ABSTRACT
Background Accumulating evidence suggests a beneficial effect of tumor necrosis factor-alpha (TNF-α) inhibitors on the outcomes of COVID-19 disease, which, however, is not validated by all studies. We aimed to perform a systematic review and meta-analysis of existing reports to investigate the impact of anti-TNF treatments on the clinical outcomes of COVID-19 patients. Methods A systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID-19 outcomes for patients receiving anti-TNF therapy by September-2021 were included. Pooled effect measures were calculated using a random-effects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta‐analysis were described qualitatively. Results In total, 84 studies were included in the systematic review, and 31 were included in the meta-analysis. Patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases had a lower probability of hospitalisation (25 studies, pooled OR=0.34, 95%CI:0.30–0.38, I2=0) and severe disease defined as intensive care unit admission or death (eight studies, pooled OR=0.38, 95%CI: 0.27–0.55, I2=0). After adjustment for validated predictors of adverse disease outcomes, patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases preserved a lower probability of hospitalisation (eight studies, pooled OR=0.53, 95%CI:0.42–0.67, I2=0) and severe disease (two studies, pooled OR=0.63, 95%CI: 0.41–0.96, I2=0). No difference was found for the risk for hospitalisation due to COVID-19 in populations without COVID-19 for patients receiving anti-TNF treatment compared to non-anti-TNF (three studies, 5,994,958 participants, pooled Risk Ratio=0.97, 95%CI: 0.68–1.39, I2=20) adjusted for age, sex and comorbidities. Conclusion TNF-α inhibitors are associated lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.
ABSTRACT
Background: Accumulating evidence suggests a beneficial effect of tumor necrosis factor-alpha (TNF-α) inhibitors on the outcomes of COVID-19 disease, which, however, is not validated by all studies. We aimed to perform a systematic review and meta-analysis of existing reports to investigate the impact of anti-TNF treatments on the clinical outcomes of COVID-19 patients. Methods: A systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID-19 outcomes for patients receiving anti-TNF therapy by September-2021 were included. Pooled effect measures were calculated using a randomeffects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta-analysis were described qualitatively. Results: In total, 84 studies were included in the systematic review, and 31 were included in the meta-analysis. Patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases had a lower probability of hospitalisation (25 studies, pooled OR=0.34, 95%CI:0.30-0.38, I2=0) and severe disease defined as intensive care unit admission or death (eight studies, pooled OR=0.38, 95%CI: 0.27-0.55, I2=0). After adjustment for validated predictors of adverse disease outcomes, patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases preserved a lower probability of hospitalisation (eight studies, pooled OR=0.53, 95%CI:0.42-0.67, I2=0) and severe disease (two studies, pooled OR=0.63, 95%CI: 0.41-0.96, I2=0). No difference was found for the risk for hospitalisation due to COVID-19 in populations without COVID-19 for patients receiving anti-TNF treatment compared to non-anti-TNF (three studies, 5,994,958 participants, pooled Risk Ratio=0.97, 95%CI: 0.68-1.39, I2=20) adjusted for age, sex and comorbidities. Conclusion: TNF-α inhibitors are associated lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.
ABSTRACT
Background: Pulmonary embolism (PE) is reported in around2.6-8.9% of COVID-19 hospitalized adult patients, but it is very rare in children and adolescents with symptomatic infection from SARS-CoV-2. Aims: This is the case of a15-year-old male patient with COVID-19 complicated by deep vein thrombosis (DVT) who developed PE. Methods: The patient presented with fever and a four-day history of pain and swelling of the right lower limb, without any history of injury. It is notable that15 days before admission, he experienced diarrhea, vomiting and low-grade fever for 48 hours. The adolescent boy had short stature and was rather overweighted for his age and gender (body mass index:25.2 kg/m2), while over the last two years he was receiving anastrozole (aromatase inhibitor), for height increase. Results: On admission, due to pain, limited mobility of the right limb and edema of the ipsilateral knee, a triplex ultrasound was performed that revealed DVT extended from the right iliac to the popliteal vein. RT-PCR for SARS-CoV-2 was positive, while the rest of the laboratory results showed a prolongation in prothrombin time (16.3 seconds, normal values:10-14 sec), elevated d-dimers (10 mg/dl, n.v.: < 0.5 mg/dl), high levels of factor VIII (214 IU/dl, n.v: 50-150 IU/dl), low levels of antithrombin (36 IU/ml, n.v.: 80-120 IU/ml) and increased ferritin (346 μg/L, n.v.:10-150 μg/L). Initial management consisted of antibiotic therapy plus anticoagulation with subcutaneous low molecular weight heparin (LMWH) i.e. tinzaparin in therapeutic dose. Soon after admission the patient developed severe hypotension with low diastolic blood pressure, refractive to IV normal saline boluses while his oxygen saturation dropped to 94% few hours later. A CT pulmonary angiogram (CTPA) was performed revealing a big thrombus with longitudinal diameter of3 cm, in the left pulmonary artery, establishing the diagnosis of PE on the ground of DVT. After PE diagnosis, the patient was transferred to the intensive care unit (ICU) for 48 hours, and subsequently at the special SARS-CoV-2 ward for 4 weeks. He completed a ten-day course of intravenous dexamethasone and anticoagulation treatment was switched to oral warfarin, after completion of three weeks of LWMH. Apart from COVID-19 whose hypercoagulable physis is already well-established the patient had additional risk factors predisposing to thromboembolic episodes. More precisely, he was overweight and under aromatase inhibitor therapy (which can be procoagulant by increasing testosterone levels). Moreover, the preexisting symptoms from the gastrointestinal system, could have predisposed him to DVT in view of dehydration and increased viscosity. On top of it, it is noteworthy that the patient had excessive screen time for his tele-education the last three weeks prior to the onset of VTE, meaning there were long periods of immobilization. Additionally, during the course of COVID-19 infection he had low levels of antithrombin, a serious prothrombotic condition attributed to the disease. Summary/Conclusion: This case underlines the fact that pediatric patients with COVID-19, are predisposed to the development of thromboembolic events, especially in the presence of preexisting prothrombotic risk factors. Larger studies in pediatric population with SARS-CoV-2 infection are needed, for the establishment of recommendations regarding risk evaluation, hemostatic monitoring and application of anticoagulation in outpatient, as well as hospitalized patients.
ABSTRACT
BACKGROUND: Healthcare workers (HCWs) have been disproportionately affected by coronavirus disease 2019 (COVID-19), which may be driven, in part, by nosocomial exposure. If HCW exposure is predominantly nosocomial, HCWs in paediatric facilities, where few patients are admitted with COVID-19, may lack antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and be at increased risk during the current resurgence. AIM: To compare the seroprevalence of SARS-CoV-2 amongst HCWs in paediatric facilities in seven European countries and South Africa (N=8). METHODS: All categories of paediatric HCWs were invited to participate in the study, irrespective of previous symptoms. A single blood sample was taken and data about previous symptoms were documented. Serum was shipped to a central laboratory in London where SARS-CoV-2 immunoglobulin G was measured. FINDINGS: In total, 4114 HCWs were recruited between 1st May and mid-July 2020. The range of seroprevalence was 0-16.93%. The highest seroprevalence was found in London (16.93%), followed by Cape Town, South Africa (10.36%). There were no positive HCWs in the Austrian, Estonian and Latvian cohorts; 2/300 [0.66%, 95% confidence interval (CI) 0.18-2.4] HCWs tested positive in Lithuania; 1/124 (0.81%, 95% CI 0.14-4.3) HCWs tested positive in Romania; and 1/76 (1.3%, 95% CI 0.23-7.0) HCWs tested positive in Greece. CONCLUSION: Overall seroprevalence amongst paediatric HCWs is similar to their national populations and linked to the national COVID-19 burden. Staff working in paediatric facilities in low-burden countries have very low seroprevalence rates and thus are likely to be susceptible to COVID-19. Their susceptibility to infection may affect their ability to provide care in the face of increasing cases of COVID-19, and this highlights the need for appropriate preventative strategies in paediatric healthcare settings.