The present study aimed to evaluate the effectiveness of two doses of CoronaVac in preventing SARS-CoV-2 symptomatic disease with virological confirmation, as well as in the prevention of COVID-19 moderate and severe cases. A test-negative unmatched case-control design was used, in which cases were patients with suspected COVID-19 (presenting at least two of the following symptoms: fever, chills, sore throat, headache, cough, runny nose, olfactory or taste disorders) with virological confirmation, and controls were those whose SARS-CoV-2 test was negative. As for exposure, participants were classified as unvaccinated, or vaccinated with a complete schedule. Suspected COVID-19 cases were identified from March to November 2021, in two cities located in the State of São Paulo, Brazil. All participants signed the Informed Consent Form before enrollment. RT-PCR results and vaccination data were obtained from the local surveillance systems. Up to two phone calls were made to obtain information on the outcome of the cases. A total of 2981 potential participants were screened for eligibility, of which 2163 were included, being 493 cases and 1670 controls. Vaccination, age, the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset, and the educational level were the variables independently associated with the outcome. The adjusted vaccine effectiveness for symptomatic COVID-19 (AVE) was 39.0 % (95 % CI 6.0-60.0 %). The AVE in the prevention of moderate and severe disease was 91.0 % (95 % CI 76.0-97.0 %). Our results were influenced by the waning of the Gamma variant, in the second trimester of 2021, followed by the increase in vaccination coverage, and a drop in the number of cases in the second half of the year. The study demonstrated the high effectiveness of CoronaVac in preventing moderate/severe COVID-19 cases.

UNASSIGNED: Although Coronavirus disease 2019 (COVID-19) vaccination is critical to control its spread, vaccine hesitancy varies significantly among the United States population; moreover, some vaccine recipients experienced various adverse effects. We aim to assess the impact of COVID-19 vaccine hesitancy in a university-affiliated community, the factors affecting participants\' decisions, and their adverse effects.
UNASSIGNED: A pre-vaccination online Institutional Review Board IRB-approved survey was emailed in Nov/Dec 2020, 2 months before the implementation of state-policy protocols for COVID-19 vaccination. A post-vaccination survey was emailed in May/June 2021, two months after protocol execution. A third follow-up survey was sent in Nov/Dec 2021, and a fourth was sent in June/July 2022. The study population included three groups of adult participants: university students, faculty, and staff-(MS), university health system patients-(MP), and Cancer Center patients-(MCP). The study was designed as a longitudinal cohort study. Statistical analyses were performed using SPSS.
UNASSIGNED: With a combined response rate of 26% (40,578/157,292) among the four surveys, 15,361 participants completed the first survey (MS = 4,983, MP = 9,551, and MCP = 827). 2/3 of participants (63.5%) were willing to get vaccinated, with a significant difference in acceptance among groups, MS:56.6%, MP:66.2%, and MCP:71.6% (p < 0.05). Vaccine acceptance rates reached 89% in the second survey after the vaccine\'s approval, with a lower acceptance rate of MS:84.6% than with MP:90.74% and MCP:92.47% participants (p < 0.05). Safety and effectiveness concerns were the main factors affecting participants\' decisions in all the first three surveys; however, participants reported these concerns decreased between pre-vaccination, post-vaccination, and follow-up surveys with 87%, 56%, and 46%, respectively(p < 0.05). More than two-thirds of the participants (70%) reported having either minor/moderate symptoms (61.6%) or major symptoms (8.6%) after getting some of the vaccine doses (p < 0.05).
UNASSIGNED: The hesitance of COVID-19 vaccination was associated with concerns regarding its safety and efficacy. Vaccine acceptance rose higher than expected after protocol execution, likely due to continuous education, whereas safety and efficacy remain factors hindering vaccine acceptance. Continuous education focusing on safety and efficacy of the vaccine can reduce vaccine hesitancy and raise the rates of vaccination.

UNASSIGNED: To characterize long-term patient-reported symptoms and quality of life, in adults after COVID-19.
UNASSIGNED: Cross-sectional study in Cantabria (Northern Spain) including adults with PCR-confirmed SARS-CoV-2 infection (n = 694) with a time period between 4.7 and 24 month post-SARS-CoV-2 diagnosis, and their close contacts (n = 663) (PCR negative and without suspected infection) obtained from simple random sampling of a total of 47,773 cases and 94,301 close contacts. The ISARIC survey was used as screening tool with self-reported \"non-feeling fully recovery (NFFR)\" defined as primary outcome.
UNASSIGNED: 16.57% (n = 115/694) reported NFFR. Most prevalent symptoms were in order of frequency: Fatigue (54.8%); Loss of smell (40.9%); Problems speaking or communicating (29.6%); Loss of taste (28.7%); Confusion/lack of concentration (27.8%); Persistent muscle pain (24.3%) and Shortness of breath/breathlessness (23.5%). When comparing the three ordinal groups (Close contacts, COVID-19 feeling recovered, and COVID-19 NFFR) the prevalence of these symptoms was increasingly higher among each ordinal group (p < 0.001). Female gender was significantly associated with NFFR: (adjusted odds ratio (aOR) = 1.56); as well as older age: aOR per 10 year increment = 1.15. Lastly, they scored on average 9.63 points less in Euroquol.
UNASSIGNED: More than 15% of patients in our real-life population-based study, reported NFFR, being female sex and older age independent predictors of this condition. Most symptoms in these patients were in accordance with WHO definition of post COVID-19 condition in adults, and were less prevalent in COVID-19 feeling recovered and close contact respectively, with a statistically significant dose-response pattern, and with a large decrease in quality of life according to Euroquol.
UNASSIGNED: Caracterizar los síntomas y la calidad de vida informados a largo plazo después de un episodio agudo de COVID-19.
UNASSIGNED: Estudio transversal en Cantabria (norte de España) que incluye adultos con infección por SARS-CoV-2 confirmada por PCR (n = 694) tras un periodo entre 4,7 y 24 meses desde el diagnóstico y sus contactos estrechos (n = 663), obtenidos por muestreo aleatorio simple a partir de 47.773 casos y 94.301 contactos. Se utilizó la encuesta ISARIC, estableciéndose como variable resultado principal la respuesta «no-sentirse completamente recuperado (NSCR)».
UNASSIGNED: El 16,57% (n = 115/694) declararon NSCR. Los síntomas más prevalentes fueron, por orden de frecuencia: fatiga (54,8%), pérdida del olfato (40,9%), problemas para hablar o comunicarse (29,6%), pérdida del gusto (28,7%), confusión/falta de concentración (27,8%), dolor muscular persistente (24,3%) y dificultad para respirar/falta de aire (23,5%). Al comparar los tres grupos ordinales (contactos estrechos, COVID-19 recuperados y COVID-19 NSCR), la prevalencia de estos síntomas fue mayor en cada grupo (p < 0,001). El sexo femenino se asoció significativamente con NSCR: Odds Ratio ajustada (aOR) = 1,56), así como la edad avanzada: aOR por cada 10 años = 1,15. Por último, obtuvieron en Euroquol una puntuación media de 9,63 puntos menos.
UNASSIGNED: Más del 15% de los pacientes reportaron NSCR, siendo el sexo femenino y la edad factores predictores independientes. La mayoría de los síntomas en estos pacientes coincidieron con los de la definición de condición post-COVID-19 de la OMS y fueron menos prevalentes en contactos estrechos y COVID-19 que se sintieron recuperados, con un patrón dosis respuesta, y con una menor calidad de vida según Euroquol.

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital-Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 - 128], 133 days in the HighC group [95% CI: 124 - 141] and 144 days in the NoC group [95% CI: 121 - 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic.
METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020.
RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn\'t undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001).
CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.

OBJECTIVE: To assess the incidence of Descemet\'s membrane endothelial keratoplasty (DMEK) rejection potentially associated with coronavirus disease 2019 (COVID-19) infection or vaccination, and its association with known rejection risk factors during the first two years of the pandemic.
METHODS: This retrospective study included patients with DMEK rejection between January 2020 and December 2021. Diagnostic criteria were based on symptoms, visual acuity, and other clinical assessments. Risk factors for graft rejection were considered, and a telephone survey was conducted to identify possible preceding COVID-19 infection or vaccination.
RESULTS: Of 58 patients, 44 were included. Six patients (14%) reported COVID-19 infection, with one immediate endothelial graft rejection (EGR) post-infection. After vaccine availability, 13 of 36 patients had EGR at an average of 2.7 months post-vaccination. Five (38%) had immediate EGR following vaccination, four of which had concomitant risk factors for rejection.
CONCLUSIONS: Although the risk of endothelial graft rejection (EGR) associated with COVID-19 infection or vaccination appears to be extremely low, there may be a causative relationship, especially in patients with pre-existing risk factors for EGR. A temporary increase in anti-rejection treatment following COVID-19 infection or vaccination is recommended, especially in patients with pre-existing risk factors, along with closer monitoring during the subsequent 4 to 8 weeks.

UNASSIGNED: Head-end elevation (HEE) is known to improve oxygenation and respiratory mechanics. In ARDS, poor lung compliance limits positive pressure ventilation causing delivery of inadequate minute ventilation (MVe). We observed that, in moderate-to-severe COVID-19 ARDS, the respiratory system compliance (Crs) reduces upon elevating the head-end of the bed, and vice-versa, which can be utilized to improve ventilation and avoid respiratory acidosis.We hypothesized that increasing the degree of HEE reduces Crs.
UNASSIGNED: We included 20 consecutive mechanically ventilated, moderate-to-severe COVID-19 ARDS patients in this pilot study (CTRI/2021/06/034,182). The Crs, Mve and Rinsp were recorded at 0°, 10°, 20° and 30° HEE. Repeated measures ANOVA was used to determine significant differences in measurements with increasing degrees and repeated measures correlation (rmcorr) for correlation.
UNASSIGNED: Repeated measures ANOVA showed a significant difference (p < 0.0001) between values of Crs, MVe and Rinsp. Rmcorr showed a strong negative correlation between increasing degrees and Crs and Mve (r-0.87 [95% CI -0.79 to -0.92, p < 0.0001 and r-0.77 [95% CI -0.64 to -0.85, p < 0.0001]) and a moderate negative correlation for Rinsp (r-0.67; 95% CI -0.79 to -0.50; p < 0.0001).
UNASSIGNED: Increasing degree of HEE reduces compliance in moderate-to-severe COVID-19 ARDS. Reducing HEE may optimize ventilation and mitigate ventilator induced lung injury.

UNASSIGNED: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties.
UNASSIGNED: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia.
UNASSIGNED: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization.
UNASSIGNED: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events.
UNASSIGNED: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

Direct thrombin inhibitors, including argatroban, are increasingly used for anticoagulation during venovenous extracorporeal membrane oxygenation (VV ECMO). In many centers activated partial thromboplastin time (aPTT) is used for monitoring, but it can be affected by several confounders. The aim of this study was to evaluate the safety and efficacy of anticoagulation with argatroban titrated according to diluted thrombin time targets (hemoclot™ assay) compared to anti-Xa guided anticoagulation with unfractionated heparin (UFH).
METHODS: This cohort study included adults at two tertiary care centers who required VV ECMO for severe COVID-19-related acute respiratory distress syndrome (CARDS). Patients received center-dependent argatroban or UFH for anticoagulation during ECMO. Argatroban was guided following a hemoclot™ target range of 0.4-0.6 μg/ml. UFH was guided by anti-factor Xa (antiXa) levels (0.2-0.3 IU/ml). The primary outcome was safety of argatroban compared to UFH, assessed by time to first clinically relevant bleeding event or death during ECMO. Secondary outcomes included efficacy (time to thromboembolism) and feasibility (proportion of anticoagulation targets within range).
RESULTS: From 2019 to 2021 57 patients were included in the study with 27 patients (47 %) receiving argatroban and 30 patients (53 %) receiving UFH. The time to the first clinically relevant bleeding or death during ECMO was similar between groups (HR (argatroban vs. UFH): 1.012, 95 % CI 0.44-2.35, p = 0.978). Argatroban was associated with a decreased risk for thromboembolism compared to UFH (HR 0.494 (95 % CI 0.26-0.95; p = 0.034)). The overall proportion of anticoagulation within target ranges was not different between groups (46 % (23-54 %) vs. 46 % (37 %-57 %), p = 0.45).
CONCLUSIONS: Anticoagulation with argatroban according to hemoclot™ targets (0.4-0.6 μg/ml) compared to antiXa guided UFH (0.2-0.3 IU/ml) is safe and may prolong thromboembolism-free time in patients with severe ARDS requiring VV ECMO.

BACKGROUND: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials.
METHODS: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 μg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome.
BACKGROUND: ISRCTN86534580.
RESULTS: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n = 2157), usual care (n = 3256), and other treatments (n = 3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months.
CONCLUSIONS: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted.
BACKGROUND: UKRI/National Institute of Health Research (MC_PC_19079).