Cytomegalovirus appendicitis in solid organ transplant patients,two cases and a review

Cytomegalovirus (CMV) disease is a common complication following solid organ transplantation with a variety of gastrointestinal (GI) tract manifestations. CMV appendicitis, however, is a rare complication in a solid organ transplant patient, having been reported only once previously. We have recently seen two cases in solid organ transplant recipients at our institution, one a liver recipient and the other a heart recipient. Both patients underwent surgical resection. Pathologic evaluation of both resected appendices as well as polymerase chain reaction (PCR) amplification for CMV from the serum revealed the virus as the etiology. Both patients received induction intravenous ganciclovir followed by oral valganciclovir and have done well post-operatively. Tissue-invasive CMV disease should be considered in the differential diagnosis for solid organ transplant patients with symptoms suggesting acute or chronic appendicitis. Both PCR testing as well as pathologic review of tissue specimens should be considered to ensure accurate diagnosis and management.     

An overview of COVID-19 in solid organ transplantation

BackgroundThe COVID-19 pandemic has influenced the field of solid organ transplantation (SOT) in many ways. COVID-19 has led to programmatic impacts and changes in donor and recipient selection. Several studies have evaluated the course, optimal treatment, and prevention of COVID-19 in SOT recipients.ObjectivesTo review the literature on COVID-19 in SOT recipients.SourcesPubMed, Web of Science, and Google Scholar were searched. The search was restricted to articles published between January 1, 2019 and December 1, 2021.ContentThe COVID-19 pandemic initially led to a decreased volume of solid organ transplants. However, transplant volumes at most centres have rebounded. Donor selection remains an incompletely defined issue. Several reports suggest that donor-derived SARS-CoV-2 infections occur only in lung transplant recipients and that other organs from SARS-CoV-2 PCR-positive donors could potentially be safely used. However, these data are limited to case series. Transplantation for end-stage lung disease after COVID-19 infection is increasingly common and has been performed with acceptable outcomes. In acute COVID-19 in a transplant candidate, transplantation should be delayed when feasible. After adjustment, mortality after COVID-19 appear similar in SOT recipients compared to the general population, with notable increased use of antiviral and anti-inflammatory treatment options. Prevention of COVID-19 is key in SOT recipients. Vaccination of SOT recipients and anyone who is in contact with SOT recipients is one of the cornerstones of prevention. Nonpharmacological interventions such as face coverings, hand hygiene, and physical distancing remain ever important as well.ImplicationsThe COVID-19 pandemic continues to have an important impact on SOT candidates and recipients. Prevention of infection is the most important measure and requires careful attention to approaches to vaccination and messaging of the ongoing need for face coverings, physical distancing, and hand hygiene.     

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

BackgroundAvailable data show that COVID-19 vaccines may be less effective in immunocompromised populations, who are at increased risk of severe COVID-19.ObjectivesWe conducted a systematic review of literature to assess immunogenicity, efficacy and effectiveness of COVID-19 vaccines in immunocompromised populations.Data sourcesWe searched Medline and Embase databases.Study eligibility criteria, patients, interventionsWe included studies of COVID-19 vaccines after complete vaccination in immunocompromised patients until 31 August 2021. Studies with <10 patients, safety data only and case series of breakthrough infections were excluded.MethodsRisk of bias was assessed via the tool developed by the National Institutes of Health on interventional and observational studies. Immunogenicity was assessed through non-response rate defined as no anti-SARS-CoV-2 spike protein antibodies, efficacy and effectiveness by the relative reduction in risk of SARS-CoV-2 infection or COVID-19. We collected factors associated with the risk of non-response. We presented collected data by immunosuppression type.ResultsWe screened 5917 results, included 162 studies. There were 157 on immunogenicity in 25 209 participants, including 7835 cancer or haematological malignancy patients (31.1%), 6302 patients on dialysis (25.0%), 5974 solid organ transplant recipients (23.7%) and 4680 immune-mediated disease patients (18.6%). Proportion of non-responders seemed higher among solid organ transplant recipients (range 18–100%) and patients with haematological malignancy (range 14–61%), and lower in patients with cancer (range 2–36%) and patients on dialysis (range 2–30%). Risk factors for non-response included older age, use of corticosteroids, immunosuppressive or anti-CD20 agent. Ten studies evaluated immunogenicity of an additional dose. Five studies evaluated vaccine efficacy or effectiveness: three on SARS-CoV-2 infection (range 71–81%), one on COVID-19-related hospitalization (62.9%), one had a too small sample size.ConclusionsThis systematic review highlights the risk of low immunogenicity of COVID-19 vaccines in immunocompromised populations, especially solid organ transplant recipients and patients with haematological malignancy. Despite lack of vaccine effectiveness data, enhanced vaccine regimens may be necessary.     

COVID-19 and liver dysfunction: A systematic review and meta-analysis of retrospective studies

Recently, Coronavirus Disease 2019 (COVID-19) pandemic is the most significant global health crisis. In this study, we conducted a meta-analysis to find the association between liver injuries and the severity of COVID-19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed- or random-effects model was applied to pool data. Publication bias Egger's test was also performed. Meta-analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID-19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID-19. Liver dysfunction was associated with a severe outcome of COVID-19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes.     

COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis

Background/AimsData of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody.MethodsWe collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses.ResultsTwenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76–90%) and 91% (95% CI, 83–95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76–86%) in chronic hepatitis B, 96% (95% CI, 93–97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75–91%) in cirrhosis and 85% (95% CI, 78–90%) in non-cirrhosis, 86% (95% CI, 78–92%) for inactivated vaccine and 89% (95% CI, 71–96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55–75%) after two doses of mRNA vaccines and 88% (95% CI, 58–98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30–89%). Prevalence of adverse events was 27% (95% CI, 18–38%) and 63% (95% CI, 39–82%) among CLD and LT groups, respectively.ConclusionsCLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.     

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study

ObjectivesWe 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.MethodsThis 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.ResultsOf 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 m², 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.ConclusionsKidney 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.     

Remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

BackgroundThe benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use.ObjectivesTo evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements.Data sourcesBeginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022.Study eligibility criteriaRandomised controlled trials; all languages.ParticipantsAll hospitalized adults with COVID-19.InterventionsRemdesivir, in comparison to either placebo, or standard of care.Assessment of risk of biasWe used the ROB-2 criteria.Methods of data synthesisThe primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important.ResultsWe identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5–1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79–0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88–1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen.ConclusionsBased on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated.     

Anakinra was not associated with lower mortality in hospitalised COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials

The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of anakinra on mortality in patients with COVID-19. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on treatment of COVID-19 with anakinra, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). Five Randomized controlled trials (enrolling 1859 participants) met the inclusion criteria. There was no statistically significant difference in 14-day mortality (RR 0.78, 95% CI 0.43–1.39; P = 0.40), 28-day mortality (RR 1.06, 95% CI 0.89–1.26; P = 0.51), and 90-day mortality (RR 1.01, 95% CI 0.73–1.39; P = 0.97) between the two groups. Sensitivity analyses further confirmed these results. Anakinra was not associated with reduced mortality in hospitalised patients with COVID-19. Anakinra probably should not be used routinely in COVID-19 patients.     

Improved COVID-19 ICU admission and mortality outcomes following treatment with statins: a systematic review and meta-analysis

IntroductionApproximately 1% of the world population has now been infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). With cases still rising and vaccines just beginning to rollout, we are still several months away from seeing reductions in daily case numbers, hospitalisations, and mortality. Therefore, there is a still an urgent need to control the disease spread by repurposing existing therapeutics. Owing to antiviral, anti-inflammatory, immunomodulatory, and cardioprotective actions, statin therapy has been considered as a plausible approach to improve COVID-19 outcomes.Material and methodsWe carried out a meta-analysis to investigate the effect of statins on 3 COVID-19 outcomes: intensive care unit (ICU) admission, tracheal intubation, and death. We systematically searched the PubMed, Web of Science, Scopus, and ProQuest databases using keywords related to our aims up to November 2, 2020. All published observational studies and randomised clinical trials on COVID-19 and statins were retrieved. Statistical analysis with random effects modelling was performed using STATA16 software.ResultsThe final selected studies (n = 24 studies; 32,715 patients) showed significant reductions in ICU admission (OR = 0.78, 95% CI: 0.58–1.06; n = 10; I² = 58.5%) and death (OR = 0.70, 95% CI: 0.55–0.88; n = 21; I² = 82.5%) outcomes, with no significant effect on tracheal intubation (OR = 0.79; 95% CI: 0.57–1.11; n = 7; I²= 89.0%). Furthermore, subgroup analysis suggested that death was reduced further by in-hospital application of stains (OR = 0.40, 95% CI: 0.22–0.73, n = 3; I² = 82.5%), compared with pre-hospital use (OR = 0.77, 95% CI: 0.60–0.98, n = 18; I² = 81.8%).ConclusionsThese findings call attention to the need for systematic clinical studies to assess both pre- and in-hospital use of statins as a potential means of reducing COVID-19 disease severity, particularly in terms of reduction of ICU admission and total mortality reduction.     

Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis

BackgroundPost-acute coronavirus 2019 (COVID-19) syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity.ObjectivesTo estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods.Data sourcesSearches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed.Study eligibility criteria, participants and interventionsArticles in English that reported the prevalence of persistent symptoms among individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness.MethodsRandom-effect meta-analysis was performed to produce a pooled prevalence for each symptom at four different follow-up time intervals. Between-study heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study-level variables. Risk of bias was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively.ResultsAfter screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257 348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder, and difficulty concentrating (32%, 25%, 24%, and 22%, respectively, at 3- to <6-month follow-up); effort intolerance, fatigue, sleep disorder, and dyspnea (45%, 36%, 29%, and 25%, respectively, at 6- to <9-month follow-up); fatigue (37%) and dyspnea (21%) at 9 to <12 months; and fatigue, dyspnea, sleep disorder, and myalgia (41%, 31%, 30%, and 22%, respectively, at >12-month follow-up). There was substantial between-study heterogeneity for all reported symptom prevalences. Meta-regressions identified statistically significant effect modifiers: world region, male sex, diabetes mellitus, disease severity, and overall study quality score. Five of six studies including a comparator group consisting of COVID-19–negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms.ConclusionsThis systematic review found that a large proportion of patients experience post-acute COVID-19 syndrome 3 to 12 months after recovery from the acute phase of COVID-19. However, available studies of post-acute COVID-19 syndrome are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptom definitions and measurements, and longer follow-up.     

Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis

Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (−3.7 g/L, 95% CI, −5.3 to −2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.     

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis

ObjectivesCytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.MethodsData sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I². We assessed the certainty of evidence using the GRADE approach.ResultsOf 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I² = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I² = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I² = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively.ConclusionsCumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.     

Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis

Currently approved therapies for COVID-19 are mostly limited by their low availability, high costs or the requirement of parenteral administration by trained medical personnel in an in-hospital setting. Quercetin is a cheap and easily accessible therapeutic option for COVID-19 patients. However, it has not been evaluated in a systematic review until now. We aimed to conduct a meta-analysis to assess the effect of quercetin on clinical outcomes in COVID-19 patients. Various databases including PubMed, the Cochrane Library and Embase were searched from inception until 5 October 2022 and results from six randomized controlled trials (RCTs) were pooled using a random-effects model. All analyses were conducted using RevMan 5.4 with odds ratio (OR) as the effect measure. Quercetin decreased the risk of intensive care unit admission (OR = 0.31; 95% confidence interval (CI) 0.10–0.99) and the incidence of hospitalisation (OR = 0.25; 95% CI 0.10–0.62) but did not decrease the risk of all-cause mortality and the rate of no recovery. Quercetin may be of benefit in COVID-19 patients, especially if administered in its phytosome formulation which greatly enhances its bioavailability but large-scale RCTs are needed to confirm these findings.     

New-onset diabetes in COVID-19 and clinical outcomes: A systematic review and meta-analysis

BACKGROUNDDiabetes mellitus (DM) is associated with adverse clinical outcomes and high mortality in patients with coronavirus disease 2019 (COVID-19). The relationship between diabetes and COVID-19 is known to be bidirectional.AIMTo analyze the rate of new-onset diabetes in COVID-19 patients and compare the clinical outcomes of new-onset diabetes, pre-existing diabetes, hyperglycemic, and non-diabetes among COVID-19 patients.METHODSWe used the Meta-analysis of Observational Studies in Epidemiology statement for the present meta-analysis. Online databases were searched for all peer-reviewed articles published until November 6, 2020. Articles were screened using Covidence and data extracted. Further analysis was done using comprehensive meta-analysis. Among the 128 studies detected after thorough database searching, seven were included in the quantitative analysis. The proportion was reported with 95% confidence interval (CI) and heterogeneity was assessed using I².RESULTSAnalysis showed that 19.70% (CI: 10.93-32.91) of COVID-19 patients had associated DM, and 25.23% (CI: 19.07-32.58) had associated hyperglycemia. The overall mortality rate was 15.36% (CI: 12.57-18.68) of all COVID-19 cases, irrespective of their DM status. The mortality rate was 9.26% among non-diabetic patients, 10.59% among patients with COVID-19 associated hyperglycemia, 16.03% among known DM patients, and 24.96% among COVID-19 associated DM patients. The overall occurrence of adverse events was 20.52% (CI: 14.21-28.70) among COVID-19 patients in the included studies, 15.29% among non-diabetic patients, 20.41% among patients with COVID-19 associated hyperglycemia, 20.69% among known DM patients, and 45.85% among new-onset DM. Meta-regression showed an increasing rate of mortality among new hyperglycemic patients, known diabetics, and new-onset DM patients in comparison to those without diabetes.CONCLUSIONA significantly higher rate of new onset DM and hyperglycemia was observed. Higher mortality rates and adverse events were seen in patients with new-onset DM and hyperglycemia than in the non-diabetic population.     

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression

ObjectivesD-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19.MethodsA literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468).ResultsThirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 ​% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 ​% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 ​% confidence interval, CI 0.42 to 0.77; p ​< ​0.001). There was extreme between-study heterogeneity (I² ​= ​90.2 ​%; p ​< ​0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p ​= ​0.048) and D-dimer (p ​= ​0.001).ConclusionsProlonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.     

Prevalence of unwillingness and uncertainty to vaccinate against COVID-19 in older people: A systematic review and meta-analysis

The coronavirus disease 2019 (COVID-19) has been shown to have more severe health outcomes in older people specifically in relation to mortality and disability. Vaccination seems to be efficacious and safe for preventing the negative consequences of COVID-19, but vaccine hesitancy seems to be high in older adults. We therefore aimed to investigate the prevalence of unwillingness and the uncertainty to vaccinate against COVID-19 in older people and the factors that can be associated with the unwillingness to vaccinate. For this work, we searched several databases until 18th June 2021 for studies reporting the prevalence of unwillingness and the uncertainty to vaccinate against COVID-19 in people aged >60 years. A meta-analysis of the prevalence, with the correspondent 95% confidence intervals (CIs), was proposed. Factors that can be associated with the unwillingness to vaccinate against COVID-19 were explored through multivariable analyses and reported as odds ratios (ORs). Among 662 papers initially screened, we included 15 studies for a total of 9753 older adults. The prevalence of unwillingness to vaccinate against COVID-19 in older people was 27.03% (95%CI: 15.10–38.95%), whilst the correspondent figure of uncertainty was 19.33% (95%CI: 12.28–26.39). The risk of being unvaccinated was significantly higher in Hispanics (OR=1.197; 95%CI: 1.010–1.418) and in case of low education (OR=1.678; 95%CI: 1.170–2.408) and low income (OR=1.287; 95%CI: 1.127–1.469). In conclusion, the hesitancy for COVID-19 vaccination is a relevant problem in older people, particularly in those with a low income, a low level of education, and in Hispanics living in the United States.     

Efficacy of early treatment with hydroxychloroquine in people with mild to moderate COVID-19: a systematic review and meta-analysis

IntroductionNo early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.Material and methodsRandomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.ResultsFive RCTs (n = 1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow-up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR = 0.80, 95% CI: 0.47–1.36, I² = 2%, 5 RCTs, low QoE), all-cause mortality (RR = 0.77, 95% CI: 0.16–3.68, I² = 0%, 5 RCTs, very low QoE), symptom resolution (RR = 0.94, 95% CI: 0.77–1.16, I² = 71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR = 1.02, 95% CI: 0.82–1.27, I² = 65%, 2 RCTs, low QoE). There was a larger non-significant increase of adverse events with hydroxychloroquine vs. controls (RR = 2.17, 95% CI: 0.86–5.45, I² = 92%, 5 RCTs, very low QoE).ConclusionsHydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.     

Effect of COVID-19 vaccination on semen parameters: A systematic review and meta-analysis

The aim of this study was to investigate the effect of coronavirus disease 2019 (COVID-19) vaccination on semen parameters through systematic review and meta-analysis. PubMed, EMBASE, Web of Science, and Cochrane Library were comprehensively searched by June 2022. Studies were considered eligible if they compared semen parameters before and after COVID-19 vaccination or between vaccinated and unvaccinated men, with no restrictions on vaccine types or doses. The effect size was calculated as mean difference (MD) with 95% confidence interval (CI) using a random-effects model. Subgroup and sensitivity analyses were conducted to assess the sources of heterogeneity measured by the I² statistic, with publication bias evaluated by Egger's test. Twelve cohort studies involving 914 participants fulfilled the inclusion criteria. In a comparison of vaccinated versus unvaccinated group, the pooled data revealed no significant differences in semen volume (MD = 0.18 ml, 95% CI −0.02 to 0.38), sperm concentration (MD = 1.16 million/ml, 95% CI −1.34 to 3.66), total sperm motility (MD = −0.14%, 95% CI −2.84 to 2.56), progressive sperm motility (MD = −1.06%, 95% CI −2.88 to 0.77), total sperm count (MD = 5.92 million, 95% CI −10.22 to 22.05), total motile sperm count (MD = 2.18 million, 95% CI −1.28 to 5.63), total progressively motile sperm count (MD = −3.87 million, 95% CI −13.16 to 5.43), and sperm morphology (MD = 0.07%, 95% CI −0.84 to 0.97). The results also remained similar across messenger ribonucleic acid, viral-vector, and inactivated COVID-19 vaccines. Sensitivity analysis identified two individual studies that contributed to heterogeneity, while the effect size was not materially altered. No obvious publication bias was detected among included studies. Our finding suggested that COVID-19 vaccination had no detrimental impact on semen quality, which could be potentially helpful to reduce male vaccine hesitancy and increase vaccination coverage.