Objective: To investigate post-intubation laryngeal complications in severe COVID-19 patients. Methods: From September 2020 to April 2021, consecutive patients presenting with laryngological symptoms following severe COVID-19 infection and related intubation were included. Demographic, age, gender, comorbidities, symptoms, intubation duration, tracheostomy features, and laryngeal findings were collected. Videolaryngostroboscopy findings were analyzed by two senior laryngologists in a blind manner. Results: Forty-three patients completed the evaluations. The intubation duration was <14 days in 22 patients (group 1) and >14 days in 21 patients (group 2). The following abnormalities were found on an average post-intubation time of 51.6 days: posterior glottic stenosis (N=14), posterior commissure hypertrophy (N=19) or laryngeal diffuse edema (N=10), granuloma (N=8), laryngeal necrosis (N=2), vocal fold atrophy (N=2), subglottic stenosis (N=1) and glottic flange (N=1). Sixteen patients required surgical treatment (N=17 procedures). The number of intubation days was significantly higher in patients with posterior glottic stenosis (26.1 ± 9.4) compared with those presenting posterior commissure hypertrophy (11.5 ± 2.9) or granuloma (15.1 ± 5.8; p<0.001). Fourteen patients required surgical management. Conclusion: Prolonged intubation used in severe COVID-19 patients is associated with significant laryngeal disorders. Patients with a history of >2-week intubation have a higher risk of posterior glottic stenosis.

Influenza A infection can mimic coronavirus disease 2019 (COVID-19) in case of their signs and symptoms, making it almost impossible to distinguish them clinically, necessitating using high-precision assays in such patients. Clinicians should be careful in treating such patients merely based on their unspecific manifestations.

Reducing drug development timelines is an industry-wide goal to bring medicines to patients in need more quickly. This was exemplified in the COVID-19 pandemic where reducing development timelines had a direct impact on the number of lives lost to the disease. The use of drug substance produced using cell pools, as opposed to clones, has the potential to shorten development timelines. Toward this goal, we have developed a novel technology, GPEx® Lightning, that allows for rapid, reproducible, targeted recombination of transgenes into more than 200 Dock sites in the CHO genome. This allows for rapid production of high expressing stable cell pools and clones that reach titers of 4 to 12 g/L in generic fed-batch production. These pools and clones are highly stable in both titer and glycosylation, showing strong similarity in glycosylation profiles.

Various neurological symptoms have been reported as the side effect of COVID-19 vaccines. Vaccine-associated acute Cerebellitis is very uncommon. Here, we report a 45-year-old female with acute onset cerebellitis, beginning 10 days after administration of Sinopharm vaccine. Her CSF COVID-19 PCR was found to be positive, with no pulmonary symptoms.

We analysed the influenza epidemic that occurred in Australia during the 2022 winter using an age-structured dynamic transmission model which accounts for past epidemics to estimate the population susceptibility to an influenza infection. We applied the same model to five European countries. Our analysis suggests Europe might experience an early and moderately large influenza epidemic. Also, differences may arise between countries, with Germany and Spain experiencing larger epidemics, than France, Italy and the UK, especially in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately four weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

It is well understood that natural disasters interact to affect the resilience and prosperity of communities and disproportionately affect low income families and communities of color. However, given the lack of a common theoretical framework, it is rare for these interactions to be well understood or quantified. As an example, we consider the interaction of severe weather events (e.g., hurricanes and tornadoes) and epidemics (e.g., COVID-19). Observing events unfolding in southeastern U.S. communities has caused us to conjecture that the interactive effects of catastrophic disturbances and stressors might be much more considerable than previously recognized. For instance, hurricane evacuations increase human aggregation, a key factor that affects the transmission of acute respiratory infections like SARS-CoV-2. Similarly, weather damage to health infrastructure could significantly reduce a community’s ability to provide services to people sick with COVID-19 and other diseases. As globalization and human population and movement continue to increase and weather events due to climate change are becoming more intense and severe, such complex interactions are expected to magnify and significantly impact environmental and human health.

COVID-19 afflicts patients with acute symptoms and longer-term sequelae. One of the sequelae is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is often difficult to diagnose, having no established tests. In this article, we synthesize information from literature reviews on patients with ME/CSF that developed after recovery from COVID-19.

The COVID-19 pandemic has pushed health policy frontstage and exposed the stark differences in government capacities to respond to the crisis. This has created new demands for comparative heath policy to support knowledge creation on a large scale. However, comparative health policy has been ill prepared; studies have focused on health systems and used typologies together with descriptive, quantitative methods. This clouds the view for the multi-level nature of health policy, the diverse actors involved and the many societal facets of governance performance. We argue for health policy as a bottom-up process with diverse interests and suggest researching these processes comparatively to support policy learning. This calls for expanding the methodology of comparative health policy to include approaches that make greater use of explorative, qualitative research. We introduce possible developmental pathways to illustrate what this may look like. Firstly, the Pan-European Commission points to novel transnational and cross-sectoral collaborations, and a coordinated policy response to global challenges like the pandemic. Secondly, feminist networks show how to shift the focus towards social inequalities and the health needs of women and vulnerable populations. Thirdly, researchers demonstrate the value of new knowledge emerging from small-scale bottom-up comparisons based on structured assessment frameworks. Together, these developmental pathways demonstrate the potential to refocus comparative health policy towards greater responsiveness to the societal performance of governments, such as social inequalities created by the COVID-19 pandemic. This also opens opportunities for strengthening the global outlook of comparative health policy.

A Coronavirus Disease 2019 (COVID-19) epidemiological model incorporating a boosted infection-acquired immunity and heterogeneity in infection-acquired immunity among recovered individuals is designed. The model is used to investigate whether incorporating these two processes can induce new epidemiological insights. Analytical findings reveal co-existence of multiple endemic equilibria on either regions divided by the fundamental threshold (control reproduction number). Numerical findings conducted to validate analytical results show that heterogeneity in infection-acquired immunity among recovered individuals can induce various bifurcation structures such as reversed backward bifurcation, forward bifurcation, backward bifurcation and reversed hysteresis effect. Moreover, numerical results show that reversed backward bifurcation is annihilated or switches to the usual forward bifurcation if infection-acquired immunity among recovered individuals with strong immunity is assumed to be everlasting. However, this is only possible if primary infection is more likely than reinfection. In case reinfection is more likely to occur than primary infection, reversed backward bifurcation structure switches to a backward bifurcation phenomenon. Further, longer duration of infection-acquired immunity does lead to COVID-19 decline over time but does not lead to flattening of the COVID-19 peak.

Background Multiple myeloma (MM) patients have variable responses to mRNA vaccination to COVID-19. Little is known regarding their vaccine-induced antibody levels over time. Methods We monitored spike IgG antibody levels over 24 weeks among a subset of 18 MM patients who showed a full response after two mRNA vaccinations. MM patients had a more rapid decline in antibody levels as compared to 8 healthy controls, with power law half-lives of 72 days (versus 107 days) and exponential half-lives of 37 days (versus 51 days). Results The patients with longer SARS-CoV-2 antibody half-lives were more likely to have undetectable monoclonal protein than those with shorter half-lives, suggesting better disease control may correlate with longer duration of vaccine-induced antibodies. Regardless, by 16 weeks post-second dose of mRNA vaccination, the majority of patients had antibody levels below 250 binding arbitrary units per milliliter, which would be unlikely to contribute significantly to preventing COVID-19. Conclusions Thus, even MM patients who respond adequately to vaccination are likely to require more frequent booster doses than the general population.

Venous thrombosis rarely occurs in patients’ after administered COVID-19 viral mRNA vaccination rather than vector vaccination. The occurrence of superior mesenteric vein (SMV) is rarer. We herein present an image of an SMV trunk thrombosis after COVID-19 mRNA vaccination.

The rapid adaptation of SARS-CoV-2 within the host species and the increased viral transmission triggered the evolution of different SARS-CoV-2 variants. Though numerous monoclonal antibodies (mAbs) have been identified as prophylactic therapy for SARS-CoV-2, the ongoing surge in the number of SARS-CoV-2 infections shows the importance of understanding the mutations in the spike and developing novel vaccine strategies to target all variants. Here, we report the map of experimentally validated 74 SARS-CoV-2 neutralizing mAb binding epitopes of all variants. The majority (87.84%) of the potent neutralizing epitopes are localized to the receptor-binding domain (RBD) and overlap with each other, whereas limited (12.16%) epitopes are found in the N-terminal domain (NTD). Notably, 69 out of 74 mAb targets have at least one mutation at the epitope sites. The potent epitopes found in the RBD show higher mutations (4-10aa) compared to lower or modest neutralizing antibodies, suggesting that these epitopes might co-evolve with the immune pressure. The current study shows the importance of determining the critical mutations at the antibody recognition epitopes, leading to the development of broadly reactive immunogens targeting multiple SARS-CoV-2 variants. Further, vaccines inducing both humoral and cell-mediated immune responses might prevent the escape of SARS-CoV-2 variants from neutralizing antibodies.

Background: COVID-19 vaccine is critical in preventing SARS-CoV-2 infection and transmission. However, obesity’s effect on immune responses to COVID-19 vaccines is still unknown. Methods: We performed a meta-analysis of the literature and compared immune responses to COVID-19 vaccines among persons with and without obesity. We used Pubmed, Embase, Web of Science, and Cochrane Library to identify all related studies up to April 2022. The Stata.14 software was used to analyze the selected data. Results: Totally, 11 studies were included in the present meta-analysis. Five of them provided absolute values of antibody titers in the obese group and non-obese group. Overall, we found that the obese population was significantly associated with lower antibody titers (SMD = -0.228, 95% CI (-0.437, -0.019), P<0.001) after COVID-19 vaccination. Significant heterogeneity was present in most pooled analyses but was reduced after subgroup analyses. No publication bias was observed in the present analysis. The Trim and Fill method did not change the results in the primary analysis. Conclusion: The present meta-analysis suggested that obesity was significantly associated with decreased responses to SARS-CoV-2 vaccines. Future studies should be performed to unravel this relationship to prevent COVID-19 infection and transmission.

Background There is a need for vaccines that can induce effective systemic, respiratory mucosal and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA and cellular immunity. Methods The aim of the present study was to determine the effectiveness of a new administration method of intratracheal (IT) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AS03 (S1-AS03 vaccine). Results S1-SF-10-IT vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-IT showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AS03-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AS03-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF10-IT, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusion Based on the need for effective systemic, respiratory and cellular immunity, the S1-SF-10-IT vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.

Comment on: Effects of COVID-19 vaccination on platelet counts and bleeding in children, adolescents, and young adults with immune thrombocytopenia

Coronavirus disease 2019 (COVID-19) can cause various complications. Pneumothorax secondary to COVID-19 is relatively uncommon and bilateral pneumothorax is even more so. In patients with poor general health to undergo surgery for pneumothorax, internal treatments are essential to relieving refractory pneumothorax.

Psychological stress has evolved as an important health concern across the globe. The vulnerability to stress and the ramifications of it have only worsened during the time of the COVID-19 pandemic. This necessitates a timely diagnosis of stress before the condition progresses to chronicity. In this context, the popularity of social media like Twitter, where large numbers of users share opinions without any social stigma, has emerged as a major resource of human opinions. This has led to an increased research interest in social media-based stress detection techniques. However, tweet-level stress detection techniques in the literature have left a void in leveraging the text information in tweets, especially the presence of sarcastic expressions in the tweet’s text content. To this end, a novel method called “Sarcasm-based Tweet-Level Stress Detection” (STSD) is proposed in this work with the modification of the logistic loss function to detect tweet-level stress by availing the information of sarcasm that exists in the tweet-content. The principle of the STSD model is to minimise the loss for non-sarcastic tweets while maximising the loss for sarcastic tweets. Furthermore, an extensive preprocessing and dimensionality reduction is performed using kernel principal component analysis (kernel PCA) to improve the performance by reducing the dimensions. The experimental results show that the proposed STSD model, when applied along with kernel PCA, records a significant improvement in accuracy by a minimum of 5.25% and a maximum of 9.19% over baseline models. Also, there is an increment in F1-score by at least 0.085 points and a maximum of 0.164 points when compared to the baseline models.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from 11/6/2020 to 11/5/2021 at one of the Mayo Clinic hospitals. Results: Among 3,029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended the five-day course. Among them, 2,169 (80%) completed treatment during hospitalization, while 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p<0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p=0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p<0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

BACKGROUND Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation (MIR 19 ®) targeting a conserved sequence in known SARS-CoV-2 variants for treatment of COVID-19. METHODS We conducted an open-label, randomized controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled MIR 19 ® (3.7mg and 11.1 mg/day: groups 1 and 2, respectively) in comparison with standard etiotropic drug treatment (group 3) in patients hospitalized with moderate COVID-19. The primary endpoint was the time to clinical improvement according to predefined criteria within 14 days of randomization. RESULTS Patients from group1 had a significantly reduced (median 6 days (95% confidence interval [CI]: 5-7, HR 1.75, P=0.0005) time to clinical improvement compared to patients from group 3 (8 days (95% CI: 7-10). Normalized oxygen saturation (SpO 2>94%) occurred quicker in the group 1 (median 5 days (95% CI: 4–5, HR 1.59, P=0.0033) than in the group 3 (6 days, 95% CI: 5–8). Treatment with MIR 19® was well tolerated and safe. CONCLUSIONS MIR 19 ®, a SARS-CoV-2-specific siRNA-peptide dendrimer formulation is safe and significantly reduces time to clinical improvement in hospitalized moderate COVID-19 patients compared to standard therapy in a randomized controlled trial. MIR 19 ® treatment targets a sequence which is identical in all SARS-CoV-2 variants known so far and hence should be applicable for all of them.

We report two cases of previously healthy young men with COVID-19 infection who developed acute ischemic stroke due to large vessel occlusion followed by secondary events concerning for a further thromboembolic event. We hypothesize that the hypercoagulable state related to COVID-19 exacerbated the underlying hereditary thrombophilia due to MTHFR-gene mutation.

Objective: The causative virus of COVID-19 is SARS-CoV-2. The aim of the present study was to invastigate the in vivo virucidal activity of nasal irrigation with saline, nasal irrigation with Povidone-iodine (PVP-I) 1%, nasal irrigation with hypertonic alkaline and nasal irrigation with PVP-I 1% against SARS CoV- 2. Design: The present study was a prospective randomized clinical trial. Setting: A multicenter study involving tertiary care centers. Participants: The study included adult outpatients whose qualitative SARS-CoV-2 RT-PCR tests in nasopharyngeal swabs were positive. One hundred twenty patients divided into four equal groups. Standard COVID-19 treatment was given to group 1 (n=30), nasal irrigation containing isotonic solution was added to patients’ treatment in group 2 (n=30), nasal irrigation containing 1% PVP solution was added to patients’ treatment in group 3(n=30), and nasal irrigation containing 1% PVP solution and nasal irrigation containing hypertonic alkaline solution was added to patients’ treatment in group 4 (n=30). Main outcome measures: On the first day of diagnosis (day 0), nasopharyngeal swab samples were taken, on the 3rd and 5th days the nasopharyngeal viral load reduction in quantitative RT-PCR tests were calculated. Results: Between the 0-3rd Day and 0-5th days, the nasopharyngeal viral load reduction was significant in all groups (p< .05). In paired comparisons of groups, the nasopharyngeal viral load decrease in group 4 in first 3 days was significantly lower than all groups (p < .05). The nasopharyngeal viral load degrease in groups 3 and 4 in the first 5 days were significantly lower than group 1 (p < .05). Conclussion: This study was reveal that the use of hypertonic alkaline nasal irrigation together with 1% povidone-iodine was more effective in reducing viral load in the early period. The decreased nasopharyngeal viral load may reduce the carriage of infectious SARS-CoV-2 in patients. Our results suggest that 1% povidone-iodine and hypertonic alkaline nasal irrigation may be promising modality to prevent the COVID-19 epidemic.

As the COVID-19 continues to mutate, the number of infected people is increasing dramatically, and the vaccine is not enough to fight the mutated strain. In this paper, a SEIR-type fractional model with reinfection and vaccine inefficacy is proposed, which can successfully capture the mutated COVID-19 pandemic. The existence, uniqueness, boundedness and nonnegativeness of the fractional model are derived. Based on the basic reproduction number R 0 , locally stability and globally stability are analyzed. The sensitivity analysis evaluate the influence of each parameter on the R 0 and rank key epidemiological parameters. Finally, the necessary conditions for implementing fractional optimal control are obtained by Pontryagin's Maximum Principle, and the corresponding optimal solutions are derived for mitigation COVID-19 transmission. The numerical results show that humans will coexist with COVID-19 for a long time under the current control strategy. Furthermore, it is particularly important to develop new vaccines with higher protection rates.

Objective: SARS-COV-2 pandemic had a profound impact on acute bronchiolitis epidemiology, especially in RSV diffusion and the burden of disease with implications on the management of prophylaxis and health resources. We aimed to compare clinical and epidemiological characteristics of bronchiolitis before and during the SARS-CoV-2 pandemic.   Methods: We conducted an observational study involving children aged 0-2 years with bronchiolitis admitted to a tertiary children’s hospital during the last 5 years. Demographic, clinical, microbiological, and outcome data were collected. Comparison between pre- and post-pandemic period, RSV positive versus non-RSV patients, and SARS-CoV-2 positive vs negative patients were carried out.    Results: A total of 647 patients admitted for bronchiolitis were included (264 female,40.8%, median age 78 days). Molecular diagnostic tests were performed in 617 patients (95.4%) with RSV detected in 62.5% of patients. SARS-CoV-2 was found in 3.9% of hospitalized bronchiolitis (3.9%). We observed a progressive increase in bronchiolitis admissions and a statistically significant increase over the years in the need for respiratory support. Conversely, this was not true for mechanical ventilation, duration of respiratory support, ICU admission, and length of stay. During the pandemic period children with prematurity increased, although only 1 child had an indication for prophylaxis. Discussion: We confirm the stronger impact of bronchiolitis in the 2021-22 season, which is likely explained by the higher prevalence of RSV and the immunity debt theory. However, our findings were conflicting in terms of worsening clinical severity. The increase of children with prematurity and the inter-seasonal spread of RSV highlight the importance of epidemiological surveillance systems that monitor RSV circulation.