UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

The coronavirus disease 2019 (COVID-19) has caused immense devastation globally with many outcomes that are now extending to its long-term sequel called long COVID. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects not only lungs, but also the brain and heart in association with endothelial cell dysfunction, coagulation abnormalities, and thrombosis leading to cardio-cerebrovascular health issues. Fatigue, cognitive decline, and brain fog are common neurological symptoms in persisting long COVID. Neurodegenerative processes and SARS-CoV-2 infection manifest overlapping molecular mechanisms, such as cytokine dysregulation, inflammation, protein aggregation, mitochondrial dysfunction, and oxidative stress. Identifying the key molecules in these processes is of importance for prevention and treatment of this disease. In particular, Dipeptidyl peptidase IV (DPPIV), a multifunctional peptidase has recently drawn attention as a potential co-receptor for SARS-CoV-2 infection and cellular entry. DPPIV is a known co-receptor for some other COVID viruses including MERS-Co-V. DPPIV regulates the immune responses, obesity, glucose metabolism, diabetes, and hypertension that are associated with cerebrovascular manifestations including stroke. DPPIV likely worsens persisting COVID-19 by disrupting inflammatory signaling pathways and the neurovascular system. This review highlights the neurological, cellular and molecular processes concerning long COVID, and DPPIV as a potential key factor contributing to cerebrovascular dysfunctions following SARS-CoV-2 infection.

At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation demands rapid development and production timelines of safe and effective vaccines for delivering life-saving medications quickly to patients. Typical biologics production relies on using the lengthy and arduous approach of stable single-cell clones. Here, we used an alternative approach, a stable cell pool that takes only weeks to generate compared to a stable single-cell clone that needs several months to complete. We employed the membrane, envelope, and highly immunogenic spike proteins of SARS-CoV-2 to produce virus-like particles (VLPs) using the HEK293-F cell line as a host system with an economical transfection reagent. The cell pool showed the stability of protein expression for more than one month. We demonstrated that the production of SARS-CoV-2 VLPs using this cell pool was scalable up to a stirred-tank 2 L bioreactor in fed-batch mode. The purified VLPs were properly assembled, and their size was consistent with the authentic virus. Our particles were functional as they specifically entered the cell that naturally expresses ACE-2. Notably, this work reports a practical and cost-effective manufacturing platform for scalable SARS-CoV-2 VLPs production and chromatographic purification.

(1) Background/Objectives: Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) Methods: The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) Results: Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73-0.90; p < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use-initiated within the median of 3.5 days from the start of IMV-(aHR, 0.67; 95% CI, 0.60-0.76; p < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42-0.69; p < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO2/FiO2 data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72-1.25; p = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53-0.98; p = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06-0.78; p = 0.02). (4) Conclusions: Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival.

Angioedema is a condition characterized by non-pitting swelling of the subcutaneous or submucosal tissues in particular the face, lips, and oral cavity. Angiotensin-converting enzyme (ACE) inhibitors are known to contribute to the development of angioedema by increasing the levels of bradykinin and its active metabolites. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is hypothesized to contribute to the development of angioedema by modifying ACE II levels and further increasing the level of bradykinin in patients taking ACE inhibitors. African Americans may be at particular risk of developing angioedema with concomitant SARS-CoV-2 infection and ACE inhibitor use. This case involves a 31-year-old African American male diagnosed with coronavirus disease 2019 (COVID-19) who developed angioedema while taking an ACE inhibitor.

In April 2020, the Aboriginal and Torres Strait Islander COVID-19 Point-of-Care (POC) Testing Program was initiated to improve access to rapid molecular-based SARS-CoV-2 detection in First Nations communities. At capacity, the program reached 105 health services across Australia. An external review estimated the program contributed to averting between 23,000 and 122,000 COVID-19 infections within 40 days of the first infection in a remote community, equating to cost savings of between AU$337 million and AU$1.8 billion. Essential to the quality management of this program, a customised External Quality Assessment (EQA) program was developed with the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP). From July 2020 to May 2022, SARS-CoV-2 EQA participation ranged from 93 to 100%. Overall concordance of valid EQA results was high (98%), with improved performance following the first survey. These results are consistent with those reported by 12 Australian and 4 New Zealand laboratories for three SARS-CoV-2 RNA EQA surveys in March 2020, demonstrating that SARS-CoV-2 RNA POC testing in primary care settings can be performed to an equivalent laboratory analytical standard. More broadly, this study highlights the value of quality management practices in real-world testing environments and the benefits of ongoing EQA program participation.

We conducted a cross-sectional study to evaluate cellular and humoral immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection and examine how lymphocyte subpopulations in peripheral blood correlate with cellular and humoral immunogenicity in adult allogeneic hematopoietic cell transplantation (HCT) recipients. The median period from SARS-CoV-2 vaccination or infection to sample collection was 110.5 days (range, 6-345 days). The median SARS-CoV-2 spike-specific antibody level was 1761 binding antibody units (BAU)/ml (range, 0 to > 11,360 BAU/ml). Enzyme-linked immunosorbent spot (ELISpot) assay of T cells stimulated with SARS-CoV-2 spike antigens showed that interferon-gamma (IFN-γ)-, interleukin-2 (IL-2)-, and IFN-γ + IL-2-producing T cells were present in 68.9%, 62.0%, and 56.8% of patients, respectively. The antibody level was significantly correlated with frequency of IL-2-producing T cells (P = 0.001) and IFN-γ + IL-2-producing T cells (P = 0.006) but not IFN-γ-producing T cells (P = 0.970). Absolute counts of CD8+ and CD4+ central memory T cells were higher in both IL-2- and IFN-γ + IL-2-producing cellular responders compared with non-responders. These data suggest that cellular and humoral immunogenicity against SARS-CoV-2 vaccination or infection is associated with the memory phenotype of T cells and B cells in adult allogeneic HCT recipients.

The emergence of coronavirus disease 2019 (COVID-19), a novel identified pneumonia resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has significantly impacted and posed significant challenges to human society. The papain-like protease (PLpro) found in the nonstructural protein 3 of SARS-CoV-2 plays a vital role in viral replication. Moreover, PLpro disrupts the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 from host proteins. Consequently, PLpro has emerged as a promising drug target against SARS-CoV-2 infection. Computational studies have reported that ciclesonide can bind to SARS-CoV-2 PLpro. However, the inhibitory effects of ciclenoside on the PLpro have not been experimentally evaluated. Here, we evaluated the inhibitory effects of synthetic glucocorticoids (sGCs), including ciclesonide, on SARS-CoV-2 PLpro in vitro assay. Ciclesonide significantly inhibited the enzymatic activity of PLpro, compared with other sGCs and its IC50 was 18.4 ± 1.89 µM. These findings provide insights into the development of PLpro inhibitors.

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage.

Many emerging and re-emerging infectious diseases are prevalent, and the number of patients with allergies is increasing. Therefore, the importance of purifying the living environment is increasing. Photocatalysts undergo extreme redox reactions and decompose organic matter upon exposure to the excitation light. In contrast to ultraviolet light and disinfectants, which are standard methods for inactivating viruses and eliminating microorganisms, photocatalysts can decompose toxic substances, such as endotoxins and allergens, rendering them harmless to the human body. Photocatalysts have attracted significant attention as potential antiviral and antimicrobial agents. This review outlines the antiviral, antimicrobial, and anti-allergenic effects of photocatalysts. Especially, we have discussed the inactivation of SARS-CoV-2 in liquids and aerosols, elimination of Legionella pneumophila in liquids, decomposition of its endotoxin, decomposition of cat and dog allergens, and elimination of their allergenicity using photocatalysts. Furthermore, we discuss future perspectives on how photocatalysts can purify living environments, and how photocatalytic technology can be applied to companion animals and the livestock industry.