Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways

Abstract:

The physio-affective phenome of Long COVID-19 is predicted by (a) immune-inflammatory biomarkers of the acute infectious phase, including peak body temperature (PBT) and oxygen saturation (SpO2), and (b) the subsequent activation of immune and oxidative stress pathways during Long COVID. The purpose of this study was to delineate the effects of PBT and SpO2 during acute infection, as well as the increased neurotoxicity on the physical, psychological, social and environmental domains of health-related quality of life (HR-QoL) in people with Long COVID.

We recruited 86 participants with Long COVID and 39 normal controls, assessed the WHO-QoL-BREF (World Health Organization Quality of Life Instrument-Abridged Version, Geneva, Switzerland) and the physio-affective phenome of Long COVID (comprising depression, anxiety and fibromyalgia-fatigue rating scales) and measured PBT and SpO2 during acute infection, and neurotoxicity (NT, comprising serum interleukin (IL)-1β, IL-18 and caspase-1, advanced oxidation protein products and myeloperoxidase, calcium and insulin resistance) in Long COVID.

We found that 70.3% of the variance in HR-QoL was explained by the regression on the physio-affective phenome, lowered calcium and increased NT, whilst 61.5% of the variance in the physio-affective phenome was explained by calcium, NT, increased PBT, lowered SpO2, female sex and vaccination with AstraZeneca and Pfizer. The effects of PBT and SpO2 on lowered HR-QoL were mediated by increased NT and lowered calcium yielding increased severity of the physio-affective phenome which largely affects HR-QoL.

In conclusion, lowered HR-Qol in Long COVID is largely predicted by the severity of neuro-immune and neuro-oxidative pathways during acute and Long COVID.

Source: Maes M, Al-Rubaye HT, Almulla AF, Al-Hadrawi DS, Stoyanova K, Kubera M, Al-Hakeim HK. Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways. Int J Environ Res Public Health. 2022 Aug 19;19(16):10362. doi: 10.3390/ijerph191610362. PMID: 36011997. https://www.mdpi.com/1660-4601/19/16/10362/htm (Full text)

Correlation of respiratory muscle function and cardiopulmonary exercise testing in post-acute COVID-19 syndrome

To the editors,

We read the paper published by Hennigs et al. [] with great interest and thank the authors for shifting the focus to studying respiratory muscle function in Post-COVID-19 patients. The authors report striking pathological findings of mouth occlusion pressure (MOP) measurements in previously hospitalized but also non-hospitalized patients presenting with post-acute COVID-19 syndrome (PACS). In their study, Hennigs and co-authors found a high proportion of patients, more frequently females, with decreased maximum inspiratory pressure (MIP, or PImax), suggesting impairment of respiratory muscle strength. Additionally, their data indicate that increased neuroventilatory or central ventilatory drive (P0.1) may have a role in perceived respiratory distress in patients suffering from Post-COVID-19 fatigue. With this letter, we would like to share complementary data from a case series correlating MIP and P0.1 with cardiopulmonary exercise testing (CPET) in patients with PACS. Furthermore, we aim to elaborate on the limitations of MOP measurements, particularly MIP.

Read the rest of this article HERE.

Source: Leo F, Bülau JE, Semper H, Grohé C. Correlation of respiratory muscle function and cardiopulmonary exercise testing in post-acute COVID-19 syndrome. Infection. 2022 Aug 16:1–4. doi: 10.1007/s15010-022-01899-4. Epub ahead of print. PMID: 35972679; PMCID: PMC9379900. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379900/ (Full text)

Long-COVID neurological symptoms are associated with D-dimer levels in COVID-19 patients

Abstract:

Background: Coronavirus disease 2019 (COVID-19) is a disease designated as a global pandemic by the WHO that can manifest clinically as neurological disorders that can occur in the acute phase or after the acute phase (long COVID-19), such as headache, myalgia, anosmia, and cognitive impairment. These neurological disorders as symptoms of long COVID-19 are presumably caused by hypercoagulable conditions characterized by an increase in D-dimer level. This study aims to determine the correlation of long COVID-19 neurological symptoms with hypercoagulable conditions and the role of D-dimer as a biomarker of long COVID-19 neurological symptoms.

Methods: This was a cross-sectional study involving 31 patients with long COVID-19 symptoms. Admitted long COVID-19 cases with recorded D-dimer levels and definitive outcomes were included consecutively. Long COVID-19 neurological symptoms were collected. D-dimer level was measured using immunofluorescence assay and reported in fibrinogen equivalent units (ìg/mL). The correlation between D-dimer levels and neurological clinical manifestations was assessed by using ordinal regression analysis. The p-value of <0.05 was considered statistically significant.

Results: The mean age of the subjects was 38.81 ± 11.58 years and 18 (58.06%) were female. Long COVID neurological symptoms comprised myalgia, anosmia and cephalgia, and most subjects complained of myalgia (80.65%). On multivariable analysis, long-COVID-19 neurological symptoms were significantly correlated with D-dimer [odds ratio (OR) = 1.05; p=0.020].

Conclusion: The number of neurological long COVID symptoms were significantly correlated with level of D-Dimer. Ultimately, more clarity is needed on the neurological impact of COVID-19, its diagnosis, and its treatment.

Source: Mirawati, D. K., Budianto, P., Danuaji, R., Subandi, S., Ristinawati, I., & Prabaningtyas, H. R. (2022). Long-COVID neurological symptoms are associated with D-dimer levels in COVID-19 patients. Universa Medicina41(2), 169–175. https://doi.org/10.18051/UnivMed.2022.v41.169-175 https://univmed.org/ejurnal/index.php/medicina/article/view/1246

Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients

Abstract:

Background and objectives: Latest studies have revealed that an increasing number of Corona Virus Disease of 2019 (COVID-19) patients may continue to feel symptoms after the acute phase. This study aimed to evaluate the prevalence of musculoskeletal symptoms after the acute phase of COVID-19 and its associated factors.

Methods: We designed a cross-sectional study from January 2021 to April 2021. An online questionnaire was designed and sent to patients who had recovered from COVID-19. The questionnaire contained questions on participants’ demographic characteristics, COVID-19 course at its acute phase, and musculoskeletal symptoms after recovering from COVID-19. Musculoskeletal symptoms associations with patients’ characteristic and COVID-19 course was evaluated.

Result: 239 patients, including 72 (30.1%) males and 167 (69.9%) females with a mean age of 37.96 years (SD=11.19), were included in the study. 98.74% of our patients had experienced at least one musculoskeletal symptom after recovering from COVID-19, and the most common symptom was fatigue, as 91.2% of participants experienced this symptom, followed by myalgia, headache, and low back pain. High BMI, hospitalization, and ICU admission were associated with a higher risk of musculoskeletal symptoms.

Conclusion: This study indicated a high prevalence of persistent musculoskeletal symptoms among patients who recovered from COVID-19. Modifiable factors, such as BMI, can be targeted to reduce the prevalence of musculoskeletal symptoms in COVID-19 survivors and reduce its burden.

Source: Azadvari M, Haghparast A, Nakhostin-Ansari A, Emami Razavi SZ, Hosseini M. Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients. Heliyon. 2022 Aug 11:e10148. doi: 10.1016/j.heliyon.2022.e10148. Epub ahead of print. PMID: 35971463; PMCID: PMC9367176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367176/ (Full text)

Post-COVID-19 neurologic syndrome: Another legacy of the pandemic

Abstract:

COVID-19 quickly escalated to a global pandemic in 2020. As research on the topic continues, the medical community has found that this acute illness can cause a new chronic illness: postacute sequelae of SARS-CoV-2 (PASC). Some patients with PASC develop predominately neurologic sequelae (post-COVID-19 neurologic syndrome or PCNS). This article describes PASC and PCNS, their proposed pathogenicity and possible neurovirulence mechanisms, symptoms, and treatment recommendations.

Source: Luciew, Joshua D. MPAS, PA-C; Erickson, Rodney A. MD; Kaufman, Tara K. MD. Post-COVID-19 neurologic syndrome: Another legacy of the pandemic. JAAPA: August 9, 2022 – Volume – Issue – 10.1097/01.JAA.0000854524.40560.f3 doi: 10.1097/01.JAA.0000854524.40560.f3  https://journals.lww.com/jaapa/Fulltext/9900/Post_COVID_19_neurologic_syndrome__Another_legacy.18.aspx (Full text)

Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: a cross-sectional study

Abstract:

Objectives: Long COVID is a major public health issue. Whether long COVID is comorbid with psychiatric disorders remains unclear. Here, we investigate the association between long COVID, psychiatric symptoms and psychiatric disorders.

Design: Cross-sectional.

Settings: Bicêtre Hospital, France, secondary care.

Participants: One hundred seventy-seven patients admitted in intensive care unit during acute phase and/or reporting long COVID complaints were assessed 4 months after hospitalisation for an acute COVID.

Main outcome measures: Eight long COVID complaints were investigated: fatigue, respiratory and cognitive complaints, muscle weakness, pain, headache, paraesthesia and anosmia. The number of complaints, the presence/absence of each COVID-19 complaint as well as lung CT scan abnormalities and objective cognitive impairment) were considered. Self-reported psychiatric symptoms were assessed with questionnaires. Experienced psychiatrists assessed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based diagnoses of psychiatric disorders.

Results: One hundred and fifteen (65%) patients had at least one long COVID complaint. The number of long COVID complaints was associated with psychiatric symptoms. The number of long COVID complaints was higher in patients with psychiatric disorders (mean (m) (SD)=2.47 (1.30), p<0.05), new-onset psychiatric disorders (m (SD)=2.41 (1.32), p<0.05) and significant suicide risk (m (SD)=2.67 (1.32), p<0.05) than in patients without any psychiatric disorder (m (SD)=1.43 (1.48)). Respiratory complaints were associated with a higher risk of psychiatric disorder and new-onset psychiatric disorder, and cognitive complaints were associated with a higher risk of psychiatric disorder.

Conclusions: Long COVID is associated with psychiatric disorders, new-onset psychiatric disorders and suicide risk. Psychiatric disorders and suicide risk should be systematically assessed in patients with long COVID.

Source: Gasnier M, Choucha W, Radiguer F, Faulet T, Chappell K, Bougarel A, Kondarjian C, Thorey P, Baldacci A, Ballerini M, Ait Tayeb AEK, Herrero H, Hardy-Leger I, Meyrignac O, Morin L, Lecoq AL, Pham T, Noel N, Jollant F, Montani D, Monnet X, Becquemont L, Corruble E, Colle R; COMEBAC study group. Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: a cross-sectional study. J Neurol Neurosurg Psychiatry. 2022 Aug 11:jnnp-2021-328516. doi: 10.1136/jnnp-2021-328516. Epub ahead of print. PMID: 35953265.  https://jnnp.bmj.com/content/early/2022/08/10/jnnp-2021-328516 (Full text)

Symptom burden and immune dynamics 6 to 18 months following mild SARS-CoV-2 infection -a case-control study

Abstract:

Background: The burden and duration of persistent symptoms after non-severe COVID-19 remains uncertain. This study aimed to assess post-infection symptom trajectories in home-isolated COVID-19 cases compared to age- and time-period matched seronegative controls, and investigate immunological correlates of long COVID.

Methods: A prospective case-control study conducted between February 28th and April 4th 2020 included home-isolated COVID-19 cases followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched SARS-CoV-2 naive controls. We collected clinical data at baseline, 6, 12 and 18 months post-infection, and blood samples at 2, 4, 6 and 12 months for analysis of SARS-CoV-2 specific humoral and cellular responses.

Results: Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared to controls, adult cases had a high risk of fatigue (27% excess risk, gender and comorbidity adjusted odds ratio [aOR] 5.86, 95% confidence interval [CI]3.27-10.5), memory problems (21% excess risk, aOR 7.42, CI 3.51-15.67), concentration problems (20% excess risk, aOR 8.88, CI 3.88-20.35), and dyspnea (10% excess risk, aOR 2.66, CI 1.22-5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%, CI 1.5, 21.5, p = 0.024) and among women (excess risk 18.7%, CI 4.4, 32.9, p = 0.010). Longitudinal spike IgG was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4 + TCRβ depth was significantly associated with both dyspnea and number of symptoms at 12 months.

Conclusions: This study documents a high burden of persisting symptoms after mild COVID-19, and suggest that infection induced SARS-CoV-2 specific immune responses may influence long-term symptoms.

Source: Fjelltveit EB, Blomberg B, Kuwelker K, Zhou F, Onyango TB, Brokstad KA, Elyanow R, Kaplan IM, Tøndel C, Mohn KGI, Özgümüş T, Cox RJ, Langeland N; Bergen COVID-19 Research Group. Symptom burden and immune dynamics 6 to 18 months following mild SARS-CoV-2 infection -a case-control study. Clin Infect Dis. 2022 Aug 12:ciac655. doi: 10.1093/cid/ciac655. Epub ahead of print. PMID: 35959897; PMCID: PMC9384725. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384725/ (Full text)

Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case-control study

Abstract:

Background: The burden of post-coronavirus disease (COVID)-19 symptoms has been increasing and is of great concern in patients with pre-existing chronic medical conditions.This study aimed to delineate the post-COVID-19 neuropsychiatric symptoms among migraine patients compared to the non-migraine control group.

Methods: Two groups, each of 204 COVID-19 survivors, were enrolled in the study after 3 months of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, one group fulfilling the episodic migraine criteria and the other serving as a matching control group. Subjects were evaluated through an in-person interview for post-COVID-19 neuropsychiatric symptoms, including detailed headache patterns and severity, using the visual analogue scale.

Results: The Frequency of headache during the acute phase of COVID-19 was more frequent in migraine patients (OR = 1.60, 95%CI = 1.04-2.45, P-value = 0.031). The reported significant post-COVID-19 neuropsychiatric symptoms in migraine patients compared to controls were fatigue (OR = 1.662, 95%CI = 1.064-2.596, P-value = 0.025), anosmia/hyposmia (OR = 2.06, 95%CI = 1.164- 3.645, P-value = 0.012), cacosmia (OR = 2.663, 95%CI = 1.145-6.195, P-value = 0.019), depression (OR = 2.259, 95%CI = 1.284- 3.975, P-value = 0.004), anxiety (OR = 3.267, 95%CI = 1.747- 6.108, P-value ≤ 0.001), insomnia (OR = 2.203, 95%CI = 1.298- 3.739, P-value = 0.003), and headache (OR = 3.148, 95%CI = 1.616-6.136, P-value = ≤ 0.001).While there was no statistically significant difference between migraine patients and controls regarding the post-COVID-19 functional status score (P-value = 0.102). The pattern of post-COVID-19 headache was reported as chronic headache transformation in 17.6% of the migraine group, with the median intensity rate being 5.5 and IQR (3-7). In the control group, 14% experienced chronic headache attributed to systemic viral infection with a median intensity rate of 2 and IQR (2-5), while 12% experienced a new daily persistent headache with a median intensity of 5 and IQR (1-6).

Conclusion: The study highlighted the importance of follow-up migraine patients upon recovery from COVID-19 infection, being more vulnerable to post-COVID-19 symptoms.

Source: Magdy R, Elmazny A, Soliman SH, Elsebaie EH, Ali SH, Abdel Fattah AM, Hassan M, Yassien A, Mahfouz NA, Elsayed RM, Fathy W, Abdel-Hamid HM, Mohamed J, Hussein M. Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case-control study. J Headache Pain. 2022 Aug 12;23(1):101. doi: 10.1186/s10194-022-01468-y. PMID: 35962348; PMCID: PMC9372973. https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-022-01468-y (Full text)

Inequity and disparities mar existing global research evidence on Long COVID

Abstract:

Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead.

With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.

Source: Taghrir MH, Akbarialiabad H, Abdollahi A, Ghahramani N, Bastani B, Paydar S, Razani B, Mwangi J, Asadi-Pooya AA, Roozbeh J, Malekmakan L, Kumar M. Inequity and disparities mar existing global research evidence on Long COVID. Glob Health Promot. 2022 Aug 12:17579759221113276. doi: 10.1177/17579759221113276. Epub ahead of print. PMID: 35962520. https://pubmed.ncbi.nlm.nih.gov/35962520/

Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome

Abstract:

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them.

The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned.

Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome, namely “autoimmune autonomic dysfunction syndromes”. Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.

Source: Mahroum N, Shoenfeld Y. Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome. Pathophysiology. 2022 Jul 28;29(3):414-425. doi: 10.3390/pathophysiology29030033. PMID: 35997389. https://www.mdpi.com/1873-149X/29/3/33/htm (Full text)