Comparison of Levels of Nasal, Salivary, and Plasma Antibody to Severe Acute Respiratory Syndrome Coronavirus 2 During Natural Infection and After Vaccination.

BACKGROUND: Most studies of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) measure antibody or cellular responses in blood; however, the virus infects mucosal surfaces in the nose and conjunctivae and infectious virus is rarely if ever present in the blood. METHODS: We used luciferase immunoprecipitation assays to measure SARS-CoV-2 antibody levels in the plasma, nose, and saliva of infected persons and vaccine recipients. These assays measure antibody that can precipitate the SAR-CoV-2 spike and nucleocapsid proteins. RESULTS: Levels of plasma anti-spike antibody declined less rapidly than levels of anti-nucleocapsid antibody in infected persons. SARS-CoV-2 anti-spike antibody levels in the nose declined more rapidly than antibody levels in the blood after vaccination of infected persons. Vaccination of previously infected persons boosted anti-spike antibody in plasma more than in the nose or saliva. Nasal and saliva anti-spike antibody levels were significantly correlated with plasma antibody in infected persons who had not been vaccinated and after vaccination of uninfected persons. CONCLUSIONS: Persistently elevated SARS-CoV-2 antibody in plasma may not indicate persistence of antibody at mucosal sites such as the nose. The strong correlation of SARS-CoV-2 antibody in the nose and saliva with that in the blood suggests that mucosal antibodies are derived primarily from transudation from the blood rather than local production. While SARS-CoV-2 vaccine given peripherally boosted mucosal immune responses in infected persons, the increase in antibody titers was higher in plasma than at mucosal sites. Taken together, these observations indicate the need for development of mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs. CLINICAL TRIALS REGISTRATION: NCT01306084.

Pediatrics, Students, Allied Health and COVID-19.

This second issue of JORH for 2023 considers research relating to (1) pediatrics, (2) students, (3) various allied health professions and their related practices, and lastly, (4) COVID-19. An additional reminder is also provided to readers on the call for papers regarding a future issue on "Religion, Spirituality, Suicide, and its Prevention", as well as a new call for papers with respect to "Spiritual Care for People with Parkinson's Disease and their Caregivers".

Chaplaincy, Judaism, Ukraine, COVID-19 and JORH Jubilee.

This first issue of JORH for 2023 considers (1) the ministry of chaplains, (2) Judaism, (3) the people of war-torn Ukraine, (4) the ongoing saga of COVID-19 and, on a happier note, (5) we celebrate a belated jubilee by presenting a bibliometric analysis of the Journal of Religion and Health (1961-2021). To conclude this issue, a book review is presented, "The Desperate Hours" by award winning journalist Marie Brenner, focusing on one hospital's fight to save New York City during COVID-19. A reminder is also provided to readers on the call for papers regarding a future issue on religion, spirituality, suicide and its prevention.

Successful lung transplantation using an allograft from a COVID-19–recovered donor: a potential role for subgenomic RNA to guide organ utilization

Although the risk of SARS-CoV-2 transmission through lung transplantation from acutely infected donors is high, the risks of virus transmission and long-term lung allograft outcomes are not as well described when using pulmonary organs from COVID-19–recovered donors. We describe successful lung transplantation for a COVID-19–related lung injury using lungs from a COVID-19–recovered donor who was retrospectively found to have detectable genomic SARS-CoV-2 RNA in the lung tissue by multiple highly sensitive assays. However, SARS-CoV-2 subgenomic RNA (sgRNA), a marker of viral replication, was not detectable in the donor respiratory tissues. One year after lung transplantation, the recipient has a good functional status, walking 1 mile several times per week without the need for supplemental oxygen and without any evidence of donor-derived SARS-CoV-2 transmission. Our findings highlight the limitations of current clinical laboratory diagnostic assays in detecting the persistence of SARS-CoV-2 RNA in the lung tissue. The persistence of SARS-CoV-2 RNA in the donor tissue did not appear to represent active viral replication via sgRNA testing and, most importantly, did not negatively impact the allograft outcome in the first year after lung transplantation. sgRNA is easily performed and may be a useful assay for assessing viral infectivity in organs from donors with a recent infection.

Exploring the Digital Divide among the Bhutanese Refugee Community during COVID-19: Engaged Research in Action.

The digital divide proved a critical barrier to accessing information and healthcare during the COVID-19 pandemic and negatively impacted the Bhutanese refugee community. Moving beyond a technological model of the digital divide that highlights a lack of access to computers and the internet, we engaged the community to co-produce a dynamic approach that identifies the impact of socio-cultural and socio-environmental factors as well. Our paper reports on our community-academic research partnership and explores how the digital divide exacerbates health disparities in a midwestern Bhutanese refugee community. Combining the efforts of the community, anthropologists and social workers, this paper reports on the health disparities that confront the community as well as interventions designed to mitigate social inequities.

SARS-CoV-2 infection and persistence in the human body and brain at autopsy.

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1-3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6-14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial.

BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS. OBJECTIVE: To characterize long-term safety and efficacy of ozanimod. METHODS: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021. RESULTS: This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups. CONCLUSIONS: This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity.

NOVA primary results randomised controlled study of natalizumab Q6W versus continued Q4W treatment for MS

BackgroundNatalizumab every-6-week (Q6W) dosing is associated with lower progressive multifocal leukoencephalopathy risk than every-4-week dosing (Q4W) in retrospective analyses. NOVA is the first randomised trial to assess Q6W efficacy.ObjectiveEvaluate natalizumab Q6W efficacy in patients previously treated with natalizumab Q4W for≥12 months compared with continuation of Q4W over 72 weeks.MethodsNOVA is a randomised, controlled, open-label, rater-blinded phase 3b trial. Included patients were treated with natalizumab Q4W without relapse for ≥12 months. Patients were randomised 1:1 to Q4W (n=248) or Q6W (n=251). The primary endpoint was new/newly enlarging T2 (N/NET2) lesions. Secondary endpoints included clinical and safety outcomes.ResultsProportions of patients with N/NET2 lesions were low in both arms (Q4W:4.1%;Q6W:4.3%). Differ- ences in mean N/NET2 lesions for Q4W and Q6W (primary estimand: 0.05 vs 0.20 [P=0.0755];secondary estimand: 0.06 vs 0.31 [P=0.0437]) were driven by two Q6W patients with extreme (≥25) values. Secondary outcomes were similar for Q4W and Q6W.ConclusionsOverall, NOVA data suggest most patients stable on natalizumab Q4W can switch to Q6W without clinically meaningful loss of efficacy. Support: Biogen. Disclosures on poster.

Serological responses to human virome define clinical outcomes of Italian patients infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic respiratory infectious disease COVID-19. However, clinical manifestations and outcomes differ significantly among COVID-19 patients, ranging from asymptomatic to extremely severe, and it remains unclear what drives these disparities. Here, we studied 159 sequentially enrolled hospitalized patients with COVID-19-associated pneumonia from Brescia, Italy using the VirScan phage-display method to characterize circulating antibodies binding to 96,179 viral peptides encoded by 1,276 strains of human viruses. SARS-CoV-2 infection was associated with a marked increase in immune antibody repertoires against many known pathogenic and non-pathogenic human viruses. This antiviral antibody response was linked to longitudinal trajectories of disease severity and was further confirmed in additional 125 COVID-19 patients from the same geographical region in Northern Italy. By applying a machine-learning-based strategy, a viral exposure signature predictive of COVID-19-related disease severity linked to patient survival was developed and validated. These results provide a basis for understanding the role of memory B-cell repertoire to viral epitopes in COVID-19-related symptoms and suggest that a unique anti-viral antibody repertoire signature may be useful to define COVID-19 clinical severity.

Mental Health, Islam, Clinical Issues and COVID-19.

In this fifth issue of the Journal of Religion and Health for 2022, four key themes are revisited: (1) mental health, (2) Islam, (3) various clinical issues relating to religiosity and/or spirituality and (4) the ongoing concerns of COVID-19.

T cell responses against SARS-CoV-2 and its Omicron variant in a patient with B cell lymphoma after multiple doses of a COVID-19 mRNA vaccine.

Anti-SARS-CoV-2 antibodies are crucial for protection from future COVID-19 infections, limiting disease severity, and control of viral transmission. While patients with the most common type of hematologic malignancy, B cell lymphoma, often develop insufficient antibody responses to messenger RNA (mRNA) vaccines, vaccine-induced T cells would have the potential to 'rescue' protective immunity in patients with B cell lymphoma. Here we report the case of a patient with B cell lymphoma with profound B cell depletion after initial chemoimmunotherapy who received a total of six doses of a COVID-19 mRNA vaccine. The patient developed vaccine-induced anti-SARS-CoV-2 antibodies only after the fifth and sixth doses of the vaccine once his B cells had started to recover. Remarkably, even in the context of severe treatment-induced suppression of the humoral immune system, the patient was able to mount virus-specific CD4+ and CD8+ responses that were much stronger than what would be expected in healthy subjects after two to three doses of a COVID-19 mRNA vaccine and which were even able to target the Omicron 'immune escape' variant of the SARS-CoV-2 virus. These findings not only have important implications for anti-COVID-19 vaccination strategies but also for future antitumor vaccines in patients with cancer with profound treatment-induced immunosuppression.

Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions.

BACKGROUND: The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. METHODS: Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. RESULTS: Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. CONCLUSION: Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs.

Nursing, Diabetes, Hemodialysis and COVID-19.

Four key themes are explored in this third issue of the Journal of Religion and Health for 2022: (1) the lead topic for this issue considers the work and spiritual care provided by nurses, which is followed by a series of articles on the subject areas of (2) diabetes and (3) hemodialysis. Then, like previous issues, we again consider (4) research exploring the effects of COVID-19. Finally, this issue presents a miscellaneous collection of articles with respect to various faith dynamics and the findings from several national surveys.

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Hispanic/Latino Acculturation Profiles and Telomere Length: Latent Class Analysis on a Nationally Representative Sample.

Background: Acculturation profiles and their impact on telomere length among foreign-born Hispanics/Latinos living in the United States (US) are relatively unknown. The limited research available has linked acculturation with shortened telomere length. Objectives: To identify acculturation profiles among a US representative sample of Hispanics/Latinos and to then examine telomere length differences between profiles. Methods: We conducted a latent class analysis among a non-institutionalized US-representative sample of Hispanics/Latinos using the 1999-2002 National Health and Nutrition Examination Survey (N = 2,292). The latent variable of acculturation was assessed by length of time in the US and language used as a child, read and spoken, usually spoken at home, used to think, and used with friends (i.e., Spanish and/or English). Telomere length assessed from leukocytes was used as the distal continuous outcome. Results: We identified five profiles: (1) low acculturated [33.2% of sample]; (2) partially integrated [18.6% of sample]; (3) integrated [19.4% of sample]; (4) partially assimilated [15.1% of sample]; and (5) assimilated [13.7% of sample]. Acculturation profiles revealed nuanced differences in conditional probabilities with language use despite the length of time spent in the US. While telomere length did vary, there were no significant differences between profiles. Conclusion: Profiles identified revealed that possible life-course and generational effects may be at play in the partially assimilated and assimilated profiles. Our findings expand public health research using complex survey data to identify and assess the dynamic relationship of acculturation profiles and health biomarkers, while being among the first to examine this context using a person-centered approach.

Chaplaincy, Cancer, Aged Care and COVID-19.

Four key topics are explored in this second issue of the Journal of Religion and Health for 2022. Following a condemnation of the Russian invasion of Ukraine, (1) the lead topic for this issue forms a special section regarding contemporary chaplaincy, which is followed by (2) ongoing research concerning cancer, (3) aged care and finally (4) the continuing response to COVID-19. Previous issues of JORH have presented various articles related to these topics before; however, this particular collation provides a resourceful anthology.

The impact of the Coronavirus pandemic on New York City real estate: First evidence.

We investigate whether pandemic-induced contagion disamenities and income effects arising due to COVID-related unemployment adversely affected real estate prices of one- or two-family owner-occupied properties across New York City (NYC). First, ordinary least squares hedonic results indicate that greater COVID case numbers are concentrated in neighborhoods with lower-valued properties. Second, we use a repeat-sales approach for the period 2003-2020, and we find that both the possibility of contagion and pandemic-induced income effects adversely impacted home sale prices. Estimates suggest sale prices fell by roughly $60,000 or around 8% in response to both of the following: 1000 additional infections per 100,000 residents and a 10-percentage point increase in unemployment in a given Modified Zip Code Tabulation Area (MODZCTA). These price effects were more pronounced during the second wave of infections. On the basis of cumulative MODZCTA infection rates through 2020, the estimated COVID-19 price discount ranged from approximately 1% to 50% in the most affected neighborhoods, and averaged 14%. The contagion effect intensified in the more affluent, but less densely populated NYC neighborhoods, while the income effect was more pronounced in the most densely populated neighborhoods with more rental properties and greater population shares of foreign-born residents. This disparity implies the pandemic may have been correlated with a wider gap in housing wealth in NYC between homeowners in lower-priced and higher-priced neighborhoods.

Perspectives and experiences with COVID-19 vaccines in people with MS.

Background: People with MS may have unique perspectives on COVID-19 vaccines due to their condition and/or medications. Objective: Assess perspectives and experiences with COVID-19 vaccination, and quantify variables impacting COVID-19 vaccine willingness in people with MS. Methods: A survey captured demographics, MS characteristics, and COVID-19 infection and exposures data; opinions on COVID-19 vaccine safety, side effects, and efficacy; and experiences following vaccination. Chi-square tests and a logistic regression model were used to denote between-group differences and variables predicting vaccine willingness, respectively. Results: Most (87.8%) of the 237 participants were willing to receive the vaccine. Fifteen percent held or delayed a DMT dose for vaccination. MS symptoms worsened in a minority (7.6% first/only dose; 14.7% second dose), and most side effects were mild (80.0%; 55.3%). Those not planning to receive the vaccine were primarily concerned with long-term safety (70.4%). Medical comorbidities (adjusted odds ratio [aOR]=5.222; p=0.04) and following infection prevention precautions (aOR=6.330; p=0.008) were associated with vaccine willingness. Conclusion: Most individuals with MS surveyed plan to receive the COVID-19 vaccine. People with MS experience similar side effects to the general population, and few experience transient MS symptom worsening. These results can inform conversations on vaccination between providers and people with MS.