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Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Introduction: The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data., Methods: Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support., Results: Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70-84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37-0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46-10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09-1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07-1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities., Conclusions: Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Older adults and immunocompromised individulas are often excluded from vaccine trials., Aim: We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of trials excluding these patients decreased., Methods: Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals., Results: We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (n = 193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (n = 129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020-2021 (only COVID-19 vaccine trials) (p = 0.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p = 0.058)., Conclusions: During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas., (© 2023. The Author(s).)

Objective: To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19)., Methods: Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort., Results: Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2 ) ratio of >235 (OR, 3.75; 95% CI, 3.04-4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91-3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62-2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77-0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76-0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set., Discussion: The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings., Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine., Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models., Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038)., Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

Objectives: To describe long-COVID symptoms among older adults and to assess the risk factors for two common long-COVID symptoms: fatigue and dyspnea., Methods: This is a multicenter, prospective cohort study conducted in Israel, Switzerland, Spain, and Italy. Individuals were included at least 30 days after their COVID-19 diagnosis. We compared long-COVID symptoms between elderly (aged >65 years) and younger individuals (aged 18-65 years) and conducted univariate and multivariable analyses for the predictors of long-COVID fatigue and dyspnea., Results: A total of 2333 individuals were evaluated at an average of 5 months (146 days [95% confidence interval 142-150]) after COVID-19 onset. The mean age was 51 years, and 20.5% were aged >65 years. Older adults were more likely to be symptomatic, with the most common symptoms being fatigue (38%) and dyspnea (30%); they were more likely to complain of cough and arthralgia and have abnormal chest imaging and pulmonary function tests. Independent risk factors for long-COVID fatigue and dyspnea included female gender, obesity, and closer proximity to COVID-19 diagnosis; older age was not an independent predictor., Conclusion: Older individuals with long-COVID have different persisting symptoms, with more pronounced pulmonary impairment. Women and individuals with obesity are at risk. Further research is warranted to investigate the natural history of long-COVID among the elderly population and to assess possible interventions aimed at promoting rehabilitation and well-being., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Fatigue is the most prevalent and debilitating long-COVID (coronavirus disease) symptom; however, risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long-COVID fatigue and explored its possible pathophysiology., Methods: This was a nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long-COVID fatigue., Results: A total of 141 individuals were included. The mean age was 47 (SD: 13) years; 115 (82%) were recovering from mild coronavirus disease 2019 (COVID-19). Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long-COVID fatigue. They had a significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness, higher proportions of long-COVID symptoms, and of physical limitation in daily activities. Individuals with long-COVID fatigue also had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53); P = .038] and oxygen consumption per kilogram [27.69 (7.52) vs 30.71 (7.52); P = .036] at peak exercise. The 2 independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (OR: .79 per 10 beats/minute; 95% CI: .65-.96; P = .019) and long-COVID memory impairment (OR: 3.76; 95% CI: 1.57-9.01; P = .003)., Conclusions: Long-COVID fatigue may be related to autonomic dysfunction, impaired cognition, and decreased mood. This may suggest a limbic-vagal pathophysiology., Clinical Trials Registration: NCT04851561., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Scope: The aim of these guidelines is to provide evidence-based recommendations for the assessment and management of individuals with persistent symptoms after acute COVID-19 infection and to provide a definition for this entity, termed 'long COVID'., Methods: We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design., Recommendations: Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging, and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high-quality prospective clinical studies/trials, including a control group, to further evaluate the assessment and management of individuals with persistent symptoms of COVID-19., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Immune response to two SARS-CoV-2 mRNA vaccine doses among kidney transplant recipients (KTRs) is limited. We aimed to evaluate humoral and cellular response to a third BNT162b2 dose. In this prospective study, 190 KTRs were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were anti-spike antibody level >4160 AU/ml (neutralization-associated cutoff) and any seropositivity. Univariate and multivariate analyses were conducted to identify variables associated with antibody response. T-cell response was evaluated in a subset of participants. Results were compared to a control group of 56 healthcare workers. Among KTRs, we found a seropositivity rate of 70% (133/190) after the third dose (37%, 70/190, after the second vaccine dose); and 27% (52/190) achieved levels above 4160 AU/ml after the third dose, compared to 93% of controls. Variables associated with antibody response included higher antibody levels after the second dose (odds ratio [OR] 30.8 per log AU/ml, 95% confidence interval [CI]11-86.4, p < 0.001); and discontinuation of antimetabolite prior to vaccination (OR 9.1,95% CI 1.8-46.5, p = 0.008). T-cell response was demonstrated in 13% (7/53). In conclusion, third dose BNT162b2 improved immune response among KTRs, however 30% still remained seronegative. Pre-vaccination temporary immunosuppression reduction improved antibody response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yahav, Rahamimov, Mashraki, Ben-Dor, Steinmetz, Agur, Zingerman, Herman-Edelstein, Lichtenberg, Ben-Zvi, Bar-Haim, Cohen, Rotem, Elia, Margalit and Zvi.)

Aims: To assess the 6 months immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplanted (HTx) recipients and left ventricular assist device (LVAD)-supported patients., Methods and Results: A prospective single-centre cohort study of HTx recipients and LVAD-supported patients who received a two-dose SARSCoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). Whole blood for anti-spike IgG (S-IgG) antibodies were drawn at 6 months after the first vaccine dose. S-IgG data at 6 weeks were available for a subgroup of HTx recipients. S-IgG ≥ 50 AU/mL were interpreted positive. The cohort included 53 HTx recipients and 18 LVAD-supported patients. The median time from HTx or LVAD implantation to the 1 st vaccine dose was 90 (IQR 30, 172) months and 22 (IQR 6, 78) months, respectively. The seropositivity rates of S-IgG antibodies and their titre levels in HTx recipients and LVAD-supported patients were 45% and 83% respectively, (P = 0.006), and 35 (IQR 7, 306) AU/mL and 311 (IQR 86, 774) AU/mL, respectively, (P = 0.006). Reduced SARSCoV-2 vaccine immunogenicity in HTx recipients was associated with older age [odds ratio (OR) 0.917 confidence interval (CI 0.871, 0.966), P = 0.011] and with the use of anti-metabolites-based immunosuppressive regimens [OR 0.224 (CI 0.065, 0.777), P = 0.018]. mTOR inhibitors were associated with higher immunogenicity [OR 3.1 (CI 1.01, 9.65), P = 0.048]. Out of 13 HTx recipients who were S-IgG seropositive at 6 weeks after the first vaccine dose, 85% remained S-IgG seropositive at 6 month follow-up., Conclusions: At 6 months post-vaccination, S-IgG immunogenicity in HTx recipients is low, particularly in older HTx recipients and in those treated with anti-metabolites drugs., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The purpose of this survey is to explore changes in the management of COVID-19 during the first versus the second wave, with particular emphasis on therapies, antibiotic prescriptions, and elderly care. An internet-based questionnaire survey was distributed to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members. Therapeutic approach to patients with mild-to-moderate (PiO 2 /FiO 2 200-350) and severe (PiO 2 /FiO 2  < 200) COVID-19, antibiotic use, and reasons for excluding patients from the intensive care unit (ICU) were investigated. A total of 463 from 21 countries participated in the study. Most representatives were infectious disease specialists (68.3%). During the second wave of pandemic, physicians abandoned the use of hydroxychloroquine, lopinavir/ritonavir, and azithromycin in favor of dexamethasone, low-molecular weight heparin (LMWH), and remdesivir in mild-to-moderate COVID-19. In critically ill patients, we detected an increased use of high-dose steroids (51%) and a decrease in tocilizumab use. The use of antibiotics at hospital admission decreased but remained high in the second wave. Age was reported to be a main consideration for exclusion of patients from ICU care by 25% of responders; a third reported that elderly were not candidates for ICU admission in their center. The decision to exclude patients from ICU care was based on the individual decision of an intensivist in 59.6% of cases. The approach of physicians to COVID-19 changed over time following evidence accumulation and guidelines. Antibiotic use at hospital admission and decision to exclude patients from ICU care remain critical aspects that should be better investigated and harmonized among clinicians., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To assess the humoral immune response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation (HCT)., Methods: This is a prospective cohort study. The SARS-CoV-2 IgGII Quant (Abbott©) assay was performed 4-6 weeks after the second BNT162b2 vaccine for quantitative measurement of anti-spike antibodies., Results: The cohort included 106 adult patients. Median time from HCT to vaccination was 42 (range 4-439) months. Overall, 15/106 (14%, 95% confidence interval (CI) 7-21%) were seronegative despite vaccination, 14/52 patients on immunosuppression (27%, 95%CI 19-35%) compared to only 1/54 patients off immunosuppression (1.8%, 95%CI 1-4%) (p 0.0002). The proportion of seronegative patients declined with time; it was 46% (6/13) during the first year, 12.5% (3/24) during the second year and 9% (6/69) beyond 2 years from transplant. Patients with acute graft-versus-host disease (GVHD) (odds ratio (OR) 3.3, 95%CI 0.97-11.1, p 0.06) and moderate to severe chronic GVHD (OR 5.9, 95%CI 1.2-29, p 0.03) were more likely to remain seronegative. Vaccination was well tolerated by most patients. However, 7% (7/106) reported that GVHD-related symptoms worsened within days following vaccination., Conclusion: A significant proportion of allogeneic HCT recipients receiving immunosuppression demonstrated an inadequate humoral response to the BNT162b2 vaccine. These patients should be recognized and instructed to take appropriate precautions. Recipients who were off immunosuppression had a humoral response that was comparable to that of the general population., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Patients with specific hematological malignancies (HM) are at increased risk for severe disease and death from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy subjects, vaccination against SARS-CoV-2 has been demonstrated to be highly effective in disease prevention; however, immunocompromised patients were largely excluded from vaccine randomized controlled trials. In this review, we overview available non-randomized studies addressing effectiveness and safety of several coronavirus disease 2019 (COVID-19) vaccines in patients with HM. Overall, COVID-19 vaccines are safe in patients with HM, with adverse events similar to those in the general population. Though serology testing is not recommended as a test to evaluate vaccine effectiveness, a correlation between higher antibody levels and protection against infection has been reported. Studies evaluating humoral response to COVID-19 vaccine in HM patients demonstrate low immunogenicity, mainly in patients with lymphoproliferative disorders, as well as with certain drugs, including mainly anti-CD20 antibodies, Bruton tyrosine kinase inhibitors, and also ruxolitinib and venetoclax. Seropositivity rates of patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia following mRNA vaccination reach 40%-50%. T-cell responses to vaccination are also impaired among these patients. Better humoral response rates are reported in multiple myeloma patients and hematopoietic stem-cell transplant, reaching ∼75%-80%, but not in patients following chimeric antigen receptor T-cell therapy. Patients with chronic myeloid leukemia and myeloproliferative diseases have high response rate to vaccination. Third mRNA vaccine dose is currently recommended to all HM patients. Alternative approaches for vaccination and prevention in patients unable to mount an immune response following full vaccination are provided in the review., (© 2022 S. Karger AG, Basel.)

Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients., Methods and Analysis: BECAME is a single-centre, open-label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participants per arm will be also tested for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial., Ethics and Dissemination: The trial is approved by local ethics committee of Rabin Medical Center (RMC-0192-21). All participants will be required to provide written informed consent. Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee., Trail Registration Number: NCT04961229., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Burden of COVID-19 on Hospitals across the globe is enormous and has clinical and economic implications. In this retrospective study including consecutive adult patients with confirmed SARS-CoV-2 who were admitted between 3/2020 and 30/9/20, we aimed to identify post-discharge outcomes and risk factors for re-admission among COVID-19 hospitalized patients. Mortality and re-admissions were documented for a median post discharge follow up of 59 days (interquartile range 28,161). Univariate and multivariate analyses of risk factors for re-admission were performed. Overall, 618 hospitalized COVID-19 patients were included. Of the 544 patient who were discharged, 10 patients (1.83%) died following discharge and 50 patients (9.2%) were re-admitted. Median time to re-admission was 7 days (interquartile range 3, 24). Oxygen saturation or treatment prior to discharge were not associated with re-admissions. Risk factors for re-admission in multivariate analysis included solid organ transplantation (hazard ratio [HR] 3.37, 95% confidence interval [CI] 2.73-7.5, p = 0.0028) and higher Charlson comorbidity index (HR 1.34, 95% CI 1.23-1.46, p < 0.0001). Mean age of post discharge mortality cases was 85.0 (SD 9.98), 80% of them had cognitive decline or needed help in ADL at baseline. In conclusion, re-admission rates of hospitalized COVID-19 are fairly moderate. Predictors of re-admission are non-modifiable, including baseline comorbidities, rather than COVID-19 severity or treatment., (© 2021. The Author(s).)

Objectives: To assess whether results of observational studies of potential anti-COVID-19 drugs were reproduced in subsequent randomized controlled trials (RCTs)., Methods: This was a retrospective cross-sectional study, including studies published online between 1 January and 27 October 2020 that evaluated potential COVID-19 treatments and reported all-cause mortality., Results: Of 133 comparisons included in 117 studies, most were non-randomized (104/133, 78%). Hydroxychloroquine was the most common drug type, combined with azithromycin (n = 27, 20%) or alone (n = 22, 16%), followed by IL-6 inhibitors (n = 36, 27%) and corticosteroids (n = 26, 20%). Seventy-one percent (74/104) of non-randomized studies reported adjusted survival results and only 8% (8/104) adjusted for immortal time bias. Only two RCTs (2/29, 7%) reported significant survival benefit, both reporting treatment with corticosteroids, while 32/104 (31%) non-randomized studies showed statistically significant survival benefit associated with the intervention arm. The results of the majority (28/32, 88%) of non-randomized studies reporting survival benefit were not replicated by large-scale RCTs., Conclusions: The results of most non-randomized studies reporting survival benefit of potential anti-COVID-19 drugs were not replicated by large RCTs. Regulators and healthcare professionals should exercise caution and resist the pressure to approve and prescribe drugs of unproven efficacy and potential toxicity to optimize patient care and maintain public trust in medical science., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity., Methods: This was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity., Results: Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m 2 , 95% confidence interval (CI) 1.014-1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782-3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015-1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146-3.443, p 0.014). No serious adverse events resulting from the vaccine were reported., Conclusions: Kidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear., Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls., Design, Setting, and Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel)., Interventions: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL., Main Outcomes and Measures: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses., Results: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (β, -3.5; 95% CI, -5.6 to -1.5)., Conclusions and Relevance: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.

Vaccines have changed modern medicine, and are a mainstay in reducing morbidity and mortality from infections. Our research group recently published a study in which we found that vaccines approved by the US Food and Drugs Administration were safe with few clinically important post-approval adverse effects. The current COVID-19 pandemic presents regulators with the unprecedented challenge of balancing a public demand for the rapid development and approval of a safe and effective SARS-CoV-2 vaccine without compromising the strict pre-marketing requirements used for previous vaccines. Here, we review the approval process and safety profiles of FDA approved vaccines and discuss some of the challenges currently facing the FDA regarding the SARS-CoV-2 vaccine approval.

Background: Coronavirus disease (COVID-19) has caused a pandemic threatening millions of people worldwide. Yet studies specifically assessing the geriatric population are scarce. We aimed to examine the participation of elderly patients in therapeutic or prophylactic trials on COVID-19., Methods: In this review, randomized controlled trials (RCTs; n = 12) comparing therapeutic or prophylactic interventions registered on preprint repositories and/or published since December 2019 were analyzed. We searched in PubMed, leading journals websites, and preprint repositories for RCTs and large observational studies. We aimed to describe the age of included patients, the presence of an upper age limit and of adjusted analyses on age, any exclusion criteria that could limit participation of elderly adults such as comorbidities, cognitive impairment, limitation of life expectancy; and the assessment of long-term outcomes such as the need of rehabilitation or institutionalization. Mean participant ages were reported and compared with observational studies., Results: Twelve RCTs assessing drug therapy for COVID-19 were included. Mean age of patients included in RCTs was 56.3 years. An upper age limit was applied in three published trials (25%) and in 200/650 (31%) trials registered at clinicaltrials.gov . One trial reported a subgroup analysis in patients ≥65. Patients were excluded for liver-function abnormalities in eight trials, renal disease in six, cardiac disease or risk of torsade de pointes in five, and four for cognitive or mental criteria, which are frequent comorbidities in the oldest patients. Only three trials allowed a family member to provide consent. Patients enrolled in RCTs were on average 20 years younger than those included in large (n ≥ 1000) observational studies. Seven studies had as their primary outcome a clinical endpoint, but none reported cognitive, functional or quality of life outcomes or need for rehabilitation or long-term care facility placement., Conclusions: Elderly patients are clearly underrepresented in RCTs, although they comprise the population hardest hit by the COVID-19 pandemic. Long-term outcomes such as the need of rehabilitation or institutionalization were not reported. Future investigations should target specifically this vulnerable population.

Background Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus–induced neurologic disease (VZV-ND). Methods This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid. Results We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non–VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25–128) and 82 days (IQR, 36–132) for VZV-ND and non–VZV-ND, respectively, not reaching statistical significance (P =.056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P =.2). Conclusions We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease (CKD) is a risk factor for severe coronavirus disease 2019 (COVID-19). We aimed to evaluate the real-life effectiveness of the BNT162b2 messenger RNA vaccine for a range of outcomes in patients with CKD compared with matched controls. Methods Data from Israel's largest healthcare organization were retrospectively used. Vaccinated CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2] and maintenance dialysis patients were matched to vaccinated controls without CKD (eGFR ≥60 ml/min/1.73 m2) according to demographic and clinical characteristics. Study outcomes included documented infection with severe acute respiratory syndrome coronavirus 2, symptomatic infection, COVID-19-related hospitalization, severe disease and death. Vaccine effectiveness was estimated as the risk ratio (RR) at days 7–28 following the second vaccine dose, using the Kaplan–Meier estimator. Effectiveness measures were also evaluated separately for various stages of CKD. Results There were 67 861 CKD patients not treated with dialysis, 2606 hemodialysis (HD) patients and 70 467 matched controls. The risk of severe disease {RR 1.84 [95% confidence interval (CI) 0.95–2.67]} and death [RR 2.00 (95% CI 0.99–5.20)] was increased in nondialysis CKD patients compared with controls without CKD following vaccination. For the subgroup of patients with eGFR <30 ml/min/1.73 m2, the risk of severe disease and death was increased compared with controls [RR 6.42 (95% CI 1.85–17.51) and RR 8.81 (95% CI 1.63–13.81), respectively]. The risks for all study outcomes were increased in HD patients compared with controls. Conclusion Two doses of the BNT162b2 vaccine were found to be less efficient for patients with eGFR <30 ml/min/1.73 m2. Risk in HD patients is increased for all outcomes. These results suggest prioritizing patients with eGFR <30 ml/min/1.73 m2 for booster shots, pre- and post-exposure prophylaxis and early COVID-19 therapy. [ABSTRACT FROM AUTHOR]

Data regarding immunogenicity of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among kidney transplant recipients in the months following vaccination are lacking. We aimed to investigate humoral immune response at 3–4 months post-vaccination among a cohort of kidney transplant recipients, compared with a control group of dialysis patients. Anti-spike antibodies were tested at 1 and 3–4 months after vaccination. Of 259 kidney transplant recipients tested at a median time of 110 days from second vaccine dose, 99 (38%) were seropositive, compared with 83% (101/122) of control patients. Younger age, better renal function and lower immunosuppression levels were associated with seropositivity. A total of 14% (13/94) of participants seropositive at 1 month became seronegative at follow-up and 11% (18/165) became seropositive. The latter were mainly individuals with higher antibody levels at 1 month. Antibody levels at 3–4 months were significantly reduced in both study groups, although the decline was more pronounced in the control group. Kidney transplant recipients present poor antibody response to mRNA SARS-CoV-2 vaccination, with only 38% seropositive at 3–4 months. Nevertheless, the decay in antibody response over time is modest, and some patients may present delayed response, reaching adequate antibody levels at 3–4 months. Low seropositivity rates in this group call for investigating other immunization strategies. [ABSTRACT FROM AUTHOR]

Background: Long COVID has become a burden on healthcare systems worldwide. Research into the etiology and risk factors has been impeded by observing all diverse manifestations as part of a single entity. We aimed to determine patterns of symptoms in convalescing COVID-19 patients. Methods: Symptomatic patients were recruited from four countries. Data were collected regarding demographics, comorbidities, acute disease and persistent symptoms. Factor analysis was performed to elucidate symptom patterns. Associations of the patterns with patients' characteristics, features of acute disease and effect on daily life were sought. Results: We included 1027 symptomatic post-COVID individuals in the analysis. The majority of participants were graded as having a non-severe acute COVID-19 (N = 763, 74.3%). We identified six patterns of symptoms: cognitive, pain-syndrome, pulmonary, cardiac, anosmia-dysgeusia and headache. The cognitive pattern was the major symptoms pattern, explaining 26.2% of the variance; the other patterns each explained 6.5–9.5% of the variance. The cognitive pattern was higher in patients who were outpatients during the acute disease. The pain-syndrome pattern was associated with acute disease severity, higher in women and increased with age. The pulmonary pattern was associated with prior lung disease and severe acute disease. Only two of the patterns (cognitive and cardiac) were associated with failure to return to pre-COVID occupational and physical activity status. Conclusion: Long COVID diverse symptoms can be grouped into six unique patterns. Using these patterns in future research may improve our understanding of pathophysiology and risk factors of persistent COVID, provide homogenous terminology for clinical research, and direct therapeutic interventions. [ABSTRACT FROM AUTHOR]

We aimed to examine the rate and characteristics of retracted articles in infectious diseases and clinical microbiology. Using the Retraction Watch Database, we conducted a cross-sectional study for retracted publications categorized as 'Infectious Disease' or 'Microbiology' until June 30 2022. We included publications for which citation information was available through the Web of Science database. Study characteristics, retraction trends and number of citations before and after the retraction year were analysed. Overall, 1004 retracted publications were included, retracted between August 1968 and June 2022. The number of retractions climbed through the years, peaking in 2020–2021. A total of 614 retractions originated from USA, China, and India, of total 183 736 PubMed publications from these countries. Overall, 378 (38%) were retracted because of errors; 182 (18%) because of plagiarism; and 142 (14%) because of falsification/fabrication. Specific reasons included 'concerns/issues about data' (158, 16%); 'duplication of image' (127, 13%); and 'unreliable results' (116, 12%). Of the 347 retractions during 2020 to June 2022, 91 (26%) were COVID-19 related. Fifty of 895 (5.6%) first authors had two retracted papers, and 14 (1.6%) had ≥2 retractions. Of 824 publications cited at least once, 466 (57%) were cited more often after retraction. Retractions of infectious diseases and clinical microbiology publications are increasing. Concerning reasons such as plagiarism, falsification/fabrication and errors are not uncommon. Nonetheless, these publications continue to be commonly cited after being retracted. [ABSTRACT FROM AUTHOR]