Tag: long Covid

Long-term immunologic effects of SARS-CoV-2 infection: leveraging translational research methodology to address emerging questions

Abstract:

The current era of COVID-19 is characterized by emerging variants of concern, waning vaccine- and natural infection-induced immunity, debate over the timing and necessity of vaccine boosting, and the emergence of post-acute sequelae of SARS-CoV-2 infection. As a result, there is an ongoing need for research to promote understanding of the immunology of both natural infection and prevention, especially as SARS-CoV-2 immunology is a rapidly changing field, with new questions arising as the pandemic continues to grow in complexity.

The next phase of COVID-19 immunology research will need focus on clearer characterization of the immune processes defining acute illness, development of a better understanding of the immunologic processes driving protracted symptoms and prolonged recovery (ie, post-acute sequelae of SARS-CoV-2 infection), and a growing focus on the impact of therapeutic and prophylactic interventions on the long-term consequences of SARS-CoV-2 infection.

In this review, we address what is known about the long-term immune consequences of SARS-CoV-2 infection and propose how experience studying the translational immunology of other infections might inform the approach to some of the key questions that remain.

Source: Peluso MJ, Donatelli J, Henrich TJ. Long-term immunologic effects of SARS-CoV-2 infection: leveraging translational research methodology to address emerging questions. Transl Res. 2022 Mar;241:1-12. doi: 10.1016/j.trsl.2021.11.006. Epub 2021 Nov 12. PMID: 34780969; PMCID: PMC8588584.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588584/ (Full text)

Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations

Abstract:

BACKGROUND. After the initial surge in COVID-19 cases, large numbers of patients were discharged from a hospital without assessment of recovery. Now, an increasing number of patients report postacute neurological sequelae, known as “long COVID” — even those without specific neurological manifestations in the acute phase.

METHODS. Dynamic brain changes are crucial for a better understanding and early prevention of “long COVID.” Here, we explored the cross-sectional and longitudinal consequences of COVID-19 on the brain in 34 discharged patients without neurological manifestations. Gray matter morphology, cerebral blood flow (CBF), and volumes of white matter tracts were investigated using advanced magnetic resonance imaging techniques to explore dynamic brain changes from 3 to 10 months after discharge.

RESULTS. Overall, the differences of cortical thickness were dynamic and finally returned to the baseline. For cortical CBF, hypoperfusion in severe cases observed at 3 months tended to recover at 10 months. Subcortical nuclei and white matter differences between groups and within subjects showed various trends, including recoverable and long-term unrecovered differences. After a 10-month recovery period, a reduced volume of nuclei in severe cases was still more extensive and profound than that in mild cases.

CONCLUSION. Our study provides objective neuroimaging evidence for the coexistence of recoverable and long-term unrecovered changes in 10-month effects of COVID-19 on the brain. The remaining potential abnormalities still deserve public attention, which is critically important for a better understanding of “long COVID” and early clinical guidance toward complete recovery.

Source: Tian Tian, et al. Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations. Published February 22, 2022
Citation Information: JCI Insight. 2022;7(4):e155827. https://doi.org/10.1172/jci.insight.155827. (Full text)

Long COVID 12 months after discharge: persistent symptoms in patients hospitalised due to COVID-19 and patients hospitalised due to other causes—a multicentre cohort study

Abstract:

Background: Long-term-specific sequelae or persistent symptoms (SPS) after hospitalisation due to COVID-19 are not known. The aim of this study was to explore the presence of SPS 12 months after discharge in survivors hospitalised due to COVID-19 and compare it with survivors hospitalised due to other causes.

Methods: Prospective cohort study, the Andalusian Cohort of Hospitalised patients for COVID-19 (ANCOHVID study), conducted in 4 hospitals and 29 primary care centres in Andalusia, Spain. The sample was composed of 906 adult patients; 453 patients hospitalised due to COVID-19 (exposed) and 453 hospitalised due to other causes (non-exposed) from March 1 to April 15, 2020, and discharged alive. The main outcomes were (1) the prevalence of SPS at 12 months after discharge and (2) the incidence of SPS after discharge. Outcome data at 12 months were compared between the exposed and non-exposed cohorts. Risk ratios were calculated, and bivariate analyses were performed.

Results: A total of 163 (36.1%) and 160 (35.3%) patients of the exposed and non-exposed cohorts, respectively, showed at least one SPS at 12 months after discharge. The SPS with higher prevalence in the subgroup of patients hospitalised due to COVID-19 12 months after discharge were persistent pharyngeal symptoms (p<0.001), neurological SPS (p=0.049), confusion or memory loss (p=0.043), thrombotic events (p=0.025) and anxiety (p=0.046). The incidence of SPS was higher for the exposed cohort regarding pharyngeal symptoms (risk ratio, 8.00; 95% CI, 1.85 to 36.12), confusion or memory loss (risk ratio, 3.50; 95% CI, 1.16 to 10.55) and anxiety symptoms (risk ratio, 2.36; 95% CI, 1.28 to 4.34).

Conclusions: There was a similar frequency of long-term SPS after discharge at 12 months, regardless of the cause of admission (COVID-19 or other causes). Nevertheless, some symptoms that were found to be more associated with COVID-19, such as memory loss or anxiety, merit further investigation. These results should guide future follow-up of COVID-19 patients after hospital discharge.

Source: Rivera-Izquierdo, M., Láinez-Ramos-Bossini, A.J., de Alba, I.GF. et al. Long COVID 12 months after discharge: persistent symptoms in patients hospitalised due to COVID-19 and patients hospitalised due to other causes—a multicentre cohort study. BMC Med 20, 92 (2022). https://doi.org/10.1186/s12916-022-02292-6  (Full text)

Neural Dysregulation in Post-Covid Fatigue

Abstract:

Following infection from SARS-CoV-2, a substantial minority of people develop lingering after-effects known as ‘long COVID’. Fatigue is a common complaint with substantial impact on daily life, but the neural mechanisms behind post-COVID fatigue remain unclear. We recruited volunteers with self-reported fatigue after a mild COVID infection and carried out a battery of behavioural and neurophysiological tests assessing the central, peripheral and autonomic nervous systems. In comparison to age and gender matched volunteers without fatigue, we show underactivity in specific cortical circuits, dysregulation of autonomic function, and myopathic change in skeletal muscles. Cluster analysis revealed no sub-groupings, suggesting post-COVID fatigue is a single entity with individual variation, rather than a small number of distinct syndromes. These abnormalities on objective tests may indicate novel avenues for principled therapeutic intervention, and could act as fast and reliable biomarkers for diagnosing and monitoring the progression of fatigue over time.

Source: Anne M.E. Baker, Natalie J. Maffitt, Alessandro Del Vecchio, Katherine M. McKeating, Mark R. Baker, Stuart N. Baker, Demetris S. Soteropoulos. Neural Dysregulation in Post-Covid Fatigue.
medRxiv 2022.02.18.22271040; doi: https://doi.org/10.1101/2022.02.18.22271040 https://www.medrxiv.org/content/10.1101/2022.02.18.22271040v1.full-text (Full text)

Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic

Abstract:

The chronic neurological aspects of traumatic brain injury, post-stroke syndromes, long COVID-19, persistent Lyme disease, and influenza encephalopathy having close pathophysiological parallels that warrant being investigated in an integrated manner. A mechanism, common to all, for this persistence of the range of symptoms common to these conditions is described. While TNF maintains cerebral homeostasis, its excessive production through either pathogen-associated molecular patterns or damage-associated molecular patterns activity associates with the persistence of the symptoms common across both infectious and non-infectious conditions.

The case is made that this shared chronicity arises from a positive feedback loop causing the persistence of the activation of microglia by the TNF that these cells generate. Lowering this excess TNF is the logical way to reducing this persistent, TNF-maintained, microglial activation. While too large to negotiate the blood-brain barrier effectively, the specific anti-TNF biological, etanercept, shows promise when administered by the perispinal route, which allows it to bypass this obstruction.

Source: Clark IA. Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic. Pharmacol Res Perspect. 2022 Apr;10(2):e00926. doi: 10.1002/prp2.926. PMID: 35174650; PMCID: PMC8850677. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850677/ (Full text)

Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond

Introduction:

Black plague epidemics in Medieval Europe, the Spanish Flu pandemic during the first world war, and the pandemic of COVID-19 disease are just three devastating examples of the fragile co-existence between human beings and the microbial world. Remarkably, the human immune system with its innate and adaptive arms recognizes and clears the invading pathogens in most cases. However, like a scar after an injury, some people who had suffered from acute infections remain ill long after the clearance of the pathogen itself. These individuals develop complex fatigue-related syndromes whose pathological mechanisms remain poorly understood. A prime example of such syndromes is the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) characterized by persistent fatigue and post-exertional malaise among other symptoms (1). Unfortunately, its diagnosis remains challenging due to the inexistence of objective biomarkers that could identify cases. However, researchers are gathering around multidisciplinary networks, such as the US ME/CFS Clinician Coalition and the European Network on ME/CFS, with the aim of fostering collaboration, standardizing research and clinical practices, while accelerating biomarker discovery (2–5). Less-known fatigue-related syndromes have been recently reported after the outbreaks of Ebola virus, Dengue virus, and Chikungunya virus in the Tropics (6–8). However, it is still unclear whether these syndromes constitute clinical entities beyond ME/CFS itself.

Read the rest of this article HERE.

Source: Westermeier F, Lacerda EM, Scheibenbogen C and Sepúlveda N (2022) Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond. Front. Med. 9:862953. doi: 10.3389/fmed.2022.862953  https://www.frontiersin.org/articles/10.3389/fmed.2022.862953/full (Full text)

Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : A retrospective cohort single-center study

Abstract:

in English, German

Background: There are no outcome studies for coronavirus disease 2019 (COVID-19) survivors one year after hospital discharge in Germany.

Methods: This retrospective cohort study included all patients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalized in the departments of internal medicine of the Klinikum Saarbrücken, a tertiary care hospital, between March 15 and December 31, 2020. A telephone interview with survivors was conducted at least 12 months after discharge. The interview was initiated with an open-ended question whether the patient had fully recovered from the disease. In the event of a subjective incomplete recovery, the patient was prompted to report any continuous or frequent symptoms that had not occurred prior to COVID-19. Finally, independent of the open-ended question response, all patients were asked closed questions which addressed new symptom onset of persistent fatigue, cognitive dysfunction, headache, muscle and joint pain following COVID-19.

Results: In all, 235 survivors were contacted and 162 could be included in the analysis. In 55 of 162 interviews (34.0%) at least one persistent COVID-19 symptom (PCS) was spontaneously reported. Four of 55 survivors with PCS reported five additional symptoms on the closed questions. One survivor, who responded positively to the open-ended question, reported new onset PCS in response to the closed questions. Physical fatigue (24.7%), cognitive dysfunction (14.8%), shortness of breath (8.6%), muscle and joint pain (6.8%) and headache (6.2%) were the most frequently reported PCS.

Conclusions: Despite an interview technique aimed to reduce attribution bias by patients, one third of COVID-19 inpatient survivors report PCS one year after hospitalization.

The complete article is written in English.

Source: Zuschlag D, Grandt D, Custodis F, Braun C, Häuser W. Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : A retrospective cohort single-center study. Schmerz. 2022 Feb 25:1–9. doi: 10.1007/s00482-022-00626-0. Epub ahead of print. PMID: 35217881; PMCID: PMC8877740. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877740/ (Full study)

COVID-19 and Mitochondrial Non-Coding RNAs: New Insights From Published Data

Abstract:

Scientists all around the world are working to investigate new ways to prevent and treat COVID-19, and recent research has been focusing on the effects of a syndrome commonly called “long COVID.” People affected by this syndrome usually suffer from symptoms like the ones observed in several types of fatigue syndrome. As these syndromes are often linked to mitochondrial dysfunction, researchers hypothesized that a dysfunction in the mitochondrial metabolism might be part of the causes of long COVID. However, while there are a few studies investigating the effect of SARS-CoV-2 infection on mitochondrial metabolism, the effect on the transcription of mitochondrial non-coding RNAs has not been investigated yet. Thus, using publicly available data, I explored the effect of SARS-CoV-2 on the expression of several mitochondrial non-coding RNAs in patients recovering from COVID-19.

No change in the expression of long non-coding RNAs was detected at any stage of the infection, but up to 43 small mitochondrial RNAs have their expression altered during the recovery from COVID-19. This result suggests that the SARS-CoV-2 infection somehow affected the metabolism of small mitochondrial RNAs specifically without altering the overall mitochondrial transcription. Despite these being only preliminary results on a small cohort, the analyses clearly showed that individuals infected by SARS-CoV-2 retain an altered expression of these small RNAs. This persistent alteration in the expression of small mitochondrial RNAs might be involved in the long COVID syndrome and further studies are needed to confirm the possibility.

Source: Pozzi A. COVID-19 and Mitochondrial Non-Coding RNAs: New Insights From Published Data. Front Physiol. 2022 Feb 4;12:805005. doi: 10.3389/fphys.2021.805005. PMID: 35185603; PMCID: PMC8856670. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856670/ (Full text)

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection

Abstract:

The global pandemic of SARS-CoV-2 has affected several hundred million people, and many infected people have suffered from a milder initial infection but have never fully recovered. This observational study investigates the pain burden in sufferers of post-COVID-19 syndrome after a milder initial infection.

One hundred post-COVID-19 patients filled out questionnaires regarding sociodemographic data, previous comorbidities, present pharmacological treatment, pain intensity and pain localisation. Health-related quality of life, fatigue, emotional status, and insomnia were measured by validated questionnaires. Multiple post-COVID-19 symptoms, including post-exertional malaise, were evaluated by a symptom questionnaire. Among the 100 participants (mean age 44.5 years), 82% were women, 61% had higher education, and 56% were working full or part time. Nine participants reported previous pain or inflammatory conditions. Among the most painful sites were the head/face, chest, lower extremities, and migrating sites. Generalised pain was self-reported by 75 participants and was estimated in 50 participants. Diagnosis of fibromyalgia according to the 2016 criteria was suspected in 40 participants. Subgroup analyses indicated that comorbidities might play a role in the development of pain.

In conclusion, a major part of sufferers from post-COVID-19 syndrome develop pain, and in addition to its many disabling symptoms, there is an urgent need for pain management in post-COVID-19 syndrome.

Source: Bileviciute-Ljungar I, Norrefalk JR, Borg K. Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection. J Clin Med. 2022 Jan 31;11(3):771. doi: 10.3390/jcm11030771. PMID: 35160223; PMCID: PMC8836662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836662/ (Full text)

Covid-19: Vaccinated people are less likely to get long covid, review finds

People who had been fully vaccinated against covid-19 were around half as likely to develop long covid symptoms as people who had received only one vaccine dose or were unvaccinated, the UK Health Security Agency has said.1

The agency conducted a rapid review of evidence, including 15 UK and international studies up to January 2022. Being vaccinated was defined as having two doses of the Pfizer-BioNTech, Oxford-AstraZeneca, or Moderna vaccine or one dose of the Janssen vaccine.

The review found that vaccine effectiveness against most post-covid symptoms in adults was highest in people over 60 and lowest in those aged 19 to 35.

Around 2% of the UK population have reported symptoms of long covid (or “post-covid syndrome”), which can last for more than four weeks after the initial SARS-CoV-2 infection. The most common symptoms are fatigue, shortness of breath, and muscle or joint pain.

Read the rest of this article HERE.

Source: Mahase E. Covid-19: Vaccinated people are less likely to get long covid, review finds. BMJ. 2022 Feb 16;376:o407. doi: 10.1136/bmj.o407. PMID: 35172970. https://www.bmj.com/content/376/bmj.o407 (Full text)