Risk Factors For Severe Disease Research Articles

Baseline predictors of disease severity in immune checkpoint inhibitor-induced inflammatory arthritis.

The objective of this study was to determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor-induced inflammatory arthritis (ICI-inflammatory arthritis). Participants were adults with rheumatologist diagnosed ICI-inflammatory arthritis. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of inflammatory arthritis >6 months after ICI cessation and requirement of CSs. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate. One hundred and twenty-six patients with ICI-inflammatory arthritis were included; 53 patients (42%) required a csDMARD/bDMARD. In the univariate logistic regression analysis, higher clinical disease activity index (CDAI), tenosynovitis, longer symptom duration before first rheumatology visit and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; in addition, there was a trend towards those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein-4)/PD-1 (Programmed cell death protein-1) therapy and CS use at baseline were associated with a higher risk of persistent inflammatory arthritis. Higher levels of disease activity, tenosynovitis and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI-inflammatory arthritis, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial CS dose, earlier rheumatology referral, and adoption of immunosuppression beyond CSs to improve outcomes.

Exploring the Network between Adipocytokines and Inflammatory Response in SARS-CoV-2 Infection: A Scoping Review.

Adipose tissue is actually regarded as an endocrine organ, rather than as an organ that merely stores energy. During the COVID-19 pandemic, obesity has undoubtedly emerged as one of the most important risk factors for disease severity and poor outcomes related to SARS-CoV-2 infection. The aberrant production of cytokine-like hormones, called adipokines, may contribute to alterations in metabolism, dysfunction in vascular endothelium and the creation of a state of general chronic inflammation. Moreover, chronic, low-grade inflammation linked to obesity predisposes the host to immunosuppression and excessive cytokine activation. In this respect, understanding the mechanisms that link obesity with the severity of SARS-CoV-2 infection could represent a real game changer in the development of new therapeutic strategies. Our review therefore examines the pathogenic mechanisms of SARS-CoV-2, the implications with visceral adipose tissue and the influences of the adipose tissue and its adipokines on the clinical behavior of COVID-19.

Anti-SARS-Cov-2 IgG Antibody Response in COVID- 19 Ischemic Heart Disease Patients

Background: Coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has reached pandemic status, overwhelmed health care systems, strangled the global economy, and led to a devastating loss of life. The presence of cardiovascular comorbidities in COVID-19 patients acts as risk factor for disease severity and is associated with higher rates of cardiac injury, cardiac attack, intensive care unit admission and high mortality. Without pre-existing cardiovascular comorbidities, COVID-19 itself can cause serious heart damage. Serum Anti-SARS-CoV-2 IgG estimation is an important tool for monitoring of COVID-19 patients. Objectives: To assess post COVID-19 Anti-SARS-CoV-2 IgG antibody response in Ischemic heart disease patients. Method: This cross-sectional analytical study was conducted in the Department of Biochemistry, Dhaka Medical College, Dhaka during the period of January 2021 to December 2021. For this study, a total number of 70 diagnosed COVID-19 patients with or without IHD, were selected according to inclusion and exclusion criteria from Cardiology Department (OPD and Indoor) and Post COVID-19 Follow-up Clinic of Dhaka Medical College Hospital, Dhaka. Among 70 subjects, 35 were post COVID-19 with IHD patients (Cases in group-A) and 35 were post COVID-19 without IHD patients (Comparison group in Group-B). By using safety measures, informed written consent was taken from each patient and venous blood sample was collected for estimation of serum Anti-SARS-CoV-2 IgG level. The results were compared statistically between two groups and the significance was defined as p<0.05. Results: Mean ± SD years of age of the subjects in group-A and Group-B were 57.62 ± 11.32 years and 54.14 ± 11.29 years respectively. Majority of patients were in >60 year’s age group followed by 51-60 years. The serum Anti-SARS-CoV-2 IgG level was significantly higher in group-A than Group-B (Median [IQR]: 10786.5 ......

DENV-specific IgA contributes protective and non-pathologic function during antibody-dependent enhancement of DENV infection.

Dengue represents a growing public health burden worldwide, accounting for approximately 100 million symptomatic cases and tens of thousands of fatalities yearly. Prior infection with one serotype of dengue virus (DENV) is the greatest known risk factor for severe disease upon secondary infection with a heterologous serotype, a risk which increases as serotypes co-circulate in endemic regions. This disease risk is thought to be mediated by IgG-isotype antibodies raised during a primary infection, which poorly neutralize heterologous DENV serotypes and instead opsonize virions for uptake by FcγR-bearing cells. This antibody-dependent enhancement (ADE) of infection leads to a larger proportion of susceptible cells infected, higher viremia and greater immunopathology. We have previously characterized the induction of a serum IgA response, along with the typical IgM and IgG responses, during dengue infection, and have shown that DENV-reactive IgA can neutralize DENV and competitively antagonize IgG-mediated ADE. Here, we evaluate the potential for IgA itself to cause ADE. We show that IgG, but not IgA, mediated ADE of infection in cells expressing both FcαR and FcγRs. IgG-mediated ADE stimulated significantly higher pro-inflammatory cytokine production by primary human macrophages, while IgA did not affect, or slightly suppressed, this production. Mechanistically, we show that DENV/IgG immune complexes bind susceptible cells significantly more efficiently than DENV/IgA complexes or virus alone. Finally, we show that over the course of primary dengue infection, the expression of FcγRI (CD64) increases during the period of acute viremia, while FcγRIIa (CD32) and FcαR (CD89) expression decreases, thereby further limiting the ability of IgA to facilitate ADE in the presence of DENV. Overall, these data illustrate the distinct protective role of IgA during ADE of dengue infection and highlight the potential therapeutic and prognostic value of DENV-specific IgA.

Clinical characteristics and predictors of human mpox outcome during the 2022 outbreak in Nigeria: a cohort study

Research from sub-Saharan Africa that contributes to our understanding of the 2022 mpox (formerly known as monkeypox) global outbreak is insufficient. Here, we describe the clinical presentation and predictors of severe disease among patients with mpox diagnosed between Feb 1, 2022, and Jan 30, 2023 in Nigeria. We did a cohort study among laboratory-confirmed and probable mpox cases seen in 22 mpox-treatment centres and outpatient clinics across Nigeria. All individuals with confirmed and probable mpox were eligible for inclusion. Exclusion criteria were individuals who could not be examined for clinical characterisation and those who had unknown mortality outcomes. Skin lesion swabs or crust samples were collected from each patient for mpox diagnosis by PCR. A structured questionnaire was used to document sociodemographic and clinical data, including HIV status, complications, and treatment outcomes from the time of diagnosis to discharge or death. Severe disease was defined as mpox associated with death or with a life-threatening complication. Two logistic regression models were used to identify clinical characteristics associated with severe disease and potential risk factors for severe disease. The primary outcome was the clinical characteristics of mpox and disease severity. We enrolled 160 people with mpox from 22 states in Nigeria, including 134 (84%) adults, 114 (71%) males, 46 (29%) females, and 25 (16%) people with HIV. Of the 160 patients, distinct febrile prodrome (n=94, 59%), rash count greater than 250 (90, 56%), concomitant varicella zoster virus infection (n=48, 30%), and hospital admission (n=70, 48%) were observed. Nine (6%) of the 160 patients died, including seven (78%) deaths attributable to sepsis. The clinical features independently associated with severe disease were a rash count greater than 10 000 (adjusted odds ratio 26·1, 95% CI 5·2-135·0, p<0·0001) and confluent or semi-confluent rash (6·7, 95% CI 1·9-23·9). Independent risk factors for severe disease were concomitant varicella zoster virus infection (3·6, 95% CI 1·1-11·5) and advanced HIV disease (35·9, 95% CI 4·1-252·9). During the 2022 global outbreak, mpox in Nigeria was more severe among those with advanced HIV disease and concomitant varicella zoster virus infection. Proactive screening, management of co-infections, the integration and strengthening of mpox and HIV surveillance, and preventive and treatment services should be prioritised in Nigeria and across Africa. None.

Clinical Outcomes in Patients With COVID-19 and Hematologic Disease.

Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and nonmalignant hematologic diseases and COVID-19. Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-days all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic. Thirty-days all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-months overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients. Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed.

Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial.

The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study. Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5days of symptom onset were assigned to the intervention (n=77) or placebo (n=79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11-13days post-symptom onset. One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11-13days post-symptom onset (p=0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed. The intervention reduced symptoms of mild/moderate COVID-19. DOH-27-062021-9191 (South African National Clinical Trials Register).

Trends in severe outcomes in SARS-CoV-2-positive hospitalized patients with rheumatic diseases: a monocentric observational and case-control study in northern Italy.

Rheumatic disease patients are at greater risk of infection due to their disease, comorbidities, and immunosuppressive therapy. COVID-19 outcomes in this patient setting appeared to be similar to those of the general population. However, data on this topic were mainly related to small studies on a limited number of patients. Consequently, to date, this field remains poorly explored, particularly in the pre-vaccine era. This monocentric study aimed to describe the intrahospital mortality in rheumatic patients with SARS-CoV-2 consecutively hospitalized from 21 February to 31 December 2020, before anti-SARS-CoV-2 vaccine administration spread, compared with non-rheumatic patients. Of 2491 included patients, 65 [3%, median (interquartile range) age 75 (64.76-82.239 years, 65% women] were suffering from rheumatic diseases. A total of 20 deaths were reported [case fatality rate 31%, 95% confidence interval (CI): 19-42] compared with 433 deaths (19%, 95% CI: 17-20) in patients without rheumatic diseases (p=0.024). However, the rheumatic disease was not associated with a significant increase in univariate mortality hazards (hazard ratio 1.374, 95% CI: 0.876-2.154), and after adjustment (hazard ratio 1.199, 95% CI: 0.759-1.894) by age, sex and Charlson comorbidity index. The incidence of intensive care unit admission, death, and discharge in the case-control study was comparable between rheumatic and non-rheumatic patients. The presence of rheumatic diseases in SARS-CoV-2-hospitalized patients did not represent an independent risk factor for severe disease or mortality.

A Patient with Severe Fever with Thrombocytopenia Syndrome, Activated Partial Thromboplastin Time Prolongation, and Transient Antiphospholipid Antibodies.

A prolonged activated partial thromboplastin time (APTT) is observed in patients with severe fever with thrombocytopenia syndrome (SFTS) and is one of the risk factors for severe disease. The mechanism underlying a prolonged APTT is largely unknown. The presence of antiphospholipid (aPL) antibodies in various viral infections has been documented but never reported in a patient with SFTS. We herein report the first SFTS patient with APTT prolongation and concurrent transiently positive aPL antibodies (lupus anticoagulants and anticardiolipin antibodies) with no coagulation factor deficiency.

Transient low T3 syndrome in patients with COVID-19: a new window for prediction of disease severity.

To investigate the relationship of low T3 syndrome with disease severity in patients with COVID-19. The clinical data of 145 patients with COVID-19 were retrospectively collected, and patients were divided into a low T3 group and a normal T3 group. Logistic regression models were used to assess predictive performance of FT3. Receiver operating characteristic (ROC) analysis was used to evaluate the use of low T3 syndrome in predicting critical disease. Kaplan-Meier analysis was used to analyze the impact of low T3 syndrome on mortality. The prevalence of low T3 level among COVID-19 patients was 34.48%. The low T3 group was older, and had lower levels of hemoglobin, lymphocytes, prealbumin, and albumin, but higher levels of white blood cells, neutrophils, CRP, ESR, and D-dimer (all p<0.05). The low T3 group had greater prevalences of critical disease and mortality (all p <0.05). Multivariate logistic regression analysis showed that the Lymphocytes, free T3 (FT3), and D-dimer were independent risk factors for disease severity in patients with COVID-19. ROC analysis showed that FT3, lymphocyte count, and D-dimer, and all three parameters together provided reliable predictions of critical disease. Kaplan-Meier analysis showed the low T3 group had increased mortality (p<0.001). Six patients in the low T3 group and one patient in the normal T3 group died. All 42 patients whose T3 levels were measured after recovery had normal levels after discharge. Patients with COVID-19 may have transient low T3 syndrome at admission, and this may be useful for predicting critical illness.

The evolution of folate supplementation - from one size for all to personalized, precision, poly-paths.

Folate is a crucial nutrient that supports physiological functions. Low folate levels is a risk factor for several diseases, including cardiovascular diseases and neural tube defects. The most used folate supplement is folic acid, a synthetic oxidative form, and folic acid grain fortification is a success story of public health. However, the metabolic conversion of folic acid to bioactive tetrahydrofolate requires several enzymes and cofactors. Therefore, these factors influence its bioavailability and efficacy. In contrast, 5-methyltetrahydrofolate is used directly and participates in one-carbon metabolism, and the use of 5-methyltetrahydrofolate as an alternative folate supplement has increased. The metabolism of 5-methyltetrahydrofolate is primarily dependent on the transmembrane transporter, reduced folate carrier (RFC), and the RFC gene SLC19A1 variant is a functional polymorphism that affects folate status indexes. Recent studies demonstrated that the expression of RFC and cystathionine β-synthase, another enzyme required for homocysteine clearance, increases significantly by supplementation with calcitriol (vitamin D3), suggesting that calcitriol intake promotes the bioavailability of folate and has synergistic effects in homocysteine clearance. The advancements in biomedical and cohort studies and clinical trials have enhanced our understanding of the critical roles of folate and the regulation of one-carbon metabolism. We anticipate that the field of folate supplementation is poised to evolve from one size for all to personalized, precision, poly-paths (3Ps), which is a critical measure to meet individual needs, maximize health benefits, and minimize side effects.

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS. Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.

Epidemiology, Clinical Characteristics and Risk Factors for Severity of Chronic Disseminated Candidiasis in Jerusalem, Israel.

Chronic disseminated candidiasis (CDC) occurs mostly in patients with acute hematologic malignancy and its clinical manifestations derive from immune reconstitution following neutrophil recovery. The aim of this study was to describe epidemiological and clinical characteristics of CDC and define risk factors for disease severity. Demographic and clinical data were collected from medical files of patients with CDC hospitalized in two tertiary medical centers in Jerusalem between 2005 and 2020. Associations between different variables and disease severity were evaluated, as well as characterization of Candida species. The study included 35 patients. CDC incidence slightly increased during study years and the average number of involved organs and disease duration was 3 ± 1.26 and 178 ± 123days, respectively. Candida grew in blood in less than third of cases and the most common isolated pathogen was Candida tropicalis (50%). Histopathological or microbiological workup in patients who underwent an organ biopsy demonstrated Candida in about half of the patients. Nine months after starting antifungals, 43% of the patients still didn't have resolution of organ lesions in imaging modalities. Factors associated with protracted and extensive disease were prolonged fever prior to CDC and absence of candidemia. A C- Reactive Protein (CRP) cutoff level of 7.18mg/dL was found to predict extensive disease. In conclusion, CDC incidence is increasing and the number of involved organs is higher than previously described. Clinical factors such as fever duration prior to CDC and absence of candidemia can predict severe course of disease and assist in treatment decisions and follow-up planning.

#5520 EFFICACY OF MRNA VACCINE BNT162B2 AGAINST NOVEL SARS-COV-2 VIRUS IN END-STAGE KIDNEY DISEASE

Abstract Background and Aims Covid-19 pandemic affected more than 600 million people worldwide. Chronic kidney disease was shown to be a significant risk factor for disease severity. The introduction of the novel mRNA vaccines against SARS-CoV-2 prompted studies to evaluate their efficacy and safety. This study aims to assess the humoral response to the BNT162b2 vaccine, its durability, the booster effect, and breakthrough infections among end-stage renal disease patients (ESRD). Methods A one-year, single center, observational prospective study was conducted between 2021 and 2022. The cohort included adult dialysis patients (n = 143), kidney transplant recipients (11), and healthy controls (n = 75). Demographic and clinical data were retrieved from electronic medical records. All participants received 30 µg/dose of BNT162b2 mRNA vaccine, at 0 and 3 weeks. A third vaccine (booster) was administered at least 6 months after the first dose. SARS-CoV-2 infection was diagnosed based on PCR test of nasal and oropharyngeal swabs. Infections that occurred from January 2022 were attributed to omicron variant. Longitudinal blood samples were collected as indicated in Figure after the first vaccine dose (V1) and after the booster dose (V3). Humoral immune response was assessed by measuring serum IgG antibodies against the receptor-binding domain of the SARS-CoV-2 S1 subunit, using the ABBOTT kit. The study protocol was approved by the Institutional Review Board and was conducted in adherence to the Declaration of Helsinki. Results Twenty-eight weeks after two doses of vaccine, the median antibody levels were significantly lower in dialysis and transplant patients compared with healthy controls (122 AU/mL (2–4,557) and 6 AU/mL (1–217) vs 831 AU/mL (117–40,000), respectively). Furthermore, only 75% of dialysis patients developed positive antibody response (&amp;gt;50 AU/mL) as compared to 100% in controls (see Figure 1). A significant waning of immunity was seen over time in both dialysis and healthy participants (p &amp;lt; .0001). Four weeks after a booster dose, antibody levels surged and did not differ between dialysis and healthy participants 13,840 ± 15,126 AU/mL vs 18,080 ± 13,354 AU/mL, respectively (p = .283). Non-responder rate among dialysis patients dropped from 21% after a 2-dose vaccination to 7% after a booster dose. Lower antibody levels measured at 28-week after the first vaccination were associated with higher risk for Covid-19 infection (p = .021). Of note, all infection cases occurred in subjects with antibody levels below 1050 AU/mL. However, no association was found between antibody levels and Covid-19-omicron variant infection rate among dialysis patients and healthy controls (p = 0.650). Conclusions Dialysis patients had a blunted humoral immune response after two doses of BNT162b2 vaccine compared with healthy controls, which improved after a booster dose. Based on the observed omicron variant breakthrough infections, further studies are needed to improve the vaccines' efficacy against the evolving SARS-CoV-2 variants.

Risk factors for disease severity among children with Covid-19: a clinical prediction model

BackgroundChildren account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19.MethodsWe identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state’s pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy.ResultsA total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram’s sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 – 0·92) respectively.ConclusionOur nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.

Clinical and inflammation marker features of cancer patients with COVID-19: data of Istanbul, Turkey multicenter cancer patients (2020–2022)

Objective We aimed to identify a rapid, accurate, and accessible biomarker in the early stages of COVID-19 that can determine the prognosis of the disease in cancer patients. Methods A total number of 241 patients with solid cancers who had a COVID-19 diagnosis between March 2020 and February 2022 were included in the study. Factors and ten different markers of inflammation were analyzed by year of diagnosis of COVID-19 and grouped by severity of infection. Results Hospitalization, referral to the intensive care unit (ICU), mechanical ventilation, and death were more frequent in 2020 than in 2021 and 2022 (mortality rates, respectively, were 18.8%, 3.8%, and 2.5%). Bilateral lung involvement and chronic lung disease were independent risk factors for severe disease in 2020. In 2021–2022, only bilateral lung involvement was found as an independent risk factor for severe disease. The neutrophil-to-lymphocyte platelet ratio (NLPR) with the highest area under the curve (AUC) value in 2020 had a sensitivity of 71.4% and specificity of 73.3% in detecting severe disease (cut-off > 0.0241, Area Under the Curve (AUC) = 0.842, p <.001). In 2021–2022, the sensitivity of the C-reactive protein-to-lymphocyte ratio (CRP/L) with the highest AUC value was 70.0%, and the specificity was 73.3% (cut-off > 36.7, AUC = 0.829, p = .001). Conclusions This is the first study to investigate the distribution and characteristics of cancer patients, with a focus on the years of their COVID-19 diagnosis. Based on the data from our study, bilateral lung involvement is an independent factor for severe disease, and the CRP/L inflammation index appears to be the most reliable prognostic marker.

COVID-19 in inherited metabolic disorders: Clinical features and risk factors for disease severity.

Old age, obesity, and certain chronic conditions are among the risk factors for severe COVID-19. More information is needed on whether inherited metabolic disorders (IMD) confer risk of more severe COVID-19. We aimed to establish COVID-19 severity and associated risk factors in patients with IMD currently followed at a single metabolic center. Among all IMD patients followed at a single metabolic referral center who had at least one clinic visit since 2018, those with accessible medical records were reviewed for SARS-CoV-2 tests. COVID-19 severity was classified according to the WHO recommendations, and IMD as per the international classification of IMD. Among the 1841 patients with IMD, 248 (13.5%) had tested positive for COVID-19, 223 of whom gave consent for inclusion in the study (131 children and 92 adults). Phenylalanine hydroxylase (48.4%) and biotinidase (12.1%) deficiencies were the most common diagnoses, followed by mucopolysaccharidoses (7.2%). 38.1% had comorbidities, such as neurologic disabilities (22%) or obesity (9.4%). The majority of COVID-19 episodes were asymptomatic (16.1%) or mild (77.6%), but 6 patients (2.7%) each had moderate and severe COVID-19, and two (0.9%) had critical COVID-19, both of whom died. 3 patients had an acute metabolic decompensation during the infection. Two children developed multisystem inflammatory syndrome (MIS-C). Long COVID symptoms were present in 25.2%. Presence of comorbidities was significantly associated with more severe COVID-19 in adults with IMD (p<0.01), but not in children (p=0.45). Compared to other categories of IMD, complex molecule degradation disorders were significantly associated with more severe COVID-19 in children (p<0.01); such a significant IMD category distinction was not found in adults. This is the largest study on COVID-19 in IMD patients relying on real-word data and objective definitions, and not on merely expert opinions or physician surveys. COVID-19 severity and long COVID incidence in IMD are probably similar to the general population, and the risk of acute metabolic decompensation is not likely to be greater than that in other acute infections. Disease category (complex molecule degradation) in children, and comorbidities in adults may be associated with COVID-19 severity in IMD. Additionally, the first documented accounts of COVID-19 in 27 different IMD are recorded. The high occurrence of MIS-C may be coincidental, but warrants further study.

Obesity and Viral Infections

The 2019 novel coronavirus disease (COVID-19) triggered a rapidly expanding global pandemic. The presence of obesity in patients with COVID-19 has been established as a risk factor for disease severity, hospital admission, and mortality. Thus, it is imperative those living with obesity be vaccinated against COVID-19. Although there is a timeframe COVID-19 vaccines are efficacious in those living with obesity, more studies need to be conducted to ensure that those long-lasting protection is maintained, as obesity has implications on the immune system.

Multimorbidity and social determinants of health in the US prior to the COVID-19 pandemic and implications for health outcomes: a cross-sectional analysis based on NHANES 2017–2018

Multimorbidity increases the risk of all-cause mortality, and along with age, is an independent risk factor for severe disease and mortality from COVID-19. Inequities in the social determinants of health contributed to increased mortality from COVID-19 among disadvantaged populations. This study aimed to evaluate the prevalence of multimorbid conditions and associations with the social determinants of health in the US prior to the pandemic.Methods Data from the 2017–18 cycle of NHANES were used to determine the prevalence of 13 chronic conditions, and the prevalence of having 0, 1, or 2 or more of those conditions, among the US adult population aged ≥ 20 years. Multimorbidity was defined as having 2 or more of these conditions. Data were stratified according to demographic, socioeconomic and indicators of health access, and analyses including logistic regression, performed to determine the factors associated with multimorbidity.Results The prevalence of multimorbidity was 58.4% (95% CI 55.2 to 61.7). Multimorbidity was strongly associated with age and was highly prevalent among those aged 20–29 years at 22.2% (95% CI 16.9 to 27.6) and continued to increase with older age. The prevalence of multimorbidity was highest in those defined as Other or multiple races (66.9%), followed in decreasing frequency by rates among non-Hispanic Whites (61.2%), non-Hispanic Blacks (57.4%), Hispanic (52.0%) and Asian (41.3%) groups.Logistic regression showed a statistically significant relationship between multimorbidity and age, as expected. Asian race was associated with a reduced likelihood of 2 or more chronic conditions (OR 0.4; 95% CI 0.35 to 0.57; P < 0.0001). Socioeconomic factors were related to multimorbidity. Being above the poverty level (OR 0.64; 95% CI 0.46 to 0.91, p = 0.013); and a lack of regular access to health care (OR 0.61 (95% CI 0.42 to 0.88, p = 0.008) were both associated with a reduced likelihood of multimorbidity. Furthermore, there was a borderline association between not having health insurance and reduced likelihood of multimorbidity (OR 0.63; 95% CI 0.40 to 1.0; p = 0.053).Conclusions There are high levels of multimorbidity in the US adult population, evident from young adulthood and increasing with age. Cardiometabolic causes of multimorbidity were highly prevalent, especially obesity, hyperlipidemia, hypertension, and diabetes; conditions subsequently found to be associated with severe disease and death from COVID-19. A lack of access to care was paradoxically associated with reduced likelihood of comorbidity, likely linked to underdiagnosis of chronic conditions. Obesity, poverty, and lack of access to healthcare are factors related to multimorbidity and were also relevant to the health impact of the COVID-19 pandemic, that must be addressed through comprehensive social and public policy measures. More research is needed on the etiology and determinants of multimorbidity, on those affected, patterns of co-morbidity, and implications for individual health and impact on health systems and society to promote optimal outcomes. Comprehensive public health policies are needed to tackle multimorbidity and reduce disparities in the social determinants of health, as well as to provide universal access to healthcare.

Paenibacillus thiaminolyticus sepsis and meningoencephalitis in a 37-day old preterm infant

Introduction: The Paenibacillus genus consists of saprophytic organisms that are commonly associated with soil, water, plants, feces, and diseased insect larvae. Human infection is rare. This disease typically occurs in immunocompromised hosts, adults with a history of intravenous drug use, and hosts with prosthetic medical devices. There are a limited number of case reports describing Paenibacillus infections in neonates. This is the second published instance of pediatric meningoencephalitis caused by Paenibacillus thiaminolyticus in a preterm infant with intrauterine drug exposure. Case Report: A 37-day-old male infant with a history of prematurity of 33 weeks completed gestation presented to the Emergency Department for acute onset poor feeding, poor color, and unresponsiveness at home. Examination revealed cyanosis, apnea, and hypotonia. Vital signs were significant for hypotension and hypothermia. Initial labs revealed a metabolic acidosis, elevated C-reactive protein, normal complete white blood cell count, and a negative viral respiratory pathogen panel. Aerobic blood culture and cerebrospinal fluid (CSF) culture were positive for P. thiaminolyticus within 24 hours. Cranial ultrasound and magnetic resonance imaging revealed changes concerning for liquefactive meningoencephalitis. The infant was admitted to the neonatal intensive care unit (NICU) and ultimately discharged home on a “do not resuscitate/do not intubate” status and later died at 11 months of age. Conclusion: Paenibacillus species are common environmental organisms but can cause devastating disease in neonates. This is the second reported case of a preterm infant with P. thiaminolyticus infection and inutero drug exposure (IUDE), supporting that prematurity and IUDE may be risk factors for severe disease.