Tag: long covid symptoms

Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a recent worldwide coronavirus disease-2019 (COVID-19) pandemic. SARS-CoV-2 primarily causes an acute respiratory infection but can progress into significant neurological complications in some. Moreover, patients with severe acute COVID-19 could develop debilitating long-term sequela.

Long-COVID is characterized by chronic symptoms that persist months after the initial infection. Common complaints are fatigue, myalgias, depression, anxiety, and “brain fog,” or cognitive and memory impairments. A recent study demonstrated that a mild COVID-19 respiratory infection could generate elevated proinflammatory cytokines and chemokines in the cerebral spinal fluid.

This commentary discusses findings from this study, demonstrating that even a mild respiratory SARS-CoV-2 infection can cause considerable neuroinflammation with microglial and macrophage reactivity. Such changes could also be gleaned by measuring chemokines and cytokines in the circulating blood. Moreover, neuroinflammation caused by mild SARS-CoV-2 infection can also impair hippocampal neurogenesis, deplete oligodendrocytes, and decrease myelinated axons.

All these changes likely contribute to cognitive deficits in long-COVID syndrome. Therefore, strategies capable of restraining neuroinflammation, maintaining better hippocampal neurogenesis, and preserving oligodendrocyte lineage differentiation and maturation may prevent or reduce the incidence of long-COVID after SARS-CoV-2 respiratory infection.

Source: Wei ZD, Liang K, Shetty AK. Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments. Aging Dis. 2023 Sep 24. doi: 10.14336/AD.2023.10918. Epub ahead of print. PMID: 37815903. https://www.aginganddisease.org/EN/10.14336/AD.2023.10918 (Full text)

How long is Long-COVID? Symptomatic improvement between 12 and 18 months in a prospective cohort study

Abstract:

Introduction COVID-19 infection can precede, in a proportion of patients, a prolonged syndrome including fatigue, exercise intolerance, mood and cognitive problems. This study aimed to describe the profile of fatigue-related, exercise-related, mood-related and cognitive-related outcomes in a COVID-19-exposed group compared with controls.

Methods 113 serving UK Armed Forces participants were followed up at 5, 12 (n=88) and 18 months (n=70) following COVID-19. At 18 months, 56 were in the COVID-19-exposed group with 14 matched controls. Exposed participants included hospitalised (n=25) and community (n=31) managed participants. 43 described at least one of the six most frequent symptoms at 5 months: fatigue, shortness of breath, chest pain, joint pain, exercise intolerance and anosmia. Participants completed a symptom checklist, patient-reported outcome measures (PROMs), the National Institute for Health cognitive battery and a 6-minute walk test (6MWT). PROMs included the Fatigue Assessment Scale (FAS), Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and Patient Checklist-5 (PCL-5) for post-traumatic stress.

Results At 5 and 12 months, exposed participants presented with higher PHQ-9, PCL-5 and FAS scores than controls (ES (effect size) ≥0.25, p≤0.04). By 12 months, GAD-7 was not significantly different to controls (ES <0.13, p=0.292). Remaining PROMs lost significant difference by 18 months (ES ≤0.11, p≥0.28). No significant differences in the cognitive scales were observed at any time point (F=1.96, p=0.167). At 5 and 12 months, exposed participants recorded significantly lower distances on the 6MWT (ηp2≥0.126, p<0.01). 6MWT distance lost significant difference by 18 months (ηp2<0.039, p>0.15).

Conclusions This prospective cohort-controlled study observed adverse outcomes in depression, post-traumatic stress, fatigue and submaximal exercise performance up to 12 months but improved by 18-month follow-up, in participants exposed to COVID-19 compared with a matched control group.

Source: Barker-Davies RM, O’Sullivan O, Holdsworth DA, et alHow long is Long-COVID? Symptomatic improvement between 12 and 18 months in a prospective cohort studyBMJ Mil Health Published Online First: 03 October 2023. doi: 10.1136/military-2023-002500 https://militaryhealth.bmj.com/content/early/2023/10/03/military-2023-002500.abstract (Full text available as PDF file)

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

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)

The Long Road of Long COVID: Specific Considerations for the Allergist and Immunologist

Abstract:

Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating.

Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases.

Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions.

Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents.

The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.

Source: Bellanti JA, Novak P, Faitelson Y, Bernstein JA, Castells MC. The Long Road of Long COVID: Specific Considerations for the Allergist and Immunologist. J Allergy Clin Immunol Pract. 2023 Sep 27:S2213-2198(23)01045-0. doi: 10.1016/j.jaip.2023.09.014. Epub ahead of print. PMID: 37774781. https://www.sciencedirect.com/science/article/abs/pii/S2213219823010450

Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts

Abstract:

Background: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID).

Aim: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations.

Methods: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae.

Results: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans.

Conclusion: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

Source: Sherif ZA, Deverapalli M, Challa SR, Martirosyan Z, Whitesell P, Pizuorno AM, Naqvi Z, Tulloch IK, Oskrochi G, Brim H, Ashktorab H. Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts. World J Methodol. 2023 Sep 20;13(4):323-336. doi: 10.5662/wjm.v13.i4.323. PMID: 37771866; PMCID: PMC10523249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523249/ (Full text)