Tag: long Covid

Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register

Abstract:

Background and objectives: To understand the course of recovery from coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) and to determine its predictors, including patients’ pre-COVID-19 physical and mental health status.

Methods: This prospective and longitudinal cohort study recruited patients with MS who reported COVID-19 from March 17, 2020, to March 19, 2021, as part of the United Kingdom MS Register (UKMSR) COVID-19 study. Participants used online questionnaires to regularly update their COVID-19 symptoms, recovery status, and duration of symptoms for those who fully recovered. Questionnaires were date stamped for estimation of COVID-19 symptom duration for those who had not recovered at their last follow-up. The UKMSR holds demographic and up-to-date clinical data on participants as well as their web-based Expanded Disability Status Scale (web-EDSS) and Hospital Anxiety and Depression Scale (HADS) scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis.

Results: Of the 7,977 patients with MS who participated in the UKMSR COVID-19 study, 599 reported COVID-19 and prospectively updated their recovery status. Twenty-eight hospitalized participants were excluded. At least 165 participants (29.7%) had long-standing COVID-19 symptoms for ≥4 weeks and 69 (12.4%) for ≥12 weeks. Participants with pre-COVID-19 web-EDSS scores ≥7, participants with probable anxiety and/or depression (HADS scores ≥11) before COVID-19 onset, and women were less likely to report recovery from COVID-19.

Discussion: Patients with MS are affected by postacute sequelae of COVID-19. Preexisting severe neurologic impairment or mental health problems appear to increase this risk. These findings can have implications in tailoring their post-COVID-19 rehabilitation.

Source: Garjani A, Middleton RM, Nicholas R, Evangelou N. Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register. Neurol Neuroimmunol Neuroinflamm. 2021 Nov 30;9(1):e1118. doi: 10.1212/NXI.0000000000001118. PMID: 34848503; PMCID: PMC8631790. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631790/ (Full text)

Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol

Abstract:

Background: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to “long-haul” COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or self-isolation.

Methods: This paper describes a protocol for NeuroCOVID-19, a longitudinal observational study of adults aged 20-75 years at Sunnybrook Health Sciences Centre in Toronto, Ontario, that began in April 2020. We aim to recruit 240 adults, 60 per group: people who contracted COVID-19 and were admitted to hospital (group 1), people who contracted COVID-19 and self-isolated (group 2), people who experienced influenza-like symptoms at acute presentation but tested negative for COVID-19 and self-isolated (group 3, control) and healthy people (group 4, control). Participants are excluded based on premorbid neurologic or severe psychiatric illness, unstable cardiovascular disease, and magnetic resonance imaging (MRI) contraindications. Initial and 3-month follow-up assessments include multiparametric brain MRI and electroencephalography. Sensation and cognition are assessed alongside neuropsychiatric assessments and symptom self-reports. We will test the data from the initial and follow-up assessments for group differences based on 3 outcome measures: MRI cerebral blood flow, MRI resting state fractional amplitude of low-frequency fluctuation and electroencephalography spectral power.

Interpretation: If neurophysiologic alterations are detected in the COVID-19 groups in our NeuroCOVID-19 study, this information could inform future research regarding interventions for long-haul COVID-19. The study results will be disseminated to scientists, clinicians and COVID-19 survivors, as well as the public and private sectors to provide context on how brain measures relate to lingering symptoms.

Source: MacIntosh BJ, Ji X, Chen JJ, Gilboa A, Roudaia E, Sekuler AB, Gao F, Chad JA, Jegatheesan A, Masellis M, Goubran M, Rabin J, Lam B, Cheng I, Fowler R, Heyn C, Black SE, Graham SJ. Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol. CMAJ Open. 2021 Nov 30;9(4):E1114-E1119. doi: 10.9778/cmajo.20210023. PMID: 34848552; PMCID: PMC8648350. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648350/ (Full text)

Post-COVID-19 syndrome: Something to think about

The disease caused by the new coronavirus detected in 2019 (COVID-19), which arose in the Asian continent and later spread worldwide, has generated more than 3.5 million deaths, in America, 1.6 million have been registered, and in Mexico, around 223,000 , in the latter, it is equivalent to 10% of the population that suffered from COVID-19.

With the above, we must take the next step and ask ourselves: do we have to worry about the 90% who survived the acute infection? The answer is yes. The symptoms caused by COVID-19 can continue more than 4 weeks after the onset of the disease and are known as a post-COVID-19 syndrome.

The syndrome has a persistent cough, dyspnea, chest pain, and fatigue, and it may be present in one-third of survivors regardless of the severity of the initial infection 1 . The cause has not yet been founded; however, we know that the transforming growth factor-beta is involved. This cytokine promotes cell repair through fibrosis, which may explain the persistence of the symptoms 2 . It can also present with neurological disorders characterized by post-traumatic stress syndrome, neuropathy, and critically ill myopathy, especially in patients who required invasive mechanical ventilation support in intensive care units and general care wards 3 .

Regarding treatment, there is nothing specific but general recommendations such as identifying the syndrome and documentation of the present symptoms, leaving as a cornerstone the follow-up of patients after hospital discharge without forgetting those who kept at home.

Who can follow up? It can be done by family or general practitioner, with interventions of a pulmonary rehabilitator, and last the pulmonologist and cardiologist if there is an exacerbation of the symptoms 4 . It should be noted that people who have post-COVID-19 syndrome are predisposed to develop depression, anxiety, and obsessive-compulsive disorder 5 . Therefore, the purposeful search and evaluation by psychology and psychiatry are essential.

Finally, the post-COVID-19 syndrome can be considered as a chronic disease, which generates the need to implement strategies that include continuing education for health personnel and, above all, the dissemination of information to the general public. It is probably not enough in the months to follow, but no strategy has better results than the one that does not start with a vision for the future since this will be a large percentage of the consultation in general for a long time.

Source: Moral OR. Post-COVID-19 syndrome: Something to think about. Cir Cir. 2021;89(6):848-849. English. doi: 10.24875/CIRU.21000510. PMID: 34851597. https://www.cirugiaycirujanos.com/frame_esp.php?id=593

Controlling the Burden of COVID-19 by Manipulating Host Metabolism

Abstract:

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause global health problems, but its impact would be minimized if the many effective vaccines that have been developed were available and in widespread use by all societies. This ideal situation is not occurring so other means of controlling COVID-19 are needed. In this short review, we make the case that manipulating host metabolic pathways could be a therapeutic approach worth exploring. The rationale for such an approach comes from the fact that viruses cause metabolic changes in cells they infect, effective host defense mechanisms against viruses requires the activity of one or more metabolic pathways, and that hosts with metabolic defects such as diabetes are more susceptible to severe consequences after COVID-19.

We describe the types of approaches that could be used to redirect various aspects of host metabolism and the success that some of these maneuvers have had at controlling other virus infections. Manipulating metabolic activities to control the outcome of COVID-19 has to date received minimal attention. Manipulating host metabolism will never replace vaccines to control COVID-19 but could be used as an adjunct therapy to the extent of ongoing infection.

Source: Miller L, Berber E, Sumbria D, Rouse BT. Controlling the Burden of COVID-19 by Manipulating Host Metabolism. Viral Immunol. 2021 Dec 13. doi: 10.1089/vim.2021.0150. Epub ahead of print. PMID: 34905407. https://pubmed.ncbi.nlm.nih.gov/34905407/

Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome

Introduction:

In circumstances of COVID-19 epidemiological uncertainty, the causes and consequences of the disease remain important issues.

The aim of this study was to investigate obesity as a potential predisposition and chronic fatigue syndrome (CFS) as a possible consequence of COVID-19.

The study was conducted in two parts: a theoretical part, in which a literature review was performed, and an empirical part, in which COVID-19 patient survey data were analysed. To identify the main findings regarding the relationship between obesity and COVID-19, the literature review was focused on the investigation of systematic reviews and meta-analyses by three databases – Medline(via  PubMed),  Cochrane  COVID-19  Study  Register,  and  PROSPERO  (International prospective register of systematic reviews).

The patient survey was performed to investigate the relationship between obesity and severity of the disease, as well as the presence of CFS symptoms in COVID-19 patients in Latvia.

The main findings of the literature review showed that obesity increases the risk of hospitalisation, disease severity, clinical complications, poor outcomes, and mortality. The results of the patient survey showed that overweight and obesity were more critical factors for men (males) suffering with COVID-19 than for women (females) in Latvia.

The patient group with obesity caused almost half of all hospitalisations. The research data assumed that CFS  patients  were  not  a  high-risk  group  for  COVID-19,  but  COVID-19  caused  CFS-like symptoms in patients and potentially increased the number of undiagnosed patients.

In the context of further epidemiological uncertainty and the possibility of severe post-viral consequences, preventive measures are becoming increasingly important.

Source: Arāja, Diāna, Rovīte, Vita, Murovska, Modra, Terentjeva, Anna, Vaidere, Diāna, Vecvagare, Katrīne and Vīksna, Ludmila. Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome. Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences., vol.75, no.6, 2021, pp.411-416. https://sciendo.com/article/10.2478/prolas-2021-0061 (Full text)

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long‐Haul COVID‐19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls.
Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress.
Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response.
Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.
Source: Campen CMCv, Rowe PC, Visser FC. Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medicina. 2022; 58(1):28. https://doi.org/10.3390/medicina58010028  (Full text)

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

Abstract:

Background: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months.

Methods: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM.

Results: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51-70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06-13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, – 0.19 [- 0.28 to – 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty.

Conclusions: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning. Clinical trial registration NCT04401254 May 26, 2020.

Source: Hodgson CL, Higgins AM, Bailey MJ, Mather AM, Beach L, Bellomo R, Bissett B, Boden IJ, Bradley S, Burrell A, Cooper DJ, Fulcher BJ, Haines KJ, Hopkins J, Jones AYM, Lane S, Lawrence D, van der Lee L, Liacos J, Linke NJ, Gomes LM, Nickels M, Ntoumenopoulos G, Myles PS, Patman S, Paton M, Pound G, Rai S, Rix A, Rollinson TC, Sivasuthan J, Tipping CJ, Thomas P, Trapani T, Udy AA, Whitehead C, Hodgson IT, Anderson S, Neto AS; COVID-Recovery Study Investigators and the ANZICS Clinical Trials Group. The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study. Crit Care. 2021 Nov 8;25(1):382. doi: 10.1186/s13054-021-03794-0. PMID: 34749756; PMCID: PMC8575157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575157/ (Full text)

Establishing the prevalence of common tissue‐specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection

Summary:

Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons.

We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies.

Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies.

Source: Richter AG, Shields AM, Karim A, et al. Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection. Clin Exp Immunol. 2021;205(2):99-105. doi:10.1111/cei.13623 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239842/ (Full article)

Diverse functional autoantibodies in patients with COVID-19

Abstract:

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome).

We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

Source: Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE; Yale IMPACT Team, Dela Cruz C, Farhadian SF, Schulz WL, Ma S, Grubaugh ND, Ko AI, Iwasaki A, Ring AM. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021 Jul;595(7866):283-288. doi: 10.1038/s41586-021-03631-y. Epub 2021 May 19. PMID: 34010947. https://pubmed.ncbi.nlm.nih.gov/34010947/

Stellate ganglion block reduces symptoms of Long COVID: A case series

Abstract:

After recovering from COVID-19, a significant proportion of symptomatic and asymptomatic individuals develop Long COVID. Fatigue, orthostatic intolerance, brain fog, anosmia, and ageusia/dysgeusia in Long COVID resemble “sickness behavior,” the autonomic nervous system response to pro-inflammatory cytokines (Dantzer et al., 2008). Aberrant network adaptation to sympathetic/parasympathetic imbalance is expected to produce long-standing dysautonomia. Cervical sympathetic chain activity can be blocked with local anesthetic, allowing the regional autonomic nervous system to “reboot.” In this case series, we successfully treated two Long COVID patients using stellate ganglion block, implicating dysautonomia in the pathophysiology of Long COVID and suggesting a novel treatment.

Source: Liu LD, Duricka DL. Stellate ganglion block reduces symptoms of Long COVID: A case series. J Neuroimmunol. 2021 Dec 8;362:577784. doi: 10.1016/j.jneuroim.2021.577784. Epub ahead of print. PMID: 34922127. https://www.jni-journal.com/article/S0165-5728(21)00311-8/fulltext (Full text)