Nutritional deficiencies that may predispose to long COVID

Abstract:

Multiple nutritional deficiencies (MND) confound studies designed to assess the role of a single nutrient in contributing to the initiation and progression of disease states. Despite the perception of many healthcare practitioners, up to 25% of Americans are deficient in five-or-more essential nutrients. Stress associated with the COVID-19 pandemic further increases the prevalence of deficiency states. Viral infections compete for crucial nutrients with immune cells. Viral replication and proliferation of immunocompetent cells critical to the host response require these essential nutrients, including zinc. Clinical studies have linked levels of more than 22 different dietary components to the likelihood of COVID-19 infection and the severity of the disease. People at higher risk of infection due to MND are also more likely to have long-term sequelae, known as Long COVID.

Source: Schloss, J.V. Nutritional deficiencies that may predispose to long COVID. Inflammopharmacol (2023). https://doi.org/10.1007/s10787-023-01183-3 https://link.springer.com/article/10.1007/s10787-023-01183-3 (Full text)

Epidemiological and clinical perspectives of long COVID syndrome

Abstract:

Long COVID, or post-acute COVID-19 syndrome, is characterized by multi-organ symptoms lasting 2+ months after initial COVID-19 virus infection. This review presents the current state of evidence for long COVID syndrome, including the global public health context, incidence, prevalence, cardiopulmonary sequelae, physical and mental symptoms, recovery time, prognosis, risk factors, rehospitalization rates, and the impact of vaccination on long COVID outcomes. Results are presented by clinically relevant subgroups.

Overall, 10-35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic stress disorder, memory loss, and difficulty concentrating. Delineating these issues will be crucial to inform appropriate post-pandemic health policy and protect the health of COVID-19 survivors, including potentially vulnerable or underrepresented groups. Directed to policymakers, health practitioners, and the general public, we provide recommendations and suggest avenues for future research with the larger goal of reducing harms associated with long COVID syndrome.

Source: Huerne K, Filion KB, Grad R, Ernst P, Gershon AS, Eisenberg MJ. Epidemiological and clinical perspectives of long COVID syndrome. Am J Med Open. 2023 Jun;9:100033. doi: 10.1016/j.ajmo.2023.100033. Epub 2023 Jan 18. PMID: 36685609; PMCID: PMC9846887. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846887/ (Full text)

Ambient air pollution exposure linked to long COVID among young adults: a nested survey in a population-based cohort in Sweden

Summary:

Background: Post COVID-19 conditions, also known as long COVID, are of public health concern, but little is known about their underlying risk factors. We aimed to investigate associations of air pollution exposure with long COVID among Swedish young adults.

Methods: We used data from the BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology [in Swedish]) cohort. From October 2021 to February 2022 participants answered a web-questionnaire focusing on persistent symptoms following acute SARS-CoV-2 infection. Long COVID was defined as symptoms after confirmed infection with SARS-CoV-2 lasting for two months or longer. Ambient air pollution levels (particulate matter ≤2.5 μm [PM2.5], ≤10 μm [PM10], black carbon [BC] and nitrogen oxides [NOx]) at individual-level addresses were estimated using dispersion modelling.

Findings: A total of 753 participants with SARS-CoV-2 infection were included of whom 116 (15.4%) reported having long COVID. The most common symptoms were altered smell/taste (n = 80, 10.6%), dyspnea (n = 36, 4.8%) and fatigue (n = 34, 4.5%). Median annual PM2.5 exposure in 2019 (pre-pandemic) was 6.39 (interquartile range [IQR] 6.06–6.71) μg/m3. Adjusted Odds Ratios (95% confidence intervals) of PM2.5 per IQR increase were 1.28 (1.02–1.60) for long COVID, 1.65 (1.09–2.50) for dyspnea symptoms and 1.29 (0.97–1.70) for altered smell/taste. Positive associations were found for the other air pollutants and remained consistent across sensitivity analyses. Associations tended to be stronger among participants with asthma, and those having had COVID during 2020 (versus 2021).

Interpretation: Ambient long-term PM2.5 exposure may affect the risk of long COVID in young adults, supporting efforts for continuously improving air quality.

Source: Zhebin Yu, Sandra Ekström, Tom Bellander, Petter Ljungman, Göran Pershagen, Kristina Eneroth et al. Ambient air pollution exposure linked to long COVID among young adults: a nested survey in a population-based cohort in Sweden. The Lancet. Published: March 07, 2023 DOI:https://doi.org/10.1016/j.lanepe.2023.100608 (Full text)

Demographic And Clinical Factors Associated With Long COVID

Risk factors for postacute sequelae of SARS-CoV-2 infection (“long COVID”) in community-dwelling populations remain poorly understood. Large-scale data, follow-up, comparison groups, and a consensus definition of long COVID are often lacking. Using data from the OptumLabs Data Warehouse on a nationwide sample of commercial and Medicare Advantage enrollees from the period January 2019 through March 2022, we examined demographic and clinical factors associated with long COVID, using two definitions of people who suffer symptoms long after they were first diagnosed with COVID-19 (“long haulers”).

We identified 8,329 long haulers using the narrow definition (diagnosis code), 207,537 long haulers using the broad definition (symptom based), and 600,161 non–long haulers (comparison group).

On average, long haulers were older and more likely female, with more comorbidities. Among narrow-definition long haulers, the leading risk factors for long COVID included hypertension, chronic lung disease, obesity, diabetes, and depression. Their time between initial COVID-19 diagnosis and diagnosis of long COVID averaged 250 days, with racial and ethnic differences. Broad-definition long haulers exhibited similar risk factors. Distinguishing long COVID from the progression of underlying conditions can be challenging, but further study may advance the evidence base related to the identification, causes, and consequences of long COVID.

Source: Song Z, Giuriato M. Demographic And Clinical Factors Associated With Long COVID. Health Aff (Millwood). 2023 Mar;42(3):433-442. doi: 10.1377/hlthaff.2022.00991. PMID: 36877912. https://pubmed.ncbi.nlm.nih.gov/36877912/

Predictors of impaired functioning among long COVID patients

Abstract:

Background: There is limited information on what acute factors predict more long-term symptoms from COVID-19.

Objective: Our objective was to conduct an exploratory factor analysis of self-reported symptoms at two time points of Long COVID-19.

Methods: Data from patients with Long COVID-19 were collected at the initial two weeks of contracting SARS CoV-2 and the most recent two weeks, with a mean duration of 21.7 weeks between the two-time points. At time point 2, participants also complete the Coronavirus Impact Scale (CIS), measuring how the COVID-19 pandemic affected various dimensions of their lives (e.g., routine, access to medical care, social/family support, etc.).

Results: At time 1, a three-factor model emerged consisting of Cognitive Dysfunction, Autonomic Dysfunction and Gastrointestinal Dysfunction. The analysis of time 2 resulted in a three-factor model consisting of cognitive dysfunction, autonomic dysfunction, and post-exertional malaise. Using factor scores from time 1, the Autonomic Dysfunction and the Gastrointestinal Dysfunction factor scores significantly predicted the CIS summary score at time two. In addition, the same two factor scores at time 1 predicted the occurrence of myalgic encephalomyelitis/chronic fatigue syndrome at time 2.

Conclusion: As Cognitive and Autonomic Dysfunction emerged as factors for both time points, suggesting health care workers might want to pay particular attention to these factors that might be related to later symptoms and difficulties with returning to pre-illness family life and work functioning.

Source: Jason LA, Dorri JA. Predictors of impaired functioning among long COVID patients. Work. 2023 Mar 8. doi: 10.3233/WOR-220428. Epub ahead of print. PMID: 36911958. https://content.iospress.com/articles/work/wor220428 (Full text)

Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review

Abstract:

Background: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors.

Methods: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, Cochrane Library, medRxiv and bioRxiv up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness.

Results: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36% ([95% CI 15.27-32.53]). The generalized symptom (19.57%, [95% CI 9.85-31.52]) was reported most commonly, followed by respiratory (14.76%, [95% CI 7.22-24.27]), neurologic (13.51%, [95% CI 6.52-22.40]), and psychiatric (12.30%, [95% CI 5.38-21.37]). Dyspnoea (22.75%, [95% CI 9.38-39.54]), fatigue (20.22%, [95% CI 9.19-34.09]), and headache (15.88%, [95% CI 6.85-27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3-6, 6-12, and >12 months were 26.41% ([95% CI 14.33-40.59]), 20.64% ([95% CI 17.06-24.46]), and 14.89% ([95% CI 6.09-26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors.

Conclusions: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

Source: Zheng YB, Zeng N, Yuan K, Tian SS, Yang YB, Gao N, Chen X, Zhang AY, Kondratiuk AL, Shi PP, Zhang F, Sun J, Yue JL, Lin X, Shi L, Lalvani A, Shi J, Bao YP, Lu L. Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review. J Infect Public Health. 2023 Mar 7. doi: 10.1016/j.jiph.2023.03.005. Epub ahead of print. PMCID: PMC9990879. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990879/ (Full text)

COVID-19 long-term sequelae: Omicron versus Alpha and Delta variants

Abstract:

Background: The study aimed to assess the association between three predominant SARS-CoV-2 variants (Alpha, Delta, and Omicron) and the risk of developing long COVID (persistence of physical, medical, and cognitive symptoms more than 4 weeks after infection), post-COVID-19 syndrome (symptoms extending beyond 12 weeks), and viral persistence (testing positive beyond 4 weeks despite clinical resolution).

Methods: Retrospective study of 325 patients hospitalized for COVID-19 with genomic sequencing information. For each SARS-CoV-2 variant, sample characteristics, frequency of symptoms, and long-term sequelae were compared using Chi-squared test, Fisher’s exact test, Kruskal-Wallis test, and Dunn’s test as appropriate. Odds ratios (OR) were calculated using logistic regression models to assess the association of risk factors and sequelae.

Results: The adjusted model showed that the Omicron (vs Alpha) variant (OR, 0.30; 95% CI0.16-0.56), admission to ICU (OR, 1.14; 95% CI 1.05-1.23), and being treated with antiviral or immunomodulatory drugs (OR, 2.01; 95% CI 1.23-3.27) predicted long COVID and post-COVID-19 syndrome. Viral persistence showed no difference between variants.

Conclusions: The Omicron variant was associated with significantly lower odds of developing long-term sequelae from COVID-19 compared with previous variants, while severity of illness indicators increased the risk. Vaccination status, age, sex, and comorbidities were not found to predict sequelae development. This information has implications for both health managers and clinicians when deciding on the appropriate clinical management and subsequent outpatient follow-up of these patients. More studies with non-hospitalized patients are still necessary.

Source: Hernández-Aceituno A, García-Hernández A, Larumbe-Zabala E. COVID-19 long-term sequelae: Omicron versus Alpha and Delta variants. Infect Dis Now. 2023 Feb 27:104688. doi: 10.1016/j.idnow.2023.104688. Epub ahead of print. PMID: 36858287; PMCID: PMC9970656. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970656/ (Full text)

Is exposure to Epstein-Barr virus a risk factor for long-covid?

Abstract:

Background: A viral etiology to chronic fatigue syndrome (CFS) has long been postulated, and Epstein-Barr Virus (EBV) was the first CFS associated virus. CFS and Long-COVID share features, potentially implicating a similar etiology. This study evaluated if EBV exposure is associated with post-COVID syndrome (Long-COVID)

Methods: Intermountain Healthcare electronic health records were queried to identify patients diagnosed with COVID-19 and tested for EBV between March 6, 2020 and April 13, 2022. A subsequent diagnosis of Long-COVID (ICD-10 U09.9) was evaluated using survival methods.

Results: Overall, 296,959 patients had COVID-19 and 590 had concurrent EBV test results [207 (35.1%) were EBV positive]. Subjects averaged 27.4±18.4 years of age (range: 0-86); 57.6% were female. Hospitalization occurred in 61 subjects (10.3%) within 30 days of COVID-19 diagnosis, with 17 (2.9%) requiring intensive care. Long-COVID was found in 29 (4.9%) subjects (just 10 were among the 61 hospitalized for COVID-19), with 15 (7.2%) EBV positive (Figure) and 14 (3.7%) EBV negative (HR=2.09, 95% CI=1.01, 4.34; p=0.042). EBV risk remained in multivariable analyses. Race, hyperlipidemia, and tobacco use also predicted Long-COVID, with histories of anticoagulant and vitamin D use were protective.

Conclusion: In a large prospectively-collected registry, EBV positivity was associated with an elevated risk of Long-COVID. This suggests that EBV may be a predisposing risk factor for or co-precipitant of Long-COVID.

Source: Horne B, Knowlton K, Le V, et al. IS EXPOSURE TO EPSTEIN-BARR VIRUS A RISK FACTOR FOR LONG-COVID?. J Am Coll Cardiol. 2023 Mar, 81 (8_Supplement) 1784. https://doi.org/10.1016/S0735-1097(23)02228-3 (Full text)

Predictors of Long-COVID-19 and its Impact on Quality of Life: Longitudinal Analysis at 3, 6 and 9 Months after Discharge from a Portuguese Centre

Abstract:

Introduction: Long-COVID-19 impacts health-related quality of life (HR-QoL) but data is scarce. The aim of this study was to describe and prospectively assess the prevalence and risk factors for long-COVID-19 after hospital discharge, and to evaluate its impact on patient HR-QoL.

Material and methods: Single-centre longitudinal study including all COVID-19 patients discharged between December 2020 and February 2021. Patients were contacted remotely at three, six and nine months. Data were collected as follows: 1) Long-COVID-19 symptoms were self-reported; 2) HRQoL were assessed using the 3-level EuroQoL-5D (EQ-5D-3L) questionnaire. Pregnant women, demented, bedridden, and non-Portuguese-speaking patients were excluded.

Results: The three-, six- and nine-month assessments were completed by 152, 117 and 110 patients (median age: 61 years; male sex: 56.6%). Long-COVID-19 (≥ 1 symptom) was reported by 66.5%, 62.4% and 53.6% of patients and HR-QoL assessment showed impairment of at least some domain in 65.8%, 69.2% and 55.4% of patients at three, six and nine months, respectively. Fatigue was the most common long-COVID-19 symptom. Anxiety/depression domain was the most frequently affected in all three time-points, peaking at six months (39%), followed by pain/discomfort and mobility domains. Long-COVID-19 was associated with the impairment of all EQ-5D-3L domains except for self-care domain at each time-point. Neither intensive care unit admission nor disease severity were associated with long-COVID-19 nor with impairment of any EQ-5D-3L domain. After adjusting for sex, age, frailty status, and comorbid conditions, long-COVID-19 remained significantly associated with HR-QoL impairment at three (OR 4.27, 95% CI 1.92 – 9.52, p < 0.001), six (OR 3.46, 95% CI 1.40 – 8.57, p = 0.007) and nine months (OR 4.13, 95% CI 1.62 – 10.55, p = 0.003) after hospital discharge. In a longitudinal analysis, patients reporting long-COVID-19 at three months had an EQ-5D-3L index value decreased by 0.14 per visit (p < 0.001) compared to those without long-COVID-19 and both groups had a non-significant change in mean EQ-5D-3L index over the nine-month period (time-point assessment, Z = 0.91, p = 0.364).

Conclusion: Clinical sequelae associated with long-COVID-19 can persist for at least nine months after hospital discharge in most patients and can impair long-term HR-QoL in more than half of patients regardless of disease severity, and clinicodemographic characteristics.

Source: Gaspar P, Dias M, Parreira I, Gonçalves HD, Parlato F, Maione V, Atalaia Barbacena H, Carreiro C, Duarte L. Predictors of Long-COVID-19 and its Impact on Quality of Life: Longitudinal Analysis at 3, 6 and 9 Months after Discharge from a Portuguese Centre. Acta Med Port. 2023 Feb 24. doi: 10.20344/amp.19047. Epub ahead of print. PMID: 36827994. https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19047 (Full text)

Vaccination status and long COVID symptoms in patients discharged from hospital

Abstract:

Effective vaccination against coronavirus mitigates the risk of hospitalisation and mortality; however, it is unclear whether vaccination status influences long COVID symptoms in patients who require hospitalisation. The available evidence is limited to outpatients with mild disease.

Here, we evaluated 412 patients (age: 60 ± 16 years, 65% males) consecutively admitted to two Hospitals in Brazil due to confirmed coronavirus disease 2019 (COVID-19). Compared with patients with complete vaccination (n = 185) before infection or hospitalisation, those with no or incomplete vaccination (n = 227) were younger and had a lower frequency of several comorbidities.

Data during hospitalisation revealed that the no or incomplete vaccination group required more admissions to the intensive care unit (ICU), used more corticosteroids, and had higher rates of pulmonary embolism or deep venous thrombosis than the complete vaccination group. Ninety days after hospital discharge, patients with no or incomplete vaccination presented a higher frequency of symptoms (≥ 1) than patients with complete vaccination (40 vs. 27%; p = 0.013).

After adjusting for confounders, no or incomplete vaccination (odds ratio [OR] 1.819; 95% confidence interval [CI] 1.175-2.815), female sex (OR 2.435; 95% CI 1.575-3.764) and ICU admission during hospitalisation (OR 1.697; 95% CI 1.062-2.712) were independently associated with ≥ 1 symptom 90 days after hospital discharge.

In conclusion, even in patients with severe COVID-19, vaccination mitigates the probability of long COVID symptoms.

Source: Nascimento TCDC, do Valle Costa L, Ruiz AD, Ledo CB, Fernandes VPL, Cardoso LF, Junior JMV, Saretta R, Kalil-Filho R, Drager LF. Vaccination status and long COVID symptoms in patients discharged from hospital. Sci Rep. 2023 Feb 11;13(1):2481. doi: 10.1038/s41598-023-28839-y. PMID: 36774419; PMCID: PMC9922040. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922040/ (Full text)