Decreased memory B cells frequencies in COVID-19 Delta variant vaccine breakthrough infection
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ABSTRACT: The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
Project description:BackgroundThe clinical features of coronavirus disease 2019 (COVID-19) patients in the COVID-19 vaccination era need to be clarified because breakthrough infection after vaccination is not uncommon.MethodsWe retrospectively analyzed hospitalized COVID-19 patients during a delta variant-dominant period 6 months after the national COVID-19 vaccination rollout. The clinical characteristics and risk factors for severe progression were assessed and subclassified according to vaccination status.ResultsA total of 438 COVID-19 patients were included; the numbers of patients in the unvaccinated, partially vaccinated and fully vaccinated groups were 188 (42.9%), 117 (26.7%) and 133 (30.4%), respectively. The vaccinated group was older, less symptomatic and had a higher Charlson comorbidity index at presentation. The proportions of patients who experienced severe progression in the unvaccinated and fully vaccinated groups were 20.3% (31/153) and 10.8% (13/120), respectively. Older age, diabetes mellitus, solid cancer, elevated levels of lactate dehydrogenase and chest X-ray abnormalities were associated with severe progression, and the vaccination at least once was the only protective factor for severe progression. Chest X-ray abnormalities at presentation were the only predictor for severe progression among fully vaccinated patients.ConclusionIn the hospitalized setting, vaccinated and unvaccinated COVID-19 patients showed different clinical features and risk of oxygen demand despite a relatively high proportion of patients in the two groups. Vaccination needs to be assessed as an initial checkpoint, and chest X-ray may be helpful for predicting severe progression in vaccinated patients.
Project description:Introduction: Randomized, controlled trials of molnupiravir in real-world use during the Omicron wave are scarce. The frequency of hospitalization and death is low, so further research is needed to confirm the virological efficacy of molnupiravir. Methods: A single-center, randomized, controlled clinical trial was conducted, and 111 hospitalized coronavirus disease 2019 (COVID-19) patients were randomly assigned at a ratio of 1:1. Fifty-three patients in the molnupiravir group were administered 800 mg of molnupiravir twice daily for 5 days in addition to the standard therapy, and 58 patients in the control group only received the standard therapy in accordance with local guidelines. The antiviral effect and adverse events were evaluated during the follow-up. Results: The median viral clearance time in the molnupiravir group was significantly shorter than that in the control group (p = 0.003). Furthermore, patients who started molnupiravir therapy within 3 days had significantly shorter viral clearance time than the controls (p = 0.003). In the vaccinated subgroup, molnupiravir therapy was also associated with a shorter viral clearance time (p = 0.003). A total of three adverse events, which were minor, were reported in the molnupiravir group. One of the patients had mild liver function abnormalities, and all of them were resolved without intervention. However, the remission time was similar between the two tested groups. Conclusion: Molnupiravir exhibited good viral replication inhibitor efficacy in patients with Omicron variant vaccine breakthrough COVID-19 infection. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200059796].
Project description:Vaccine breakthrough by an emergent SARS-CoV-2 variant poses a great risk to global public health. To determine the SARS-CoV-2 variant responsible for 6 cases of vaccine breakthrough. Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 by qPCR for Wuhan-Hu1 and Alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. Transmission event occurred at events surrounding a wedding outside of Houston, TX. Two patients from India, likely transmitted the Delta variant to other guests. Following a positive SARS-CoV-2 qPCR test at a third-party site, six fully vaccinated patients were investigated. Three males and three females ranged from 53 to 69 years old. One patient suffered from diabetes while three others were classified as overweight. No significant other comorbidities were identified. None of the patients had a history of failed vaccination. Question: Which SARS-CoV-2 variant is responsible for 6 cases of vaccine breakthrough, one interventional monoclonal antibody treatment, and one death?Findings: Viral sequencing revealed 6 vaccinated patients were infected with the Delta SARS-CoV-2 variant. With no histories of vaccine breakthrough, this suggests Delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152.Meaning: Delta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with increased transmissibility over Alpha variant and possible vaccine breakthrough.
Project description:BackgroundThis study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health.MethodsNasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x.ResultsViral sequencing revealed an infection cluster of 6 vaccinated patients infected with the delta (B.1.617.2) SARS-CoV-2 variant. With no history of vaccine breakthrough, this suggests the delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152.ConclusionsDelta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with previously described increased transmissibility over alpha variant and now, possible vaccine breakthrough.FundingParts of this work was supported by the National Institute of Allergy and Infectious Diseases (1U19AI144297) and Baylor College of Medicine internal funding.
Project description:ObjectivesThis study aimed to evaluate factors associated with the risk of COVID-19 pneumonia in children (aged <10 years) and adolescents (aged 10-19 years) before (March 2020-April 2021) and during (May-July 2021) the Delta (B.1.617.2) variant emergence.Study designA retrospective and nationwide cohort study was conducted in Mexico.MethodsData from 26,961 laboratory-confirmed cases of COVID-19 were analyzed. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to evaluate the association of the evaluated exposures with the risk of COVID-19 pneumonia.ResultsThe overall incidence rate of pneumonia was 23.0 per 10,000 person-days, and it was lower during the Delta variant emergence (30.3 vs. 9.4 person-days, p < 0.001). In multiple analysis, a decreased risk of pneumonia was observed among those cases occurring in May 2021 or later (vs. March 2020-April 2021, RR = 0.98, 95% CI 0.97-0.99) and among older patients (RRper year = 0.998, 95% CI 0.996-0.998). Other comorbidities (namely, obesity, chronic kidney disease, diabetes mellitus, immunosuppression, or malignant tumors) were associated with an increased risk of severe COVID-19 manifestations.ConclusionsOur findings suggest that during the Delta variant emergence, children and adolescent patients were at reduced risk of COVID-19 pneumonia in Mexico. Further research is needed to identify factors determining the observed scenario.
Project description:Genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have repeatedly altered the course of the coronavirus disease 2019 (COVID-19) pandemic. Delta variants are now the focus of intense international attention because they are causing widespread COVID-19 globally and are associated with vaccine breakthrough cases. We sequenced 16,965 SARS-CoV-2 genomes from samples acquired March 15, 2021, through September 20, 2021, in the Houston Methodist hospital system. This sample represents 91% of all Methodist system COVID-19 patients during the study period. Delta variants increased rapidly from late April onward to cause 99.9% of all COVID-19 cases and spread throughout the Houston metroplex. Compared with all other variants combined, Delta caused a significantly higher rate of vaccine breakthrough cases (23.7% for Delta compared with 6.6% for all other variants combined). Importantly, significantly fewer fully vaccinated individuals required hospitalization. Vaccine breakthrough cases caused by Delta had a low median PCR cycle threshold value (a proxy for high virus load). This value was similar to the median cycle threshold value for unvaccinated patients with COVID-19 caused by Delta variants, suggesting that fully vaccinated individuals can transmit SARS-CoV-2 to others. Patients infected with Alpha and Delta variants had several significant differences. The integrated analysis indicates that vaccines used in the United States are highly effective in decreasing severe COVID-19, hospitalizations, and deaths.
Project description:The aims of this study were to describe the characteristics of patients hospitalized with delta SARS-CoV-2 breakthrough infection, and to identify factors associated with pneumonia on chest Computed Tomography (CT) and mortality. The clinical records of 229 patients (105 F), with a median age of 81 (interquartile range, IQR, 73-88) years old, hospitalized between June and December 2021 after completion of the primary vaccination cycle, were retrospectively analyzed, retrieving data on comorbidities, Clinical Frailty Scale (CFS), clinical presentation and outcomes. Multimorbidity (91.7% with ≥2 chronic illnesses) and frailty (61.6% with CFS ≥ 5) were highly prevalent. CFS (OR 0.678, 95% CI 0.573-0.803, p < 0.001) and hypertension were independently associated with interstitial pneumonia. Mortality was 25.1% and unrelated with age. PaO2/FiO2 on blood gas analysis performed upon admission (OR 0.986, 95% CI 0.977-0.996, p = 0.005), and CFS (OR 1.723, 95% CI 1.152-2.576, p = 0.008) were independently associated with mortality only in subjects < 85 years old. Conversely, serum PCT levels were associated with mortality in subjects ≥ 85 years old (OR 3.088, 95% CI 1.389-6.8628, p = 0.006). In conclusion, hospitalization for COVID-19 breakthrough infection mainly involved geriatric patients, with those aged ≥ 85 more characterized by decompensation of baseline comorbidities rather than typical COVID-19 respiratory symptoms.