Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest

People admitted to hospital with covid-19 who reported “long covid” symptoms five months after discharge had made only limited improvement after a full year, preliminary data from the PHOSP-COVID study show.

Researchers said that their results, released as a preprint on 16 December,1 showed that patients who experienced the most severe symptoms also had raised levels of substances associated with whole body inflammation and tissue damage and repair, suggesting autoimmune involvement.

The study, led by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, is following up 2230 adults admitted to hospital with covid-19. At five months after discharge only 2.5 in 10 people felt fully recovered.2 This was largely unchanged after 12 months, at less than 3 in 10 patients, in the 807 people assessed so far.

Chris Brightling, professor of respiratory medicine at the University of Leicester and chief investigator for the study, said, “People who were hospitalised and went on to develop long covid are not getting substantially better a year after they were discharged from hospital.

“Many patients in our study had not fully recovered at five months, and most of these reported little positive change in their health condition at one year.”

Rachael Evans, associate professor at the University of Leicester and respiratory consultant at Leicester’s Hospitals, who is the paper’s lead author, said, “Healthcare professionals will need to proactively continue assessing their patients for some time to come in order to identify their ongoing healthcare needs and provide support.

“We urgently need healthcare packages and medicines that target the potentially treatable traits of long covid to help people feel better and get back to their normal lives. Without these, long covid has the potential to become highly prevalent as a new long term condition.”

Ongoing inflammatory process

The most common long covid symptoms reported by patients were fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness, and patients said that their health related quality of life remained substantially worse one year after hospital discharge than before they had the SARS-CoV-2 infection.

A cluster analysis on the five month data revealed four distinct groups of patients based on the severity of symptoms they experienced: in 39% symptoms were considered mild, in 30% severe, in 20% very severe, and in 11% they were moderate or primarily affected cognition.

Blood samples taken at five months were analysed for around 300 substances linked to inflammation and immunity. These showed that patients in the “very severe” group had higher levels of substances associated with whole body inflammation, tissue damage, and tissue repair, while those reporting poor cognition appeared to have higher levels of substances linked to “brain fog,” suggesting possible neuro-inflammation.

Brightling said that the results suggested “an ongoing inflammatory process” and that other studies had indicated an increase in autoimmunity in some cases against specific organs such as heart or skeletal muscle. “We’re working very closely with immunologists to try to unpick that and see whether autoimmunity may be one of the key drivers [of long covid],” he said.

Source: Ingrid Torjesen. Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest. BMJ 2021;375:n3092. Published 15 December 2021. https://www.bmj.com/content/375/bmj.n3092 (Full text)

Cognitive sequelae of long COVID may not be permanent. A prospective study

Abstract:

Background and purpose: Cognitive decline is a recognized manifestation of long COVID, even among patients who experience mild disease. However, there is no evidence regarding the length of cognitive decline in these patients. This study aimed to assess whether COVID-19-related cognitive decline is a permanent deficit or if it improves over time.

Methods: Cognitive performance was evaluated by means of the Montreal Cognitive Assessment (MoCA) in COVID-19 survivors and noninfected individuals. All study participants had four cognitive evaluations, two of them before the pandemic and the other two, 6 and 18 months after the initial SARS-CoV-2 outbreak infection in the village. Linear mixed effects models for longitudinal data were fitted to assess differences in cognitive performance across COVID-19 survivors and noninfected individuals.

Results: The study included 78 participants, 50 with history of mild COVID-19 and 28 without. There was a significant-likely age-related-decline in MoCA scores between the two prepandemic tests (β = -1.53, 95% confidence interval [CI] = -2.14 to -0.92, p < 0.001), which did not differ across individuals who later developed COVID-19 when compared to noninfected individuals. Six months after infection, only COVID-19 survivors had a significant decline in MoCA scores (β = -1.37, 95% CI = -2.14 to -0.61, p < 0.001), which reversed after 1 additional year of follow-up (β = 0.66, 95% CI = -0.11 to 1.42, p = 0.092). No differences were noticed among noninfected individuals when both postpandemic MoCA scores were compared.

Conclusions: Study results suggest that long COVID-related cognitive decline may spontaneously improve over time.

Source: Del Brutto OH, Rumbea DA, Recalde BY, Mera RM. Cognitive sequelae of long COVID may not be permanent: A prospective study. Eur J Neurol. 2021 Dec 16. doi: 10.1111/ene.15215. Epub ahead of print. PMID: 34918425. https://pubmed.ncbi.nlm.nih.gov/34918425/

Symptoms and management of long COVID: A scoping review

Abstract:

Aim: This scoping review aims to describe published work on the symptoms and management of long COVID conditions.

Background: Symptoms and management of COVID-19 have focused on the acute stage. However, long-term consequences have also been observed.

Methods: A scoping review was performed based on the framework suggested by Arksey and O’Malley. We conducted a literature search to retrieve articles published from May 2020 to March 2021 in CINHAL, Cochrane library, Embase, PubMed and Web of science, including backward and forward citation tracking from the included articles. Among the 1880 articles retrieved, 34 articles met our criteria for review: 21 were related to symptom presentation and 13 to the management of long COVID.

Results: Long COVID symptoms were described in 21 articles. Following COVID-19 treatment, hospitalised patients most frequently reported dyspnoea, followed by anosmia/ageusia, fatigue and cough, while non-hospitalised patients commonly reported cough, followed by fever and myalgia/arthralgia. Thirteen studies described management for long COVID: Focused on a multidisciplinary approach in seven articles, pulmonary rehabilitation in three articles, fatigue management in two articles and psychological therapy in one study.

Conclusion: People experience varied COVID-19 symptoms after treatment. However, guidelines on evidence-based, multidisciplinary management for long COVID conditions are limited in the literature. The COVID-19 pandemic may extend due to virus mutations; therefore, it is crucial to develop and disseminate evidence-based, multidisciplinary management guidelines.

Relevance to clinical practice: A rehabilitation care plan and community healthcare plans are necessary for COVID-19 patients before discharge. Remote programmes could facilitate the monitoring and screening of people with long COVID.

Source: Chiyoung Cha PhD, RN,Gumhee Baek Master Candidate, RN. Symptoms and management of long COVID: A scoping review. First published: 15 December 2021. https://doi.org/10.1111/jocn.16150

Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode

Summary:

AIM OF THE STUDY: Patients surviving COVID-19 have been described as being at risk of developing sequelae. We aimed to investigate and elicit persistent symptoms, emotional status and quality-of-life in patients discharged after an acute COVID-19 episode.

METHODS: Patient-reported outcome measures were collected during a telephone interview 30 days and 1 year after discharge. Patients’ general health status was evaluated using questions based on their symptoms, emotional status was assessed using the items 9 to 12 of the HeartQoL questionnaire and quality of life was assessed at 1 year through the EQ-5D-5L. In patients with a history of cardiovascular disease, all 14 items of the HeartQoL questionnaire were completed to derive the HeartQoL global score.

RESULTS: Among 687 patients who survived after being hospitalised for COVID-19 at the University Hospitals of Geneva between 26 February and 26 April 2020, 184 (27%) and 165 (24%), respectively, participated in the follow-up at 30 days and 1 year. Of these 184 participants, 62% were male, median age was 58 years and 21% had a past medical history of cardiovascular disease. At one month after discharge, 61% (113/184) of patients presented fatigue and 28% (52/184) dyspnoea. One year after discharge, the main complaints were persistent fatigue in 27% (45/165) of patients, neurological problems in 17% (28/165) and dyspnoea in 14% (23/165). Eight percent (14/184) of patients declared being significantly worried 1 month after discharge and 5% (9/184) feeling depressed. The number of patients reporting being significantly worried or depressed at 1 year was lower. Regarding the quality of life at 1 year, the median EQ-5D-5L visual analogue scale score was 80 (interquartile range 70–90).

CONCLUSIONS: Approximately half of patients reported some symptoms 1 year after discharge following an acute episode of COVID-19. The predominant symptom was persistent fatigue both at 1-month and at 1-year follow-up. Emotional status and quality of life appeared satisfactory.

ClinicalTrials.gov number: NCT04384029

Source: Elena Tessitorea, Sandra Handgraafa, Antoine Poncetb, Maëlle Achardac, Stefan Höferd, Sebastian Carballoe, Christophe Martie, Cédric Follonierac, François Girardinfg, François Macha, David Carballoa. Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode. Swiss Med Wkly. 2021;151:w30093. Publication Date: 13.12.2021. https://smw.ch/article/doi/smw.2021.w30093 (Full text)

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

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)

Can l-carnitine reduce post-COVID-19 fatigue?

Abstract:

A significant number of patients infected with the new coronavirus suffer from chronic fatigue syndrome after COVID-19, and their symptoms may persist for months after the infection. Nevertheless, no particular treatment for post-disease fatigue has been found. At the same time, many clinical trials have shown the effectiveness of l-carnitine in relieving fatigue caused by the treatment of diseases such as cancer, MS, and many other diseases. Therefore, it can be considered as a potential option to eliminate the effects of fatigue caused by COVID-19, and its consumption is recommended in future clinical trials to evaluate its effectiveness and safety.

Source: Vaziri-Harami R, Delkash P. Can l-carnitine reduce post-COVID-19 fatigue? Ann Med Surg (Lond). 2022 Jan;73:103145. doi: 10.1016/j.amsu.2021.103145. Epub 2021 Dec 13. PMID: 34925826; PMCID: PMC8667465. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667465/ (Full text)

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)

Neuro-COVID-19

Abstract:

Neuromuscular manifestations of new coronavirus disease 2019 (COVID-19) infection are frequent, and include dizziness, headache, myopathy, and olfactory and gustatory disturbances. Patients with acute central nervous system disorders, such as delirium, impaired consciousness, stroke and convulsive seizures, have a high mortality rate.

The encephalitis/encephalopathy that causes consciousness disturbance and seizures can be classified into three conditions, including direct infection with the SARS-CoV-2 virus, encephalopathy caused by central nervous system damage secondary to systemic hypercytokinemia (cytokine storm) and autoimmune-mediated encephalitis that occurs after infection.

The sequelae, called post-acute COVID-19 syndrome or long COVID, include neuromuscular manifestations, such as anxiety, depression, sleep disturbance, muscle weakness, brain fog and cognitive impairment. It is desirable to establish diagnostic criteria and treatment for these symptoms. Vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, bilateral facial paralysis, encephalitis and opsoclonus-myoclonus syndrome have been reported as adverse reactions after the COVID-19 vaccine, although these are rare.

Source: Shimohata T. Neuro-COVID-19. Clin Exp Neuroimmunol. 2021 Sep 29:10.1111/cen3.12676. doi: 10.1111/cen3.12676. Epub ahead of print. PMID: 34899999; PMCID: PMC8652810.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652810/ (Full text)

Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19

Abstract:

Many patients who had coronavirus disease 2019 (COVID-19) had at least one symptom that persisted after recovery from the acute phase. Our purpose was to review the empirical evidence on symptom prevalence, complications, and management of patients with long COVID. We systematically reviewed the literature on the clinical manifestations of long COVID-19, defined by the persistence of symptoms beyond the acute phase of infection. Bibliographic searches in PubMed and Google Scholar were conducted to retrieve relevant studies on confirmed patients with long COVID that were published prior to August 30, 2021.

The most common persistent symptoms were fatigue, cough, dyspnea, chest pains, chest tightness, joint pain, muscle pain, loss of taste or smell, hair loss, sleep difficulties, anxiety, and depression. Some of the less common persistent symptoms were skin rash, decreased appetite, sweating, inability to concentrate, and memory lapses. In addition to these general symptoms, some patients experienced dysfunctions of specific organs, mainly the lungs, heart, kidneys, and nervous system.

A comprehensive understanding of the persistent clinical manifestations of COVID-19 can improve and facilitate patient management and referrals. Prompt rehabilitative care and targeted interventions of these patients may improve their recovery from physical, immune, and mental health symptoms.

Source: Wu L, Wu Y, Xiong H, Mei B, You T. Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19. Front Med (Lausanne). 2021 Nov 22;8:761314. doi: 10.3389/fmed.2021.761314. PMID: 34881263; PMCID: PMC8645792. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645792/ (Full text)