Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection. METHODS: Electronic literature searches on PubMed, MEDLINE, CINAHL, EMBASE, Web of Science databases, and on medRxiv/bioRxiv preprint servers were conducted up to October 1, 2023. Studies reporting data on post-COVID symptoms at two-years after infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for meta-analytical pooled prevalence of each symptom. RESULTS: From 742 studies identified, twelve met inclusion criteria. The sample included 7912 COVID-19 survivors (50.7% female; age: 59.5, SD: 16.3). Post-COVID symptoms were assessed at a follow-up of 722.9 (SD: 51.5) days after. The overall methodological quality of studies was moderate (mean: 6/10, SD: 1.2 points). The most prevalent post-COVID symptoms two-years after SARS-CoV-2 infection were fatigue (28.0%, 95%CI 12.0-47.0), cognitive impairments (27.6%, 95%CI 12.6-45.8), and pain (8.4%, 95%CI 4.9-12.8). Psychological disturbances such as anxiety (13.4%, 95%CI 6.3-22.5) and depressive (18.0%, 95%CI 4.8-36.7) levels as well as sleep problems (20.9%, 95%CI 5.25-43.25) were also prevalent. Pooled data showed high heterogeneity (I2 ≥ 75%). CONCLUSION: This meta-analysis shows the presence of post-COVID symptoms in 30% of patients two-years after COVID-19. Fatigue, cognitive disorders, and pain were the most prevalent post-COVID symptoms. Psychological disturbances as well as sleep problems were still present two-years after COVID-19.

Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review.

PURPOSE: Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID. METHODS: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. RESULTS: From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID. CONCLUSION: Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.

Infusion reactions to adeno-associated virus (AAV)-based gene therapy: Mechanisms, diagnostics, treatment and review of the literature.

The use of adeno-associated virus (AAV) vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion-associated reactions (IARs) pose a significant challenge to the safety and efficacy of AAV-based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll-like receptor activation and subsequent production of pro-inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies (Nabs) and T-cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre-existing Nabs, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu-like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre- and postadministration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV-based gene therapy.

Humoral Response in Hemodialysis Patients Post-SARS-CoV-2 mRNA Vaccination: A Systematic Review of Literature.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected over 600 million individuals and caused nearly 7 million deaths worldwide (10 January 2023). Patients with renal disease undergoing hemodialysis are among those most adversely affected, with an increased predisposition to SARS-CoV-2 infection and death. This systematic review aimed to pool evidence assessing the humoral response of hemodialysis patients (HDP) post-mRNA SARS-CoV-2 vaccination. A systematic search of the literature was performed through MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers up to 10 January 2023. Cohort and case-control studies were included if they reported an immune response in one group of patients undergoing hemodialysis who received mRNA SARS-CoV-2 vaccination compared with another group of patients receiving the same vaccine but not on hemodialysis. The methodological quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was not deemed appropriate due to the high heterogeneity between studies. From the 120 studies identified, nine (n = 1969 participants) met the inclusion criteria. Most studies (n = 8/9, 88%) were of high or medium methodological quality (≥6/9 stars). The results revealed that HDP developed lower antibody levels across all timepoints post-vaccination when compared with controls. Patients with chronic kidney disease elicited the highest antibody immune response, followed by HDP and, lastly, kidney transplant recipients. Overall, post-vaccination antibody titers were comparatively lower than in the healthy population. Current results imply that robust vaccination strategies are needed to address waning immune responses in vulnerable populations.

Adjunctive Dexmedetomidine in Alcohol Withdrawal Syndrome: A Systematic Review and Meta-analysis of Retrospective Cohort Studies and Randomized Controlled Trials.

OBJECTIVE: To investigate whether dexmedetomidine (DEX), as adjunctive therapy to benzodiazepine (BZD), is superior to BZD alone in critically ill patients with alcohol withdrawal syndrome (AWS). DATA SOURCES: PubMed Central, Cochrane CENTRAL, ClinicalTrials.gov and Google Scholar were used as search databases. Specific keywords and MeSH terms were "dexmedetomidine," "benzodiazepine," and "alcohol withdrawal syndrome." The last search was on September 16, 2022. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) and nonrandomized/cohort studies exploring the use of DEX in the management of AWS were included. A total of 12 studies were included in the systematic review and 7 in the meta-analysis. DATA SYNTHESIS: The intensive care unit length of stay (ICU LOS) was found to have a mean difference (MD) of 48.06 [37.48, 58.64], P = <0.001 for the cohort subgroup, significantly favoring the DEX arm, but, in contrast, pooled RCT data showed a result of -20.07 [-36.86, -3.28], P = 0.02, a shorter ICU LOS for the DEX arm. Bradycardia and hypotension incidence significantly favored the BZD arm in both subgroups. This study compares the effectiveness of adjunctive DEX in clinical practice and aims to help providers in critical decision-making by compiling and analyzing the best current available evidence of its use in AWS. CONCLUSIONS: Based on low to very low level of evidence, adjunctive DEX showed no significant difference for ICU LOS when compared with BZD alone. Pooled randomized trials potentially show a benefit but are similarly limited by their low quality of evidence.

Adjunctive PD-1 inhibitor versus standard chemotherapy in recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis.

Objective: To investigate whether Adjunctive PD-1 inhibitors have improved clinical outcomes compared to chemotherapy alone in platinum-pretreated and platinum-naive recurrent or metastatic nasopharyngeal carcinoma (R/M NPCA). Methods: The study involved a literature search from PubMed, Cochrane CENTRAL, and Google Scholar for randomized clinical trials (RCTs) on the use of PD-1 inhibitors versus chemotherapy alone in patients with R/M NPCA. Bias was assessed using Cochrane collaboration's risk of bias tool. Overall Survival (OS) was examined as the primary endpoint. Secondary endpoints were Progression-Free Survival (PFS), Objective Response Rate, Disease Control Rate (DCR), Duration of Response, and Serious/Grade ⩾3 Adverse Events. Outcomes were measured with either Mean Difference, Risk ratio (RR), or Hazard ratios (HRs) at 95% confidence interval. Results: Four RCTs were included in the meta-analysis and systematic review. OS for the monotherapy subgroup was a HR of 0.87 [0.67, 1.13] (p = 0.30) while the combination subgroup had 0.64 [0.45, 0.90] (p = 0.01). The monotherapy subgroup exhibited significantly worse outcomes in PFS (HR 1.31 [1.01, 1.68]) (p = 0.04) and DCR (RR 1.52 [1.12, 2.05]) (p = 0.007) but no significant difference in other outcomes. For combination therapy, a statistically significant benefit can be seen in all outcomes except DCR (RR 0.62 [0.38, 1.01]) (p = 0.06) which was a non-significant benefit favoring PD-1 inhibitors. Conclusion: Combination PD-1 inhibitor + chemotherapy followed by maintenance PD-1 inhibitor therapy is superior to chemotherapy alone in the first-line treatment of R/M NPCA, implying a potential benefit with the use of PD-1 inhibitors + chemotherapy with maintenance PD-1 inhibitors as first-line in R/M NPCA compared to standard chemotherapy alone.

Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review.

Background: Although COVID-19 vaccination decreases the risk of severe illness, it is unclear whether vaccine administration may impact the prevalence of long-COVID. The aim of this systematic review is to investigate the association between COVID-19 vaccination and long-COVID symptomatology. Methods: MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were searched up to June 20, 2022. Peer-reviewed studies or preprints monitoring multiple symptoms appearing after acute SARS-CoV-2 infection either before or after COVID-19 vaccination collected by personal, telephone or electronic interviews were included. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Findings: From 2584 studies identified, 11 peer-reviewed studies and six preprints were included. The methodological quality of 82% (n=14/17) studies was high. Six studies (n=17,256,654 individuals) investigated the impact of vaccines before acute SARS-CoV-2 infection (vaccine-infection-long-COVID design). Overall, vaccination was associated with reduced risks or odds of long-COVID, with preliminary evidence suggesting that two doses are more effective than one dose. Eleven studies (n=36,736 COVID-19 survivors) investigated changes in long-COVID symptoms after vaccination (infection-long-COVID-vaccine design). Seven articles showed an improvement in long-COVID symptoms at least one dose post-vaccination, while four studies reported no change or worsening in long-COVID symptoms after vaccination. Interpretation: Low level of evidence (grade III, case-controls, cohort studies) suggests that vaccination before SARS-CoV-2 infection could reduce the risk of subsequent long-COVID. The impact of vaccination in people with existing long-COVID symptoms is still controversial, with some data showing changes in symptoms and others did not. These assumptions are limited to those vaccines used in the studies. Funding: The LONG-COVID-EXP-CM study supported by a grant of Comunidad de Madrid.

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review.

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) messenger RNA (mRNA) vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6-month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain immunoglobulin G (IgG) and anti-spike IgG, ranging from 94% to 95% at 90-180 days and 55%-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.

Balanced electrolyte solutions versus isotonic saline in adult patients with diabetic ketoacidosis: A systematic review and meta-analysis.

BACKGROUND: Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However, balanced electrolyte solutions (BES) have been proposed as an alternative due to a lower propensity to cause hyperchloremic metabolic acidosis. Evidence regarding the use of BES in DKA remains limited. OBJECTIVES: To determine if the use of BES in fluid resuscitation leads to faster resolution of DKA compared to IS. METHODS: The study involves a comprehensive search of literature from PubMed, Cochrane CENTRAL, Google Scholar, and Science Direct of clinical trials addressing the use of BES vs IS in fluid resuscitation in DKA. The time to resolution of DKA was examined as the primary endpoint. Pooled hazard ratios (HR) and Mean Difference (MD) in hours with their 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: The literature search included 464 studies that were screened individually. A total of 9 studies were identified but 6 studies were excluded due to irrelevance in the outcome of interest and target population. The pooled hazard ratio HR significantly revealed 1.46 [1.10 to 1.94] (p = 0.009) with 12% heterogeneity while MD was -3.02 (95% CI -6.78-0.74; p = 0.12) with heterogeneity of 85%. CONCLUSION: Considering the evidence from pooled small randomized trials with moderate overall certainty of evidence, the use of BES in DKA was associated with faster rates of DKA resolution compared to IS.

Effects of age, sex, serostatus, and underlying comorbidities on humoral response post-SARS-CoV-2 Pfizer-BioNTech mRNA vaccination: a systematic review.

With the advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences of the Coronavirus Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses to prevent SARS-CoV-2 infections. Despite effectiveness and safety, inter-individual immune response heterogeneity has been observed in recipients of mRNA-based vaccines. As a novel disease, the specific immune response mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral response plays a crucial role in affording immunoprotection and preventing debilitating sequelae from COVID-19. As such, this paper focused on the possible effects of age, sex, serostatus, and comorbidities on humoral response (i.e. total antibodies, IgG, and/or IgA) of different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search of literature was performed through PubMed, Cochrane CENTRAL, Google Scholar, Science Direct, medRxiv, and Research Square. Studies were included if they reported humoral response to COVID-19 mRNA vaccines. A total of 32 studies were identified and reviewed, and the percent differences of means of reported antibody levels were calculated for comparison. Findings revealed that older individuals, male sex, seronegativity, and those with more comorbidities mounted less humoral immune response. Given these findings, several recommendations were proposed regarding the current vaccination practices. These include giving additional doses of vaccination for immunocompromised and elderly populations. Another recommendation is conducting clinical trials in giving a combined scheme of mRNA vaccines, protein vaccines, and vector-based vaccines.