 days (p < 0.001). VE declined for Pfizer-BioNTech (88% to 79%, p < 0.001) and Moderna (93% to 87%, p < 0.001) products, for younger adults (18-64 years) [91% to 87%, p = 0.005], and for adults ≥65 years of age (87% to 78%, p < 0.001). In models using restricted cubic splines, similar changes were observed. CONCLUSION: In a period largely pre-dating Omicron variant circulation, effectiveness of two mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.

Early Treatment, Inflammation and Post-COVID Conditions (preprint)

ABSTRACT Background: Post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC. Methods: Among 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models. Results: One-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC. There was a trend for decreased PCC in those with early CCP treatment (<5 days after symptom onset) compared to late CCP treatment. Conclusion: Increased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. METHODS: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. RESULTS: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). CONCLUSIONS: In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. CLINICAL TRIALS REGISTRATION: NCT04373460.

Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021-April 2022.

Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines. Methods: Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE. Results: A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary. Conclusions: Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.