Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19.

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects the respiratory system but can quickly become systemic, harming multiple organs and leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, and immune cells can efficiently eliminate the virus. However, 20% of individuals develop severe respiratory illness and multiple organ failure. Virus replication has been described in several organs in patients who died from COVID-19, suggesting a compromised immune response. Immunodeficiency and autoimmunity are responsible for this impairment and facilitate viral escape. Mutations in IFN signal transduction and T cell activation are responsible for the inadequate response in young individuals. Autoantibodies are accountable for secondary immunodeficiency in patients with severe infection or prolonged COVID-19. Antibodies against cytokines (interferons α, γ and ω, IL1ß, IL6, IL10, IL-17, IL21), chemokines, complement, nuclear proteins and DNA, anticardiolipin, and several extracellular proteins have been reported. The type and titer of autoantibodies depend on age and gender. Organ-specific autoantibodies have been described in prolonged COVID-19. Their role in the disease is under study. Autoimmunity and immunodeficiency should be screened as risk factors for severe or prolonged COVID-19.

The unmet need for COVID-19 treatment in immunocompromised patients.

BACKGROUND: Immunocompromised (IC) patients are at increased risk of severe and/or prolonged COVID-19. MAIN TEXT: The recent study by Scaglione et al., addresses the issue of IC outpatients with SARS-CoV-2 infection. Authors describe the real-life use of SARS-CoV-2 antivirals and/or monoclonal antibodies and the clinical benefit in high-risk COVID-19 patients. The study supports the use of early combination therapy in a subgroup of extremely high risk patients, and considers the combined strategy as a gold standard regimen to both increase the effectiveness of early treatment, especially in IC individuals, and, reduce the emergence of SARS-CoV-2 escape mutants. CONCLUSION: A tailored and standardised therapeutic approach in case of IC out and inpatients with SARS-CoV-2 infection is needed.

Professional identity, job satisfaction, and intention to stay among clinical nurses during the prolonged COVID-19 pandemic: A mediation analysis.

AIM: This study aims to examine the relationship between professional identity and job satisfaction and their impact on intention to stay among clinical nurses in China during the prolonged COVID-19 pandemic. METHODS: A cross-sectional survey was conducted from April 30 to May 25, 2021, in China. Data were collected using professional identity, job satisfaction, and intention to stay questionnaires from 1425 clinical nurses. A single mediation analysis was utilized to test the interrelationship among the variables, and the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist as a reporting guide. RESULTS: Nurses indicated a medium level of professional identity, job satisfaction, and intention to stay, with mean scores of 3.85, 3.25, and 3.47, respectively. The professional identity displayed positive indirect effect on nurses' intention to stay through job satisfaction (indirect effect = 0.498, 95% CI [0.439, 0.558]). CONCLUSION: Cultivating professional identity among nurses can increase their job satisfaction and ultimately enhance the intention to stay in the nursing profession. However, this study also suggests paying more attention to job satisfaction to keep nursing retention. These may be helpful to retain the nursing workforce.

Life and Stress of Japanese Children and Adolescents During the Prolonged Coronavirus Disease 2019 (COVID-19) Pandemic

This study surveyed adult web monitor enrollees about the lives of and stress experienced by Japanese children and adolescents during the prolonged coronavirus disease 2019 (COVID-19) pandemic. The survey was conducted on February 10, 2022 (after the sixth wave) and August 19, 2022 (during the seventh wave of the COVID-19 pandemic in Japan), with 231 and 217 survey participants, respectively. The questionnaire was designed so that adults could assess the frequency of exercise, and difficulties experienced by children and adolescents around them. Regarding exercise opportunities, 22% of parents of middle and high school children reported that children's exercise opportunities "stayed the same” or "increased considerably” in the first survey. Whereas, in the second survey, all parents of middle and high school children reported that children's exercise opportunities "decreased.” Regarding stress, 17% of parents of adolescents 18 years and older responded that the stress experienced was the "same as before” or "a little less than before” in the first survey, but all of these parents responded "quite a bit” to the same question in the second survey. The findings suggest that the life changes caused by the COVID-19 pandemic may have a significant impact on children and adolescents and may increase stress. The long-term effects of the COVID-19 pandemic on children and adolescents should be further investigated. © Fuji Technology Press Ltd.

Immunocompromised Patients with Protracted COVID-19: a Review of "Long Persisters".

Purpose of Review: Certain immunocompromised individuals are at risk for protracted COVID-19, in which SARS-CoV-2 leads to a chronic viral infection. However, the pathogenesis, diagnosis, and management of this phenomenon remain ill-defined. Recent Findings: Herein, we review key aspects of protracted SARS-CoV-2 infection in immunocompromised individuals, or the so-called long persisters, and describe the clinical presentation, risk factors, diagnosis, and treatment modalities of this condition, as well as intra-host viral evolution. Based on the available data, we also propose a framework of criteria with which to approach this syndrome. Summary: Protracted COVID-19 is an uncharacterized syndrome affecting patients with B-cell depletion; our proposed diagnostic approach and definitions will inform much needed future research.

Headache in Post-COVID-19 Patients: Its Characteristics and Relationship with the Quality of Life.

Little is known on the characteristics of headaches associated with coronavirus disease 2019 (COVID-19) in Indonesia. The objective of this study was to describe the characteristics of headache in post-COVID-19 patients, and its impact on the patients' quality of life (QoL), as well as to determine the associated determinants of the poor QoL. A cross-sectional study was conducted in Banda Aceh, Indonesia. The demographic characteristics, clinical symptoms of COVID-19, characteristics of headache, and the QoL were collected and assessed. Headache was diagnosed and characterized using the International Classification of Headache Disorders, version 3 (ICHD-3). QoL was assessed using a Short Form 36 Health Survey (SF-36) tool. A logistic regression model was used to investigate the associated determinants of poor QoL in post-COVID-19 patients. A total of 215 post-COVID-19 patients were included in the final analysis, and 21.4% (46/215) of them had a poor QoL due to headache following COVID-19. Those who were unemployed and who contracted COVID-19 less than three months prior to the study had higher odds of having poor QoL compared to those who were employed and who contracted COVID-19 more than three months prior to the study. Low QoL was also related to headache that occurred less than one month after recovering from COVID-19 (compared to that which occurred longer than one month after); had a high frequency; had a combination sensation of pulsating, pressing, fiery, and stabbing pain; had a high severity score; and had additional symptoms accompanying the headache. In conclusion, headache related to COVID-19 is associated with low QoL among post-COVID-19 patients. A guideline on prevention measures of headache on COVID-19 patients, therefore, needs to be established to avoid long-term consequences.

Favorable Outcome Following Sotrovimab Monoclonal Antibody in a Patient with Prolonged SARS-CoV-2 Omicron Infection with HIV/AIDS.

Persistent viral shedding or prolonged coronavirus disease 2019 (COVID-19) symptom is one of unresolved problem in immunocompromised individuals. We herein report an HIV/AIDS patient with Pneumocystis jirovecii pneumonia and prolonged COVID-19, possibly due to immune reconstitution inflammatory syndrome. His viral shedding and COVID-19 symptoms persisted for 39 days but were promptly resolved following sotrovimab monoclonal antibody therapy. This case suggests that prolonged COVID-19 and persistent viral shedding due to severe cellular immunodeficiency can occur in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron infection and that sotrovimab is effective in the treatment of prolonged COVID-19 caused by omicron/BA.1.

Prolonged COVID-19 in an Immunocompromised Patient Treated with Obinutuzumab and Bendamustine for Follicular Lymphoma.

A patient with follicular lymphoma treated with obinutuzumab and bendamustine experienced prolonged coronavirus disease-2019 (COVID-19). One month after the symptoms transiently improved, the patient experienced exacerbated COVID-19 symptoms. The patient recovered from COVID-19 with remdesivir and dexamethasone and was discharged 77 days after the disease onset. The patient completed a primary series of SARS-CoV-2 vaccinations on day 176, but the anti-spike protein IgG was not detected later. A careful observation to detect any subsequent relapse of COVID-19 symptoms is necessary in immunocompromised patients. Chemotherapy should be based on the disease status and type of lymphoma.

Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts.

Immunocompromised hosts with prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been implicated in the emergence of highly mutated SARS-CoV-2 variants. Spike mutations are of particular concern because the spike protein is a key target for vaccines and therapeutics for SARS-CoV-2. Here, we report the emergence of spike mutations in two immunocompromised patients with persistent SARS-CoV-2 reverse transcription (RT)-PCR positivity (>90 days). Whole-genome sequence analysis of samples obtained before and after coronavirus disease 2019 (COVID-19) treatment demonstrated the development of partial therapeutic escape mutations and increased intrahost SARS-CoV-2 genome diversity over time. This case series thus adds to the accumulating evidence that immunocompromised hosts with persistent infections are important sources of SARS-CoV-2 genome diversity and, in particular, clinically important spike protein diversity. IMPORTANCE The emergence of clinically important mutations described in this report highlights the need for sustained vigilance and containment measures when managing immunocompromised patients with persistent COVID-19. Even as jurisdictions across the globe start lifting pandemic control measures, immunocompromised patients with persistent COVID-19 constitute a unique group that requires close genomic monitoring and enhanced infection control measures, to ensure early detection and containment of mutations and variants of therapeutic and public health importance.

Factors Associated With Underprivileged E-Learning, Session Jam Phobia, and the Subsequent Mental Distress Among Students Following the Extended University Closure in Bangladesh.

Severe session jam phobia (SJP), the extent of underprivileged online education, and subsequent mental health disorders among students have emerged as distinguished global problems due to the overwhelming effects of coronavirus disease 2019 (COVID-19). The purpose of this research was to evaluate the impact of extended COVID-19 lockdown and its mediating factors on current e-Learning activities, the prevalence of severe SJP and psychological distress among university students in Bangladesh. A web-based cross-sectional study was conducted to assemble responses through Google Form by applying a simple snowball sampling technique among university students aged 18 years or above in Bangladesh. All ethical considerations were maintained, and univariate, bivariate, and multivariate analyses were employed to analyze the acquired data set. Among the total analyzed data (n = 1,122), the male and female ratio was almost 1:1, and a remarkable segment (63.7%) was aged between 21-24 years. Alarmingly, around 50-60% of the students were suffering from severe SJP, prevailing underprivileged education in the e-Learning platform, and severe mental distress. Logistic regression analyses demonstrated that the students from public universities, lower- and mid-income families, lower-aged, and junior years education groups were significantly (p < 0.05) more underprivileged than their counter groups. Besides, the monthly family income and university type significantly influenced the extent of severe SJP. Finally, the students who were female, rustic, come from low-income families (below 25,000 BDT), who had academic uncertainty, job insecurity, online exam phobia, and dissatisfaction with e-Learning education, were significantly suffering from moderate to severe mental distress. The current evidence demonstrates that a substantial number of Bangladeshi university students are struggling with extreme session jam phobia, underprivileged e-Learning education, and subsequent psychological distress, which need to be immediately addressed through concerted efforts by the government, parents, and university authorities.

Intensive care management in guillain barré syndrome accompanying prolonged Covid-19-A case report.

One of the neurological complications associated with COVID-19 is Guillain Barre Syndrome (GBS). It is possible to be a complication of COVID19 due to the similarity of respiratory complication between both clinical entities. The aim of this case report is to present a case followed in the intensive care unit (ICU) with the coexistence of prolonged COVID-19 and GBS. The 68-year-old patient, whose COVID-19 symptoms had been going on for 5 weeks, was followed for 5 days in the ICU due to GBS diagnosis. During this period, the patient's symptoms regressed with IVIG treatment. ICU physicians should be careful that some neurological complications may accompany in some prolonged COVID-19 cases and that one of these may be GBS.

Prolonged SARS-CoV-2 nucleic acid conversion time in military personnel outbreaks with presence of specific IgG antibodies.

Coronavirus disease 2019 (COVID-19) is transmitted person-to-person mainly by close contact or droplets from respiratory tract. However, the actual time of viral shedding is still uncertain as well as the different routes of transmission. We aimed to characterize RNA shedding from nasopharyngeal and rectal samples in prolonged cases of mild COVID-19 in young male soldiers. Seventy patients from three different military locations were monitored after recommending to follow more strict isolation measures to prevent the spread of the virus. Then, nasopharyngeal, rectal, and blood samples were taken. SARS-CoV-2 RNA was detected by RT-PCR and specific antibodies by chemiluminescent immunoassays. The median nucleic acid conversion time (NACT) was 60 days (IQR: 7-85 days). Rectal swabs were taken in 60 % of patients. Seven patients (10 %) were positive in nasopharyngeal and rectal swabs, and five (7.14 %) remained positive in rectal swabs, but negative in nasopharyngeal samples. Four patients (5.71 %) that had been discharged, were positive again after 15 days. No significant difference was found in nucleic acid conversion time between age groups nor clinical classification. Maintaining distancing among different positive patients is essential as a possible re-exposure to the virus could cause a longer nucleic acid conversion time in SARS-COV-2 infections.

Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail.

A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient's family. Current decisions to take revolve around patient's follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.