Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome

Abstract:

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort.

A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome).

In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05).

Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Source: Queiroz MAF, Neves PFMD, Lima SS, Lopes JDC, Torres MKDS, Vallinoto IMVC, Bichara CDA, Dos Santos EF, de Brito MTFM, da Silva ALS, Leite MM, da Costa FP, Viana MNDSA, Rodrigues FBB, de Sarges KML, Cantanhede MHD, da Silva R, Bichara CNC, van den Berg AVS, Veríssimo AOL, Carvalho MDS, Henriques DF, Dos Santos CP, Nunes JAL, Costa IB, Viana GMR, Carneiro FRO, Palacios VRDCM, Quaresma JAS, Brasil-Costa I, Dos Santos EJM, Falcão LFM, Vallinoto ACR. Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome. Front Cell Infect Microbiol. 2022 Jun 30;12:922422. doi: 10.3389/fcimb.2022.922422. PMID: 35846757; PMCID: PMC9279918. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279918/ (Full text)

The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study

COVID-19 can cause symptoms that last weeks or months after the infection has gone, with a significant impairment of quality of life. Palmitoylethanolamide (PEA) is a naturally occurring lipid mediator that has an entourage effect on the endocannabinoid system mitigating the cytokine storm. The aim of this retrospective study is to evaluate the potential efficacy of PEA in the treatment of long COVID.
Patients attending the Neurological Out Clinic of the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy) from August 2020 to September 2021 were screened for potential inclusion in the study. We included only long COVID patients who were treated with PEA 600 mg two times daily for about 3 months. All patients performed the post-COVID-19 Functional Status (PCFS) scale. Thirty-three patients (10 males, 43.5%, mean age 47.8 ± 12.4) were enrolled in the study. Patients were divided into two groups based on hospitalization or home care observation. A substantial difference in the PCFS score between the two groups at baseline and after treatment with PEA were found. We found that smoking was a risk factor with an odds ratio of 8.13 CI 95% [0.233, 1.167]. Our findings encourage the use of PEA as a potentially effective therapy in patients with long COVID.
Source: Raciti L, De Luca R, Raciti G, Arcadi FA, Calabrò RS. The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study. Medical Sciences. 2022; 10(3):37. https://doi.org/10.3390/medsci10030037  https://www.mdpi.com/2076-3271/10/3/37/htm (Full text)

Neurological manifestations of post-COVID-19 syndrome S1-guideline of the German society of neurology

Abstract:

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to COVID-19 (COrona VIrus Disease-2019). SARS-CoV-2 acute infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases. Neurological manifestations are commonly reported during the post-acute phase and are also present in Long-COVID (LCS) and post-COVID-19 syndrome (PCS).

In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of COVID-19. In December 2021 this S1 guideline was revised and guidance for the care of patients with post-COVID-19 syndrome regarding neurological manifestations was added. This is an abbreviated version of the post-COVID-19 syndrome chapter of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).

Source: Franke C, Berlit P, Prüss H. Neurological manifestations of post-COVID-19 syndrome S1-guideline of the German society of neurology. Neurol Res Pract. 2022 Jul 18;4(1):28. doi: 10.1186/s42466-022-00191-y. PMID: 35843984; PMCID: PMC9288923. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288923/ (Full text)

Postural balance and its association with functionality and quality of life in non-hospitalized patients with post-acute COVID-19 syndrome

Abstract:

Background and objectives: The neuromuscular system is responsible for performing adequate muscle activities to maintain postural balance. Since COVID-19 can cause damage to this system, long-term sequelae might alter control of postural stability. This study aimed to evaluate the postural balance of patients with post-acute COVID-19 syndrome (PCS) who were not hospitalized and to evaluate the correlations of changes in postural balance with general fatigue, muscle strength, and quality of life (QoL).

Methods: This was a cross-sectional study in which 40 patients with PCS and 40 controls underwent balance assessment through the Berg Balance Scale (BBS) and Tinetti Balance Scale (TBS). They were evaluated for general fatigue by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, handgrip strength (HGS), and quality of life (QoL) by the Short Form-36 (SF-36).

Results: When compared to controls, patients with PCS had lower BBS and TBS scores (p = 0.001 for both). The FACIT-F score was lower in PCS patients (p = 0.0001). HGS was slightly lower in the PCS patients, but not statistically significant (p = 0.09). Regarding QoL, PCS patients showed worse evaluations in five dimensions of the SF-36 (physical functioning, physical role limitations, bodily pain, general health perceptions, and mental health). Both the BBS and TBS scores had statistically significant positive correlations with the FACIT-F score, HGS, and two SF-36 dimensions (physical role limitations and emotional role limitations).

Conclusions: Patients with PCS show worse postural balance than controls, which is associated with general fatigue, lower HGS, and poor QoL. Postural balance assessment should be considered in the follow-up and rehabilitation of PCS.

Source: de Sousa KCA, Gardel DG, Lopes AJ. Postural balance and its association with functionality and quality of life in non-hospitalized patients with post-acute COVID-19 syndrome. Physiother Res Int. 2022 Jul 17:e1967. doi: 10.1002/pri.1967. Epub ahead of print. PMID: 35842844. https://onlinelibrary.wiley.com/doi/10.1002/pri.1967 (Full text)

Spectrum of neurological manifestations among acute COVID-19 and long COVID-19 – A retrospective observational study

Abstract:

Objective. Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological symptoms. To compare the clinical features, imaging and treatments in patients with and without COVID 19. To compare the mortality and in-hospital stay among patients with and without COVID 19 and negative patients.

Materials and methods:In this retrospective, single-center study, we included all the patients who attended the department of neurology with neurologic symptoms with confirmed COVID-19 and long COVID-19 from June 2020 to January 2021. Data on clinical signs, diagnosis, laboratory findings were collected and analyzed from the records for positive patients and compared with neurologic patients without COVID-19 admitted in the same period.

Statistical analysis: The mean values between study groups were compared using an independent sample t-test and Mann Whitney u test. Categorical outcomes were compared using the Chi square test. Data was analyzed using coGuide software.

Results: Headache was the common neurologic manifestation present in COVID positive patients compared to COVID negative patients (39.13%). There was no statistically significant difference between the two groups in baseline parameters. Laboratory parameters like CRP, Serum Ferritin, LDH, D-dimer, ESR, and IL-6 showed a significant increase in COVID positive patients (P <0.05). In-hospital mortality was more in COVID positive patients than COVID negative patients (P <0.011).

Conclusion:The study showed varied neurologic symptoms in COVID patients, with headache as the common symptom. Hospital stay, morbidity, mortality, and inflammatory parameters were more in COVID positive patients compared to COVID negative patients.

Source: Pooja Dugani, Anish Mehta, Sunil V Furtado, R. Pradeep, Mahendra Javali, Purushottam Acharya, Vijayashree Thyagaraj, R. Srinivasa. Spectrum of neurological manifestations among acute COVID-19 and long COVID-19 – A retrospective observational study. Ref: Ro J Neurol. 2022;21(2) DOI: 10.37897/RJN.2021.2.14.  https://rjn.com.ro/articles/2022.2/RJN_2022_2_Art-14.pdf (Full text)

Long COVID and its Management

Abstract:

The pandemic of COVID-19 is the biggest public health crisis in 21st Century. Besides the acute symptoms after infection, patients and society are also being challenged by the long-term health complications associated with COVID-19, commonly known as long COVID. While health professionals work hard to find proper treatments, large amount of knowledge has been accumulated in recent years. In order to deal with long COVID efficiently, it is important for people to keep up with current progresses and take proactive actions on long COVID. For this purpose, this review will first introduce the general background of long COVID, and then discuss its risk factors, diagnostic indicators and management strategies. This review will serve as a useful resource for people to understand and prepare for long COVID that will be with us in the foreseeable future.

Source: Koc HC, Xiao J, Liu W, Li Y, Chen G. Long COVID and its Management. Int J Biol Sci 2022; 18(12):4768-4780. doi:10.7150/ijbs.75056. Available from https://www.ijbs.com/v18p4768.htm (Full text)

Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study

Abstract:

Background: The long-COVID syndrome (LCS), defined by residual symptoms from acute COVID-19 for <60 days, affects about one-third of all COVID survivors and is an emerging public health challenge. Empirical data about the range of symptoms or the utility of acupuncture alone for the LCS are very limited.

Case: This observational case study of a 46-year-old male with LCS was conducted to preliminarily define the range of symptoms, a Traditional Chinese Medicine (TCM) diagnostic structure, and evaluate the potential utility of prescribed acupuncture for LCS.

Results: The primary TCM diagnostic patterns from this patient’s LCS presentation included Lung Qi and Yin Deficiency, Qi and Blood Stagnation, and Spleen Qi Deficiency with dampness. Acupuncture for this patient was associated with reduced symptoms and signs of LCS.

Conclusion: A preliminary TCM diagnostic structure for LCS was defined. Acupuncture appears to have been helpful for a patient with LCS. Further research is needed to demonstrate the efficacy of acupuncture and/or other TCM modalities for LCS.

Source: Hollifield M, Cocozza K, Calloway T, Lai J, Caicedo B, Carrick K, Alpert R, Hsiao AF. Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study. Med Acupunct. 2022 Jun 1;34(3):172-176. doi: 10.1089/acu.2021.0088. Epub 2022 Jun 16. PMID: 35832108; PMCID: PMC9248334. https://www.liebertpub.com/doi/10.1089/acu.2021.0088 (Full text)

The Role of Acupuncture for Long COVID: Mechanisms and Models

Abstract:

Objective: To establish an evidence-based role for acupuncture as a safe and effective treatment for managing Long COVID in the integrative medical setting.

Background: COVID-19 progresses to a chronic state, termed Long COVID, in about 30% of cases with estimates as high as 40% for prolonged illness. Symptoms are diverse and range over several body systems, including unrelenting fatigue, persistent malaise, chronic pain, and mood changes. Early clinical reports suggest acupuncture can effectively address both symptoms and the underlying causes of Long COVID.

Evidence: Historically, acupuncture is well defined in Traditional Chinese Medicine writings to treat influenza-like febrile illnesses. Contemporary scientific literature and case studies support the value of acupuncture for symptoms associated with acute and chronic respiratory viral infections, such as influenza, including SARS and COVID-19. Recent reports provide early evidence of acupuncture’s effectiveness in managing Long COVID symptoms and may also have disease-modifying benefits.

Conclusion: Acupuncture is a viable adjunctive health care modality as part of a multidisciplinary approach for symptom control and disease management to improve quality of life in Long COVID patients. Since acupuncture may favorably modify the length and outcome of this condition, the model of acupuncture presented in this article warrants broader use in the integrative clinical setting and for further research.

Source: Williams JE, Moramarco J. The Role of Acupuncture for Long COVID: Mechanisms and Models. Med Acupunct. 2022 Jun 1;34(3):159-166. doi: 10.1089/acu.2021.0090. Epub 2022 Jun 16. PMID: 35832109; PMCID: PMC9248327. https://www.liebertpub.com/doi/10.1089/acu.2021.0090 (Full text)

Conceptualizing a Traditional Chinese Medicine and Pathology of Arousal Diagnostic and Pathophysiological Framework for Postacute Sequelae of COVID-19

Abstract:

Introduction: The postacute sequelae of COVID-19 (PASC) is a serious heterogeneous condition that affects a significant minority of those who endured COVID-19. PASC involves multiple body systems and an illness trajectory that has stages now being identified in medical research.

Objective: Traditional Chinese Medicine (TCM) and acupuncture are well suited to conceptualize and treat PASC and other postviral conditions. No description of TCM theory and its relationship with modern medical theory about PASC and its illness trajectory currently exists.

Conclusion: The authors provide an overview of the potential value of TCM for conceptualizing and treating PASC with a few examples and clarify directions for research.

Source: Calloway T, Hsiao AF, Brand M, Lai J, Geise C, Caceido B, Alpert R, Hollifield M. Conceptualizing a Traditional Chinese Medicine and Pathology of Arousal Diagnostic and Pathophysiological Framework for Postacute Sequelae of COVID-19. Med Acupunct. 2022 Jun 1;34(3):167-171. doi: 10.1089/acu.2022.0022. Epub 2022 Jun 16. PMID: 35832113; PMCID: PMC9248333. https://www.liebertpub.com/doi/10.1089/acu.2022.0022 (Full text)

Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes?

Abstract:

A variety of rehabilitation programmes can be offered to Long COVID patients, specifically physical training. Indeed 90% of these patients reports impairments of verticalization, stability and spatial orientation, making difficult exercise in the gym. The aim of our study was to assess the effectiveness and safety of aquatic exercise techniques as part of a comprehensive rehabilitation program for patients with Long COVID.

The first of a two-stage program involved development of aquatic exercises technique, which was evaluated in 12 patients with impaired upright posture control before and after exercising by “Habilect” video gait analysis system. During the second phase, effectiveness and safety of aqua exercises were tested in water pool as part of a comprehensive rehabilitation programme conducted in 23 patients with Long COVID outcomes. Physical examination, 6-minute step test, Euro-QL-5D questionnaire, Borg scale, laser Doppler flowmetry, cardiointervalography, and spirometry were performed before and after the aquatic exercises program.

After the training with aquatic exercises, indices of deviations of the main body axes of the head and the body mass centre ameliorated, as well as direction of body movement vector decreased (p<0.05). This study demonstrated a statistically significant improvement in exercise tolerance in both groups, as measured by the 6-minute step test after rehabilitation. The comparison group averaged 236.7 metres [126; 380] (T=8, p=0.047) after the rehabilitation course and the intervention group averaged 233.71 metres [150; 320] (T=8.0, p=0.047). When tested with the Euro-QL-5D questionnaire, a post-treatment improvement was noted in the comparison group on the anxiety/depression subscale (3 [3;3] (T=0, p=0.043)).

In the intervention group, laser Doppler flowmetry revealed a statistically significant increase in microcirculation (6.36 standard units after rehabilitation) [5.54; 8.17] (T=7.0, p=0.004), and a decrease of oxidative metabolism index of 6.89 standard units. [4.76; 6.96] (T=4.0, p=0.03). No serious adverse events were reported. In conclusion, the developed aquatic exercises technique seems to contribute to recovery of impaired upright posture and motor function, normalizing the walking pattern.

Source: Lobanov AA, Irina A Grishechkina, Andronov SV, Gleb N Barashkov, Andrey I Popov, Anatoliy D Fesyun, Elena P Ivanova, Maccarone MC, Stefano Masiero. Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes? Eur J Transl Myol. 2022 Jul 14. doi: 10.4081/ejtm.2022.10698. Epub ahead of print. PMID: 35833897.  https://pubmed.ncbi.nlm.nih.gov/35833897/ (Full text: Follow link on page)