Tag: long Covid

Low-dose naltrexone use for the management of post-acute sequelae of COVID-19

Abstract:

The global prevalence of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) stands at approximately 43 % among individuals who have previously had acute COVID-19. In contrast, in the United States, the National Center for Health Statistics (NCHS) estimates that around 11 % of individuals who have been infected with SARS-CoV-2 go on to experience long COVID. The underlying causes of PASC remains under investigation, and there are no currently established FDA-approved therapies.

One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increase systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC.

We performed a retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status. This observation warrants testing in rigorous, randomized, placebo-controlled clinical trials.

Source: Bonilla H, Tian L, Marconi VC, Shafer R, McComsey GA, Miglis M, Yang P, Bonilla A, Eggert L, Geng LN. Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. Int Immunopharmacol. 2023 Oct 5;124(Pt B):110966. doi: 10.1016/j.intimp.2023.110966. Epub ahead of print. PMID: 37804660. https://www.sciencedirect.com/science/article/pii/S1567576923012912 (Full text)

Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection

Abstract:

It is still unclear why certain individuals after viral infections continue to have severe symptoms. We investigated if predicting myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) development after contracting COVID-19 is possible by analyzing symptoms from the first two weeks of COVID-19 infection.
Using participant responses to the 54-item DePaul Symptom Questionnaire, we built predictive models based on a random forest algorithm using the participants’ symptoms from the initial weeks of COVID-19 infection to predict if the participants would go on to meet the criteria for ME/CFS approximately 6 months later.
Early symptoms, particularly those assessing post-exertional malaise, did predict the development of ME/CFS, reaching an accuracy of 94.6%. We then investigated a minimal set of eight symptom features that could accurately predict ME/CFS. The feature reduced models reached an accuracy of 93.5%. Our findings indicated that several IOM diagnostic criteria for ME/CFS occurring during the initial weeks after COVID-19 infection predicted Long COVID and the diagnosis of ME/CFS after 6 months.
Source: Hua C, Schwabe J, Jason LA, Furst J, Raicu D. Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection. Psych. 2023; 5(4):1101-1108. https://doi.org/10.3390/psych5040073 https://www.mdpi.com/2624-8611/5/4/73

Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity

Abstract:

Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs).

Methods: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge.

Results: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts.

Conclusion: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.

Source: Berentschot Julia C., Drexhage Hemmo A., Aynekulu Mersha Daniel G., Wijkhuijs Annemarie J. M., GeurtsvanKessel Corine H., Koopmans Marion P. G., Voermans Jolanda J. C., Hendriks Rudi W., Nagtzaam Nicole M. A., de Bie Maaike, Heijenbrok-Kal Majanka H., Bek L. Martine, Ribbers Gerard M., van den Berg-Emons Rita J. G., Aerts Joachim G. J. V., Dik Willem A., Hellemons Merel E. Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity. Frontiers in Immunology, vol 14, 2023. DOI=10.3389/fimmu.2023.1254899 ISSN=1664-3224 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1254899/full (Full text)

 

Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study

Abstract:

Objective: To determine if patients that develop lingering neurologic symptoms of fatigue and “brain fog” after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology.

Design: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function.

Results: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion.

Conclusions: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19.

Source: Wright TJ, Pyles RB, Sheffield-Moore M, Deer RR, Randolph KM, McGovern KA, Danesi CP, Gilkison CR, Ward WW, Vargas JA, Armstrong PA, Lindsay SE, Zaidan MF, Seashore J, Wexler TL, Masel BE, Urban RJ. Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study. Mol Cell Endocrinol. 2023 Oct 8:112071. doi: 10.1016/j.mce.2023.112071. Epub ahead of print. PMID: 37816478. https://www.sciencedirect.com/science/article/abs/pii/S0303720723002228

THU581 Possible Markers For Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I

Abstract:

Almost three years have passed since coronavirus disease 2019 (COVID-19) pandemic broke out, and along with the number of acute COVID-19 patients, the number of patients suffering from chronic prolonged symptoms after COVID-19, long COVID, or post COVID-19 condition, has also increased.

We established an outpatient clinic specialized for COVID-19 after care (CAC) in Okayama University Hospital in Japan in February 2021. Our recent study has revealed that the most common symptom is “fatigue”, a part of which potentially may develop into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, the pathogenesis and specific prognosticator have yet to be elucidated. The aim of this study was to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19.

This retrospective observational study investigated the patients who visited our CAC outpatient clinic between February 2021 and March 2022. Of the 234 patients, 139 (59.4%) had fatigue symptoms, of whom 50 (21.4%) met the criteria for ME/CFS (ME/CFS group), while other 89 did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients’ backgrounds were not significantly different among the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and Self-Rating Depression Scale (SDS).

Of note, serum ferritin levels, which were correlated to FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/mL; interquartile range (IQR), 58.8-353.8) than those of non-ME/CFS (98.2 μg/mL; 40.4-251.5) and no-fatigue (86.7 μg/mL; 37.5-209.0) groups, and this trend was prominent in the female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in the serum, and that insulin-like growth factor (IGF)-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05).

Collectively, we revealed that serum ferritin levels could be a possible predictor for developing ME/CFS related to long COVID, especially in female patients. Earlier studies have suggested that hyperferritinemia is a clinical feature in the patients of long COVID, in which hepcidin-like effects could also be involved. Our present study also uncovered a relationship between hyperferrinemia and endocrine disorders among patients developing ME/CFS after COVID-19, although further investigations are necessary to understand the characteristics of ferritin metabolism.

Presentation: Thursday, June 15, 2023

Source: Yukichika Yamamoto, Yuki Otsuka, Kazuki Tokumasu, Naruhiko Sunada, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Toru Hasegawa, Hideharu Hagiya, Fumio Otsuka, THU581 Possible Markers For Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I, Journal of the Endocrine Society, Volume 7, Issue Supplement_1, October-November 2023, bvad114.1370, https://doi.org/10.1210/jendso/bvad114.1370 (Full text available as PDF file)

Is Pulmonary Involvement a Distinct Phenotype of Post-COVID-19?

Abstract:

Background: COVID-19 infection often provokes symptoms lasting many months: most commonly fatigue, dyspnea, myalgia and mental distress symptoms. In this study, we searched for clinical features of post-COVID-19 condition (PCC) and differences between patients with and without pulmonary involvement.
Methods: A total of 282 patients with a mean age of 57 years (SD +/− 12 years) underwent assessment up to 12 weeks after COVID-19 recovery. The course of acute disease, past medical history and clinical symptoms were gathered; pulmonary function tests were performed; radiographic studies were assessed and follow-up examinations were conducted. Patients with and without detectable pulmonary lesions were divided into separate groups.
Results: Patients within the pulmonary group were more often older (59 vs. 51 y.o.; p < 0.001) males (p = 0.002) that underwent COVID-19-related hospitalization (p < 0.001) and were either ex- or active smokers with the median of 20 pack-years. We also managed to find correlations with hypertension (p = 0.01), liver failure (p = 0.03), clinical symptoms such as dyspnea (p < 0.001), myalgia (p = 0.04), headache (p = 0.009), sleeplessness (p = 0.046), pulmonary function tests (such as FVC, TLCO, RV and TLC; p < 0.001) and several basic laboratory tests (D-dimer, cardiac troponin, WBC, creatinine and others).
Conclusions: Our results indicate that initial pulmonary involvement alters the PCC, and it can be used to individualize clinical approaches.
Source: Bartczak KT, Miłkowska-Dymanowska J, Pietrusińska M, Kumor-Kisielewska A, Stańczyk A, Majewski S, Piotrowski WJ, Lipiński C, Wawrocki S, Białas AJ. Is Pulmonary Involvement a Distinct Phenotype of Post-COVID-19? Biomedicines. 2023; 11(10):2694. https://doi.org/10.3390/biomedicines11102694 https://www.mdpi.com/2227-9059/11/10/2694 (Full text)

Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study

Abstract:

As the emergency phase of the COVID-19 pandemic subsides, the long-term health problems caused by SARS-CoV-2 infection are becoming increasingly clear. So-called Long COVID, or post COVID-19 condition, is a debilitating illness that impacts functioning for months and even years after infection. Alongside physical symptoms, Long COVID has a particularly insidious effect on cognition and language. While many studies have documented non-linguistic cognitive impairments in people with Long COVID, what has not been documented to any significant extent is the presence and duration of language difficulties in Long COVID. This study addresses this lack of research by examining the cognitive-linguistic skills of 41 adults with Long COVID.

These adults were assessed at two time points using a test protocol of 12 language tasks. This paper describes the findings of the 6-month follow-up study. Results indicate that difficulties in immediate and delayed verbal recall persist long after the onset of COVID symptoms, even as improvements occur in verbal fluency and the informativeness of spoken discourse.

It is argued that these difficulties are a significant contributing factor in a lack of work return in these adults. Implications of these findings for the provision of speech-language pathology services to these adults and occupational health policies relating to Long COVID are discussed.

Source: Louise Cummings. Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study. Language and Health. Available online 2 October 2023. https://www.sciencedirect.com/science/article/pii/S2949903823000325 (Full text)

Integrating patient-reported physical, mental, and social impacts to classify long COVID experiences

Abstract:

Long COVID was originally identified through patient-reported experiences of prolonged symptoms. Many studies have begun to describe long COVID; however, this work typically focuses on medical records, instead of patient experiences, and lacks a comprehensive view of physical, mental, and social impacts.

As part of our larger My COVID Diary (MCD) study, we captured patient experiences using a prospective and longitudinal patient-reported outcomes survey (PROMIS-10) and free-text narrative submissions. From this study population, we selected individuals who were still engaged in the MCD study and reporting poor health (PROMIS-10 scores < 3) at 6 months (n = 634). We used their PROMIS-10 and narrative data to describe and classify their long COVID experiences.

Using Latent Class Analysis of the PROMIS-10 data, we identified four classifications of long COVID experiences: a few lingering issues (n = 107), significant physical symptoms (n = 113), ongoing mental and cognitive struggles (n = 235), and numerous compounding challenges (n = 179); each classification included a mix of physical, mental, and social health struggles with varying levels of impairment. The classifications were reinforced and further explained by patient narratives. These results provide a new understanding of the varying ways that long COVID presents to help identify and care for patients.

Source: Vartanian K, Fish D, Kenton N, Gronowski B, Wright B, Robicsek A. Integrating patient-reported physical, mental, and social impacts to classify long COVID experiences. Sci Rep. 2023 Sep 28;13(1):16288. doi: 10.1038/s41598-023-43615-8. PMID: 37770554; PMCID: PMC10539528. https://www.nature.com/articles/s41598-023-43615-8 (Full text)

15-month post-COVID syndrome in outpatients: Attributes, risk factors, outcomes, and vaccination status – longitudinal, observational, case-control study

Abstract:

Background: While the short-term symptoms of post-COVID syndromes (PCS) are well-known, the long-term clinical characteristics, risk factors and outcomes of PCS remain unclear. Moreover, there is ongoing discussion about the effectiveness of post-infection vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) to aid in PCS recovery.

Methods: In this longitudinal and observational case-control study we aimed at identifying long-term PCS courses and evaluating the effects of post-infection vaccinations on PCS recovery. Individuals with initial mild COVID-19 were followed for a period of 15 months after primary infection. We assessed PCS outcomes, distinct symptom clusters (SC), and SARS-CoV-2 immunoglobulin G (IgG) levels in patients who received SARS-CoV-2 vaccination, as well as those who did not. To identify potential associating factors with PCS, we used binomial regression models and reported the results as odds ratios (OR) with 95% confidence intervals (95%CI).

Results: Out of 958 patients, follow-up data at 15 month after infection was obtained for 222 (23.2%) outpatients. Of those individuals, 36.5% (81/222) and 31.1% (69/222) were identified to have PCS at month 10 and 15, respectively. Fatigue and dyspnea (SC2) rather than anosmia and ageusia (SC1) constituted PCS at month 15. SARS-CoV-2 IgG levels were equally distributed over time among age groups, sex, and absence/presence of PCS. Of the 222 patients, 77.0% (171/222) were vaccinated between 10- and 15-months post-infection, but vaccination did not affect PCS recovery at month 15. 26.3% of unvaccinated and 25.8% of vaccinated outpatients improved from PCS (p= .9646). Baseline headache (SC4) and diarrhoea (SC5) were risk factors for PCS at months 10 and 15 (SC4: OR 1.85 (95%CI 1.04-3.26), p=.0390; SC5: OR 3.27(95%CI 1.54-6.64), p=.0009).

Conclusion: Based on the specific symptoms of PCS our findings show a shift in the pattern of recovery. We found no effect of SARS-CoV-2 vaccination on PCS recovery and recommend further studies to identify predicting biomarkers and targeted PCS therapeutics.

Source: Augustin M, Stecher M, Wüstenberg H, Di Cristanziano V, Sandaradura de Silva U, Picard LK, Pracht E, Rauschning D, Gruell H, Klein F, Wenisch C, Hallek M, Schommers P, Lehmann C. 15-month post-COVID syndrome in outpatients: Attributes, risk factors, outcomes, and vaccination status – longitudinal, observational, case-control study. Front Immunol. 2023 Sep 12;14:1226622. doi: 10.3389/fimmu.2023.1226622. PMID: 37781408; PMCID: PMC10540070. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540070/ (Full text)

Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome

Abstract:

Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms.

Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021-May 2022 (median 243 days post-COVID-19 infection). DNA virus-related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls.

Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p < 0.001), significantly less cumulative DNA virus-related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).

Source: Gyöngyösi M, Lukovic D, Mester-Tonczar J, Zlabinger K, Einzinger P, Spannbauer A, Schweiger V, Schefberger K, Samaha E, Bergler-Klein J, Riesenhuber M, Nitsche C, Hengstenberg C, Mucher P, Haslacher H, Breuer M, Strassl R, Puchhammer-Stöckl E, Loewe C, Beitzke D, Hasimbegovic E, Zelniker TA. Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome. NPJ Vaccines. 2023 Sep 29;8(1):145. doi: 10.1038/s41541-023-00739-2. PMID: 37773184; PMCID: PMC10541897. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541897/ (Full text)