R-Propranolol Has Broad-Spectrum Anti-Coronavirus Activity and Suppresses Factors Involved in Pathogenic Angiogenesis

The SARS-CoV-2 pandemic highlighted the need for broad-spectrum antivirals to increase our preparedness. Patients often require treatment by the time that blocking virus replication is less effective. Therefore, therapy should not only aim to inhibit the virus, but also to suppress pathogenic host responses, e.g., leading to microvascular changes and pulmonary damage. Clinical studies have previously linked SARS-CoV-2 infection to pathogenic intussusceptive angiogenesis in the lungs, involving the upregulation of angiogenic factors such as ANGPTL4. The β-blocker propranolol is used to suppress aberrant ANGPTL4 expression in the treatment of hemangiomas. Therefore, we investigated the effect of propranolol on SARS-CoV-2 infection and the expression of ANGPTL4. SARS-CoV-2 upregulated ANGPTL4 in endothelial and other cells, which could be suppressed with R-propranolol. The compound also inhibited the replication of SARS-CoV-2 in Vero-E6 cells and reduced the viral load by up to ~2 logs in various cell lines and primary human airway epithelial cultures. R-propranolol was as effective as S-propranolol but lacks the latter's undesired β-blocker activity. R-propranolol also inhibited SARS-CoV and MERS-CoV. It inhibited a post-entry step of the replication cycle, likely via host factors. The broad-spectrum antiviral effect and suppression of factors involved in pathogenic angiogenesis make R-propranolol an interesting molecule to further explore for the treatment of coronavirus infections.

Impact of changes in human airway epithelial cellular composition and differentiation on SARS-CoV-2 infection biology.

The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface (ALI) cultures of well-differentiated primary human tracheal and bronchial epithelial cells were employed to study the impact of epithelial cellular composition and differentiation on SARS-CoV-2 infection by transcriptional (RNA sequencing) and immunofluorescent analyses. Changes of cellular composition were investigated by varying time of differentiation or by using specific compounds. We found that SARS-CoV-2 primarily infected ciliated cells but also goblet cells and transient secretory cells. Viral replication was impacted by differences in cellular composition, which depended on culturing time and anatomical origin. A higher percentage of ciliated cells correlated with a higher viral load. However, DAPT-treatment, which increased number of ciliated cells and reduced goblet cells, decreased viral load, indicating the contribution of goblet cells to infection. Cell-entry factors, especially cathepsin L and transmembrane protease serine 2, were also affected by differentiation time. In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract.

R-Propranolol Has Broad-Spectrum Anti-Coronavirus Activity and Suppresses Factors Involved in Pathogenic Angiogenesis.

The SARS-CoV-2 pandemic highlighted the need for broad-spectrum antivirals to increase our preparedness. Patients often require treatment by the time that blocking virus replication is less effective. Therefore, therapy should not only aim to inhibit the virus, but also to suppress pathogenic host responses, e.g., leading to microvascular changes and pulmonary damage. Clinical studies have previously linked SARS-CoV-2 infection to pathogenic intussusceptive angiogenesis in the lungs, involving the upregulation of angiogenic factors such as ANGPTL4. The ß-blocker propranolol is used to suppress aberrant ANGPTL4 expression in the treatment of hemangiomas. Therefore, we investigated the effect of propranolol on SARS-CoV-2 infection and the expression of ANGPTL4. SARS-CoV-2 upregulated ANGPTL4 in endothelial and other cells, which could be suppressed with R-propranolol. The compound also inhibited the replication of SARS-CoV-2 in Vero-E6 cells and reduced the viral load by up to ~2 logs in various cell lines and primary human airway epithelial cultures. R-propranolol was as effective as S-propranolol but lacks the latter's undesired ß-blocker activity. R-propranolol also inhibited SARS-CoV and MERS-CoV. It inhibited a post-entry step of the replication cycle, likely via host factors. The broad-spectrum antiviral effect and suppression of factors involved in pathogenic angiogenesis make R-propranolol an interesting molecule to further explore for the treatment of coronavirus infections.

COVID-19 and sustainability in textile, apparel and fashion use: An assessment of trends

Apart from the many social and health problems it has caused, the COVID-19 pandemic has had a severe impact on most sectors of the economy worldwide. One of the areas where such impact is noticeable is the textile, apparel, and fashion (TAF) industry. The lockdowns and limited access to retailer outlets resulted in a considerable drop in consumption, creating problems related to the excess of stock, the decrease of sales, and the disposal of non-used items. This paper outlines the implications of the COVID-19 on the TAF sectors and European retailers. It analyzes how the current supply chains exacerbated stock control problems, and it reports on the changes in consumption during the pandemic. The worldwide restrictive measures implemented to cope with the COVID-19 pandemic were responsible for significant profit losses. Also, the decrease in consumption, caused by several geographically wide lockdowns, prompted a subsequent reduction in orders and sales, resulting in a significant number of constraints. The implementation of more environmentally friendly processes, including sustainable circularity as a competitiveness source to keep the TAF sectors in the loop and reduce greenhouse gas emissions, may help address the problems associated with the COVID-19 pandemic in the sustainability context, as reported in this paper. © The Author(s) 2022.

Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine.

We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received two doses of inactivated vaccination. We collected blood samples before the third dose and again after one month and six months, and found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by six months.

Biologic use and outcomes among adults with severe asthma treated by US subspecialists.

BACKGROUND: Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States. OBJECTIVE: To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA. METHODS: CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described. RESULTS: Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (> 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both P < .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E. CONCLUSION: Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03373045.

Immunogenicity of a third dose of BNT162b2 to ancestral SARS-CoV-2 & Omicron variant in adults who received two doses of inactivated vaccine.

BACKGROUND: Limited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. METHODS: We conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. RESULTS: In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p < 0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p < 0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by 45 fold from Day 0 to Day 28 against the ancestral virus (p < 0.001) and rose by 11 fold against the Omicron variant (p < 0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. CONCLUSIONS: A third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier.

Intrinsic and effective severity of COVID-19 cases infected with the ancestral strain and Omicron BA.2 variant in Hong Kong (preprint)

Background: Understanding severity of infections with SARS-CoV-2 and its variants is crucial to inform public health measures. Here we used COVID-19 patient data from Hong Kong to characterise the severity profile of COVID-19 and to examine factors associated with fatality of infection. Methods: Time-varying and age-specific effective severity measured by case-hospitalization risk and hospitalization risk was estimated with all individual COVID-19 case data collected in Hong Kong from 23 January 2020 through to 26 October 2022 over six epidemic waves, in comparison with estimates of influenza A(H1N1)pdm09 during the 2009 pandemic. The intrinsic severity of Omicron BA.2 was compared with the estimate for the ancestral strain with the data from unvaccinated patients without previous infections. Factors potentially associated with the fatality risk of hospitalized Omicron patients were also examined. Results: With 32,222 COVID-19 hospitalizations and 9,669 deaths confirmed over 6 epidemic waves in Hong Kong, the time-varying hospitalization fatality risk dramatically increased from below 10% before the largest fifth wave of Omicron BA.2, to 41% during the peak of the fifth wave when hospital resources were severely constrained. The age-specific fatality risk in unvaccinated hospitalized Omicron cases was comparable to the estimates for unvaccinated cases with the ancestral strain. During epidemics predominated by Omicron BA.2, the highest fatality risk was amongst unvaccinated patients aged [≥]80 years and the risk was inversely associated with the number of vaccination doses received. Conclusions: Omicron has comparable intrinsic severity to the ancestral Wuhan strain although the effective severity is substantially lower in Omicron cases due to vaccination. With a moderate-to-high coverage of vaccination, hospitalized COVID-19 patients caused by Omicron subvariants appeared to have similar age-specific risks of fatality to patients hospitalized with influenza A(H1N1)pdm09.

COVID-19 and sustainability in textile, apparel and fashion use: an assessment of trends

Apart from the many social and health problems it has caused, the COVID-19 pandemic has had a severe impact on most sectors of the economy worldwide. One of the areas where such impact is noticeable is the textile, apparel, and fashion (TAF) industry. The lockdowns and limited access to retailer outlets resulted in a considerable drop in consumption, creating problems related to the excess of stock, the decrease of sales, and the disposal of non-used items. This paper outlines the implications of the COVID-19 on the TAF sectors and European retailers. It analyzes how the current supply chains exacerbated stock control problems, and it reports on the changes in consumption during the pandemic. The worldwide restrictive measures implemented to cope with the COVID-19 pandemic were responsible for significant profit losses. Also, the decrease in consumption, caused by several geographically wide lockdowns, prompted a subsequent reduction in orders and sales, resulting in a significant number of constraints. The implementation of more environmentally friendly processes, including sustainable circularity as a competitiveness source to keep the TAF sectors in the loop and reduce greenhouse gas emissions, may help address the problems associated with the COVID-19 pandemic in the sustainability context, as reported in this paper. © The Author(s) 2022.

Impact of the COVID-19 Pandemic on Incidence of Asthma Exacerbations and Hospitalizations in US Subspecialist-Treated Patients with Severe Asthma: Results from the CHRONICLE Study.

Purpose: Patients with severe asthma (SA) are at an increased risk of asthma-related hospitalizations and exacerbations. Despite concerns that COVID-19 circulation would increase exacerbations of SA, anecdotal reports suggest that social distancing and exposure avoidance may have led to reduced exacerbations. Patients and methods: CHRONICLE is an ongoing noninterventional observational study of 3100 subspecialist-treated patients with SA. Eligible adults (≥ 18 years of age) have (1) current use of monoclonal antibody (ie, biologic) therapy for SA, (2) use of maintenance systemic corticosteroids (mSCS) or other systemic immunosuppressants for ≥ 50% of the prior 12 months for SA, or (3) persistently uncontrolled asthma while treated with high-dosage inhaled corticosteroids with additional controllers. For enrolled patients, electronic medical records were reviewed to record all exacerbations and asthma-related hospitalizations. Descriptive analyses were conducted of the monthly incidence of exacerbations, exacerbation-related visits to the emergency department (ED), and asthma hospitalizations from July 2018 through July 2021. Results: Exacerbations, exacerbation-related ED visits, and hospitalizations decreased since April 2020. Exacerbations in 2020 were 20% to 52% lower in April through August relative to the same months in 2019. Exacerbations remained lower than the prior year through May 2021. Similar results were observed by United States (US) census region, with an earlier decrease in exacerbation rates in the western US versus other regions. Across all months, exacerbation rates were lower among biologic recipients. Conclusion: In a clinical cohort of subspecialist-treated patients with SA, there was a meaningful reduction in exacerbations, exacerbation-related ED visits, and asthma hospitalizations following COVID-19-related stay-at-home orders and social distancing recommendations. Reasons for these reductions are likely multifactorial, including reduced viral infections due to less social contact and altered patient behavior.

The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

SARS-CoV-2 infection and vaccination generates enormous host response heterogeneity and an age-dependent loss of immune response quality. How the pre-exposure T cell repertoire contributes to this heterogeneity is poorly understood. We combined analysis of SARS-CoV-2-specific CD4+ T cells pre- and post-vaccination with longitudinal T cell receptor tracking. We identified strong pre-exposure T cell variability that correlated with subsequent immune response quality and age. High-quality responses, defined by strong expansion of high-avidity spike-specific T cells, high interleukin 21 production, and specific immunoglobulin G, depended on an intact naïve repertoire and exclusion of pre-existing memory T cells. In the elderly, T cell expansion from both compartments was severely compromised. Our results reveal that an intrinsic defect of the CD4+ T cell repertoire causes the age-dependent decline of immune response quality against SARS-CoV-2 and highlight the need for alternative strategies to induce high-quality T cell responses against newly arising pathogens in the elderly. Graphical Determinants of immune response quality to SARS-CoV-2 remain poorly defined. Saggau et al. examine spike-specific naïve and memory T cells pre- and post-vaccination and track pre-existing memory T cell receptors. They define T cell parameters of high-quality vaccine responses and identify high pre-existing memory and low naïve T cell contributions as predictors of low-quality responses, particularly in the elderly.

Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study) (preprint)

Background: There are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. Methods: We conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. Results: We enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac ("CC-C", n=101) or BNT162b2 ("CC-B", n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac ("BB-C", n=118) or BNT162b2 ("BB-B", n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Third doses significantly increased neutralising PRNT50 antibody titers against ancestral virus and Omicron BA.1 variant in all four study arms, and against Omicron BA.2 in all arms except CC-C, with statistically significant improvements for recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. Boosting of CD4+ T cells only occurred in CoronaVac-primed arms, but we did not identify overall differences between vaccine groups in CD4+ and CD8+ T cell responses. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). Conclusions: Similar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine (preprint)

IntroductionThird doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses. MethodsWe administered BNT162b2 as a third dose to adults aged [≥]30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2. ResultsWe administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity. ConclusionsWhile antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.

Strength and durability of antibody responses to BNT162b2 and CoronaVac.

We studied 2780 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine ("Comirnaty", BioNTech/Fosun Pharma). We compared rates of antibody waning over time using an enzyme-linked immunosorbent assay for spike receptor binding domain and a surrogate virus neutralization test. We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women. The weaker and less durable responses following CoronaVac support earlier provision of third doses to persons who previously received two doses of this vaccine.

A SINGLE INSTITUTION RETROSPECTIVE STUDY OF PALLIATIVE RADIOTHERAPY FOR BONE METASTASES: COMPARING THE FIRST SIX MONTHS OF THE 2020 COVID-19 PANDEMIC WITH THE SAME CALENDAR PERIOD DURING 2019

Purpose: To compare treatment courses received by patients with bone metastases during the first six months of the 2020 COVID-19 pandemic with those received during the same calendar period during 2019. Materials and Methods: Our radiotherapy information system was searched for palliative-intent treatment courses prescribed during the six-month period beginning March 14, 2020, the day that COVID-19 measures were operationalized at our institution. The same period during 2019 was similarly searched. Bone metastases cases were identified by reviewing stored images of radiotherapy plans for all treatment courses returned in the search. Descriptive statistics were used to analyze the cohorts. Results: From 1399 courses returned in the search, 1242 were confirmed as bone metastases cases. From 2019 to 2020 the number of patients treated for bone metastases fell from 398 to 377 (5% decline) and the number of courses they received fell from 633 to 609 (4% decline). Of all courses received in 2019 and 2020 respectively, the proportion of 1-fraction courses rose from 51% (234 of 633) to 59% (359 of 609) and the proportion of 2-fraction courses rose from 3% (18 of 633) to 11% (65 of 609). The proportion of 5-fraction courses fell from 42% (266 of 633) to 28% (172 of 609) and the proportion of 6 or more fraction courses fell from 2% (10 of 633) to 0.2% (1 of 609). The three most common dose fractionation schedules received in 2019 were 8Gy/1 (49% [309 of 633]), 20Gy/5 (31% [197 of 633]) and 15Gy/5 (6% [37 of 633]), and those received in 2020 were 8Gy/1 (54% [329 of 609]), 20Gy/5 (20% [122 of 609]) and 16Gy/2 (9% [56 of 609]). Conclusions: Compared to the same calendar period in 2019, during the first six months of the 2020 COVID-19 pandemic the number of patients treated with bone metastases and the total number of radiotherapy courses they received decreased modestly. The proportions of 1-fraction and 2-fraction courses increased noticeably, while the proportions of 5-fraction and 6 or more fraction courses decreased. An in-depth radiographic analysis is ongoing that will describe the morphologic characteristics of all treated bone metastases;data will be presented.

Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets.

Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer's disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.

Strength and durability of antibody responses to BNT162b2 and CoronaVac (preprint)

We studied 2864 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine (Comirnaty, BioNTech/Fosun Pharma). We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women.

BNT162b2 vaccine boosts neutralizing antibodies to ancestral SARS-CoV-2 & Omicron variant in adults who previously received two doses of inactivated vaccine (preprint)

BackgroundLimited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. MethodsWe conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged [≥]30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. ResultsIn 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p<0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p<0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by at least 24 fold from Day 0 to Day 28 against the ancestral virus (p<0.001) and rose by at least 11 fold against the Omicron variant (p<0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. ConclusionsA third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier. SummaryIn this open label trial of Chinese adults aged [≥]30 years who received two doses of inactivated COVID-19 vaccine 6 months earlier, third-dose mRNA vaccine substantially improved antibody levels against the ancestral virus and Omicron variant with well-tolerated safety profile.

Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies.

BACKGROUND: The persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID. METHODS: 23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls. RESULTS: While anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected. CONCLUSION: Although the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.

Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort.

INTRODUCTION: In light of the SARS-CoV-2 pandemic, protecting vulnerable groups has become a high priority. Persons at risk of severe disease, for example, those receiving immunosuppressive therapies for chronic inflammatory cdiseases (CIDs), are prioritised for vaccination. However, data concerning generation of protective antibody titres in immunosuppressed patients are scarce. Additionally, mRNA vaccines represent a new vaccine technology leading to increased insecurity especially in patients with CID. OBJECTIVE: Here we present for the first time, data on the efficacy and safety of anti-SARS-CoV-2 mRNA vaccines in a cohort of immunosuppressed patients as compared with healthy controls. METHODS: 42 healthy controls and 26 patients with CID were included in this study (mean age 37.5 vs 50.5 years). Immunisations were performed according to national guidelines with mRNA vaccines. Antibody titres were assessed by ELISA before initial vaccination and 7 days after secondary vaccination. Disease activity and side effects were assessed prior to and 7 days after both vaccinations. RESULTS: Anti-SARS-CoV-2 antibodies as well as neutralising activity could be detected in all study participants. IgG titres were significantly lower in patients as compared with controls (2053 binding antibody units (BAU)/mL ±1218 vs 2685±1102). Side effects were comparable in both groups. No severe adverse effects were observed, and no patients experienced a disease flare. CONCLUSION: We show that SARS-CoV-2 mRNA vaccines lead to development of antibodies in immunosuppressed patients without considerable side effects or induction of disease flares. Despite the small size of this cohort, we were able to demonstrate the efficiency and safety of mRNA vaccines in our cohort.