Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment

Abstract:

Background: Cognitive deficits have been increasingly reported as possible long-term manifestations after SARS-CoV-2 infection.

Aims: In this study we aimed at evaluating the factors associated with cognitive deficits 6 months after hospitalization for Coronavirus Disease 2019 (COVID-19).

Methods: One hundred and six patients, discharged from a pneumology COVID-19 unit between March 1 and May 30 2020, accepted to be evaluated at 6 months according to an extensive neurological protocol, including the Montreal Cognitive Assessment (MoCA).

Results: Abnormal MoCA scores at 6 months follow-up were associated with higher pre-hospitalization National Health System (NHS) score (Duca et al. in Emerg Med Pract 22:1-2, 2020) (OR 1.27; 95% CI 1.05-1.6; p = 0.029) and more severe pulmonary disease expressed by the Brescia-COVID Respiratory Severity Scale (Duca et al. in Emerg Med Pract 22:1-2, 2020) (BCRSS > 1OR 4.73; 95% CI 1.53-14.63; p = 0.003) during the acute phase of the disease.

Discussion: This longitudinal study showed that the severity of COVID-19, indicated by BCRSS, and a complex score given by age and premorbid medical conditions, expressed by NHS, play a major role in modulating the long-term cognitive consequences of COVID-19 disease.

Conclusions: These findings indicate that the association of age and premorbid factors might identify people at risk for long-term neurological consequences of COVID-19 disease, thus deserving longer and proper follow-up.

Source: Cristillo V, Pilotto A, Cotti Piccinelli S, Bonzi G, Canale A, Gipponi S, Bezzi M, Leonardi M, Padovani A; Neuro Covid Next Study group. Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment. Aging Clin Exp Res. 2022 Jan 11:1–4. doi: 10.1007/s40520-021-02042-3. Epub ahead of print. PMID: 35014002; PMCID: PMC8747881. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747881/ (Full text)

Evaluation of 3-month follow-up of patients with post-acute COVID-19 syndrome

Abstract:

Background: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. This study aimed to evaluate patients with post-acute COVID-19 over 12 weeks of follow-up.

Methods: The study included 151 patients who were diagnosed with COVID-19 by real-time PCR of a nasopharyngeal swab 1 month earlier, had radiologic findings consistent with COVID-19 pneumonia, and presented to the post-COVID-19 outpatient clinic between May and August 2021. The patients were divided into three groups based on COVID-19 severity: non-severe pneumonia (group 1), severe pneumonia (group 2), and severe pneumonia requiring intensive care (group 3).

Results: Evaluation of laboratory parameters at 4 and 12 weeks showed that group 3 had higher lactose dehydrogenase (LDH) level and lower mean platelet volume than the other groups at both time points (p=0.001 for all). Group 3 also had lower FVC%, FEV1%, and DLCO/VA% compared to groups 1 and 2 at week 4 (p=0.001, 0.004, 0.001, respectively) and compared to group 1 at 12 weeks (p=0.002, 0.03, 0.001, respectively). Patients with persistent dyspnea at 12 weeks had significantly lower FEV1%, FVC%, DLCO/VA%, and saturation levels in room air and significantly higher LDH, pro-BNP, D-dimer, and heart rate compared to those without dyspnea (p=0.001 for all).

Conclusion: Although the lungs are most commonly affected after COVID-19 infection, vascular and endothelial damage also causes multisystem involvement. Our study indicates that laboratory values, radiological signs, and pulmonary functional capacity improved in most patients after 12 weeks of follow-up. This article is protected by copyright. All rights reserved.

Source: Kerget B, Çelik E, Kerget F, Aksakal A, Uçar EY, Araz Ö, Akgün M. Evaluation of 3-month follow-up of patients with post-acute COVID-19 syndrome. J Med Virol. 2022 Jan 9. doi: 10.1002/jmv.27579. Epub ahead of print. PMID: 35001367. https://pubmed.ncbi.nlm.nih.gov/35001367/

Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report

Abstract:

Background: Post-COVID-19 fatigue is a frequent symptom in COVID-19 survivors, which substantially limits patients to achieve full recovery and potentially restrains return to work. The previous literature has not yet reported the use of pulsed electromagnetic fields in this indication.

Methods: Over the course of 5 weeks, 10 sessions of pulsed electromagnetic field treatment with a high magnetic flux density were applied to a patient suffering from post-COVID-19 fatigue syndrome. Fatigue, work ability, quality of life as well as anxiety, depression, stress level, and resilience were evaluated using validated patient-reported outcome measures.

Results: Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later.

Conclusion: The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome, which could reduce clinical and economic health consequences. Clinical sham-controlled studies are needed to evaluate the effect of pulsed electromagnetic fields in this indication.

Source: Wagner B, Steiner M, Markovic L, Crevenna R. Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report. Wien Med Wochenschr. 2022 Jan 10:1–6. doi: 10.1007/s10354-021-00901-2. Epub ahead of print. PMID: 35006516; PMCID: PMC8743351. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743351/ (Full text)

Role of Nutritents for COVID-19 recovery: an integrative approach

Introduction: Many patients (“long-haulers”) suffer lingering illness following COVID-19. The aim of this presentation is to evaluate the evidence of nutrient deficiencies affecting immune function and chronic symptoms from covid19 infection in a subgroup of patients. We will discuss the potential benefit of supplementing with multi-nutrients as an integrative approach to reducing long-hauler symptoms.

Methods: A narrative review followed a search of Medline/Pubmed, CINAHL, Google Scholar for studies published between January 2000 and March 2021, using key terms “coronavirus”, “COVID-19”, “immune system”, “inflammation”, “microbiome”, “oxidative stress”, “mitochondrial function”, “micronutrients”, “vitamin”, “minerals”, and “antioxidants”. Six reviews were selected which examined on the role of nutrients in immune and neurological function, including inflammatory processes, microbiome homeostasis, and mitochondrial function.

Results: Symptoms of long-haulers may be similar to myalgic encephalomyelitis/chronic fatigue syndrome associated with mitochondria dysfunction due to oxidative stress. Similar findings of chronic inflammation and microbiome dysbiosis associated with mood disorders also suggest the association between nutrient deficiencies and immuno-neurological functions. Nutrients required for optimal immune function included: antioxidants such as CoQ10 is required for mitochondrial function and is depleted quickly during acute immune response. Vitamins C and E and selenium also have antioxidant properties that can decrease proinflammatory cytokines and increase leukocyte and NK cell function. The B vitamins are involved in decrease pro-inflammatory cytokines and increase NK cell activities. Similarly, these nutrients are required for optimal neurological functioning in the CNS.

Conclusion: Initial evidence suggests chronic inflammatory processes in the CNS may contribute to the symptoms of covid-19 long-haulers. Given the complementary roles of different nutrient in immune response and CNS pathways, integrating multiple nutrients as treatment for long-haulers warrants further study.

Source: Leung B. Role of Nutritents for COVID-19 recovery: an integrative approach European Journal of Integrative Medicine. 2021 Dec;48:101978-101978. PMCID: PMC8696099. https://europepmc.org/article/pmc/pmc8696099#free-full-text (Full text)

Long COVID symptoms and duration in SARS-CoV-2 positive children – a nationwide cohort study

Abstract:

Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of ‘long COVID’ in children. A nationwide cohort study of 37,522 children aged 0-17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%).

An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6-17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04-0.06), loss of smell RD 0.01 (CI 0.01-0.01), loss of taste RD 0.01 (CI 0.01-0.02) and muscle weakness RD 0.01 (CI 0.00-0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12-0.13), loss of taste RD 0.10 (CI 0.09-0.10), fatigue RD 0.05 (CI 0.05-0.06), respiratory problems RD 0.03 (CI 0.03-0.04), dizziness RD 0.02 (CI 0.02-0.03), muscle weakness RD 0.02 (CI 0.01-0.02) and chest pain RD 0.01 (CI 0.01-0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children ‘long COVID’ symptoms resolved within 1-5 months.

Conclusions: Long COVID in children is rare and mainly of short duration.

What is Known:

• There are increasing reports on ‘long COVID’ in adults.

• Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group.

What is New:

• 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks (‘long COVID’), when compared to a control group.

• The most common ‘long COVID’ symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems.

• These ‘long COVID’ symptoms cannot be assigned to psychological sequelae of social restrictions.

• Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not ‘long COVID’ symptoms.

• In most cases ‘long COVID’ symptoms resolve within 1-5 months.

Source: Borch L, Holm M, Knudsen M, Ellermann-Eriksen S, Hagstroem S. Long COVID symptoms and duration in SARS-CoV-2 positive children – a nationwide cohort study. Eur J Pediatr. 2022 Jan 9:1–11. doi: 10.1007/s00431-021-04345-z. Epub ahead of print. PMID: 35000003; PMCID: PMC8742700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742700/ (Full text)

Cerebrospinal Fluid Analysis Post-COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection

Abstract:

This study was undertaken to assess whether SARS-CoV-2 causes a persistent central nervous system infection. SARS-CoV-2-specific antibody index and SARS-CoV-2 RNA were studied in cerebrospinal fluid following COVID-19. Cerebrospinal fluid was assessed between days 1 and 30 (n = 12), between days 31 and 90 (n = 8), or later than 90 days (post-COVID-19, n = 20) after COVID-19 diagnosis. SARS-CoV-2 RNA was absent in all patients, and in none of the 20 patients with post-COVID-19 syndrome were intrathecally produced anti-SARS-CoV-2 antibodies detected. The absence of evidence of SARS-CoV-2 in cerebrospinal fluid argues against a persistent central nervous system infection as a cause of neurological or neuropsychiatric post-COVID-19 syndrome.

Source: Schweitzer F, Goereci Y, Franke C, Silling S, Bösl F, Maier F, Heger E, Deiman B, Prüss H, Onur OA, Klein F, Fink GR, Di Cristanziano V, Warnke C. Cerebrospinal Fluid Analysis Post-COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection. Ann Neurol. 2022 Jan;91(1):150-157. doi: 10.1002/ana.26262. Epub 2021 Nov 22. PMID: 34724243; PMCID: PMC8653324. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653324/ (Full text)

PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response

Abstract:

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1β, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19.

This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.

Source: Loretelli C, Abdelsalam A, D’Addio F, Ben Nasr M, Assi E, Usuelli V, Maestroni A, Seelam AJ, Ippolito E, Di Maggio S, Loreggian L, Radovanovic D, Vanetti C, Yang J, El Essawy B, Rossi A, Pastore I, Montefusco L, Lunati ME, Bolla AM, Biasin M, Antinori S, Santus P, Riva A, Zuccotti GV, Galli M, Rusconi S, Fiorina P. PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response. JCI Insight. 2021 Dec 22;6(24):e146701. doi: 10.1172/jci.insight.146701. PMID: 34784300. https://insight.jci.org/articles/view/146701 (Full text)

The Long-COVID Syndrome: smoking and enhanced suicide risk

Extract:

The QJM has been at the forefront in highlighting the mental health problems associated with COVID-19 infection in society.1–6 In a Commentary piece in this issue of the Journal, Leo Sher, Professor of Psychiatry from the Mount Sinai School of Medicine, highlights the role of smoking being associated with a worse prognosis in acute infections and enhancing the risk of suicide in patients suffering persistent disabling symptoms associated with the Long-COVID Syndrome.

It is well recognized that smoking is associated with suicidal ideation, suicide attempts, suicide death and a contributing factor in the pathophysiology of suicide. The author highlights the evidence that suggests that the COVID-19 pandemic has led to increased tobacco consumption as smokers use more tobacco to cope with pandemic-related stress, anxiety, depression and loneliness. Smoking will have significant psychobiological effects resulting in enhanced impulsivity and aggression which will be compounded by in particular the brain-related symptoms…

Source: Seamas C Donnelly, The Long-COVID Syndrome: smoking and enhanced suicide risk, QJM: An International Journal of Medicine, Volume 114, Issue 11, November 2021, Page 765, https://doi.org/10.1093/qjmed/hcab300

Global surveillance, research, and collaboration needed to improve understanding and management of long COVID

The scale of chronic ill health and disability after COVID-19 has been described as the next big global health challenge. Prevalence estimates of a post-COVID-19 condition, long COVID, or post-acute sequelae of SARS-CoV-2 vary according to definition, methodology, and population. A recent systematic review reported persistent symptoms at 3–6 months in a median of 57% (range 13–92) of hospitalised patients (six studies) and 26% (2–62) of non-hospitalised patients (ten studies). This study and other reviews identified few studies from low-income settings, but with more than 245 million SARS-CoV-2 infections reported globally, millions of people are likely to already be experiencing long-term illness. While COVID-19 vaccines have reduced the risk of severe COVID-19 and death, continued high rates of SARS-CoV-2 infection will lead to further disability, having a huge impact on individuals, their families, health services, and society.

Read the rest of this article HERE.

Source: Ward H, Flower B, Garcia PJ, Ong SWX, Altmann DM, Delaney B, Smith N, Elliott P, Cooke G. Global surveillance, research, and collaboration needed to improve understanding and management of long COVID. Lancet. 2021 Dec 4;398(10316):2057-2059. doi: 10.1016/S0140-6736(21)02444-2. Epub 2021 Nov 10. PMID: 34774190; PMCID: PMC8580495. (Full text)

Physiological predictors of long-term effects of covid-19 in patients with sars-cov-2: focus on lymphocyte proliferation-improving micronutrients

Abstract

Patients with long-term effects of coronavirus disease, the so-called “long-term COVID-19 syndrome” (long-COVID-19) after SARS-CoV-2 infection, have a postponed recovery lasting from 4 weeks and up to six months, spread worldwide.

Physiological predictors based on human blood biomarkers and host-virus responses to SARS-CoV-2 are still unknown. There is growing evidence about the impact of micronutrients on improving lymphocyte proliferation and their essential roles for a functioning human immune system and regulating metabolic health. This paper aims to review information about micronutrients in patients with SARS-CoV-2 infection that determines long-COVID-19 outcomes and highlight the importance of diagnostics in predictors of long-COVID-19.

We reviewed articles returned from searches on PubMed/SCOPUS/Web of Science/ EMBASE databases using a combination of terms “long COVID-19”, “long-term effects of COVID-19”, “post-COVID-19 symptoms”, “COVID-19 associated stress”, “micronutrients”. Evidence indicates the relationship between lymphocyte proliferation improving micronutrient level and long-COVID-19 induction. Zinc, selenium, iron, manganese have an immunomodulatory function in innate and adaptive immune responses to viral infection. Anti-inflammatory functions of Vits A and B groups include the regulation of lymphocyte proliferation and metabolic health. Further research using sampling and artificial intelligence-assisted algorithms could assist in the recognition of the correlation of micronutrients and long-COVID-19 clinical outcomes.

Source: Karkhut S-M, Muzyka I, Savytska M, Dzhyoieva K, Pohoretska Y, Ivanchenko N, Zayachkivska O, Schloss JV, Szabo S. PHYSIOLOGICAL PREDICTORS OF LONG-TERM EFFECTS OF COVID-19 IN PATIENTS WITH SARS-COV-2: FOCUS ON LYMPHOCYTE PROLIFERATION-IMPROVING MICRONUTRIENTS. Proc Shevchenko Sci Soc Med Sci [Internet]. 2021Dec.12 [cited 2022Jan.18];65(2). Available from: https://mspsss.org.ua/index.php/journal/article/view/560