Association of vaccine status, reinfections, and risk factors with Long COVID syndrome

Abstract:

The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to determine the prevalence of Long COVID syndrome within a population of Northeastern Mexico, correlating it with patients’ comorbidities, number of COVID-19 reinfection, and vaccination status. Employing an observational cross-sectional approach, we administered a comprehensive questionnaire covering medical history, demographics, vaccination status, COVID-related symptoms, and treatment.

Our participant cohort included 807 patients, with an average age of 41.5 (SD 13.6) years, and women accounting 59.3% of the cohort. The follow-up was 488 (IQR 456) days. One hundred sixty-eight subjects (20.9%) met Long COVID criteria. Long COVID-19 was more prevalent when subjects had reinfections (p = 0.02) and less frequent when they had a complete vaccination scheme (p = 0.05).

Through logistic regression, we found that male gender (OR 0.5, p ≤ 0.001), blood types of AB- (OR 0.48, p = 0.003) and O- (OR 0.27, p ≤ 0.001) in comparison with A+ and two doses of vaccines (OR 0.5, p = 006) to be protective factors against Long COVID; while higher BMI (OR 1.04, p = 0.005) was a risk factor.

We saw that the prevalence of Long COVID was different within vaccinated patients and specific blood types, while being female and a higher BMI were associated with an increased risk of having long-COVID.

Source: Romero-Ibarguengoitia ME, Rodríguez-Torres JF, Garza-Silva A, Rivera-Cavazos A, Morales-Rodriguez DP, Hurtado-Cabrera M, Kalife-Assad R, Villarreal-Parra D, Loose-Esparza A, Gutiérrez-Arias JJ, Mata-Porras YG, Ojeda-Salazar DA, Sanz-Sánchez MA, González-Cantú A, Azzolini E, Rescigno M. Association of vaccine status, reinfections, and risk factors with Long COVID syndrome. Sci Rep. 2024 Feb 2;14(1):2817. doi: 10.1038/s41598-024-52925-4. PMID: 38307886; PMCID: PMC10837423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10837423/ (Full text)

Patient Experiences Navigating Care Coordination For Long COVID: A Qualitative Study

Abstract:

Background: Little is known about how to best evaluate, diagnose, and treat long COVID, which presents challenges for patients as they seek care.

Objective: Understand experiences of patients as they navigate care for long COVID.

Design: Qualitative study involving interviews with patients about topics related to seeking and receiving care for long COVID.

Participants: Eligible patients were at least 18 years of age, spoke English, self-identified as functioning well prior to COVID infection, and reported long COVID symptoms continued to impact their lives at 3 months or more after a COVID infection.

Approach: Patients were recruited from a post-COVID recovery clinic at an academic medical center from August to September 2022. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis.

Key results: Participants (n=21) reported experiences related to elements of care coordination: access to care, evaluation, treatment, and ongoing care concerns. Some patients noted access to care was facilitated by having providers that listened to and validated their symptoms; other patients reported feeling their access to care was hindered by providers who did not believe or understand their symptoms. Patients reported confusion around how to communicate their symptoms when being evaluated for long COVID, and they expressed frustration with receiving test results that were normal or diagnoses that were not directly attributed to long COVID. Patients acknowledged that clinicians are still learning how to treat long COVID, and they voiced appreciation for providers who are willing to try new treatment approaches. Patients expressed ongoing care concerns, including feeling there is nothing more that can be done, and questioned long-term impacts on their aging and life expectancy.

Conclusions: Our findings shed light on challenges faced by patients with long COVID as they seek care. Healthcare systems and providers should consider these challenges when developing strategies to improve care coordination for patients with long COVID.

Source: MacEwan SR, Rahurkar S, Tarver WL, Forward C, Eramo JL, Teuschler L, Gaughan AA, Rush LJ, Stanwick S, McConnell E, Schamess A, McAlearney AS. Patient Experiences Navigating Care Coordination For Long COVID: A Qualitative Study. J Gen Intern Med. 2024 Feb 2. doi: 10.1007/s11606-024-08622-z. Epub ahead of print. PMID: 38308155. https://link.springer.com/article/10.1007/s11606-024-08622-z (Full text)

Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease

Abstract:

Importance: While the understanding of inflammation in the pathogenesis of many neurological diseases is now accepted, this special commentary addresses the need to study chronic inflammation in the propagation of cognitive Fog, Asthenia, and Depression Related to Inflammation which we name Brain FADE syndrome. Patients with Brain FADE syndrome fall in the void between neurology and psychiatry because the depression, fatigue, and fog seen in these patients are not idiopathic, but instead due to organic, inflammation involved in neurological disease initiation.

Observations: A review of randomized clinical trials in stroke, multiple sclerosis, Parkinson’s disease, COVID, traumatic brain injury, and Alzheimer’s disease reveal a paucity of studies with any component of Brain FADE syndrome as a primary endpoint. Furthermore, despite the relatively well-accepted notion that inflammation is a critical driving factor in these disease pathologies, none have connected chronic inflammation to depression, fatigue, or fog despite over half of the patients suffering from them.

Conclusions and relevance: Brain FADE Syndrome is important and prevalent in the neurological diseases we examined. Classical “psychiatric medications” are insufficient to address Brain FADE Syndrome and a novel approach that utilizes sequential targeting of innate and adaptive immune responses should be studied.

Source: Khalid A. Hanafy, Tudor G. Jovin. Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease. Front. Immunol., 17 January 2024, Sec. Inflammation, Volume 15 – 2024 | https://doi.org/10.3389/fimmu.2024.1332776 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1332776/full (Full text)

Clinical and Laboratory Characteristics of Fatigue-dominant Long-COVID subjects: A Cross-Sectional Study

Abstract:

Background: Long-COVID is defined by persistent symptoms following COVID-19 infection. Approximately 71% of individuals with long-COVID experience ongoing fatigue, post-exertional malaise, and cognitive impairments, which share pathological similarities with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This similarity has prompted studies to explore the characteristics of long-COVID to gain a better understanding of ME/CFS. To gain insights, we investigated the clinical and laboratory characteristics of individuals with fatigue-dominant long-COVID.

Methods: We enrolled 100 subjects (36 males, 64 females) with long-COVID who had a higher score than 60 in modified Korean version of the Chalder Fatigue Scale (mKCFQ11) and higher than 5 in fatigue-focused Visual Analogue Scale (VAS). To investigate fatigue symptoms, the mKCFQ11, the Multidimensional Fatigue Inventory (MFI-20), and VAS for fatigue and brain-fog, along with the Short Form Survey (SF-12) were employed. We also measured three cytokines and cortisol levels for immunological and endocrinological indicators. As a cross-sectional observational study, the data were collected at a single point in time.

Results: The mean scores on the measurements showed severe fatigue, and these scores were significantly correlated, with no differences based on sex, the post-COVID period, or age. Among the laboratory tests, plasma cortisol levels had a significant negative correlation with fatigue scores and a positive correlation with living quality. The negative correlation between cortisol levels and mKCFQ11 scores appeared to be more specific to mental fatigue than physical, which conflicted with other measurements.

Conclusion: Our findings provide the first insights into the characteristics of fatigue in individuals with long-COVID, particularly in terms of fatigue severity and cortisol levels. These results serve as valuable reference data for clinicians dealing with fatigue symptoms in long-COVID patients and for researchers exploring post-viral fatigue symptoms, including ME/CFS, in the future.

Source: Lee JS, Choi Y, Joung JY, Son CG. Clinical and Laboratory Characteristics of Fatigue-dominant Long-COVID subjects: A Cross-Sectional Study. Am J Med. 2024 Feb 6:S0002-9343(24)00057-3. doi: 10.1016/j.amjmed.2024.01.025. Epub ahead of print. PMID: 38331137. https://pubmed.ncbi.nlm.nih.gov/38331137/

Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19

Highlights:

  • A subset of patients experienced persistent fatigue symptoms after COVID-19.
  • Treatment with low-dose naltrexone (LDN) and NAD+ was well tolerated.
  • Treatment increased SF-36 quality of life scores.
  • Treatment also improved fatigue symptom scores.
  • A subset of patients were clinically responsive.

Abstract:

A subset of patients experiences persistent fatigue symptoms after COVID-19, and patients may develop long COVID, which is characterized by lasting systemic symptoms. No treatments for this condition have been validated and are urgently warranted.

In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19.

We detected a significant increase from baseline in SF-36 survey scores after 12 weeks of treatment (mean total SF-36 score 36.5 [SD: 15.6] vs. 52.1 [24.8]; p < 0.0001), suggestive of improvement of quality of life. Furthermore, participants scored significantly lower on the Chalder fatigue scale after 12 weeks of treatment (baseline: 25.9 [4.6], 12 weeks: 17.4 [9.7]; p < 0.0001).

We found a subset of 52 % of patients to be responders after 12 weeks of treatment. Treatment was generally safe, with mild adverse events previously reported for LDN, which could be managed with dose adjustments. The iontophoresis patches were associated with mild, short-lived skin irritation in 25 % of patients.

Our data suggest treatment with LDN and NAD+ is safe and may be beneficial in a subset of patients with persistent fatigue after COVID-19. Larger randomized controlled trials will have to confirm our data and determine which patient subpopulations might benefit most from this strategy.

Source: Anar Isman, Andy Nyquist, Bailey Strecker, Girish Harinath, Virginia Lee, Xingyu Zhang, Sajad Zalzala. Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19. Brain, Behavior, & Immunity – Health, Volume 36, 2024, 100733, ISSN 2666-3546, https://doi.org/10.1016/j.bbih.2024.100733. https://www.sciencedirect.com/science/article/pii/S2666354624000115 (Full text)

Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection

Abstract:

Many patients surviving SARS-CoV-2 infection suffer from long-term symptoms (long COVID or post COVID) such as shortness of breath, fatigue, loss of taste or smell and cognitive deterioration. However, few data are available concerning blood cell counts and haematological parameters during the post-COVID period.

We analysed haematological data from 83 patients previously admitted to the internal medicine unit of our institution because of symptomatic SARS-CoV-2 infection; all data were obtained within 1-12 months from disease onset. A control group of 70 apparently healthy, age- and sex-matched COVID-19 negative individuals was assessed for comparison. Blood cell counts improved in the post-COVID period, but 81% of patients had persistent abnormalities, compared with 50% in the control group, p < 0.001.

Most common haematological findings included anaemia (40%), reduced lymphocyte (43%) or eosinophil counts (38%) and low IgM memory B cells and correlated with advanced age, number of chronic comorbidities, female gender, altered renal function, reduced baseline Hb and procalcitonin concentrations and increased RDW. Data on lymphocytes and IgM memory B cells show that impaired immune responses may persist for up to one year in the post-COVID period, possibly contributing to long-term symptoms, especially in female patients.

Source: Bergamaschi G, Barteselli C, Calabretta F, Lenti MV, Merli S, Rossi CM, Di Sabatino A. Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection. Intern Emerg Med. 2024 Jan;19(1):125-133. doi: 10.1007/s11739-023-03459-6. Epub 2023 Nov 24. PMID: 38001354. https://pubmed.ncbi.nlm.nih.gov/38001354/

Decreased risk of COVID-19 and long COVID in patients with psoriasis receiving IL-23 inhibitor: A cross-sectional cohort study from China

Abstract:

Background: Although clinical trials and real-world data suggest that the risk of COVID-19 and its complications is not exacerbated in patients with psoriasis treated by biological agents, the evidence for this is still limited.

Objectives: We aimed to assess the outcomes of COVID-19 among Chinese patients with psoriasis treated by IL-23 inhibitor, and to compare these variables in patients receiving other therapies.

Methods: A cross-sectional cohort study was conducted to compare psoriasis treatment with IL-23 inhibitor to other treatment methods. All the patients received a questionnaire that contained questions about their psoriasis treatment, COVID-19 symptoms, and related risk factors. The prevalence of COVID-19 was calculated, and logistic regression analyses were performed to determine the association between treatment method and COVID-19 risk. The symptoms of COVID-19 and long COVID were described for each treatment group.

Results: Between December 2022 and February 2023, 732 patients with psoriasis were included in the final analysis. 549 patients had a SARS-CoV-2 infection during the study period. Our results showed that individuals who worked outdoors had a decreased risk of COVID-19, as did those who had other allergic disease. With regard to the effect of the treatment regimens, IL-23 inhibitor treatment was associated with a decreased risk of COVID-19 compared to almost all the other treatments except acitretin. Fever was the most common symptom, but the maximum temperature and duration of fever were comparable among the treatment groups. Patients treated with IL-23 inhibitor were more likely to be asymptomatic after recovery compared to patients treated with methotrexate, narrow-bound ultra violet B, or TNF-α inhibitor.

Conclusions: IL-23 inhibitor treatment may lower the risk of COVID-19 and long COVID. Thus, IL-23 inhibitor treatment might be beneficial and positively considered for patients with psoriasis who require systemic treatment during periods when there is a surge in COVID-19 cases.

Source: Hu Y, Huang D, Jiang Y, Yu Q, Lu J, Ding Y, Shi Y. Decreased risk of COVID-19 and long COVID in patients with psoriasis receiving IL-23 inhibitor: A cross-sectional cohort study from China. Heliyon. 2024 Jan 9;10(2):e24096. doi: 10.1016/j.heliyon.2024.e24096. PMID: 38293509; PMCID: PMC10826651. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826651/ (Full text)

Herbal Medicines for Long COVID: A Phase 2 Pilot Clinical Study

Abstract:

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID.

Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored.

Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence.

Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Source:Kim, T.; Yoon, J.; Kim, S.; Kang, B.; Kang, J.W.; Kwon, S. Herbal Medicines for Long COVID: A Phase 2 Pilot Clinical Study. Preprints 2024, 2024011605. https://doi.org/10.20944/preprints202401.1605.v1 https://www.preprints.org/manuscript/202401.1605/v1 (Full text available as PDF file)

Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults

Abstract:

Background: The impact of vaccination prior to infection on postacute sequelae of coronavirus disease 2019 (COVID-19, PASC), also known as long COVID, remains unclear. Here we assess the protective effect of vaccination on long COVID in a community-based setting.

Methods: The Immunity Associated with SARS-CoV-2 (IASO) study is an ongoing prospective cohort of working adults that began in October 2020. Participants are actively followed for severe acute respiratory syndrome coronavirus 2 infection. We compared the prevalence of symptoms and symptom severity in vaccinated compared to unvaccinated cases. Our primary definition of long COVID was the presence of symptoms at 90 days postinfection; 30 days postinfection was also examined.

Results: Overall, by 90 days postinfection, 13% of cases had long COVID, with 27% of unvaccinated cases and 8% of vaccinated cases reporting long COVID (relative risk [RR], 0.31 [95% confidence interval {CI}, .22–.42]). Vaccination was also associated with significantly lower average severity scores at all timepoints (eg, relative severity at 90 days postinfection: −2.70 [95% CI, −1.68 to −3.73]). In the pre-Omicron era, 28% of unvaccinated cases and 18% of vaccinated cases reported long COVID (P = .07), and vaccinated cases reported less severe symptoms including less difficulty breathing (P = .01; 90-day RR, 0.07).

Conclusions: Vaccinated cases had lower prevalence of long COVID and reduced symptom severity.

Source: Hannah E Maier, Theresa Kowalski-Dobson, Ashley Eckard, Carmen Gherasim, David Manthei, Alyssa Meyers, Dawson Davis, Kevin Bakker, Kathleen Lindsey, Zijin Chu, Lauren Warsinske, Matthew Arnold, Anna Buswinka, Emily Stoneman, Riccardo Valdez, Aubree Gordon, Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults, Open Forum Infectious Diseases, Volume 11, Issue 2, February 2024, ofae039, https://doi.org/10.1093/ofid/ofae039 https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofae039/7585852 (Full text)

Post-COVID Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia in the Pediatric Population

Abstract:

Purpose of Review: Long COVID, or post-COVID Condition, is increasingly recognized in children and adolescents, despite being less studied compared with the adult population. Recent studies are documenting that inappropriate sinus tachycardia (IST) or postural orthostatic tachycardia syndrome (POTS) may be key clinical problems in patients with long COVID, and preliminary findings have shown that these may be important features also in children. However, POTS and IST are poorly known among non-specialized pediatricians, and this gap may limit access to appropriate care for children and adolescents with long COVID or other post-viral fatigue syndromes. In this review, we critically evaluate the available literature investigating the burden of post-COVID-19 IST and POTS in children and young people, their pathogenesis, and available evidence for their management in the pediatric population.

Recent Findings: In line with adult studies, there is increasing evidence that also children with long COVID may suffer from IST and POTS. Case reports and case series, as well as pediatric experience from other conditions, suggest that IST and POTS can be treated also in the pediatric population

Summary: IST and POTS are under-recognized conditions in children. Clinical findings as well as diagnostics like 24-h ECG and heart rate variability are non-invasive tests to diagnose IST and POTS. If properly recognized, these conditions are treatable.

Source: Spera, F.R., Mistrulli, R., Salerno, L. et al. Post-COVID Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia in the Pediatric Population. Curr Clin Micro Rpt (2024). https://doi.org/10.1007/s40588-024-00217-w (Full text available as PDF file)