Editorial commentary on special issue of COVID-19 pandemic

This special issue of The Journal of Biomedical Research presents rigorous empirical analysis related to COVID-19 research in responding to the current global COVID-19 pandemic. Selected articles from different disciplines not only offer broader perspectives on combating the outbreaks, but also disseminate the most updated findings on this new challenge for human being to the field.     

Therapeutic management of hereditary angioedema due to C1 inhibitor deficiency

Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is a rare genetic disease characterized by recurrent swellings of the subcutaneous and submucosal tissues that can manifest as cutaneous edema, abdominal pain and laryngeal edema with airway obstruction. These symptoms have a significant impact on patients’ quality of life. The reduction in C1-INH function leads to uncontrolled activation of the contact system and generation of bradykinin, the mediator of increased vascular permeability and edema formation. In the past, few treatment options were available; however, several new therapies with proven efficacy have recently become available to treat and prevent HAE attacks, such as plasma-derived and recombinant C1-INHs that replace the deficient protein, bradykinin receptor antagonist (icatibant) that blocks bradykinin activity and kallikrein inhibitor (ecallantide) that prevents bradykinin release. Such therapies can improve disease outcome. This article reviews the therapeutic management of HAE, which involves the treatment of acute attacks and prophylaxis.     

Predicting anxiety and depression over 12 months of the COVID-19 pandemic: A machine learning study

Objectives

The coronavirus disease 2019 (COVID-19) pandemic was associated with substantial increases in anxiety and depressive symptoms. To understand individual risk, we examined a large set of potential risk factors for anxiety and depression in the pandemic context.

Methods

Adults in the United States (N = 1200) completed eight online self-report assessments over 12 months of the COVID-19 pandemic. Area under the curve scores summarized cumulative experiences of anxiety and depression over the assessment period. A machine learning approach to elastic net regularized regression was used to select predictors of cumulative anxiety and depression severity from a set of 68 sociodemographic, psychological, and pandemic-related baseline variables.

Results

Cumulative anxiety severity was most strongly explained by stress and depression-related variables (such as perceived stress) and select sociodemographic characteristics. Cumulative depression severity was predicted by psychological variables, including generalized anxiety and depressive symptom reactivity. Being immunocompromised or having a medical condition were also important.

Conclusions

By considering many predictors, findings provide a more complete view than previous studies focused on specific predictors. Important predictors included psychological variables suggested by prior research and variables more specific to the pandemic context. We discuss how such findings can be used in understanding risk and planning interventions.     

C1 INH concentrate in the therapy of hereditary angioedema

Ten acute attacks were managed in nine patients with hereditary angioedema by means of the infusion of a C1 INH concentrate produced on large scale. No side effects were observed.     

C1-inhibitor concentrate home therapy for hereditary angioedema: a viable, effective treatment option

Economic and political factors have led to the increased use of home therapy programmes for patients who have traditionally been treated in hospital. Many patients with hereditary angioedema (HAE) experience intermittent severe attacks that affect their quality of life and may be life-threatening. These attacks are treated with C1-inhibitor concentrate which, for most patients, is infused at the local hospital. Home therapy programmes for HAE are currently being established. This paper reviews the extent of use of these programmes and summarizes the advantages and potential disadvantages of the concept so far.     

The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency

Patients with hereditary angioedema (HAE) tend to produce autoantibodies and have a propensity to develop immunoregulatory disorders. We characterize the profile of autoantibodies in a group of HAE patients and investigate their memory B cells' phenotype and activation status. We studied the activity status phenotype, Toll-like receptor (TLR)-9 expression and total phosphotyrosine in B cells isolated from HAE patients. Additionally, the following autoantibodies were assessed in the serum of 61 HAE patients: anti-nuclear, rheumatoid factor, anti-cardiolipin, anti-tissue transglutaminase, anti-endomysial, anti-Saccharomyces cerevisiae, anti-thyroid and anti-neutrophil cytoplasmic antibodies. In 47·5% of HAE patients we detected at least one of the tested autoantibodies. Expression of CD69, CD5 and CD21 was found to be significantly higher on memory B cells from HAE patients compared to healthy controls (4·59 ± 4·41 versus 2·06 ± 1·81, P = 0·04, 8·22 ± 7·17 versus 3·65 ± 3·78, P = 0·05, 2·43 ± 0·54 versus 1·92 ± 0·41, P = 0·01, respectively). Total phosphotyrosine in B cells from HAE patients was significantly higher compared to healthy controls (4·8 ± 1·1 versus 2·7 ± 1·3, P = 0·0003). Memory B cells isolated from the HAE group contained higher amounts of TLR-9 compared to healthy controls (8·17 ± 4·1 versus 4·56 ± 1·6, P = 0·0027). Furthermore, the expression of TLR-9 in memory B cells from HAE patients with autoantibodies was significantly higher than the control group (10 ± 4·7 versus 4·56 ± 1·6, P = 0·0002) and from that in HAE patients without autoantibodies (10 ± 4·7 versus 5·8 ± 0·9, P = 0·036). HAE patients have enhanced production of autoantibodies due most probably to the increased activation of B cells, which was found to be in association with a high expression of TLR-9.     

Identification of psychological flexibility and inflexibility profiles during the COVID-19 pandemic

Background

The first coronavirus disease 2019 (COVID-19) wave and lockdown adversely affected the lives of people in diverse ways.

Aims

This study used a person-centered approach to identify patterns of engagement in the 12 psychological flexibility (PF) and inflexibility (PI) processes to manage the first COVID-19 wave and lockdown hardships.

Materials & Methods

A total of 1035 Italian adults completed an online survey.

Results

Latent profile analyses conducted on the 12 PI/PF processes measured by the Multidimensional Psychological Flexibility Inventory identified five profiles; three reflected gradations of high to low PF with corresponding inverse levels of PI, while two represented more complex relationships between PI and PF. After controlling for relevant socio-demographic and COVID-19/lockdown factors, the five profiles differed in mental health (depression, anxiety, and COVID-19 distress). Essentially a gradient of progressive decreases in all PI processes (except experiential avoidance) corresponded with increments in mental health across all profiles. Two profiles, which evidenced the highest levels of mental health (highly flexible and moderately flexible profiles), also had the greatest proportion of the sample 56.42% (n = 584), and the highest levels of PF and experiential avoidance.

Discussion

Findings from this and similar studies suggest intersecting complex relationships among the PI/PF processes that are likely to shift in response to changing contexts. We suggest this network of relationships is better represented by a three-dimensional PF/PI hexaflex than a simplistic two-dimensional depiction of the model.

Conclusion

Distinguishing different PF/PI profiles identified groups most at risk for the adverse mental health impacts of the pandemic and exposed variations in the mental health protective and risk roles of PF and PI processes, respectively, that can inform ACT-based mental health promotion interventions.     

Pandemics and pathology: a reflection on influenza,HIV/AIDS and SARS (COVID-19) pandemic infections

The COVID-19 pandemic has reminded pathologists of our significant roles in the management and understanding of rapidly spreading and dangerous pathogens, from identifying the agent to characterizing the clinical pathology to managing the dead. Cellular pathology – through autopsy - has depicted the main features: viral pneumonitis, acute lung injury, organising pneumonia, secondary bacterial pneumonia, thrombophilia and infarction, and systemic inflammatory response syndrome with multi-organ failure. These are similar to another viral pandemic of the 20th century, H1N1 influenza; but contrast with the second major more complicated pandemic, that of HIV/AIDS. The outcomes of these infections are compared, along with seasonal influenza and SARS-1-CoV disease. Work to be done on COVID-19 includes characterisation of the emerging ‘long COVID’ syndrome, and monitoring the complications of therapies and vaccination programs.     

Human pasteurized C1-inhibitor concentrate for the treatment of hereditary angioedema due to C1-inhibitor deficiency

Hereditary angioedema is a relatively rare genetic disorder affecting between one in 10,000 and one in 50,000 individuals worldwide. The most common clinical symptoms observed are relapsing swelling of the skin and abdominal pain attacks. However, more serious and potentially fatal laryngeal attacks can also occur. Hereditary angioedema is most frequently caused by a deficiency of C1-inhibitor. Replacement therapy with Berinert, an intravenous pasteurized C1-inhibitor concentrate derived from human plasma, is a recommended treatment for rapid resolution of acute attacks of hereditary angioedema due to C1-inhibitor deficiency. Prophylactic therapy with C1-inhibitor is also available. Future advances may improve morbidity and mortality associated with hereditary angioedema.     

Fewer non-COVID-19 respiratory tract infections and gastrointestinal infections during the COVID-19 pandemic

For preventing the spread of the coronavirus disease 2019 (COVID-19) pandemic, measures like wearing masks, social distancing, and hand hygiene played crucial roles. These measures may also have affected the expansion of other infectious diseases like respiratory tract infections (RTI) and gastro-intestinal infections (GII). Therefore, we aimed to investigate non-COVID-19 related RTI and GII during the COVID-19 pandemic. Patients with a diagnosis of an acute RTI (different locations) or acute GII documented anonymously in 994 general practitioner (GP) or 192 pediatrician practices in Germany were included. We compared the prevalence of acute RTI and GII between April 2019–March 2020 and April 2020–March 2021. In GP practices, 715,440 patients were diagnosed with RTI or GII in the nonpandemic period versus 468,753 in the pandemic period; the same trend was observed by pediatricians (275,033 vs. 165,127). By GPs, the strongest decrease was observed for the diagnosis of influenza (?71%, p < 0.001), followed by acute laryngitis (?64%, p < 0.001), acute lower respiratory infections (bronchitis) (?62%, p < 0.001), and intestinal infections (?40%, p < 0.001). In contrast, the relatively rare viral pneumonia strongly increased by 229% (p < 0.001). In pediatrician practices, there was a strong decrease in infection diagnoses, especially influenza (?90%, p < 0.001), pneumonia (?73%, p < 0.001 viral; ?76%, p < 0.001 other pneumonias), and acute sinusitis (?66%, p < 0.001). No increase was observed for viral pneumonia in children. The considerable limitations concerning social life implemented during the COVID-19 pandemic to combat the spread of SARS-CoV-2 also resulted in an inadvertent but welcome reduction in other non-Covid-19 respiratory tract and gastro-intestinal infections.