Non-randomized evaluation of hospitalization after a prescription for nirmatrelvir/ritonavir versus molnupiravir in high-risk COVID-19 outpatients.

OBJECTIVES: To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. METHODS: We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. RESULTS: All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4-3.3, P value = 0.79). CONCLUSIONS: These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.

Design and characterization of chimeric Rabies-SARS-CoV-2 virus-like particles for vaccine purposes.

Due to the high number of doses required to achieve adequate coverage in the context of COVID-19 pandemics, there is a great need for novel vaccine developments. In this field, there have been research approaches that focused on the production of SARS-CoV-2 virus-like particles. These are promising vaccine candidates as their structure is similar to that of native virions but they lack the genome, constituting a biosafe alternative. In order to produce these structures using mammal cells, it has been established that all four structural proteins must be expressed. Here we report the generation and characterization of a novel chimeric virus-like particle (VLP) that can be produced by the expression of a single novel fusion protein that contains SARS-CoV-2 spike (S) ectodomain fused to rabies glycoprotein membrane anchoring region in HEK293 cells. This protein is structurally similar to native S and can autonomously bud forming enveloped VLPs that resemble native virions both in size and in morphology, displaying S ectodomain and receptor binding domain (RBD) on their surface. As a proof of concept, we analyzed the immunogenicity of this vaccine candidate in mice and confirmed the generation of anti-S, anti-RBD, and neutralizing antibodies. KEY POINTS: • A novel fusion rabies glycoprotein containing S ectodomain was designed. • Fusion protein formed cVLPs that were morphologically similar to SARS-CoV-2 virions. • cVLPs induced anti-S, anti-RBD, and neutralizing antibodies in mice.

A phase 3, randomised, double-blind, placebo-controlled clinical trial evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine in adults (ABDALA-3 study).

Background: The pandemic of COVID-19 raised the urgent need for safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three-dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of the vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48,290 subjects were included (24,144 and 24,146 in the placebo and Abdala groups, respectively) in the context of predominant D614G variant circulation. The evaluation of the main efficacy outcomes occurred during May-June 2021, starting at May 3rd, in the context of high circulation of mutant viruses, predominantly VOC Beta. The incidence of adverse reactions for individuals in the placebo and Abdala vaccine groups were 1227/24,144 (5.1%) and 1621/24,146 (6.7%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 h. No severe adverse events with demonstrated cause-effect relationship attributable to the vaccine were reported. Symptomatic COVID-19 disease was confirmed in 142 participants in the placebo group (78.44 incidence per 1000 person-years, 95% confidence interval [CI], 66.07-92.46) and in 11 participants in Abdala vaccine group (6.05 incidence per 1000 person years; 95% CI 3.02-10.82). The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). Moderate/serious forms of COVID-19 occurred in 30 participants (28 in the placebo group and only 2 in the Abdala vaccine group) for a vaccine efficacy of 92.88% (95% CI 70.12-98.31). There were five critical patients (of which four died), all in the placebo group. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Those results, along with its immunization schedule and the advantage of easy storage and handling conditions at 2-8 °C, make this vaccine an option for the use in immunization strategies as a key tool for the control of the pandemic. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

A COVID-19 vaccine candidate based on SARS-CoV-2 spike protein and immune-stimulating complexes.

Spike protein from SARS-CoV-2, the etiologic agent of the COVID-19 pandemic disease, constitutes a structural protein that proved to be the main responsible for neutralizing antibody production. Thus, its sequence is highly considered for the design of candidate vaccines. Animal cell culture represents the best option for the production of subunit vaccines based on recombinant proteins since they introduce post-translational modifications that are important to mimic the natural antigenic epitopes. Particularly, the human cell line HEK293T has been explored and used for the production of biotherapeutics since the products derived from them present human-like post-translational modifications that are important for the protein's activity and immunogenicity. The aim of this study was to produce and characterize a potential vaccine for COVID-19 based on the spike ectodomain (S-ED) of SARS-CoV-2 and two different adjuvants: aluminum hydroxide (AH) and immune-stimulating complexes (ISCOMs). The S-ED was produced in sHEK293T cells using a 1-L stirred tank bioreactor operated in perfusion mode and purified. S-ED characterization revealed the expected size and morphology. High N-glycan content was confirmed. S-ED-specific binding with the hACE2 (human angiotensin-converting enzyme 2) receptor was verified. The immunogenicity of S-ED was evaluated using AH and ISCOMs. Both formulations demonstrated the presence of anti-RBD antibodies in the plasma of immunized mice, being significantly higher for the latter adjuvant. Also, higher levels of IFN-γ and IL-4 were detected after the ex vivo immune stimulation of spleen-derived MNCs from ISCOMs immunized mice. Further analysis confirmed that S-ED/ISCOMs elicit neutralizing antibodies against SARS-CoV-2. KEY POINTS: Trimeric SARS-CoV-2 S-ED was produced in stable recombinant sHEK cells in serum-free medium. A novel S-ED vaccine formulation induced potent humoral and cellular immunity. S-ED formulated with ISCOMs adjuvant elicited a highly neutralizing antibody titer.

Contraceptive services in Oregon's state-funded network during the COVID-19 pandemic.

OBJECTIVES: To understand how changes to in-person health care during the COVID pandemic impacted contraceptive use in Oregon's state-funded network. STUDY DESIGN: A retrospective cohort of 245,600 visits (virtual and in-person) among 70,295 women presenting to publicly funded family planning clinics in Oregon between January 2019 and June 2021. Data were abstracted from clinic records and restricted to visits of patients identifying as female, 12-51 years old, not using sterilization as a method. Contraception was grouped by effectiveness Tier (Tier 1: intrauterine device, implants; Tier 2: progestin injectable, pill/patch/ring). Multivariable logistic regression predicted the use of contraception by stage of the COVID pandemic which corresponded to service availability (prepandemic, acute: nonemergency services halted, subacute: restricted services), patient demographics, including insurance type, and clinic and geospatial characteristics. RESULTS: Overall during the acute stage, people with visits were more likely to leave with a method of contraception odds ratios (OR) 1.39 (95% confidence interval [CI] 1.24-1.57); however, it was significantly less likely to be a Tier 1 method (OR 0.82, 95% CI 0.74-0.91) as compared to prepandemic. This finding was particularly marked in rural areas (OR 0.69 [96% CI 0.58-0.83]) and among the publicly insured (OR 0.87 [95% CI 0.80-0.94]). CONCLUSIONS: Demand for contraception increased during the acute phase of the COVID pandemic, and shifts in method mix from Tier 1 to Tier 2 methods occurred. Disparities in contraceptive access persisted for those in rural locations or with public insurance. IMPLICATIONS: Lessons learned from the COVID-19 pandemic are critical to informing our future emergency response. The need for family planning services increased during the public health emergency.

Care Robotics: An Assessment of Professional Perception in the Face of the COVID-19 Pandemic.

The COVID-19 crisis accelerated the adoption of technologies. Technological advancement is also expected in robotics applied to any sector, including in healthcare. The aim is to assess the professional perception of care robotics facing COVID-19. This study aimed to (1) select a tool for assessing different aspects of healthcare, (2) analyse the professional perception about the development, usefulness and helpfulness of technologies and robotics in the field of healthcare and (3) evaluate the correlation between the perceived helpfulness of care robotics and the selected tool. We implement five validated clinical tests which integrate 80 items about a person and their clinical situation. From the sample of 46 professionals, 95.65% affirmed that technology was moderately to completely useful for professional performance in the context of the pandemic, lowering to 67.39% when asked only about robotics; 93.48% stated that the inclusion of robotics in at least one health area affected by COVID-19 would have helped them. Finally, the variables extracted from clinical tests corresponded to the most relevant health areas as identified by the professionals. This research shows the potential of care robotics oriented towards healthcare from a care paradigm.

Global shocks, cascading disruptions, and (re-)connections: viewing the COVID-19 pandemic as concurrent natural experiments to understand land system dynamics

Context For nearly three years, the COVID-19 pandemic has disrupted human well-being and livelihoods, communities, and economies in myriad ways with consequences for social-ecological systems across the planet. The pandemic represents a global shock in multiple dimensions that has already, and is likely to continue to have, far-reaching effects on land systems and on those depending on them for their livelihoods. Objectives We focus on the observed effects of the pandemic on landscapes and people composing diverse land systems across the globe. Methods We highlight the interrelated impacts of the pandemic shock on the economic, health, and mobility dimensions of land systems using six vignettes from different land systems on four continents, analyzed through the lens of socio-ecological resilience and the telecoupling framework. We present preliminary comparative insights gathered through interviews, surveys, key informants, and authors' observations and propose new research avenues for land system scientists. Results The pandemic's effects have been unevenly distributed, context-specific, and dependent on the multiple connections that link land systems across the globe. Conclusions We argue that the pandemic presents concurrent "natural experiments” that can advance our understanding of the intricate ways in which global shocks produce direct, indirect, and spillover effects on local and regional landscapes and land systems. These propagating shock effects disrupt existing connections, forge new connections, and re-establish former connections between peoples, landscapes, and land systems. Supplementary Information The online version contains supplementary material available at 10.1007/s10980-023-01604-2.

Community-led housing: Between ‘right to the city', ‘actually existing neoliberalism' and post-pandemic cities

This paper examines the Self-Managed Housing Program (Law 341), in Buenos Aires, Argentina. This programme created 45 cooperative housing units between 2001 and 2020 in consolidated urban areas currently undergoing renewal processes. It investigates the conditions that the programme has generated for the realisation of the ‘right to the city' in the context of ‘actually existing neoliberalism' and challenges posed by the COVID-19 pandemic. This paper analyses the origins of the process and mode of cooperative housing production, including tangible and intangible aspects and capacities acquired by the inhabitants. This study used a mixed quantitative and qualitative methodology. The analytical strategy focused on defining a set of dimensions that characterised the self-managed mode of production, conditions of social and urban insertion in the case studied and participants' perceptions of the influence of material characteristics and organisational arrangements during the pandemic. This paper contributes to our understanding of the socio-economic dynamics in the production of urban space by elucidating the role of the state and specific tensions arising due to bottom-up policies, specific forms adopted by urban experiences of resistance and their contribution in the promotion of concrete conditions of urban life. Finally, this paper characterises an emergent self-managed urbanism and reflects on its possibilities of dialogue with the construction of alternative local policies that challenge growing territorial inequality caused by the subordination of policies to real estate financialisation and its deepening tendencies in the pandemic context.

Global shocks, cascading disruptions, and (re-)connections: viewing the COVID-19 pandemic as concurrent natural experiments to understand land system dynamics.

Context: For nearly three years, the COVID-19 pandemic has disrupted human well-being and livelihoods, communities, and economies in myriad ways with consequences for social-ecological systems across the planet. The pandemic represents a global shock in multiple dimensions that has already, and is likely to continue to have, far-reaching effects on land systems and on those depending on them for their livelihoods. Objectives: We focus on the observed effects of the pandemic on landscapes and people composing diverse land systems across the globe. Methods: We highlight the interrelated impacts of the pandemic shock on the economic, health, and mobility dimensions of land systems using six vignettes from different land systems on four continents, analyzed through the lens of socio-ecological resilience and the telecoupling framework. We present preliminary comparative insights gathered through interviews, surveys, key informants, and authors' observations and propose new research avenues for land system scientists. Results: The pandemic's effects have been unevenly distributed, context-specific, and dependent on the multiple connections that link land systems across the globe. Conclusions: We argue that the pandemic presents concurrent "natural experiments" that can advance our understanding of the intricate ways in which global shocks produce direct, indirect, and spillover effects on local and regional landscapes and land systems. These propagating shock effects disrupt existing connections, forge new connections, and re-establish former connections between peoples, landscapes, and land systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s10980-023-01604-2.

The Use and Effectiveness of Ceftazidime-Avibactam in Real-World Clinical Practice: EZTEAM Study.

INTRODUCTION: Ceftazidime-avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime-avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime-avibactam in real-world clinical practice. METHODS: This non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime-avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime-avibactam for at least 72 h. RESULTS: Of the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime-avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime-avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled. CONCLUSION: This study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime-avibactam is one of the antibiotics to consider for treatment of MDR bacteria. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03923426.

SARS-CoV-2 Neutralizing Antibodies in Mexican Population: A Five Vaccine Comparison.

Neutralizing antibodies (NAs) are key immunological markers and are part of the humoral response of the adaptive immune system. NA assays determine the presence of functional antibodies to prevent SARS-CoV-2 infection. We performed a real-world evidence study to detect NAs that confer protection against SARS-CoV-2 after the application of five vaccines (Pfizer/BioNTech, AstraZeneca, Sinovac, Moderna, and CanSino) in the Mexican population. Side effects of COVID-19 vaccines and clinical and demographic factors associated with low immunogenicity were also evaluated. A total of 242 SARS-CoV-2-vaccinated subjects were recruited. Pfizer/BioNTech and Moderna proved the highest percentage of inhibition in a mono-vaccine scheme. Muscular pain, headache, and fatigue were the most common adverse events. None of the patients reported severe adverse events. We found an estimated contagion-free time of 207 (IQR: 182-231) and 187 (IQR: 184-189) days for Pfizer/BioNTech and CanSino in 12 cases in each group. On the basis of our results, we consider that the emerging vaccination strategy in Mexico is effective and safe.

Effect of postextubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial.

PURPOSE: High-flow nasal cannula (HFNC) oxygen therapy was noninferior to noninvasive ventilation (NIV) for preventing reintubation in a heterogeneous population at high-risk for extubation failure. However, outcomes might differ in certain subgroups of patients. Thus, we aimed to determine whether NIV with active humidification is superior to HFNC in preventing reintubation in patients with ≥ 4 risk factors (very high risk for extubation failure). METHODS: Randomized controlled trial in two intensive care units in Spain (June 2020‒June 2021). Patients ready for planned extubation with ≥ 4 of the following risk factors for reintubation were included: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 on extubation day, body mass index > 30, inadequate secretions management, difficult or prolonged weaning, ≥ 2 comorbidities, acute heart failure indicating mechanical ventilation, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, prolonged mechanical ventilation, or hypercapnia on finishing the spontaneous breathing trial. Patients were randomized to undergo NIV with active humidification or HFNC for 48 h after extubation. The primary outcome was reintubation rate within 7 days after extubation. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, length of stay, mortality, adverse events, and time to reintubation. RESULTS: Of 182 patients (mean age, 60 [standard deviation (SD), 15] years; 117 [64%] men), 92 received NIV and 90 HFNC. Reintubation was required in 21 (23.3%) patients receiving NIV vs 35 (38.8%) of those receiving HFNC (difference -15.5%; 95% confidence interval (CI) -28.3 to -1%). Hospital length of stay was lower in those patients treated with NIV (20 [12‒36.7] days vs 26.5 [15‒45] days, difference 6.5 [95%CI 0.5-21.1]). No additional differences in the other secondary outcomes were observed. CONCLUSIONS: Among adult critically ill patients at very high-risk for extubation failure, NIV with active humidification was superior to HFNC for preventing reintubation.

Humoral response after the fourth dose of the SARS-CoV-2 vaccine in the CKD spectrum: a prespecified analysis of the SENCOVAC study.

BACKGROUND: There is scarce evidence on fourth doses of SARS-CoV-2 vaccines in chronic kidney disease (CKD) patients. We have evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analyzed factors associated to persistent negative humoral response and to higher anti-Spike antibody titers as well as the efficacy of vaccination on COVID-19 severity. RESULTS: Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titers in HD (P = 0.001) and ND-CKD (P = 0.014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titers at 12 months were independently associated to repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titers and not being a KT. Breakthrough COVID-19 was registered in 137 (6%) patients, of whom 5% required admission. Admitted patients had prior titers below 620 UI/ml and median values were lower (P = 0.020) than in non-admitted patients. CONCLUSIONS: A fourth vaccine dose increased anti-Spike antibody titers or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titers or KT recipients) derived the least benefit in terms of antibody titers. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titers.

Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients: the SENCOVAC study.

BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe coronavirus disease 2019 (COVID-19). The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in CKD patients. Safety and immediate humoral response results are reported here. METHODS: Four cohorts of patients were included: kidney transplant (KT) recipients, and haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on Day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analysed. RESULTS: A total of 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (P < 0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated with KT (odds ratio 20.56, P = 0.001) and with BNT162b2 vaccine (odds ratio 6.03, P = 0.023). CONCLUSION: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Potential differences between COVID-19 vaccines should be explored in prospective controlled studies.

Humoral and cellular immunity to SARS-COV-2 after vaccination with mRNA vaccines in PLWH with discordant immune response. Influence of the vaccine administered.

Background: Data on SARS-CoV-2 mRNA vaccine immunogenicity in people living with human immunodeficiency virus (PLWH) and discordant immune response (DIR) are currently limited. Therefore, we compare the immunogenicity of these vaccines in DIR and immunological responders (IR). Methods: A prospective cohort that enrolled 89 participants. Finally, 22 IR and 24 DIR were analyzed before vaccination (T0), one (T1) and six months (T2) after receiving BNT162b2 or mRNA-1273 vaccine. Additionally, 10 IR and 16 DIR were evaluated after a third dose (T3). Anti-S-RBD IgG, neutralizing antibodies (nAb), neutralization activity, and specific memory B cells were quantified. Furthermore, specific CD4+ and CD8+ responses were determined by intracellular cytokine staining and polyfunctionality indexes (Pindex). Results: At T1, all participants developed anti-S-RBD. 100% IR developed nAb compared to 83.3% DIR. Spike-specific B cells were detected in all IR and 21/24 DIR. Memory CD4+ T cells responded in 5/9 IR and 7/9 DIR, mainly based on the expression of IFN-γ and TNF-α, with a higher Pindex in DIR. Memory CD8+ T cells responded in only four participants in each group. At T2, anti-S-RBD and nAb titers were higher in DIR than in IR. In both groups, there was an increase in specific B memory cells, higher in DIR. Six IR and five DIR maintained a specific memory CD4+ response. Memory CD8+ response was preserved in IR but was lost in DIR. In a multivariate linear regression analysis, receiving mRNA-1273 instead of BNT162b2 played a prominent role in the results. Conclusions: Our data suggest that PLWH with DIR can mount an immune response similar to those with higher CD4+, provided they receive the mRNA-1273 vaccine instead of others less immunogenic.

Reduced Muscle Strength in Patients with Long-COVID-19 Syndrome Is Mediated by Limb Muscle Mass.

Understanding the impact of COVID-19 on muscle strength may help to elucidate the organ systems that contribute to acute and chronic COVID-19 sequelae. We questioned whether patients with postdischarge symptoms after COVID-19 had compromised muscle strength compared with a control group, and if this potential relationship was mediated by the lower appendicular lean mass index (ALMI). A total of 99 patients with long-COVID-19 and 97 control participants were screened. Maximal grip strength was assessed with a TKK 5101 digital dynamometer, and leg extension 1RM was measured using EGYM Smart Strength machines. Body composition (fat mass percentage, lean mass, visceral fat and appendicular lean mass index) was determined using a whole-body dual-energy X-ray densitometer. Results showed that grip strength and leg extension strength were significantly higher in controls than in COVID-19 survivors (mean [SD], 32.82 [10.01] vs. 26.94 [10.33] kg; difference, 5.87 kg; P < 0.001) and (mean [SD], 93.98 [33.73] vs. 71.59 [33.70] kg; difference, 22.38 kg; P < 0.001), respectively). The relationship between long-COVID syndrome and grip/leg strength levels was partly mediated by ALMI, which explained 52% of the association for grip strength and 39% for leg extension. Our findings provide novel insights into the mechanisms underlying the relationship between long-COVID syndrome and grip/leg strength levels, supporting the negative effects of long-COVID syndrome on muscle function.

Philadelphia-negative chronic myeloproliferative neoplasm follow-up: when the phone rings. Changes during the COVID-19 pandemic and patient satisfaction. Experience in 30 health centers in Spain.

The SARS-CoV-2 pandemic has favored the expansion of telemedicine. Philadelphia-negative chronic myeloproliferative neoplasms (Ph-MPN) might be good candidates for virtual follow-up. In this study, we aimed to analyze the follow-up of patients with Ph-MPN in Spain during COVID-19, its effectiveness, and acceptance among patients. We present a multicenter retrospective study from 30 centers. Five hundred forty-one patients were included with a median age of 67 years (yr). With a median follow-up of 19 months, 4410 appointments were recorded. The median of visits per patient was 7 and median periodicity was 2.7 months; significantly more visits and a higher frequency of them were registered in myelofibrosis (MF) patients. 60.1% of visits were in-person, 39.5% were by telephone, and 0.3% were videocall visits, with a predominance of telephone visits for essential thrombocythemia (ET) and polycythemia vera (PV) patients over MF, as well as for younger patients (< 50 yr). The proportion of phone visits significantly decreased after the first semester of the pandemic. Pharmacological modifications were performed only in 25.7% of the visits, and, considering overall management, ET patients needed fewer global treatment changes. Telephone contact effectiveness reached 90% and only 5.4% required a complementary in-person appointment. Although 56.2% of the cohort preferred in-person visits, 90.5% of our patients claimed to be satisfied with follow-up during the pandemic, with an 83% of positive comments. In view of our results, telemedicine has proven effective and efficient, and might continue to play a complementary role in Ph-MPN patients' follow-up.

Epidemiología de la COVID-19 entre el personal de centros sanitarios y sociosanitarios del área sanitaria de A Coruña y Cee COVID-19 epidemiology in health and social health workers in the health area of A Coruña and Cee

Objetivo: Desde el comienzo de la pandemia ha sido necesario conocer la evolución epidemiológica del SARS-CoV-2. Es por ello que el objetivo de este estudio fue describir las características de la casuística de COVID-19 en el personal de centros sanitarios y sociosanitarios del área sanitaria de A Coruña y Cee durante la primera onda epidémica, así como determinar la asociación entre el cuadro clínico y/o la duración del mismo y la condición de repositivizar la RT-PCR. Material y métodos: En el periodo de estudio, se diagnosticaron 210 casos de COVID-19 entre el personal sanitario y sociosanitario del área sanitaria de A Coruña y Cee. Se llevó a cabo un análisis descriptivo de los factores sociodemográficos, así como la búsqueda de asociación entre el cuadro clínico y la duración de la detección de una RT-PCR positiva. Resultados: Las categorías profesionales más afectadas fueron la de enfermería (33,3%) y la de auxiliares de enfermería (16,2%). El tiempo medio que los casos tardaron en negativizar la RT-PCR fue de 18,3 ± 9,1 días, con una mediana de 17 días. Se observó que 26 casos (13,8%) volvían a obtener un resultado positivo en alguna RT-PCR posterior, sin cumplir criterios de reinfección. La existencia de manifestaciones cutáneas y artralgias se asoció con la repositivización tras ajustar por edad y sexo (OR=4,6 y OR=6,5;respectivamente). Conclusiones: En los profesionales sanitarios diagnosticados con COVID-19 durante la primera ola, los síntomas disnea, manifestaciones cutáneas y artralgias determinaron la repositización de la RT-PCR tras un resultado negativo previo y sin cumplir criterios de reinfección.

Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice.

The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic tool.

Improved Expression of SARS-CoV-2 Spike RBD Using the Insect Cell-Baculovirus System.

Insect cell-baculovirus expression vector system is one of the most established platforms to produce biological products, and it plays a fundamental role in the context of COVID-19 emergency, providing recombinant proteins for treatment, diagnosis, and prevention. SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. As RBD is required for many applications, in the context of pandemic it is important to meet the challenge of producing a high amount of recombinant RBD (rRBD). For this reason, in the present study, we developed a process based on Sf9 insect cells to improve rRBD yield. rRBD was recovered from the supernatant of infected cells and easily purified by metal ion affinity chromatography, with a yield of 82% and purity higher than 95%. Expressed under a novel chimeric promoter (polh-pSeL), the yield of rRBD after purification was 21.1 ± 3.7 mg/L, which is the highest performance described in Sf9 cell lines. Finally, rRBD was successfully used in an assay to detect specific antibodies in COVID-19 serum samples. The efficient strategy herein described has the potential to produce high-quality rRBD in Sf9 cell line for diagnostic purpose.