Tag: long covid symptoms

Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance

Abstract:

Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups.

Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention.

Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests.

Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.

Source: O’Connor EE, Rednam N, O’Brien R, O’Brien S, Rock P, Levine A, Zeffiro TA. Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance. medRxiv [Preprint]. 2022 Sep 23:2022.09.22.22280222. doi: 10.1101/2022.09.22.22280222. PMID: 36172134; PMCID: PMC9516858. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516858/ (Full text)

Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system

Abstract:

Background: Post-acute sequelae of COVID-19 (PASC), also now known as long COVID, has become a major global health and economic burden. Previously, we provided evidence that there is a significant insoluble fibrin amyloid microclot load in the circulation of individuals with long COVID, and that these microclots entrap a substantial number of inflammatory molecules, including those that might prevent clot breakdown. Scientifically, the most challenging aspect of this debilitating condition is that traditional pathology tests such as a serum CRP (C-reactive protein) may not show any significant abnormal inflammatory markers, albeit these tests measure only the soluble inflammatory molecules. Elevated, or abnormal soluble biomarkers such as IL-6, D-Dimer or fibrinogen indicate an increased risk for thrombosis or a host immune response in COVID-19. The absence of biomarkers in standard pathology tests, result in a significant amount of confusion for patients and clinicians, as patients are extremely sick or even bed-ridden but with no regular identifiable reason for their disease. Biomarkers that are currently available cannot detect the molecules present in the microclots we identified and are therefore unable to confirm their presence or the mechanisms that drive their formation.

Methods: Here we analysed the protein content of double-digested microclots of 99 long COVID patients and 29 healthy controls. The patients suffering from long COVID reported their symptoms through a questionnaire completed by themselves or their attending physician.

Results: Our long COVID cohort’s symptoms were found to be in line with global findings, where the most prevalent symptoms were constant fatigue (74%,) cognitive impairment (71%) and depression and anxiety (30%). Our most noteworthy findings were a reduced level of plasma Kallikrein compared to our controls, an increased level of platelet factor 4 (PF4) von Willebrand factor (VWF), and a marginally increased level of α-2 antiplasmin (α-2-AP). We also found a significant presence of antibodies entrapped inside these microclots.

Conclusion: Our results confirm the presence of pro-inflammatory molecules that may also contribute to a failed fibrinolysis phenomenon, which could possibly explain why individuals with long COVID suffer from chronic fatigue, dyspnoea, or cognitive impairment. In addition, significant platelet hyperactivation was noted. Hyperactivation will result in the granular content of platelets being shed into the circulation, including PF4. Overall, our results provide further evidence of both a failed fibrinolytic system in long COVID/PASC and the entrapment of many proteins whose presence might otherwise go unrecorded. These findings might have significant implications for individuals with pre-existing comorbidities, including cardiovascular disease and type 2 diabetes.

Source: Kruger A, Vlok M, Turner S, Venter C, Laubscher GJ, Kell DB, Pretorius E. Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system. Cardiovasc Diabetol. 2022 Sep 21;21(1):190. doi: 10.1186/s12933-022-01623-4. PMID: 36131342; PMCID: PMC9491257. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491257/ (Full text)

Memory alterations after COVID-19 infection: a systematic review

Abstract:

SARS-CoV-2 infection has a wide range of both acute and long-term symptoms. Memory alterations have been frequently reported in studies that explore cognition. The main objective of the systematic review is to update and further analyze the existing evidence of objective memory impairments in long-COVID-19 considering sample and study design characteristics, as well as to explore associations between memory performance and their epidemiological, clinical, and pathological features.

A total of 13 studies were identified by searching in PubMed, Web of Science, and PsycInfo databases up to May 6, 2022. Most studies evaluated verbal component of memory in the short-term and long-term recall up to 30 min and mainly performed a single assessment completed at 4-6 months after the infection. The samples mainly consisted of middle-aged adults that required hospitalization. Samples were not stratified by sex, age, and severity.

Poor verbal learning was reported in most cases (6-58%), followed by deficits in long-term (4-58%) and short-term (4-37%) verbal memory. Visuospatial component of memory was studied less than verbal component, showing impairment of long-term retention of visual items (10-49%). COVID-19 severity in the acute stage was not systematically associated with poor memory performance. Verbal memory deficits were associated with anxiety and depression.

The existing literature on objective memory assessment in long-COVID suggests further research is warranted to confirm memory dysfunction in association with epidemiological, pathological, and clinical factors, using both verbal and visuospatial tests, and exploring in deep long-term memory deficits.

Source: Llana T, Zorzo C, Mendez-Lopez M, Mendez M. Memory alterations after COVID-19 infection: a systematic review. Appl Neuropsychol Adult. 2022 Sep 15:1-14. doi: 10.1080/23279095.2022.2123739. Epub ahead of print. PMID: 36108666.  https://pubmed.ncbi.nlm.nih.gov/36108666/

What we already know about the Post-COVID-19 Syndrome: A narrative review

Abstract:

As an increasingly number of patients recover from the acute COVID-19 disease, it has been observed that many face long lasting symptoms, referred as the Post-COVID-19 Syndrome. This article covers the most common signs and symptoms of this syndrome, its general aspects, and important complementary exams related to the disease. The manuscript is a narrative review, gathering new evidence published about the topic.

The most common symptoms of the Post-COVID-19 Syndrome are chronic fatigue, breathlessness, depression or anxiety, pain, cough and alopecia, and many of them are still present 6 months after hospital discharge from the acute disease, depending on the gravity of the illness. It is important for patients to maintain medical follow-up to access severity of the symptoms and choose whether further investigation is necessary. There are some treatments available to some minimize the long-lasting burden of the syndrome, and the physician should access the need for treatment with the patient.

As a new disease, there is a lot of new evidence being produced rapidly, but no up-to-date protocol has already been published. Even with the vaccinations campaigns, the burden of the pandemic is yet out of sight, as it still killing thousands daily, and those who have recovered from the acute COVID-19 illness can present chronic symptoms. Therefore, we recommend health professionals to continuously up-to-date themselves, as new information is added to make better clinical decisions.

Source: RESENDE, M. D. de .; RESENDE, G. D. de .; RIQUIERI, L. N. .; SANTOS, A. F. A. dos .; CASTRO, A. C. A. de .; ROCHA, M. da C. . What we already know about the Post-COVID-19 Syndrome: A narrative review. Research, Society and Development, [S. l.], v. 11, n. 12, p. e108111234143, 2022. DOI: 10.33448/rsd-v11i12.34143. https://rsdjournal.org/index.php/rsd/article/view/34143

The majority of severe COVID-19 patients develop anti-cardiac autoantibodies

Abstract:

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens.

Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients.

Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p < 0.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment.

Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65 years) and the patients younger than 65 years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID).

Source: Fagyas M, Nagy B Jr, Ráduly AP, Mányiné IS, Mártha L, Erdősi G, Sipka S Jr, Enyedi E, Szabó AÁ, Pólik Z, Kappelmayer J, Papp Z, Borbély A, Szabó T, Balla J, Balla G, Bai P, Bácsi A, Tóth A. The majority of severe COVID-19 patients develop anti-cardiac autoantibodies. Geroscience. 2022 Sep 16:1–14. doi: 10.1007/s11357-022-00649-6. Epub ahead of print. PMID: 36112333; PMCID: PMC9483490. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483490/ (Full text)

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study

Abstract:

Background: Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS.

Methods: This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests.

Results: The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured.

Conclusions: These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms. Trial registration Registered retrospectively.

Source: Retornaz F, Rebaudet S, Stavris C, Jammes Y. Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study. J Transl Med. 2022 Sep 24;20(1):429. doi: 10.1186/s12967-022-03638-7. PMID: 36153556. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03638-7 (Full text)

Pulmonary Dysfunction after Pediatric COVID-19

Abstract:

Background: Long COVID occurs in lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field MRI may identify persistent pulmonary manifestations after SARS-CoV-2 infection.

Purpose: To characterize both morphologic and functional changes of lung parenchyma on low-field MRI in children and adolescents with post COVID-19 compared with healthy controls.

Materials and Methods: Between August and December 2021, a cross-sectional, prospective clinical trial using low-field MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes on MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive RT-PCR test and serological parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants and with long COVID.

Results: A total of 54 participants post COVID-19 infection (mean age, 11 years ±3 [SD], 56 males) and 9 healthy controls (mean age, 10 years ±3 [SD], 70 males) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (V/Q match) was reduced from 81±6.1% in healthy controls to 62±19% (P =.006) in the recovered group and 60±20% (P=.003) in the long COVID group. V/Q match was lower in post COVID patients with infection less than 180 days (63±20%, P=.03), 180 to 360 days (63±18%, P=0.03) and 360 days ago (41±12%, P<.001) as compared with the never-infected healthy controls (81±6.1%).

Conclusion: Low-field MRI showed persistent pulmonary dysfunction in both children and adolescents recovered from COVID-19 and with long COVID.

ClinicalTrials.gov: NCT04990531

Source: Heiss R, Tan L, Schmidt S, Regensburger AP, Ewert F, Mammadova D, Buehler A, Vogel-Claussen J, Voskrebenzev A, Rauh M, Rompel O, Nagel AM, Lévy S, Bickelhaupt S, May MS, Uder M, Metzler M, Trollmann R, Woelfle J, Wagner AL, Knieling F. Pulmonary Dysfunction after Pediatric COVID-19. Radiology. 2022 Sep 20:221250. doi: 10.1148/radiol.221250. Epub ahead of print. PMID: 36125379.

Higher rates of long covid symptoms in patients with mild covid-19

Abstract:

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has affected over 61 million U.S. citizens, and up to 30-80% of COVID-19 survivors may go on to develop post-acute sequelae of SARS-CoV-2 (PASC). These sequelae can be debilitating and often impair quality of life and daily function. Although it has been suggested that severity of acute COVID-19 infection is directly related to PASC development, this association remains unclear.

METHODS: This prospective cohort study was conducted through consecutive recruitment of confirmed and probable COVID-19 patients with persistent symptoms lasting ≥3 weeks from disease onset or positive SARS-CoV-2 test from academic PASC clinics at Emory University and Grady Memorial Hospital in Atlanta, GA during January-December 2021. Sociodemographic, comorbidity, and acute COVID-19 data were collected. Severe acute COVID- 19 was defined as requiring hospitalization, and critical acute COVID-19 required intensive care. New or worsening symptoms persisting ≥3 weeks from COVID-19 onset were collected using a standardized review of systems, and confirmed by clinician interview. Differences in PASC symptom type were assessed by calculating risk ratios (RR) and 95% confidence intervals (CI) using the Taylor series, and difference in PASC duration was assessed using student’s t-test. Two-tailed p-values ≤0.05 were considered significant.

RESULTS: Of 269 enrollees, median age was 52 years (range 18-93) and there were more women (74%) than men (26%). There were 152 (57%) African American, 76 (28%) White, and 21 (8%) Hispanic. Among PASC patients, the most common symptoms were dyspnea (68%), fatigue (63%), brain fog (48%), dizziness (27%), chest pain (25%), cough (23%) and headache (23%) with a median PASC duration of 132 days (range 21-523). Acute COVID-19 severity was asymptomatic in one participant, mild in 149 (55%), severe in 95 (35%), and critical in 23 (9%). Asymptomatic- mild acute COVID-19 patients had more persistent dyspnea (RR 1.33, 95%, CI 1.09- 1.61), fatigue (RR 1.53, 95%CI 1.22-1.91), brain fog (RR 2.00, 95%CI 1.44-2.67), dizziness (RR 2.03, 95%CI 1.27-3.25), and headache (RR 2.07, 95%CI 1.22-3.48) compared with severe-critical acute disease, who had a non-significant trend towards more cough and chest pain. Asymptomatic-mild participants were further from incident infection (153 days) compared to severe-critical participants (110 days) (p=0.04).

CONCLUSIONS: Contrary to previous observations, COVID-19 survivors who experienced asymptomatic-mild infections may develop higher rates of prevalent PASC symptoms compared to those with severe- critical antecedent infections. These findings are not attributable to PASC duration, as longer PASC duration has been previously associated with fewer symptoms. To ensure early identification and linkage to specialized care, clinicians should be aware of PASC in patients with antecedent asymptomatic-mild acute COVID-19 infections.

Source: Walker, T.; Truong, A.; Summers, A.; Dixit, A.; Goldstein, F.; Hajjar, I.; Echols, M.; Cook, S.; Lee, E.; Tekwani, S.; Carroll, K.; Sanz, I.; Lee, E. H.; Han, J. Higher rates of long covid symptoms in patients with mild covid-19. Journal of General Internal Medicine ; 37:S280, 2022. Article in English | EMBASE | ID: covidwho-1995854 https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1995854?lang=en

Long COVID in children and adolescents

Abstract:

Purpose of review: Although acute COVID-19 has been milder in children and young people compared with adults, there is a concern that they may suffer persistent symptoms. There is a need to define the clinical phenotype, determine those most at risk, the natural course of the condition and evaluate preventive and therapeutic strategies for both mental health and physical symptoms.

Recent findings: More recent studies with control groups reported a lower prevalence of persistent symptoms in children and young people exposed to SARS-CoV-2. A systematic review and meta-analysis found that the frequency of the majority of reported persistent symptoms is similar in SARS-CoV-2 positive cases and controls. Children and young people infected with SARS-COV-2 had small but significant increases in persisting cognitive difficulties, headache and loss of smell. Factors associated with persisting, impairing symptoms include increased number of symptoms at the time of testing, female sex, older age, worse self-rated physical and mental health, and feelings of loneliness preinfection.

Summary: This review highlights the importance of a control group in studies following SARS-CoV-2 infection, the need for case definitions and research to understand the outcomes of long COVID in children and young people.

Source: Stephenson T, Shafran R, Ladhani SN. Long COVID in children and adolescents. Curr Opin Infect Dis. 2022 Sep 12. doi: 10.1097/QCO.0000000000000854. Epub ahead of print. PMID: 36094094.  https://journals.lww.com/co-infectiousdiseases/Fulltext/2022/10000/Long_COVID_in_children_and_adolescents.14.aspx (Full text)

After the virus has cleared-Can preclinical models be employed for Long COVID research?

Abstract:

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) can cause the life-threatening acute respiratory disease called COVID-19 (Coronavirus Disease 2019) as well as debilitating multiorgan dysfunction that persists after the initial viral phase has resolved. Long COVID or Post-Acute Sequelae of COVID-19 (PASC) is manifested by a variety of symptoms, including fatigue, dyspnea, arthralgia, myalgia, heart palpitations, and memory issues sometimes affecting between 30% and 75% of recovering COVID-19 patients. However, little is known about the mechanisms causing Long COVID and there are no widely accepted treatments or therapeutics.

After introducing the clinical aspects of acute COVID-19 and Long COVID in humans, we summarize the work in animals (mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs)) to model human COVID-19. The virology, pathology, immune responses, and multiorgan involvement are explored. Additionally, any studies investigating time points longer than 14 days post infection (pi) are highlighted for insight into possible long-term disease characteristics.

Finally, we discuss how the models can be leveraged for treatment evaluation, including pharmacological agents that are currently in human clinical trials for treating Long COVID. The establishment of a recognized Long COVID preclinical model representing the human condition would allow the identification of mechanisms causing disease as well as serve as a vehicle for evaluating potential therapeutics.

Source: Jansen EB, Orvold SN, Swan CL, Yourkowski A, Thivierge BM, Francis ME, Ge A, Rioux M, Darbellay J, Howland JG, Kelvin AA. After the virus has cleared-Can preclinical models be employed for Long COVID research? PLoS Pathog. 2022 Sep 7;18(9):e1010741. doi: 10.1371/journal.ppat.1010741. PMID: 36070309; PMCID: PMC9451097. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451097/ (Full text)