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BACKGROUND: Co-infection with other pathogens can alter the severity and clinical outcomes of viral infections. However, the information regarding viral co-infections in pediatric coronavirus disease 2019 (COVID-19) cases is still limited. METHODS: This is a nationwide, retrospective cohort study using the data from the COVID-19 Registry Japan. The pediatric (<18 years), laboratory confirmed, hospitalized COVID-19 patients in the Omicron variant of concern predominant period (January 2022 to January 2024) were included. Co-infection was investigated by multiplex PCR. We compared clinical characteristics, symptoms, severity, and outcomes between children with and without co-infection. RESULTS: Among 245 hospitalized pediatric COVID-19 patients, 78 (31.8 %) had co-infections. The patient backgrounds of the "co-infection" and "SARS-CoV-2 alone" groups were similar, although age distribution was different, with a lower number of patients over 12 years in the co-infection group (n = 2, 2.6 % vs. n = 29, 17.4 %; P < 0.001). Among the patients with co-infection, the most common pathogen was enterovirus/rhinovirus (51.3 %), followed by parainfluenza virus (23.1 %) and adenovirus (12.8 %). Patients with co-infection more commonly had respiratory symptoms, including SpO2 < 96 %, shortness of breath, runny nose, and wheezing. Requirement of non-invasive oxygen support was higher in the co-infection group (n = 27, 34.6 % vs. n = 28, 16.8 %, P = 0.006). By multivariable logistic regression analysis, co-infection and presence of any comorbidity were identified as significant risk factors for necessity of oxygen therapy (odds ratio [95 % confidence interval] 2.44 [1.29-4.63] and 3.99 [2.07-7.82], respectively). CONCLUSIONS: Viral co-infection may increase the risk of respiratory distress in pediatric COVID-19 patients.

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Rationale and objectives: To analyze morphological changes in patients with COVID-19-associated pneumonia over time, a nonrigid registration technique is required that reduces differences in respiratory phase and imaging position and does not excessively deform the lesion region. A nonrigid registration method using deep learning was applied for lung field alignment, and its practicality was verified through quantitative evaluation, such as image similarity of whole lung region and image similarity of lesion region, as well as visual evaluation by a physician. Materials and methods: First, the lung field positions and sizes of the first and second CT images were roughly matched using a classical registration method based on iterative calculations as a preprocessing step. Then, voxel-by-voxel transformation was performed using VoxelMorph, a nonrigid deep learning registration method. As an objective evaluation, the similarity of the images was calculated. To evaluate the invariance of image features in the lesion site, primary statistics and 3D shape features were calculated and statistically analyzed. Furthermore, as a subjective evaluation, the similarity of images and whether nonrigid transformation caused unnatural changes in the shape and size of the lesion region were visually evaluated by a pulmonologist. Results: The proposed method was applied to 509 patient data points with high image similarity. The variances in histogram characteristics before and after image deformation were confirmed. Visual evaluation confirmed the agreement between the shape and internal structure of the lung field and the natural deformation of the lesion region. Conclusion: The developed nonrigid registration method was shown to be effective for quantitative time series analysis of the lungs.

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A 56-year-old woman who received CD19 chimeric antigen receptor-T cell therapy for refractory diffuse large B-cell lymphoma developed severe coronavirus disease 2019 (COVID-19) and was treated with nirmatrelvir/ritonavir in April 2022. However, she experienced persistent fatigue and cough and fever in June. Computed tomography revealed bilateral ground-glass opacities (GGO), and the patient was treated with corticosteroids for organizing pneumonia after COVID-19. Partial improvement was observed, but new GGO appeared despite corticosteroid therapy. Genome analysis of severe acute respiratory syndrome coronavirus 2 detected Omicron variant BA.1.1.2, which was prevalent at the time of initial infection. The patient was diagnosed with protracted COVID-19 and was treated with remdesivir, molnupiravir, nirmatrelvir/ritonavir, and tixagevimab/cilgavimab. These treatments appeared to contribute to the improvement of protracted COVID-19.

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Epigenetic changes have long-lasting impacts, which influence the epigenome and are maintained during cell division. Thus, human genome changes have required a very long timescale to become a major contributor to the current obesity pandemic. Whereas bidirectional effects of coronavirus disease 2019 (COVID-19) and obesity pandemics have given the opportunity to explore, how the viral microribonucleic acids (miRNAs) use the human's transcriptional machinery that regulate gene expression at a posttranscriptional level. Obesity and its related comorbidity, type 2 diabetes (T2D), and new-onset diabetes due to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are additional risk factors, which increase the severity of COVID-19 and its related mortality. The higher mortality rate of these patients is dependent on severe cytokine storm, which is the sum of the additional cytokine production by concomitant comorbidities and own cytokine synthesis of COVID-19. Patients with obesity facilitate the SARS-CoV-2 entry to host cell via increasing the host's cell receptor expression and modifying the host cell proteases. After entering the host cells, the SARS-CoV-2 genome directly functions as a messenger ribonucleic acid (mRNA) and encodes a set of nonstructural proteins via processing by the own proteases, main protease (Mpro), and papain-like protease (PLpro) to initiate viral genome replication and transcription. Following viral invasion, SARS-CoV-2 infection reduces insulin secretion via either inducing ß-cell apoptosis or reducing intensity of angiotensin-converting enzyme 2 (ACE2) receptors and leads to new-onset diabetes. Since both T2D and severity of COVID-19 are associated with the increased serum levels of pro-inflammatory cytokines, high glucose levels in T2D aggravate SARS-CoV-2 infection. Elevated neopterin (NPT) value due to persistent interferon gamma (IFN-γ)-mediated monocyte-macrophage activation is an indicator of hyperactivated pro-inflammatory phenotype M1 macrophages. Thus, NPT could be a reliable biomarker for the simultaneously occurring COVID-19-, obesity- and T2D-induced cytokine storm. While host miRNAs attack viral RNAs, viral miRNAs target host transcripts. Eventually, the expression rate and type of miRNAs also are different in COVID-19 patients with different viral loads. It is concluded that specific miRNA signatures in macrophage activation phase may provide an opportunity to become aware of the severity of COVID-19 in patients with obesity and obesity-related T2D.

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PURPOSE: A normal pressure extubation technique (no lung inflation before extubation), proposed by the Japanese Society of Anesthesiologists to prevent droplet infection during the coronavirus disease 2019 (COVID-19) pandemic, could theoretically increase postoperative pneumonia incidence compared with a positive pressure extubation technique (lung inflation before extubation). However, the normal pressure extubation technique has not been adequately evaluated. This study compared postoperative pneumonia incidence between positive and normal pressure extubation techniques using a dataset from the University of Tsukuba Hospital. METHODS: In our hospital, the extubation methods changed from positive to normal pressure extubation techniques on March 3, 2020 due to the COVID-19 pandemic. Thus, we compared the risk of postoperative pneumonia between the positive (April 1, 2017 to December 31, 2019) and normal pressure extubation techniques (March 3, 2020 to March 31, 2022) using propensity score analyses. Postoperative pneumonia was defined using the International Classification of Diseases, 10th Edition (ICD-10) codes (J13-J18), and we reviewed the medical records of patients flagged with these ICD-10 codes (preoperative pneumonia and ICD-10 codes for prophylactic antibiotic prescriptions for pneumonia). RESULTS: We identified 20,011 surgeries, including 11,920 in the positive pressure extubation group (mean age 48.2 years, standard deviation [SD] 25.2 years) and 8,091 in the normal pressure extubation group (mean age 47.8 years, SD 25.8 years). The postoperative pneumonia incidences were 0.19% (23/11,920) and 0.17% (14/8,091) in the positive and normal pressure extubation groups, respectively. The propensity score analysis using inverse probability weighting revealed no significant difference in postoperative pneumonia incidence between the two groups (adjusted odds ratio 0.98, 95% confidence interval 0.50 to 1.91, P = 0.94). CONCLUSIONS: These results indicated no increased risk of postoperative pneumonia associated with the normal pressure extubation technique compared with the positive pressure extubation technique. CLINICAL TRIAL NUMBER: Clinical trial number: UMIN000048589 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000055364.

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Background: Spontaneous regression (SR) of cancer remains a rare phenomenon, particularly in hepatocellular carcinoma (HCC), where limited literature exists. This case report emphasizes the significance of SR in advanced HCC, shedding light on the proposed mechanisms and addressing the scarcity of documented cases in current medical literature. Case Description: We present the case of a 67-year-old female with a history of localized HCC who underwent right hepatectomy. Surveillance imaging 4 months later revealed tumor recurrence with tumor thrombus in the main portal vein. Radioembolization was deemed unsuitable, leading to the recommendation of systemic therapy with atezolizumab and bevacizumab. Prior to receiving any treatment, the patient tested positive for coronavirus disease 2019 (COVID-19), having previously received both the messenger RNA (mRNA)-1273 vaccine series and a booster. Surprisingly, subsequent imaging 10 months after initial diagnosis showed SR of the previously identified lesions, suggesting a potential link between viral exposure, vaccination, and the observed regression. The patient eventually received treatment with atezolizumab and bevacizumab and has sustained disease control to date, 12 months after initiating treatment. Conclusions: This unique case highlights SR of advanced HCC following COVID-19 infection, raising intriguing questions about the interplay between viral infections, vaccinations, and cancer outcomes. The patient's response in the absence of systemic therapy further underscores the complexity of HCC management and prompts further investigation into the potential immunomodulatory effects of viral infections and vaccinations on cancer regression. Understanding these interactions could have implications for tailoring treatment approaches and improving outcomes in patients with advanced HCC.

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OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is divided into granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. It is one of the most severe and potentially fatal autoimmune inflammatory conditions. The etiology and pathology of AAV are complex and poorly understood. Since the onset of the Coronavirus Disease 2019 (COVID-19) pandemic, numerous reports have documented GPA cases following COVID-19, suggesting a potential link between COVID-19 and the development of GPA. This case report discusses a 16-year-old East Asian boy who developed GPA with diffuse alveolar hemorrhage after contracting COVID-19. Additionally, a literature review was conducted to gain a deeper understanding of this disorder. METHODS: The study involved a retrospective analysis of the data of a case of GPA post-COVID-19 infection, aiming to summarize the clinical characteristics of GPA post-COVID-19 infection through a search of databases (PubMed, Wanfang Data, and CNKI), supplemented by standard searches in Google Scholar, Cochrane, Scopus, and LitCovid, and to conduct a comprehensive analysis of the literature. RESULTS: A total of 12 cases were identified and, when combined with the present case, yielded 13 cases of GPA post-COVID-19 infection, comprising 5 males and 8 females with an average age of (40.6 ± 19.5) years. The interval between COVID-19 infection and the diagnosis of GPA varied from 1 day to 3 months across all cases. Mortality was reported at 7.7% (1/13). The most common clinical manifestations included cough (69.2%) and dyspnea (46.1%). Computed tomography scans revealed ground-glass opacities and multifocal pulmonary nodules. In all cases, positive findings for c-ANCA and protease 3-antibody were observed. Renal involvement was observed in more than half of the patients.

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The coronavirus disease 2019 (COVID-19) pandemic that was spread worldwide since 2019 and showed a highly contagious character affecting the lifestyle of people worldwide causing symptoms that are not limited to the respiratory system only but had multi-systemic effects that may progress to severe complications that roughly affect people's health. A newly recognized SARS-CoV-2-associated syndrome called pediatric multisystem inflammatory syndrome has been described worldwide. Initially, it was reported as hyper-inflammatory shock and "Kawasaki-like" symptoms with fever and conjunctivitis, a similar syndrome is also reported in neonates and called Multisystem Inflammatory Syndrome of neonates (MIS-N). In this paper, we presented a case of a newborn baby girl born by caesarian section affected by multisystem inflammatory syndrome of neonates presenting with respiratory distress on her third day of life, then she developed bilateral pneumothorax and pneumomediastinum respectively that required intubation, which highlights that the recognition of pneumothorax and pneumomediastinum as potential presentations of immunoglobulin G (IgG) positive MIS-N in newborns remains crucial.

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Coronavirus disease 2019 (COVID-19) often leads to a spectrum of pulmonary complications, including interstitial lung disease (ILD) with the potential for fibrotic sequelae. Assessing the presence of ongoing active inflammation versus established residual fibrosis as a result of lung parenchymal injury and repair in these patients is a clinical challenge. Better understanding of the disease process is crucial for guiding appropriate therapeutic strategies. We aim to investigate the use of positron emission tomography / computer tomography (PET/CT) scans and their role in diagnosing interstitial pneumonitis (IP) post COVID infections.

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Background: Lung cancer is the most common cause of cancer death in the UK resulting in 21% of all cancer deaths. In 2016, local lung cancer surgery services required improvement due to under-representation in cancer resections and resource scarcity during the pandemic, which affected critical care bed availability and extended postoperative stays. The aim of this service improvement was to increase the number of lung cancer resection; develop minimally invasive techniques and reduce the use of Critical Care Unit beds by 35% (a subsequent goal). Methods: A five-year plan, guided by Kotter's 8-step change model, was initiated to address these issues. This model promotes sustainable change by setting clear goals, effective communication, and stakeholder involvement. Initial changes included hiring a thoracic surgeon experienced in uniportal video assisted thoracoscopy and enhanced recovery protocols. The team grew to three thoracic surgeons by 2020. The service increased operating theatre days and adopted new postoperative practices to reduce complications and hospital stays. Lung Cancer Multidisciplinary Team Meetings were consistently covered by thoracic surgeons, ensuring comprehensive care. Data on surgical activity were collected from departmental databases and national audits, with internal audits conducted regularly. Statistical significance was tested using chi-square tests with P values <0.05. Results: The number of surgical procedures more than doubled, with primary lung cancer resections increasing nearly three-fold from 12.8% to 29.8% over six years. Postoperative complications and mortality rates remained low. Critical care bed usage dropped significantly during the pandemic, with new protocols enabling safe recovery in general surgical areas. Conclusions: The successful expansion of thoracic surgical services was attributed to the dedicated minimally invasive surgeons, enhanced recovery measures, and skilled staff. The change model facilitated efficient and dynamic progress. With the introduction of lung cancer screening programs, the demand for surgical services is expected to rise. The effective change model will be re-applied to meet this demand. The organizational change model, focused on patients and staff, achieved sustained quality improvement in lung cancer care despite challenging conditions like the coronavirus disease 2019 pandemic.

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Background: The outbreak of the novel coronavirus 19 has led to unprecedented clinical challenges globally. Various therapeutic and pharmacologic interventions have been proposed, yet evidence of their long-term efficacy remains limited. Corticosteroids (CS) have shown efficacy in the sub-acute phase of the pandemic. This study aims to evaluate the long-term effects on pulmonary function tests (PFTs) in patients treated with CS during acute coronavirus disease 2019 (COVID-19) infection. Methods: A retrospective study was conducted from February 2020 to March 2021. Clinical and demographic data were extracted from electronic medical records of patients attending the post-COVID outpatient clinic at the Pulmonary Institute of Soroka University Medical Center. A multivariate linear mixed effects model was employed to obtain adjusted estimates for the impact over time. Results: The study included 405 patients, of whom 155 (38.3%) received CS treatment. Approximately 60% completed two or more follow-up visits. PFTs [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC)] returned to baseline more rapidly (0.9% and 0.85% per month, respectively) in patients treated with CS. This accelerated recovery was observed across all patients, including those with a body mass index (BMI) above 30 kg/m2 and those with known chronic lung disease. Conclusions: Systemic CS treatment during acute COVID-19 infection was associated with a faster recovery of PFTs during long-term follow-up, even among subgroups at higher risk of long-term pulmonary damage.

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The global COVID-19 pandemic presented a period of considerable stress for healthcare professionals on a global scale. The strain on healthcare facilities nationwide has resulted in profound implications for the well-being of numerous healthcare practitioners. A heightened demand for extended working hours emerged, potentially amplifying the workload for these professionals. This study aims to scrutinize the workload levels experienced by healthcare professionals specializing in family medicine at a tertiary medical center. Our findings reveal a persistent escalation in workload over the course of the study. Notably, the overall mean workload index score exhibited a substantial increase from phase one to phase two (48.07 compared to 66.36). Recognizing the impact of workload variations according to professional roles is crucial for devising effective solutions. Consequently, comprehending the nuances of workload distribution among healthcare professionals is imperative for the successful implementation of targeted interventions.

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Background The mortality and morbidity of thrombotic events in patients with coronavirus disease 2019 (COVID-19) are increasing worldwide. The clinical impact of prophylactic anticoagulation regimens among these patients in Iran remains unclear. This study aimed to evaluate the use of prophylactic anticoagulants and outcomes among COVID-19 patients admitted to a tertiary referral hospital. Methodology Patients diagnosed with COVID-19 and hospitalized between March 20 and June 20, 2020, were included in this longitudinal study after obtaining informed consent. Demographic and clinical data were collected from the hospital information system and medical records. Outcomes during this period were also evaluated. The data were entered into the preparation checklist and analyzed using SPSS version 24 software (IBM Corp., Armonk, NY, USA), employing chi-square, Fisher's exact, and Mann-Whitney U tests. Results Of the 831 enrolled patients, 51.9% were female, and 10.6% needed to be admitted to the intensive care unit (ICU). The mean age of the patients was 57.16 ± 17.32 years, and the mortality rate was estimated to be 9.4%. Mortality rates were significantly higher at older ages, in men, patients with ICU admission, severe pulmonary involvement, malignancy, airway obstruction, ischemic heart disease, and previous cerebrovascular accidents. ICU admission and mortality were statistically significantly higher in those who received concurrent prophylactic anticoagulants and aspirin than in other individuals. Conclusions Our study demonstrated that administering prophylactic aspirin with or without anticoagulant agents in COVID-19 patients did not reduce mortality rates or ICU transfers. However, it is worth noting that anticoagulant prescription was associated with a decrease in ICU admissions, which could potentially alleviate the significantly higher mortality rates observed among ICU patients in this study. Further research is needed to explore the potential benefits of anticoagulants in COVID-19 treatment.

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BACKGROUND: The correlation between dyslipidemia and the severity of coronavirus disease 2019 has been widely categorized. Dyslipidemia is one of the most dominant disorders among these patients. Systemic inflammation accompanied by cytokine storm hemostasis modifications and severe vasculitis have all been reported to occur among COVID-19 patients, and these may contribute to some severe complications. OBJECTIVE: The aim of this study is to assess the possible relationship between dyslipidemia and the severity of coronavirus disease 2019. METHODS: This work encompassed 200 patients with coronavirus disease 2019 (100 dyslipidemic and 100 normolipidemic) who were hospitalized at Baghdad Teaching Hospital/ Medical City-Baghdad, Iraq, from October 2021 to October 2022; their ages ranged between 40 and 55. Eligible individuals had a positive nasal swab polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 infection. Every participant's anthropometric and clinical features were measured. The study includes the measurements of glycemic, lipid profile, renal function test, D-dimer, C-reactive protein, serum ferritin, and interleukin-6 in dyslipidemic and normolipidemic groups. RESULTS: Considerable increase (p= 0.001) in glycemic and lipid levels in the dyslipidemic group compared to normolipidemic. Moreover, dyslipidemic patients have higher lipid indices (ratios) than the normolipidemic group. Significant increases (p= 0.001) in serum urea and creatinine levels were found among the dyslipidemic group compared to normolipidemic. There was a non-considerable decrease (p= 0.062) in serum total protein in the dyslipidemic group concerning the normolipidemic. In contrast, a considerable decrease (p= 0.045) in serum albumin was detected in the dyslipidemic group compared to normolipidemic. D-dimer, serum C-reactive protein, ferritin, and interleukin-6 were significantly increased (p= 0.001) in the dyslipidemic group compared to normolipidemic. CONCLUSION: Dyslipidemia potentially raises the severity of coronavirus disease 2019. There was a significant disturbance in renal function tests among coronavirus disease 2019 patients. The study found a significant and statistical difference in kidney functions between dyslipidemic and normolipidemic groups. The patients, especially the dyslipidemic ones, have experienced protein abnormalities and a significant inflammation rate reflected by higher C-reactive protein and interleukin-6, which is due to the severity of coronavirus disease 2019. It is possible to conduct more research with a larger sample size. The majority of people who have dyslipidemia need to be enlightened.

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BACKGROUND: Many studies have revealed a link between non-alcoholic fatty liver disease (NAFLD) and coronavirus disease 2019 (COVID-19), making understanding the relationship between these two conditions an absolute requirement. AIM: To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD. METHODS: This systematic review was conducted in accordance with the guidelines provided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population, intervention, comparison, and outcome framework. The search strategy was run on three separate databases, PubMed/MEDLINE, Scopus, and Cochrane Central, which were systematically searched from inception until March 2024 to select all relevant studies. In addition, ClinicalTrials.gov, Medrxiv.org, and Google Scholar were searched to identify grey literature. RESULTS: After retrieval of 11 studies, a total of 39282 patients data were pooled. Mortality was found in 11.5% and 9.4% of people in NAFLD and non-NAFLD groups. In all, 23.2% of NAFLD patients and 22% of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit, with days of stay varying. Ventilatory support ranged from 5% to 40.5% in the NAFLD cohort and from 3.1% to 20% in the non-NAFLD cohort. The incidence of acute liver injury showed significance. Clinical improvement on days 7 and 14 between the two classifications was significant. Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively, with 73.3% and 76.3% of patients being discharged. Readmission rates varied. CONCLUSION: Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19. Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.

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AIM: The number of severe cases of coronavirus disease 2019 (COVID-19) has been decreasing since the emergence of the Omicron variant at the end of 2021. COVID-19 has become a common infectious disease in Japan and was downgraded to a category five infectious disease on May 8, 2023. This study aimed to compare the impact of diabetes mellitus on in-hospital mortality in COVID-19 patients since COVID-19 became a common infectious disease. PATIENTS AND METHODS: We conducted a retrospective observational study using data from an advanced critical care center in Osaka, Japan. The study included 1,381 patients of COVID-19 admitted to the center between March 1, 2020, and May 7, 2023, before COVID-19 became a category five infectious disease in Japan. Individuals younger than 18 years and pregnant women were excluded. We divided the patients into two groups: pre- and post-Omicron epidemic groups. The primary endpoint of the study was the in-hospital mortality, and the prognostic impact of diabetes mellitus was compared between the groups. RESULTS: The Kaplan-Meier curve showed a significantly lower rate of in-hospital mortality in the post-Omicron epidemic group than in the pre-Omicron epidemic group. The hazard ratio (HR) was 1.83 (95% CI, 1.36-2.50; p < 0.0001). Patients with diabetes mellitus had higher in-hospital mortality in both the pre- and post-Omicron epidemic groups; their HRs were 1.39 (95% CI, 1.21-1.59; p < 0.0001) and 1.45 (95% CI, 1.15-1.83; p = 0.0012), respectively. Diabetes mellitus had no significant interaction effect on the association between the post-Omicron epidemic and in-hospital mortality (p for interaction = 0.2154). CONCLUSION: Diabetes mellitus may continue contributing to COVID-19 in-hospital mortality in the future, as the Omicron sub-strain may still be prevalent.

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BACKGROUND: The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy. METHODS: Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation. RESULTS: We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936). CONCLUSION: COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019 (COVID-19). Patients with COVID-19 manifested symptoms mainly related to the respiratory system, but also the musculoskeletal system can be involved. COVID-19 has been described as a possible cause of knee osteonecrosis (ON). A systematic review was performed to investigate the hypothetical correlation between COVID-19 and knee ON. Methods: Inclusion criteria were all articles reporting cases of knee ON after a diagnosis of SARS-CoV-2 infection. Considering that COVID-19 is an emerging disease, all levels of evidence studies were included. Results: Finally, two case series and three case reports were included. We extracted data regarding demographic and clinical characteristics, details of magnetic resonance imaging (MRI), use of corticosteroids (CCS), temporal correlation between ON and COVID-19, treatment of the lesion and its outcomes. A total of seven cases of post-COVID knee ON have been described. Knee pain arose on average 11 weeks after the diagnosis of COVID-19. All patients had knee MRI showing ON. CCS were used to treat COVID-19-related symptoms in four cases. Conservative treatment was successful in five patients. Conclusions: The correlation between COVID-19 and ON remains unclear. Probably post-COVID-19 ON has a multifactorial origin in which factors related to the patient, consequences of COVID-19 and CCS therapy add up to cause a reduction of blood supply and bone vitality until ON is triggered. A greater number of patients is needed to clarify the role of COVID-19 in the etiopathogenesis of knee ON.