COVID-19 patients with acute pulmonary embolism have a higher mortality risk: systematic review and meta-analysis based on Italian cohorts.

BACKGROUND: Acute pulmonary embolism has been recognized as a frequent complication of COVID-19 infection influencing the clinical course and outcomes of these patients. OBJECTIVES: We performed a systematic review and meta-analysis to evaluate the mortality risk in COVID-19 Italian patients complicated by acute pulmonary embolism in the short-term period. METHODS: The study was performed in accordance with the Preferred Report Items for Systematic Reviews and Meta-analyses guidelines. PubMed-MEDLINE and Scopus databases were systematically searched for articles, published in the English language and enrolling Italian cohorts with confirmed COVID-19 infection from inception through 20 October 2021. Mortality risk data were pooled using the Mantel-Haenszel random effects models with odds ratio as the effect measure with 95% confidence interval. Heterogeneity among studies was assessed using Higgins and Thomson I2 statistic. RESULTS: Eight investigations enrolling 1.681 patients (mean age 64.9 years, 1125 males) met the inclusion criteria and were considered for the analysis. A random-effect model showed that acute pulmonary embolism was present in 19.0% of Italian patients with COVID-19 infection. Moreover, these patients were at higher mortality risk compared with those without (odds ratio: 1.76, 95% confidence interval: 1.26-2.47, P  = 0.001, I2  = 0%). Sensitivity analysis confirmed yielded results. CONCLUSION: In Italian patients with COVID-19 infection, acute pulmonary embolism was present in about one out of five and significantly associated with a higher mortality risk in the short-term period. The identification of acute pulmonary embolism in these patients remains critical to promptly identify vulnerable populations who would require prioritization in treatment and prevention and close monitoring.

[Incidence of acute pulmonary embolism in hospitalized COVID-19 Italian patients. A pooled meta-analysis]. / Tasso di embolia polmonare acuta nei pazienti ospedalizzati per COVID-19 in Italia. Metanalisi aggregata.

BACKGROUND: Acute pulmonary embolism (PE) represents a frequent and prognostically relevant complication of COVID-19. METHODS: We performed a systematic review and meta-analysis, according to the PRISMA guidelines to determine the in-hospital incidence of acute PE, based on Italian studies published on this issue. We searched PubMed and Scopus to locate all articles published between February 2020 to October 15, 2021, reporting the incidence of acute PE in Italian COVID-19 patients. The pooled in-hospital incidence of acute PE was calculated using a random-effect model and presented with relative 95% confidence interval (CI). RESULTS: We analysed data from 3287 Italian COVID-19 patients (mean age 65.7 years) included in 20 studies. The pooled in-hospital incidence of acute PE was 20% (95% CI 13.4-28.7%; I2 = 95.1%); the incidence was lower among patients hospitalized in intensive care unit (ICU) (32.3%; 95% CI 20.2-44.0%; I2 = 77.2%) compared to those admitted in general wards (47.6%; 95% CI 18.7-78.2%; I2 = 94.4%). Meta-regression showed a significant direct correlation of acute PE incidence using age, male gender and previous coronary artery disease as moderating variables. Conversely, an inverse correlation was observed in relation to the use of anticoagulation at therapeutic dose. Prophylactic and therapeutic anticoagulation was administered in 80.2% of patients (95% CI 72.5-86.2%; I2 = 91.0%); the former regimen was more frequently used compared to the latter (63.5% vs 14.3%; p<0.001). Computed tomography angiography (CTPA) was used only in 10.7% of infected patients across 7 studies. CONCLUSIONS: One in five COVID-19 patients experienced acute PE as complication of the infection during hospitalization. The in-hospital incidence of acute PE was lower in ICU compared to general wards. CTPA was scantly used. Early prophylactic anticoagulation was associated with a lower incidence of acute PE.

Prevalence of Acute Pulmonary Embolism at Autopsy in Patients With COVID-19.

To date, the actual prevalence of acute pulmonary embolism (PE) in patients with SARS-CoV-2 infection remains unknown, as systematic screening for PE is cumbersome. We performed a systematic review and meta-analysis on autoptic data to estimate the prevalence of histopathologic findings of acute PE and its relevance as a cause of death on patients with COVID-19. We searched MEDLINE-PubMed and Scopus to locate all articles published in the English language, up to August 10, 2021, reporting the autoptic prevalence of acute PE and evaluating PE as the underlying cause of death in patients with COVID-19. The pooled prevalence for both outcomes was calculated using a random-effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. We analyzed autoptic data of 749 patients with COVID-19 (mean age 63.4 years) included in 14 studies. In 10 studies, based on 526 subjects (mean age 63.8 years), a random-effect model revealed that autoptic acute PE findings were present in 27.5% of cases (95% CI 15.0 to 45.0%, I2 89.9%). Conversely, in 429 COVID-19 subjects (mean age 64.0 years) enrolled in 9 studies, acute PE was the underlying cause of death in 19.9% of cases (95% CI 11.0 to 33.3%, I2 83.3%). Autoptic findings of acute PE in patients with COVID-19 are present in about 30% of subjects, whereas a venous thromboembolic event represents the underlying cause of death in about 1 of 4 patients.

Viral Load Difference between Symptomatic and Asymptomatic COVID-19 Patients: Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to investigate the possible difference in the SARS-CoV-2 viral load between asymptomatic and symptomatic COVID-19 patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE, Scopus, Web of Science and Google Scholar for all investigations in the English language, reporting data on the threshold cycle (Ct) from real-time RT-PCR assays for the RNA-dependent RNA polymerase (RdRp), envelope (E) and nucleocapsid (N) SARS-CoV-2 genes in asymptomatic and symptomatic COVID-19 patients. Results: Overall, 703 COVID-19 patients (553 symptomatic and 150 asymptomatic) were analyzed. Five investigations reported the mean age of patients, evidencing that asymptomatic patients were younger than symptomatic patients (34.0 vs. 40.3 years, respectively). Pooled data regarding the levels of expression of the RdRp gene revealed no significant difference between symptomatic and asymptomatic subjects. Similarly, no differences were observed comparing the mean Ct values for the E and N genes. Based on real-time RT-PCR data, no differences exist in the viral load between symptomatic and asymptomatic COVID-19 subjects considering Ct values for RdRp, E and N genes' expression. Asymptomatic subjects may represent a reservoir of the infection and significantly contribute to the maintenance of the pandemic.

Prognostic Role of Anemia in COVID-19 Patients: A Meta-Analysis.

INTRODUCTION: The prevalence and prognostic implications of anemia in patients infected by the SARS-CoV-2 remains unclear. We performed a systematic review and meta-analysis to assess the prevalence and mortality risk in COVID-19 patients with anemia. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE and Scopus to locate all the articles published up to 1 September 2021, reporting data on the adjusted OR (aOR) for mortality among COVID-19 patients with anemia. The pooled prevalence of anemia among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (aOR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. RESULTS: Five studies, enrolling 9.623 COVID-19 patients [3.707 males (38.5%)], met the inclusion criteria and were included in the final analysis. The pooled prevalence of anemia was 25.6% of cases (95% CI: 8.3-56.5%), with high heterogeneity (I2 = 98.9%). Meta-regression showed that the anemia prevalence was influenced by a direct correlation with age (p = 0.007) and chronic kidney disease (p = 0.004) as moderating variables. Conversely, an inverse relationship was observed with male gender (p < 0.0001). Anemia was significantly associated with higher risk of short-term mortality (aOR: 1.69, 95% CI: 1.28-2.24, p < 0.001), with low heterogeneity (I2 = 0%). CONCLUSIONS: Anemia represents a major comorbidity in about 25% of COVID-19 patients and it is associated with about 70% higher risk of short-term mortality.

Prognostic Role of Metabolic Syndrome in COVID-19 Patients: A Systematic Review Meta-Analysis.

BACKGROUND: The prevalence and prognostic implications of metabolic syndrome (MetS) in patients infected by the SARS-CoV-2 remain unclear. We performed a systematic review and meta-analysis of prevalence and mortality risk in COVID-19 patients with MetS. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE and Scopus to locate every article published up to 1 September 2021, reporting data on MetS among COVID-19 patients. The pooled prevalence of MetS was calculated using a random effects model and presented using the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. RESULTS: Six studies, enrolling 209.569 COVID-19 patients [mean age 57.2 years, 114.188 males (54.4%)] met the inclusion criteria and were included in the final analysis. The pooled prevalence of dyslipidaemia was 20.5% of cases (95% CI: 6.7-47.8%, p = 0.03), with high heterogeneity (I2 = 98.9%). Pre-existing MetS was significantly associated with higher risk of short-term mortality (OR: 2.30, 95% CI: 1.52-3.45, p < 0.001), with high heterogeneity (I2 = 89.4%). Meta-regression showed a direct correlation with male gender (p = 0.03), hypertension (p < 0.001), DM (p = 0.01) and hyperlipidaemia (p = 0.04), but no effect when considering age (p = 0.75) and chronic pulmonary disease (p = 0.86) as moderators. CONCLUSIONS: MetS represents a major comorbidity in about 20% of COVID-19 patients and it is associated with a 230% increased risk of short-term mortality.

Relationship between echocardiographic tricuspid annular plane systolic excursion and mortality in COVID-19 patients: A Meta-analysis.

BACKGROUND: The evaluation of the tricuspid annular plane systolic excursion (TAPSE) is recommended to assess the right ventricular (RV) systolic function. We performed an updated meta-analysis of the association between TAPSE and short-term mortality in COVID-19 patients. METHODS: MEDLINE and Scopus databases were searched to locate all the articles published up to May 1, 2021, reporting data on TAPSE among COVID-19 survivors and non-survivors. The difference of TAPSE between the two groups was expressed as mean difference (MD) with the corresponding 95% confidence interval (CI) using the Mantel-Haenszel random effects model. Both Q value and I2 statistics were used to assess heterogeneity across studies. Sensitivity analysis, meta-regression, and evaluation of bias were performed. RESULTS: Twelve studies, enrolling 1272 COVID-19 patients (778 males, mean age 69.3 years), met the inclusion criteria and were included in the final analysis. Non-survivors had a lower TAPSE compared to survivors (MD =  -3.089 mm, 95% CI =  -4.087 to -2.091, p < 0.0001, I2  = 79.0%). Both the visual inspection of the funnel plot and the Egger's tests (t = 1.195, p = 0.259) revealed no evidence of publication bias. Sensitivity analysis confirmed yielded results. Meta-regression analysis evidenced that the difference in TAPSE between the two groups was only influenced by pre-existing chronic obstructive pulmonary disease (COPD, p = 0.02). CONCLUSION: COVID-19 non-survivors have a lower TAPSE when compared to survivors, especially in COPD subjects. Current data suggest that the TAPSE assessment may provide useful information regarding the short-term prognosis of COVID-19 patients during the infection.

Rethinking of osteoporosis through a sex- and gender-informed approach in the COVID-19 era.

Standards and models of reference for osteoporosis (OP) have been developed for female individuals as they are more likely to be affected by the disease. Nonetheless, OP is also responsible for one-third of hip fractures in male individuals suggesting that a sex-blinded approach to OP may lead to miss opportunities for equity in bone health. OP-related fractures, especially hip fractures, are a matter of immediate concern as they are associated with limited mobility, chronic disability, loss of independence, and reduced quality of life in both sexes. When it comes to sociocultural gender, the effect of gender domains (i.e., identity, roles, relations, and institutionalized gender) on development and management of OP is largely overlooked despite risk factors or protective conditions are gendered. Clinical trials testing the efficacy and safety of anti-OP drugs as well as non-pharmacological interventions have been conducted mainly in female participants, limiting the generalizability of the findings. The present narrative review deals with the sex and gender-based challenges and drawbacks in OP knowledge and translation to clinical practice, also considering the impact of coronavirus disease 2019 pandemic.

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study.

The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.

Is venous thromboembolism a predictable marker in older patients with COVID-19 infection? A single-center observational study.

Venous thromboembolism (VTE) represents an important clinical complication of patients with SARS-CoV-2 infection, and high plasma D-dimer levels could suggest a higher risk of hypercoagulability. We aimed to analyse if laboratory exams, risk assessment scores, comorbidity scores were useful in predicting the VTE in SARS-CoV-2 patients admitted in internal medicine (IM). We evaluated 49 older adults with suspected VTE analysing history and blood chemistry, besides we calculated the Padua Prediction Score, the modified early warning scoring (MEWS) and the modified Elixhauser index (mEI). All patients underwent venous color-doppler ultrasounds of the lower limbs. Out of the 49 patients enrolled (mean age 79.3±14 years), 10 (20.4%) had deep vein thrombosis (DVT), and they were more frequently female (80% vs 20%, p = 0.04). We could not find any association with the Padua Prediction Score, the MEWS, and the mEI. D-dimer plasma levels were also not associated with DVT. In elderly people hospitalized with SARS-CoV-2 infection hospitalized in IM, our data, although limited by the sample size, suggest that prediction and diagnosis of VTE is difficult, due to lack of precise biomarkers and scores.

Heart failure as a complication of COVID-19 infection: systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The prevalence and prognostic implications of heart failure (HF), as a complication of COVID-19 infection remains unclear. We performed a systematic review and metanalysis aimed to evaluate the pooled incidence of acute HF as a cardiac complication of COVID-19 disease and to estimate the related mortality risk in these patients. METHODS: Data were obtained searching MEDLINE, Scopus and Web of Science for all investigations published any time to 26 December 2020. If statistical heterogeneity was 50%, the results were derived from the fixed-effects model otherwise the random-effects model. RESULTS: Overall, 1064 patients [mean age 66 years, 618 males] were included in the final analysis reviewing six investigations. The cumulative in-hospital rate of COVID-19 patients complicated by acute HF ranged between 6.9 and 63.4% among the studies reviewed. A random effect model revealed a pooled incidence of COVID-19 patients complicated by acute HF in 20.2% of cases (95% CI: 11.1-33.9%, p < 0.0001 I2 = 94.4%). A second pooled analysis, based on a random-effect model, confirmed a significant increased risk of death in COVID-19 patients complicated by acute HF during the infection (OR 9.36, 95% CI 4.76-18.4, p < 0.0001, I2 = 56.6%). Meta-regression analysis, using age as moderator variable, failed in founding a statistically significant relationship with the incidence of acute HF onset as a complication of COVID-19 disease (p = 0.062) or the mortality risk among the same subjects (p = 0.053). CONCLUSIONS: Acute HF represents a frequent complication of COVID-19 infection associated with a higher risk of mortality in the short-term period.