COVID-19 Illness Research Articles

LONG-TERM OUTCOMES OF CRITICALLY ILL PATIENTS WITH COVID-19: A SYSTEMATIC REVIEW

BackgroundSurvivors of critical illness are susceptible to long-term functional impairments following admission to an intensive care unit (ICU). In the context of the COVID-19 pandemic, there has been a surge in patients admitted to ICU with severe acute respiratory syndrome coronavirus type 2. The long-term consequences of critical illness due to COVID-19 illness remain unclear. Research QuestionTo determine the long-term outcomes of adult patients admitted to ICU for COVID-19. Study Design and MethodsWe searched Ovid MEDLINE and EMBASE using subject heading and free-text terms related to long-term outcomes of critically ill patients with COVID-19. We included all articles that reported original data on outcomes from 90 days onwards for adult patients admitted to ICU for COVID-19. Data extracted included study details, patient characteristics, outcomes reported, measurement tools used and timing of assessment. ResultsA total of 14,882 studies were screened, from which 134 studies fulfilled the selection criteria. Follow-up timepoints ranged from 90 days to 2 years following critical illness. Post-hospital mortality was the most reported outcome (n=60), with the general ICU cohort having an aggregate mortality rate of 35.5% (95% CI 34.7-36.2) at 90 days and 31.6% (95%CI 30.9-32.4) at 6 months. A plethora of other outcomes were assessed, including psychological function/mental health (n=49), persistent symptoms (n=47), quality of life (n=47), physical function (n=33) and cognitive function (n=31). For each outcome, different measurement tools were employed, making data synthesis across studies difficult. InterpretationImportant evidence gaps remain regarding the long-term health outcomes and healthcare needs for survivors of critical COVID-19 illness. This review found that mortality was the most reported long-term outcome. Significant heterogeneity was evident across studies in terms of outcomes assessed, measurement instruments used and the duration of follow-up. Future research requires increased consistency in outcomes assessed and measurement tools to inform clinical practice.

The Contribution of Neutrophil Extracellular Traps to Coagulopathy in Patients with COVID-19-Related Thrombosis

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with hypercoagulability and increased incidence of thrombotic events. In this study, we investigated the levels of neutrophil extracellular trap biomarkers and von Willebrand factor to assess if these could predict the occurrence of a thrombotic event in COVID-19 patients. We enrolled 202 patients hospitalized with symptomatic COVID-19 infection. Of those, 104 patients did not experience any type of thrombotic events before or during their hospitalization. These patients were compared to the other cohort of 98, who experienced thrombotic events before or during their hospitalization. In total, 61 patients who experienced thrombotic events had the event after initial blood collection, so the predictive capacity of biomarkers in these patients was evaluated. Citrullinated histone H3 was the best predictive biomarker for thrombotic events in COVID-19 regardless of age, sex, and race; disease severity was also a significant predictor in most thrombotic event groups. These results may better inform treatment and prophylaxis of thrombotic events in COVID-19 and similar viral illnesses in the future to improve outcomes and reduce mortality.

Malnutrition is associated with severe outcome in elderly patients hospitalised with COVID-19

Some studies have identified influencing factors of COVID-19 illness in elderly, such as underlying diseases, but research on the effect of nutritional status is still lacking. This study retrospectively examined the influence of nutritional status on the outcome of elderly COVID-19 inpatients. A retrospective analysis of the clinical data of 4241 COVID-19 patients who were admitted to a third-class hospital of Nanchang between November 1, 2022 and January 31, 2023 was conducted. Nutritional status was assessed using the prognostic nutritional index (PNI) and controlling nutritional status score (CONUT). The influence of nutritional status on the outcome of COVID-19 patients was determined through multivariate adjustment analysis, restrictive cubic spline, and receiver operating characteristic curve (ROC). Compared with mild/no malnutrition, severe malnutrition substantially increased the critical outcome of COVID-19. A linear relationship was observed between the odds ratio (OR) and PNI and CONUT (P > 0.05). The area under the ROC curve indicated that PNI was the better predictor. The optimal cutoff value of PNI was 38.04 (95%CI: 0.797 ~ 0.836, AUC = 0.817), with a sensitivity of 70.7% and a specificity of 79.6%. The critical illness of elderly COVID-19 patients shows a linear relationship with malnutrition at admission. The use of PNI to assess the prognosis of COVID-19 eldeely patients is reliable, highlighting the importance for doctors to closely pay attention to the nutritional status of COVID-19 patients. Focusing on nutritional status in clinical practice can effectively reduce the critical illness of elderly COVID-19 patients.

Association of COVID-19 with acute and post-acute risk of multiple different complications and mortality in patients infected with omicron variant stratified by initial disease severity: a cohort study in Hong Kong

BackgroundFew studies have attempted to use clinical and laboratory parameters to stratify COVID-19 patients with severe versus non-severe initial disease and evaluate age-specific differences in developing multiple different COVID-19-associated disease outcomes.MethodsA retrospective cohort included patients from the electronic health database of Hong Kong Hospital Authority between 1 January 2022 and 15 August 2022 until 15 November 2022. The cohort was divided into three cohorts by age (≤ 40, 41–64, and ≥ 65 years old). Each age cohort was stratified into four groups: (1) COVID-19 critically exposed group (ICU admission, mechanical ventilation support, CRP > 80 mg/L, or D-dimer > 2 g/mL), (2) severely exposed group (CRP 30–80 mg/L, D-dimer 0.5–2 g/mL, or CT value < 20), (3) mildly–moderately exposed group (COVID-19 positive-tested but not fulfilling the criteria for the aforementioned critically and severely exposed groups), and (4) unexposed group (without COVID-19). The characteristics between groups were adjusted with propensity score-based marginal mean weighting through stratification. Cox regression was conducted to determine the association of COVID-19 disease severity with disease outcomes and mortality in the acute and post-acute phase (< 30 and ≥ 30 days from COVID-19 infection) in each age group.ResultsA total of 286,114, 320,304 and 194,227 patients with mild–moderate COVID-19 infection; 18,419, 23,678 and 31,505 patients with severe COVID-19 infection; 1,168, 2,261 and 10,178 patients with critical COVID-19 infection, and 1,143,510, 1,369,365 and 1,012,177 uninfected people were identified in aged ≤ 40, 40–64, and ≥ 65 groups, respectively. Compared to the unexposed group, a general trend tending towards an increase in risks of multiple different disease outcomes as COVID-19 disease severity increases, with advancing age, was identified in both the acute and post-acute phases. Notably, the mildly–moderately exposed group were associated with either insignificant risks (aged ≤ 40) or the lowest risks (aged > 40) for the disease outcomes in the acute phase of infection (e.g., mortality risk HR (aged ≤ 40): 1.0 (95%CI: 0.5,2.0), HR (aged 41–64): 2.1 (95%CI: 1.8, 2.6), HR (aged > 65): 4.8 (95%CI: 4.6, 5.1)); while in the post-acute phase, these risks were largely insignificant in those aged < 65, remaining significant only in the elderly (age ≥ 65) (e.g., mortality risk HR (aged ≤ 40): 0.8 (95%CI: (0.5, 1.0)), HR (aged 41–64): 1.1 (95%CI: 1.0,1.2), HR (aged > 65): 1.5 (95%CI: 1.5,1.6)). Fully vaccinated patients were associated with lower risks of disease outcomes than those receiving less than two doses of vaccination.ConclusionsThe risk of multiple different disease outcomes in both acute and post-acute phases increased significantly with the increasing severity of acute COVID-19 illness, specifically among the elderly. Moreover, future studies could improve by risk-stratifying patients based on universally accepted thresholds for clinical parameters, particularly biomarkers, using biological evidence from immunological studies.

Psychological distress among healthcare providers during the COVID-19 pandemic: patterns over time

BackgroundCOVID-19 added to healthcare provider (HCP) distress, but patterns of change remain unclear. This study sought to determine if and how emotional distress varied among HCP between March 28, 2021 and December 1, 2023.MethodsThis longitudinal study was embedded within the 42-month prospective COVID-19 Cohort Study that recruited HCP from four Canadian provinces. Information was collected at enrollment, from annual exposure surveys, and vaccination and illness surveys. The 10-item Kessler Psychological Distress Scale (K10) was completed approximately every six months after March 28, 2021. Linear mixed effects models, specifically random intercept models, were generated to determine the impact of time on emotional distress while accounting for demographic and work-related factors.ResultsBetween 2021 and 2023, the mean K10 score fell by 3.1 points, indicating decreased distress, but scores increased during periods of high levels of mitigation strategies against transmission of SARS-CoV-2, during winter months, and if taking antidepression, anti-anxiety or anti-insomnia medications. K10 scores were significantly lower for HCP who were male, older, had more children in their household, experienced prior COVID-19 illness(es), and for non-physician but regulated HCP versus nurses. A sensitivity analysis that included only those who had submitted at least five K10 surveys consisted of the factors in the full model excluding previous COVID-19 illness, occupation, and season, after adjustment. Models were also created for K10 anxiety and depression subscales.ConclusionsK10 scores decreased as the COVID-19 pandemic continued but increased during periods of high mitigation and the winter months. Personal and work-place factors also impacted HCP distress scores. Further research into best practices in distress identification and remediation is warranted to ensure future public health disasters are met with healthcare systems that are able to buffer HCP against short- and long-term mental health issues.

7053 Sex Differences in Endocrine-Related Pre-existing, COVID-19- and COVID-19 Vaccine-Related Health Conditions and Adverse Events

Abstract Disclosure: J. Knapp: Other; Self; Co-founder, Aseesa Inc. R. Karumanchi: None. C. Fee: None. S. Inslicht: None. A. Bhargava: Other; Self; Co-Founder, Aseesa Inc. COVID-19 illness-related symptoms and outcomes are highly variable, with reported sex differences. mRNA vaccines were deployed for the first-time on a large scale for COVID-19, and the endocrine effects of Pfizer’s and Moderna’s mRNA vaccines, remain to be elucidated. Associations between COVID-19 illness and/or COVID-19 vaccines and reproductive disturbances have been reported based on large nation-wide surveys and targeted studies. Yet, none of the studies have directly ascertained similarities and differences between reproductive adverse outcomes from COVID-19 illness in unvaccinated individuals versus COVID-19 mRNA vaccines in individuals without COVID-19 illness. Here, we report preliminary findings on endocrine systems from a global survey of ∼8,000-10,000 participants collected between February 2022 and October 2023. Approximately 62.5% of the participants were from the United States, and the remaining were international. Nearly 1.49% of respondents reported hospitalization after COVID-19, whereas 5.69% of the respondents reported hospitalization after vaccination in our cohort. SARS-CoV-2-related severe symptoms were reported by ∼9.3% of COVID-19 vaccinated versus 6.7% of unvaccinated individuals (p&amp;lt;0.001). Women reported more vaccine-related adverse events (AEs) than men; 30% of men and 19% of women reported no AEs after any vaccination dose. After the first dose, 60% women and 48% of men reported some AEs, whereas after the second dose, 46% of women and 40% of men reported experiencing several AEs. Sex differences were present in endocrine and autoimmune pre-existing health conditions, including thyroid disease (13%F vs 3%M), osteoporosis (6%F vs 1%M), elevated cholesterol (M&amp;gt;F), and hypertension (M&amp;gt;F). Nearly 5% of women reported pre-existing irregular menstrual cycle irregularities and hormonal changes, whereas only 2% of men reported hormonal irregularities. In unvaccinated individuals, after COVID-19 illness, nearly 6% of women reported experiencing hot flashes, whereas 7.5% reported irregular menstrual cycles. In COVID-19 vaccinated individuals without SARS-CoV-2 infection, 94.6% of men and 62.5% of women respondents reported no reproductive changes. Of those reporting reproductive AEs included hormonal changes in 5% of women and 3.5% men, hot flashes in 8.5% women and 1.9% men, heavy periods and/or dysmenorrhea in 16.7% of women, and irregular periods in17.1% of women. In summary, reproductive AEs in vaccinated individuals without COVID-19 illness were more frequent than in unvaccinated individuals with COVID-19 illness. A detailed and thorough follow-up is needed to better understand if pre-existing health conditions exacerbated vaccine-associated AEs. Presentation: 6/3/2024

7243 COVID-19 Associated Primary Autoimmune Adrenal Insufficiency: A New Clinical Entity

Abstract Disclosure: J. Naredo Rojas: None. B. Udegbe: None. I. Remba-Shapiro: None. S.L. Stockman: None. L.B. Nachtigall: None. Background: The adrenal glands express angiotensin converting enzyme and transmembrane serine protease 2 receptors for SARS-CoV-2 protein S, facilitating viral entry. Cortisol levels are decreased in COVID-19 infection in correlation with disease severity. A number of potential mechanisms could relate autoimmune adrenal insufficiency (AI) to COVID-19, but whether or not SARS-CoV-2 infection plays a direct role in the autoimmune pathogenesis of primary AI is unknown. Furthermore, while single cases have been reported, autoimmune-mediated primary adrenal insufficiency following COVID-19 illness has not been formally studied. Purpose: To determine the association and clinical presentation of primary autoimmune adrenal insufficiency in patients with COVID-19 disease. Methods: A retrospective chart review was performed on patients presenting to Massachusetts General Hospital (MGH) with primary AI in the setting of recent COVID-19 illness. Review of the literature was performed to identify additional cases. Clinical, biochemical and radiographic characteristics, and interval between the diagnosis of COVID-19 and primary AI diagnosis were evaluated. Criteria for inclusion were biochemical confirmation of AI, clinical signs and/or symptoms of adrenal insufficiency within 6 months of COVID-19 illness, and evidence of autoimmune etiology of AI. Results: Five novel cases of COVID-19 associated primary autoimmune-mediated adrenal insufficiency from our Center were identified. Review of the literature yielded five additional cases. This series combines our Center’s experience, and the cases reported to date, including a total of 10 patients, 6 men and 4 women. All men (6/6) and 2 women (2/4) were &amp;lt; 30 years old. Patients demonstrated clinical evidence of adrenal insufficiency in a median time frame of 14 days (IQR 8.5-23.3) after SARS-CoV-2 infection. Vomiting, hypotension, and hyponatremia were present in all (N=10). Other common symptoms were nausea (90%), fatigue (70%), hyperpigmentation (70%) and hyperkalemia (50%). Nine (90%) had a positive past medical and/or family history of autoimmune disease. Nine (90%) had positive 21-hydroxylase antibodies. The median serum morning cortisol level was 1.1μg/dL with an IQR of 0.7-3.0 μg/dL. The mean ACTH level was 1235.2 pg/mL with a SD of 580.1 pg/mL. The mean ACTH was 19.3 x ULN with a SD of 10.0. Adrenal imaging did not show hemorrhage or necrosis but showed atrophy in 50%. Conclusions: This series reveals that autoimmune-mediated primary adrenal insufficiency may be diagnosed in the aftermath of COVID-19 illness. Age under 30, family history and/or past medical history of autoimmune disease may be associated. Future prospective studies are needed to determine causality. Presentation: 6/1/2024

COVID-19-Associated Hospitalizations Among U.S. Adults Aged ≥18 Years - COVID-NET, 12 States, October 2023-April 2024.

Among adults, COVID-19 hospitalization rates increase with age. Data from the COVID-19-Associated Hospitalization Surveillance Network were analyzed to estimate population-based COVID-19-associated hospitalization rates during October 2023-April 2024 and identify demographic and clinical characteristics of adults aged ≥18 years hospitalized with COVID-19. Adults aged ≥65 years accounted for 70% of all adult COVID-19-associated hospitalizations, and their COVID-19-associated hospitalization rates were higher than those among younger adult age groups. Cumulative rates of COVID-19-associated hospitalization during October 2023-April 2024 were the lowest for all adult age groups during an October-April surveillance period since 2020-2021. However, hospitalization rates among all adults aged ≥75 years approached one COVID-19-associated hospitalization for every 100 persons. Among adults hospitalized with COVID-19, 88.1% had not received the 2023-2024 formula COVID-19 vaccine before hospitalization, 80.0% had multiple underlying medical conditions, and 16.6% were residents of long-term care facilities (LTCFs). Guidance for adults at high risk for severe COVID-19 illness, including adults aged ≥65 years and residents of LTCFs, should continue to focus on adopting measures to reduce risk for contracting COVID-19, advocating for receipt of recommended COVID-19 vaccinations, and seeking prompt outpatient antiviral treatment after receipt of a positive SARS-CoV-2 test result.

A digital intervention for cognitive deficits following COVID-19: a randomized clinical trial.

Post-COVID-19 cognitive deficits are common, persistent, and disabling. Evidence on effective treatments is limited. The goal of this study was to investigate the efficacy of a digital intervention to reduce cognitive and functional deficits in adults with persistent post-COVID-19 cognitive dysfunction. We used the remotely-delivered intervention in a randomized clinical trial conducted from July 13, 2021 to April 26, 2023. We hypothesized that participants in the intervention group would improve in measures of cognition and daily functioning. Participants were adults with cognitive deficits persisting >4 weeks following acute COVID-19 illness. Of 183 participants screened, 110 were enrolled; 98 participants (78.6% female; mean age = 48.1) completed at least one study visit. Participants were randomized 1:1 to the intervention (AKL-T01) or waitlist control. AKL-T01 is a digital therapeutic using a videogame interface to target attention and executive control. The intervention was delivered remotely for 6 weeks. The primary outcome was change in performance on a sustained attention measure (Digit Symbol Matching Task). The difference in the primary outcome between the intervention (n = 49) and controls (n = 49) was not statistically significant (F [3,261] = 0.12, p = 0.95). Secondary cognitive outcomes of task-switching (F[3,262] = 2.78, p = 0.04) and processing speed (F[3,267] = 4.57, p = 0.004) improved in the intervention relative to control. Secondary measures of functioning also improved in the intervention relative to control, including disability (F[1,82] = 4.02, p = 0.05) and quality of life (F[3,271] = 2.66, p = 0.05). Exploratory analyses showed a greater reduction in total fatigue (F[1,85] = 4.51, p = 0.04), cognitive fatigue (F[1,85] = 7.20, p = 0.009), and anxiety (F[1,87] = 7.42, p = 0.008) in the intervention relative to control. Despite the lack of improvement in sustained attention, select post-COVID-19 cognitive deficits may be ameliorated by targeted cognitive training with AKL-T01, with associated improvements in quality of life and fatigue. If replicated, the scalable nature of this digital intervention may help address substantial need for accessible, effective treatments among individuals with long COVID.

Increase of serum vitamin D levels in the COVID-19 pandemic: Report of a Mexican reference clinical laboratory

BackgroundThe COVID-19 pandemic prompted health professionals to look for prevention and treatment options to improve outcomes. Vitamin D3 (VitD) is a sun dependent, immunomodulatory hormone that was widely used approaching COVID-19 because of previous experience with other RTIs. Its use was recommended in clinical practice guidelines and mainstream media, motivating supplement consumption. This increased the demand for serum VitD determinations, as well as the progressive increase of serum VitD levels. ObjectiveStudy the change in mean VitD serum levels in the population of one reference clinical laboratory before and during pandemic years. MethodsWe analyzed 65,481 results (78% female, mean age of 53.47 (M = 55, IQR = 25)). ResultsThe median Vitamin D level was higher in all seasons in the pandemic years compared to previous years: spring 24 ng/dL (IQR 13.7) vs 25.4 ng/dL (IQR 17), summer 23.5 ng/dL (IQR 13.4) vs 24.2 ng/dL (IQR 16.3), autumn 23.7 ng/dL (IQR 14.3) vs 27 ng/dL (IQR 18.7), winter 22.4 ng/dL (IQR 14.9) vs 23.4 ng/dL (IQR 17.8). ConclusionsThe increase in serum VitD during the pandemic years is probably due to the recommendations of its use in guidelines of clinical practice. Although up to date the CDC and NIH have deemed there is not enough information in favor or against VitD use, epidemiology studies should be done to observe the impact of widespread VitD use in COVID-19 and other illnesses.

Design and Rationale of MYOFLAME-19 RCT: MYOcardial protection to reduce inFLAMmatory heart disease due to COVID-19 Infection using CMR Endpoints

Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute COVID-19 illness and without overt structural heart disease. Cardiac magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement prior to development of myocardial injury and impairment is missing. Prospective multicentre randomised placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodelling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no preexisting significant comorbidities or structural heart disease, undergo standardised assessments with questionnaires, CMR imaging and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical Post-COVID inflammatory involvement on baseline CMR examination are randomised to treatment with either verum or placebo for a total of 16 weeks (W16). Participants and investigators remain blinded to the group allocation throughout the study duration. The primary efficacy endpoint is the absolute change of left ventricular ejection fraction (LVEF) to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at the 5% significance level. Secondary endpoints include assessment of changes of symptoms, CMR parameters, and CPET after W16, and frequency of major adverse cardiac events after 1 year. Safety data will be analysed for frequency, severity and types of adverse events (AEs) for all treatment groups. The proportion of AEs related to the contrast agent gadobutrol will also be analysed. A calculated sample size is a total of 280 participants (accounting for 8% drop-out), randomised in 1:1 fashion to 140 in the verum and 140 placebo group. Myoflame-19 study will examine the efficacy of a myocardial protection therapy in symptomatic participants with post-COVID inflammatory cardiac involvement determined by CMR. The aim of the intervention is to reduce the symptoms and inflammatory myocardial injury, to improve exercise tolerance and preclude the development of cardiac impairment. NCT05619653.

Associations Between Acute COVID-19 Symptom Profiles and Long COVID Prevalence: Population-Based Cross-Sectional Study.

Growing evidence suggests that severe acute COVID-19 illness increases the risk of long COVID (also known as post-COVID-19 condition). However, few studies have examined associations between acute symptoms and long COVID onset. This study aimed to examine associations between acute COVID-19 symptom profiles and long COVID prevalence using a population-based sample. We used a dual mode (phone and web-based) population-based probability survey of adults with polymerase chain reaction-confirmed SARS-CoV-2 between June 2020 and May 2022 in the Michigan Disease Surveillance System to examine (1) how acute COVID-19 symptoms cluster together using latent class analysis, (2) sociodemographic and clinical predictors of symptom clusters using multinomial logistic regression accounting for classification uncertainties, and (3) associations between symptom clusters and long COVID prevalence using modified Poisson regression. In our sample (n=4169), 15.9% (n=693) had long COVID, defined as new or worsening symptoms at least 90 days post SARS-CoV-2 infection. We identified 6 acute COVID-19 symptom clusters resulting from the latent class analysis, with flu-like symptoms (24.7%) and fever (23.6%) being the most prevalent in our sample, followed by nasal congestion (16.4%), multi-symptomatic (14.5%), predominance of fatigue (10.8%), and predominance of shortness of breath (10%) clusters. Long COVID prevalence was highest in the multi-symptomatic (39.7%) and predominance of shortness of breath (22.4%) clusters, followed by the flu-like symptom (15.8%), predominance of fatigue (14.5%), fever (6.4%), and nasal congestion (5.6%) clusters. After adjustment, females (vs males) had greater odds of membership in the multi-symptomatic, flu-like symptom, and predominance of fatigue clusters, while adults who were Hispanic or another race or ethnicity (vs non-Hispanic White) had greater odds of membership in the multi-symptomatic cluster. Compared with the nasal congestion cluster, the multi-symptomatic cluster had the highest prevalence of long COVID (adjusted prevalence ratio [aPR] 6.1, 95% CI 4.3-8.7), followed by the predominance of shortness of breath (aPR 3.7, 95% CI 2.5-5.5), flu-like symptom (aPR 2.8, 95% CI 1.9-4.0), and predominance of fatigue (aPR 2.2, 95% CI 1.5-3.3) clusters. Researchers and clinicians should consider acute COVID-19 symptom profiles when evaluating subsequent risk of long COVID, including potential mechanistic pathways in a research context, and proactively screen high-risk patients during the provision of clinical care.

A SONAR report on Nirmatrelvir/ritonavir-associated rebound COVID-19: Using new databases for evaluating new diseases.

In May 2022, the Centers for Disease Control and Prevention disseminated an alert advising that "a few" persons with Nirmatrelvir/ritonavir (NM/R)-associated rebound of COVID-19 infection had been identified. Three case reports appearing as pre-print postings described the first cases. Analyses in March 2023 by NM/R's manufacturer and the Food and Drug Administration (FDA) reported no association between NM/R and COVID-19 rebound in a large phase 3 randomized clinical trial. Our study evaluated if social media databases or electronically disseminated new articles might provide insights related to the putative new toxicity, NM/R-associated COVID-19 rebound. Information on NM/R-associated COVID-19 rebound cases was abstracted from preprint postings of non-peer-reviewed manuscripts, social media websites, electronically disseminated print and television media reports, a new FDA adverse event database for drugs that received Emergency Use Approval, and news articles in scientific journals. Thirty-five persons experienced presumed or documented NM/R-associated COVID-19 rebound, based on information described in preprint services (n = 27), Twitter postings and related news articles (n = 7), and news articles without related Twitter reports (n = 1). These reports included information on dates of initial COVID-19 illness and rebound onset, COVID-19 testing, vaccine status, presentation, and outcome. A new FDA safety database identified 12,500 possible cases of this toxicity, but the quality of these data was poor. Preprint postings preceded peer-reviewed publications describing the same cases by four months. Social media websites including Instagram, Reddit, YouTube, the Center for Disease Control and Prevention's (CDC) Health Alert Network, CDC Twitter, and Facebook did not provide clinically meaningful information on individual cases. Preprint services and Twitter facilitated identification of the largest case series of NM/R-associated COVID-19 rebound. The cases were reported in non-peer-reviewed media several weeks prior to the first peer-reviewed electronically disseminated publication of one person with this diagnosis.

Covid-19 vaccination status and beliefs of individuals with co-occurring serious mental illness and alcohol use disorder

ObjectiveThe study objective was to determine factors associated with obtaining COVID-19 vaccination in people with co-occurring alcohol use disorder (AUD) and serious mental illness (SMI). MethodsSurvey responses were obtained from 135 adults with SMI seeking community-based AUD treatment about their primary series vaccination status, COVID-19 preventative practices, vaccination motivators, reasons for vaccine hesitancy, and strategies to increase vaccination uptake. Vaccinated and unvaccinated groups were compared. Responses to survey items with nominal or Likert scales were analyzed with chi-square tests of association. Logistic regression was employed to determine predictors of vaccine status. ResultsSeventy-nine percent (n=107) of participants reported they were vaccinated. A higher proportion of vaccinated participants believed COVID-19 was a serious disease. While both groups adopted preventative hygiene practices at similar rates (e.g., washing hands), vaccinated participants engaged in more interpersonal practices directly involving others (e.g., wearing masks and avoiding crowds). The strongest vaccine motivator was protecting personal health, while the primary reason for hesitancy was potential side effects. Most unvaccinated participants endorsed increased safety information availability (61.1 %) and living with a high-risk-for-severe-infection individual (55.6 %) as reasons to overcome hesitancy. ConclusionsVaccination rates, motivators, and hesitancy reasons were similar to the general United States population. Strategies to increase vaccination in this high-risk population should include education on vaccine safety and side effects and the impacts of COVID-19 and other respiratory illnesses on others.

Differences in brain structure and cognitive performance between patients with long-COVID and those with normal recovery

BackgroundThe pathophysiology of protracted symptoms after COVID-19 is unclear. This study aimed to determine if long-COVID is associated with differences in baseline characteristics, markers of white matter diffusivity in the brain, and lower scores on objective cognitive testing. MethodsIndividuals who experienced COVID-19 symptoms for more than 60 days post-infection (long-COVID) (n = 56) were compared to individuals who recovered from COVID-19 within 60 days of infection (normal recovery) (n = 35). Information regarding physical and mental health, and COVID-19 illness was collected. The National Institute of Health Toolbox Cognition Battery was administered. Participants underwent magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). Tract-based spatial statistics were used to perform a whole-brain voxel-wise analysis on standard DTI metrics (fractional anisotropy, axial diffusivity, mean diffusivity, radial diffusivity), controlling for age and sex. NIH Toolbox Age-Adjusted Fluid Cognition Scores were used to compare long-COVID and normal recovery groups, covarying for Age-Adjusted Crystallized Cognition Scores and years of education. False discovery rate correction was applied for multiple comparisons. ResultsThere were no significant differences in age, sex, or history of neurovascular risk factors between the groups. The long-COVID group had significantly (p < 0.05) lower mean diffusivity than the normal recovery group across multiple white matter regions, including the internal capsule, anterior and superior corona radiata, corpus callosum, superior fronto-occiptal fasciculus, and posterior thalamic radiation. However, the effect sizes of these differences were small (all β<|0.3|) and no significant differences were found for the other DTI metrics. Fluid cognition composite scores did not differ significantly between the long-COVID and normal recovery groups (p > 0.05). ConclusionsDifferences in diffusivity between long-COVID and normal recovery groups were found on only one DTI metric. This could represent subtle areas of pathology such as gliosis or edema, but the small effect sizes and non-specific nature of the diffusion indices make pathological inference difficult. Although long-COVID patients reported many neuropsychiatric symptoms, significant differences in objective cognitive performance were not found.

Effectiveness of COVID-19 Vaccines in People with Severe Mental Illness: A Systematic Review and Meta-Analysis.

Prior to the introduction of COVID-19 vaccines, patients with severe mental illness (SMI) were at greater risk of COVID-19-related outcomes than the general population. It is not yet clear whether COVID-19 vaccines have reduced the risk gap. We systematically searched nine international databases and three Chinese databases to identify relevant studies from December 2020 to December 2023 to compare the risk of COVID-19-related outcomes for SMI patients to those without SMI after vaccination. Random effects meta-analysis was performed to estimate the pooled odds ratio (OR) with 95% confidence intervals (CI). Subgroup analysis, sensitivity analysis, and publication bias analysis were conducted with R software 4.3.0. A total of 11 observational studies were included. Compared with controls, SMI patients were associated with a slightly increased risk of infection (pooled OR = 1.10, 95% CI, 1.03-1.17, I2 = 43.4%), while showing a 2-fold higher risk of hospitalization (pooled OR = 2.66, 95% CI, 1.13-6.22, I2 = 99.6%), even after both groups have received COVID-19 vaccines. Limited evidence suggests a higher mortality risk among SMI patients compared to controls post vaccination, but the findings did not reach statistical significance. SMI patients remain at increased risk compared to their peers in COVID-19-related outcomes even after vaccination. Vaccination appears an effective approach to prevent severe COVID-19 illness in SMI patients, and actions should be taken by healthcare providers to improve vaccination coverage in these vulnerable groups.

COVID-19 vaccination in people living with HIV: current data and perspectives.

There is no correlation between HIV per se and other risk factors for severe COVID-19 disease. Pivotal studies have shown that vaccination is one of the effective ways to prevent severe COVID-19 illness in the general population. Studies on people living with HIV (PLWH) are scarce. The majority of these studies with mRNA (BNT126b2 and mRNA-1273) and adenovirus vector (Ad26.COV2.2 and ChAdOx1) vaccines with a low number of patients included shows that PLWH on antiretroviral treatment and with CD4 count > 200/mm³ has a robust immune response. These vaccines are thus effective in preventing severe infection caused by severe acute respiratory syndrome coronavirus 2 in PLWH. However, PLWH with a CD4 count of < 200/mm³ and uncontrolled viral load (VL) seems to have a lower immune response. COVID-19 vaccines are safe in PLWH; adverse effects are mild or moderate, and their incidence is similar to non-HIV people (NHP). The CD4 count decreased significantly and transiently, and the VL rebounded insignificantly in a few patients. A complete vaccination including a third dose is, therefore, recommended. A booster dose with an mRNA vaccine is recommended in PLWH with an advanced stage of their disease.

A Real-World Experience of Rituximab: A Panacea in Therapy of Multiple Sclerosis in Low- and Middle-Income Setting.

Anti-CD20 monoclonal antibodies have received increasing attention in the past few years in the treatment of multiple sclerosis (MS). This study describes the (i) efficacy and safety of rituximab in people living with MS and (ii) assesses clinical and imaging outcomes following rituximab in MS. This is a chart review from the MS registry maintained at the institute from a University Hospital in South India. Eighty-three (M:F, 26:57) people living with MS received rituximab as immunomodulation between 2007 and 2022 with a median follow-up duration of 18 months. Fifty-nine (71%) were classified as relapsing-remitting MS, 16 (19%) were secondary progressive MS, and 8 (10%) were primary progressive MS. Seventy-two (87%) MS patients did not experience any relapse after receiving rituximab. In relapsing-remitting MS patients, the mean annualized recurrence rate dropped from 1.24 ± 1.19 to 0.16 ± 0.37. Infusion-related reaction occurred in 5 (6% of adverse events), urinary infections in 7 (8.4%), systemic infections in 3 (3%), Pneumocystis carinii pneumonia occurred in 1 (1%), and herpes zoster infection in 1 (1%) patient. Mortality was observed in 3 (3.5%) patients. While being on rituximab, 18 (22%) patients had mild COVID-19 illness and they all made complete recovery without any sequalae. Rituximab is a safe, well-tolerated, easily accessible, inexpensive, and effective therapeutic option for people with MS. Rituximab showed both clinical and radiological improvement after a median follow-up of 1.5 years. None of our patients showed any severe COVID infection nor side effects after receiving COVID vaccination.

Long COVID among people with HIV: A systematic review and meta-analysis.

People with HIV might be at an increased risk of long COVID (LC) because of their immune dysfunction and chronic inflammation and alterations in immunological responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]). This systematic review aimed to evaluate the association between HIV infection and LC and the prevalence and characteristics of and risk factors for LC among people with HIV. Multiple databases, including Embase, PubMed, PsycINFO, Web of Science, and Sociological Abstracts, were searched to identify articles published before June 2023. Published articles were included if they presented at least one LC outcome measure among people with HIV and used quantitative or mixed-methods study designs. For effects reported in three or more studies, meta-analyses using random-effects models were performed using R software. We pooled 39 405 people with HIV and COVID-19 in 17 eligible studies out of 6158 publications in all the databases. It was estimated that 52% of people with HIV with SARS-CoV-2 infection developed at least one LC symptom. Results from the random-effects model showed that HIV infection was associated with an increased risk of LC (odds ratio 2.20; 95% confidence interval 1.25-3.86). The most common LC symptoms among people with HIV were cough, fatigue, and asthenia. Risk factors associated with LC among people with HIV included a history of moderate-severe COVID-19 illness, increased interferon-gamma-induced protein 10 or tumour necrosis factor-α, and decreased interferon-β, among others. The COVID-19 pandemic continues to exacerbate health inequities among people with HIV because of their higher risk of developing LC. Our review is informative for public health and clinical communities to develop tailored strategies to prevent aggravated LC among people with HIV.

Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: Insights from prospectively collected data in the BRACE trial

BackgroundSome individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospective data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illnesses, identify factors associated with the risk of PACS, and explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses. MethodsData from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed. Symptom data were prospectively collected over 12 months, allowing detailed characterisation of symptom patterns. Participants with COVID-19 and non-COVID-19 respiratory illness episodes were compared, focussing on symptom severity, duration (including PACS using NICE and WHO definitions), and pre-existing symptoms. FindingsParticipants with COVID-19 had significantly more severe illness compared to those with non-COVID-19 respiratory illnesses (OR 7·4, 95%CI 5·6-9·7). Symptom duration meeting PACS definitions occurred in a higher proportion of COVID-19 cases than non-COVID-19 respiratory controls using both the NICE definition (2·5% vs 0·5%, OR 6·6, 95%CI 2·4-18·3) and the WHO definition (8·8% vs 3·7%, OR 2·5, 95%CI 1·4-4·3). When considering only participants with COVID-19, age (aOR 2·8, 95%CI 1·3-6·2), chronic respiratory disease (aOR 5·5, 95%CI 1·3-23·1), and pre-existing symptoms (aOR 3·0, 95%CI 1·4-6·3) were associated with an increased risk of developing PACS. Symptoms associated with PACS were also reported by participants in the months preceding their COVID-19 or non-COVID-19 respiratory illnesses (32% fatigue and muscle ache, 11% intermittent cough and shortness of breath). InterpretationHealthcare workers with COVID-19 experienced more severe and longer-lasting symptoms than those with non-COVID-19 respiratory illnesses, with a higher proportion meeting the WHO or NICE definitions of PACS. Age, chronic respiratory disease, and pre-existing symptoms increased the risk of developing PACS following COVID-19. FundingBill & Melinda Gates Foundation [INV-017302] and others (see Acknowledgements).