Coronavirus disease 2019 vaccination in transplant recipients.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) vaccination is considered one of the most promising and socioeconomically sustainable strategy to help control the pandemic and several vaccines are currently being distributed in nationwide mass immunization campaigns. Very limited data are available on benefits and risks of COVID-19 vaccination in immunocompromised patients and in particular in solid organ or hematopoietic stem cell transplant recipients as they were excluded from phase III trials. This review summarizes current knowledge, international guidelines and controversies regarding COVID-19 vaccination in these vulnerable populations. RECENT FINDINGS: Various COVID-19 vaccine platforms showed good efficacy in phase III trials in the immunocompetent and there are data arising on the safety and immunogenicity of these vaccines in the immunocompromised population. SUMMARY: Transplant recipients could benefit significantly from COVID-19 vaccination, both through active immunization provided they elicit protective vaccine responses, and probably through cocooning by immunization of caregivers and healthcare personnel and thus reducing the risk of SARS-coronavirus-2 exposure. Although awaiting more data on the safety and efficacy of COVID-19 vaccines to inform potential adaptations of vaccine regimens, we strongly recommend prioritizing COVID-19 vaccination of solid and hematopoietic stem cell transplant recipients to decrease COVID-19-related morbidity and mortality.

Vaccines for COVID-19: A Systematic Review of Feasibility and Effectiveness.

INTRODUCTION: Many potential vaccines for COVID-19 are being studied and developed. Several studies have reported on the safety and efficacy of these vaccines. This systematic review aimed to report on the current evidence concerning the feasibility and effectiveness of vaccines for COVID-19. METHODS: A systematic search was carried out utilizing the keywords in the online databases, including Scopus, Web of Science, PubMed, Embase, and Cochrane. We included both human and non-human studies because of the vaccine novelty, limiting our ability to include sufficient human studies. RESULTS: This review showed several SARS-CoV-2 vaccines to be currently under development using different platforms, including eight vaccines that are adenovirus-based vectors, six vaccines that are RNA-based formulations, one vaccine being DNA-based formulation, and other vaccines using other platforms, including lipid nanoparticles. Although the safety and efficacy profiles of these vaccines are still under debate, some countries have allowed for emergency use of some vaccines in at-risk populations, such as healthcare workers and the elderly. CONCLUSION: It is crucial to gather as much clinically relevant evidence as possible regarding the immunogenicity, efficacy, and safety profiles of available vaccines and adhere wisely to CDC protocols and guidelines for vaccine production.

Baseline factors associated with self-reported disease flares following COVID-19 vaccination among adults with systemic rheumatic disease: results from the COVID-19 global rheumatology alliance vaccine survey.

OBJECTIVE: To examine the frequency of, and risk factors for, disease flare following COVID-19 vaccination in patients with systemic rheumatic disease (SRD). METHODS: An international study was conducted from 2 April to 16 August 2021, using an online survey of 5619 adults with SRD for adverse events following COVID-19 vaccination, including flares of disease requiring a change in treatment. We examined risk factors identified a priori based on published associations with SRD activity and SARS-CoV-2 severity, including demographics, SRD type, comorbidities, vaccine type, cessation of immunosuppressive medications around vaccination and history of reactions to non-COVID-19 vaccines, using multivariable logistic regression. RESULTS: Flares requiring a change in treatment following COVID-19 vaccination were reported by 4.9% of patients. Compared with rheumatoid arthritis, certain SRD, including systemic lupus erythematosus (OR 1.51, 95% CI 1.03, 2.20), psoriatic arthritis (OR 1.95, 95% CI 1.20, 3.18) and polymyalgia rheumatica (OR 1.94, 95% CI 1.08, 2.48) were associated with higher odds of flare, while idiopathic inflammatory myopathies were associated with lower odds for flare (OR 0.54, 95% CI 0.31-0.96). The Oxford-AstraZeneca vaccine was associated with higher odds of flare relative to the Pfizer-BioNTech vaccine (OR 1.44, 95% CI 1.07, 1.95), as were a prior reaction to a non-COVID-19 vaccine (OR 2.50, 95% CI 1.76, 3.54) and female sex (OR 2.71, 95% CI 1.55, 4.72). CONCLUSION: SRD flares requiring changes in treatment following COVID-19 vaccination were uncommon in this large international study. Several potential risk factors, as well as differences by disease type, warrant further examination in prospective cohorts.

Evaluation of the Performance of a Multiplexed Serological Assay in the Detection of SARS-CoV-2 Infections in a Predominantly Vaccinated Population.

SARS-CoV-2 seroprevalence studies may be complicated by vaccination efforts. It is important to characterize the ability of serology methods to correctly distinguish prior infection from postvaccination seroreactivity. We report the performance of the Meso Scale Discovery (MSD) V-PLEX COVID-19 Coronavirus Panel 2 IgG assay. Using serum samples from a prospective cohort of paramedics, we calculated the performance of the V-PLEX nucleocapsid ("N") assay to classify prior SARS-CoV-2 infections, defined as a (i) history of a positive SARS-CoV-2 PCR test or (ii) positive serology results using the Roche Elecsys total nucleocapsid anti-SARS-Cov-2 assay. We calculated sensitivity and specificity at the optimal threshold (defined by the highest Youden index). We compared subgroups based on vaccination status, and between models that excluded prior infections 3 to 12 months before sample collection. Of 1119 participants, 914 (81.7%) were vaccinated and 60 (5.4%) had evidence of a preceding SARS-CoV-2 infection. Overall and within vaccinated and unvaccinated subgroups, the optimal thresholds were 828 AU/mL, 827 AU/mL, and 1324 AU/mL; with sensitivities of 0.95 (95% CI: 0.94 to 0.96), 0.95 (0.94 to 0.96), 0.94 (0.92 to 0.96) and specificities of 0.88 (0.86 to 0.90), 0.87 (0.85 to 0.89), and 0.94 (0.89 to 0.98), respectively. N-assay specificity was significantly better in unvaccinated (versus vaccinated) individuals (P = 0.005). Overall optimal thresholds based on the AUC values were higher for samples from unvaccinated participants, especially when examining infections within the preceding 9 months (5855 versus 1704 AU/mL). Overall, V-PLEX nucleocapsid assay cutoff values were higher among unvaccinated individuals. Specificity was also significantly higher among unvaccinated individuals. Different thresholds were required to achieve optimal test performance, especially for detecting SARS-CoV-2 infections within the preceding 9 months. IMPORTANCE Among a cohort of adult paramedics in Canada, we investigated the performance of nucleocapsid (N) antibody detection (measured with a V-PLEX assay) to identify previous COVID-19 infections and compared differences among vaccinated and unvaccinated. Our data indicate that vaccinated and unvaccinated groups require different thresholds to achieve optimal test performance, especially for detecting COVID-19 within the preceding 9 months. Overall, specificity was significantly higher among unvaccinated, compared to vaccinated individuals.

CoronaVac and ChAdOx1 Vaccination and Gamma Infection Elicited Neutralizing Antibodies against the SARS-CoV-2 Delta Variant.

The emergence of new SARS-CoV-2 variants represents a constant threat to world public health. The SARS-CoV-2 Delta variant was identified in late 2020 in India; since then, it has spread to many other countries, replacing other predominant lineages and raising concerns about vaccination efficiency. We evaluated the sensitivity of the Delta variant to antibodies elicited by COVID-19 vaccinated (CoronaVac and ChAdOx1) and convalescent individuals previously infected by earlier lineages and by the Gamma variant. No reduction in the neutralizing efficacy of the Delta variant was observed when compared to B lineage and a reduced neutralization was observed for the Gamma variant. Our results indicate that neutralization of the Delta variant is not compromised in individuals vaccinated by CoronaVac or ChAdOx1; however, a reduction in neutralization efficacy is expected for individuals infected by the Gamma variant, highlighting the importance of continuous vaccination even for previously infected individuals.

Developing Immunity Testing for SARS-CoV-2 and Other Novel Vaccines-Correlates of Immunogenicity Parameters with Protection.

During the assessment and licensing of novel vaccines, as well as post licensure follow up, it is critical to have reliable immunogenicity testing methods that relate well to real life protection [...].

A Promising Vaccination Strategy against COVID-19 on the Horizon: Heterologous Immunization.

To overcome the ongoing COVID-19 pandemic, vaccination campaigns are the highest priority of majority of countries. Limited supply and worldwide disproportionate availability issues for the approved vaccines, together with concerns about rare side-effects have recently initiated the switch to heterologous vaccination, commonly known as mixing of vaccines. The COVID-19 vaccines are highly effective in the general population. However, none of the vaccines is 100% efficacious or effective, with variants posing more challenges, resulting in breakthrough cases. This review summarizes the current knowledge of immune responses to variants of concern (VOC) and breakthrough infections. Furthermore, we discuss the scope of heterologous vaccination and future strategies to tackle the COVID-19 pandemic, including fractionation of vaccine doses and alternative route of vaccination.

Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity.

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.

Evaluation of a COVID-19 Vaccine Campaign and SARS-CoV-2 Infection and Mortality Among Adults Aged 60 Years And Older in a Middle-Income Country.

Importance: Although there are reports of COVID-19 vaccine implementation in real-world populations, these come from high-income countries or from experience with messenger RNA technology vaccines. Data on outcomes of vaccine deployment in low- or middle-income countries are lacking. Objective: To assess whether the pragmatic application of the 3 COVID-19 vaccines available in Argentina, 2 of which have no reports of evaluation in real-world settings to date, were associated with a reduction in morbidity, all-cause mortality, and mortality due to COVID-19. Design, Setting, and Participants: This cohort study used individual and ecological data to explore outcomes following vaccination with rAd26-rAd5, ChAdOx1, and BBIBP-CorV. To correct for differences in exposure times, results are shown using incidence density per 100 000 person-days from the start of the vaccination campaign (December 29, 2020) to the occurrence of an event or the end of follow-up (May 15, 2021). Participants included 663 602 people aged at least 60 years residing in the city of Buenos Aires, Argentina. Statistical analysis was performed from June 1 to June 15, 2021. Main Outcomes and Measures: Diagnosis of COVID-19 confirmed by reverse transcription-polymerase chain reaction, death from all causes, and death within 30 days of a diagnosis of COVID-19. Poisson regression models were fitted to estimate associations with all 3 outcomes. Results: Among 663 602 residents of the city of Buenos Aires included in the study, 540 792 (81.4%) were vaccinated with at least 1 dose, with 457 066 receiving 1 dose (mean [SD] age, 74.5 (8.9) years; 61.5% were female [n = 281 284]; 68.0% [n = 310 987] received the rAd26-rAd5 vaccine; 29.5% [n = 135 036] received ChAdOx1; 2.4% [n = 11 043] received BBIBP-CorV) and 83 726 receiving 2 doses (mean [SD] age, 73.4 [6.8] years; 63.5% were female [n = 53 204]). The incidence density of confirmed COVID-19 was 36.25 cases/100 000 person-days (95% CI, 35.80-36.70 cases/100 000 person-days) among those who did not receive a vaccine, 19.13 cases/100 000 person-days (95% CI, 18.63-19.62 cases/100 000 person-days) among those who received 1 dose, and 4.33 cases/100 000 person-days (95% CI, 3.85-4.81 cases/100 000 person-days) among those who received 2 doses. All-cause mortality was 11.74 cases/100 000 person-days (95% CI, 11.51-11.96 cases/100 000 person-days), 4.01 cases/100 000 person-days (95% CI, 3.78-4.24 cases/100 000 person-days) and 0.40 cases/100 000 person-days (95% CI, 0.26-0.55 cases/100 000 person-days). COVID-19-related-death rate was 2.31 cases/100 000 person-days (95% CI, 2.19-2.42 cases/100 000 person-days), 0.59 cases/100 000 person-days (95% CI, 0.50-0.67 cases/100 000 person-days), and 0.04 cases/100 000 person-days (95% CI, 0.0-0.09 cases/100 000 person-days) among the same groups. A 2-dose vaccination schedule was associated with an 88.1% (95% CI, 86.8%-89.2%) reduction in documented infection, 96.6% (95% CI, 95.3%-97.5%) reduction in all-cause death, and 98.3% (95% CI, 95.3%-99.4%) reduction in COVID-19-related death. A single dose was associated with a 47.2% (95% CI, 44.2%-50.1%) reduction in documented infection, 65.8% (95% CI, 61.7%-69.5%) reduction in all-cause death, and 74.5% (95% CI, 66%-80.8%) reduction in COVID-19-related death. Conclusions and Relevance: This study found that within the first 5 months after the start of the vaccination campaign, vaccination was associated with a significant reduction in COVID-19 infection as well as a reduction in mortality.

Insights into COVID-19 Vaccine Development Based on Immunogenic Structural Proteins of SARS-CoV-2, Host Immune Responses, and Herd Immunity.

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China's Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency's (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100-150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.

Early clinical trial data and real-world assessment of COVID-19 vaccines: Insights from the Society of Infectious Diseases Pharmacists.

As of August 2021, there were three COVID-19 vaccines available in the United States for the prevention of coronavirus 2019 (COVID-19). The purpose of this narrative review is to examine the early experience from the Emergency Use Authorization (EUA) of BNT162b2 (Pfizer, Inc./BioNTech), mRNA-1273 (Moderna, Inc.), and Ad26.COV2.S (Johnson and Johnson/Janssen Global Services, LLC) through July 2021. The EUA data from the clinical trials have largely been corroborated by real-world effectiveness investigations post-authorization. These studies indicate that immunity is obtained within 2 weeks post-vaccination and may endure for 6 months. The immunity conferred by the vaccines may also be effective against SARS-CoV-2 variants of concern. Additionally, populations not included in the emergency use authorization studies may also benefit from vaccination. This look back at the initial clinical experience can be used by the global community to inform and develop COVID-19 vaccine programs.

COVID-19 vaccines: Keeping pace with SARS-CoV-2 variants.

As the SARS-CoV-2 pandemic evolves, new variants continue to emerge. Some highly transmissible variants, such as Delta, also raised concerns about the effectiveness provided by current vaccines. Understanding immunological correlates of protection and how laboratory findings correspond to clinical effectiveness is imperative to shape future vaccination strategies.

SARS-CoV-2 new variants: Characteristic features and impact on the efficacy of different vaccines.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variants reported in different countries have posed a serious threat to human health and social fabrics worldwide. In addition, these new variants hindered the efforts of vaccines and other therapeutic developments. In this review article, we explained the emergence of new variants of SARS-CoV-2, their transmission risk, mortality rate, and, more importantly, the impact of each new variant on the efficacy of the developed vaccines reported in different literature and findings. The literature reported that with the emergence of new variants, the efficacy of different vaccines is declined, hospitalization and the risk of reinfection is increased. The reports concluded that the emergence of a variant that entirely evades the immune response triggered by the vaccine is improbable. The emergence of new variants and reports of re-infections are creating a more distressing situation and therefore demands further investigation to formulate an effective therapeutic strategy.

Analysis of antibody responses after COVID-19 vaccination in liver transplant recipients and those with chronic liver diseases.

BACKGROUND & AIMS: Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials studying the efficacy of vaccines against SARS-CoV-2. Although the clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown, many societies have recommended vaccination of this highly vulnerable patient population. METHODS: In this prospective study, we determined antibody responses to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver disease (CLD) with and without cirrhosis. RESULTS: Of the 233 patients enrolled so far, 62 were LT recipients, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Antibody titers were defined as undetectable (<0.40 U/ml), suboptimal (0.40-250 U/ml) and adequate (>250 U/ml). Of the 62 patients who had LT, antibody levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47-212 U/ml) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable antibody levels and 15 had suboptimal (median titer 41.3, range 0.49-221 U/L) antibody responses. Of the 92 patients without cirrhosis, 4 had undetectable antibody levels and 19 had suboptimal (median titer 95.5, range 4.9-234 U/L) antibody responses. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of the Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. CONCLUSIONS: Poor antibody responses after SARS-CoV-2 vaccination were seen in 61% of LT recipients and 24% of those with CLD. LAY SUMMARY: The clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown. We performed a prospective study to evaluate immune responses to COVID-19 vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 patients with cirrhosis and 92 with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody responses (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody responses when adjusted for other factors.

Recent advances in management of COVID-19: A review.

The coronavirus disease 2019 (COVID-19) pandemic caused and is still causing significant mortality and economic consequences all over the globe. As of today, there are three U.S Food and Drug administration (FDA) approved vaccines, Pfizer-BioNTech, Moderna and Janssen COVID-19 vaccine. Also, the antiviral drug remdesivir and two combinations of monoclonal antibodies are authorized for Emergency use (EUA) in certain patients. Furthermore, baricitinib was approved in Japan (April 23, 2021). Despite available vaccines and EUA, pharmacological therapy for the prevention and treatment of COVID-19 is still highly required. There are several ongoing clinical trials investigating the efficacy of clinically available drugs in treating COVID-19. In this study, selected novel pharmacological agents for the possible treatment of COVID-19 will be discussed. Point of discussion will cover mechanism of action, supporting evidence for safety and efficacy and reached stage in development. Drugs were classified into three classes according to the phase of viral life cycle they target. Phase I, the early infective phase, relies on supportive care and symptomatic treatment as needed. In phase II, the pulmonary phase, treatment aims at inhibiting viral entry or replication. Drugs used during this phase are famotidine, monoclonal antibodies, nanobodies, ivermectin, remdesivir, camostat mesylate and other antiviral agents. Finally, phase III, the hyper-inflammatory phase, tocilizumab, dexamethasone, selective serotonin reuptake inhibitors (SSRI), and melatonin are used. The aim of this study is to summarize current findings and suggest gaps in knowledge that can influence future COVID-19 treatment study design.