Long COVID-19 symptoms: clinical characteristics

Abstract:

Background: To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate.

Methods: Observational study enrolling outpatients (≥18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement).

Results: Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with >2 persistent symptoms was 27% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]).

Conclusion: We observed a slow but high recovery rate at 6 months among these outpatients.

Source: Seang S, Itani O, Monsel G, Abdi B, Marcelin AG, Valantin MA, Palich R, Fayçal A, Pourcher V, Katlama C, Tubiana R. Long COVID-19 symptoms: clinical characteristics and recovery rate among non-severe outpatients over a six-month follow-up. Infect Dis Now. 2022 Feb 11:S2666-9919(22)00038-0. doi: 10.1016/j.idnow.2022.02.005. Epub ahead of print. PMID: 35158095; PMCID: PMC8832844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832844/ (Full text)

Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes

Abstract:

Background: Myocardial injury in patients with COVID-19 is associated with increased mortality during index hospitalization; however, the relationship to long-term sequelae of SARS-CoV-2 is unknown. This study assessed the relationship between myocardial injury (high-sensitivity cardiac troponin T level) during index hospitalization for COVID-19 and longer-term outcomes.

Methods and Results: This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS-CoV-2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high-sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high-sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low-level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow-up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID-19-related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status.

Conclusions: Myocardial injury during index hospitalization for COVID-19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID-19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin-positive patients.

Source: Weber B, Siddiqi H, Zhou G, Vieira J, Kim A, Rutherford H, Mitre X, Feeley M, Oganezova K, Varshney AS, Bhatt AS, Nauffal V, Atri DS, Blankstein R, Karlson EW, Di Carli M, Baden LR, Bhatt DL, Woolley AE. Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes. J Am Heart Assoc. 2022 Jan 4;11(1):e022010. doi: 10.1161/JAHA.121.022010. Epub 2021 Dec 31. PMID: 34970914. https://www.ahajournals.org/doi/10.1161/JAHA.121.022010 (Full text)

Physical, cognitive and mental health impacts of COVID-19 following hospitalisation – a multi-centre prospective cohort study

Abstract:

Background The impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood.

Methods PHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function.

Findings We report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity.

Interpretation We identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services.

Source: Sigfrid, Louise, et al. “Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.” medRxiv (2021).  https://www.medrxiv.org/content/10.1101/2021.03.22.21254057v1.full-text (Full text)

Clinical characteristics with inflammation profiling of long-covid and association with one-year recovery following hospitalisation in the UK: a prospective observational study.

Summary:

Background: There are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. To identify potential therapeutic targets, we focussed on previously described four recovery clusters five months after hospital discharge, their underlying inflammatory profiles and relationship with clinical outcomes at one year.

Methods: PHOSP-COVID is a prospective longitudinal cohort study, recruiting adults hospitalised with COVID-19 across the UK. Recovery was assessed using patient reported outcomes measures (PROMs), physical performance, and organ function at five-months and one-year after hospital discharge. Hierarchical logistic regression modelling was performed for patient-perceived recovery at one-year. Cluster analysis was performed using clustering large applications (CLARA) k-medoids approach using clinical outcomes at five-months. Inflammatory protein profiling from plasma at the five-month visit was performed.

Findings: 2320 participants have been assessed at five months after discharge and 807 participants have completed both five-month and one-year visits. Of these, 35·6% were female, mean age 58·7 (SD 12·5) years, and 27·8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five months 501/1965 (25·5%) and one year 232/804 (28·9%). Factors associated with being less likely to report full recovery at one year were: female sex OR 0·68 (95% CI 0·46-0·99), obesity OR 0·50 (95%CI 0·34-0·74) and IMV OR 0·42 (95%CI 0·23-0·76).

Cluster analysis (n=1636) corroborated the previously reported four clusters: ‘very severe’, ‘severe’, ‘moderate/cognitive’, ‘mild’ relating to the severity of physical, mental health and cognitive impairments at five months in a larger sample. There was elevation of inflammatory mediators of tissue damage and repair in both the ‘very severe’ and the ‘moderate/cognitive’ clusters compared to the ‘mild’ cluster including interleukin-6 which was elevated in both comparisons. Overall, there was a substantial deficit in median (IQR) EQ5D-5L utility index from pre-COVID (retrospective assessment) 0·88 (0·74-1·00), five months 0·74 (0·60-0·88) to one year: 0·74 (0·59-0·88), with minimal improvements across all outcome measures at one-year after discharge in the whole cohort and within each of the four clusters.

Interpretation: The sequelae of a hospital admission with COVID-19 remain substantial one year after discharge across a range of health domains with the minority in our cohort feeling fully recovered. Patient perceived health-related quality of life remains reduced at one year compared to pre-hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.

Source: Rachael A EvansOlivia C LeavyMatthew RichardsonOmer ElneimaHamish J C McAuleyAarti ShikotraAmisha SingapuriMarco Sereno et al. Clinical characteristics with inflammation profiling of long-covid and association with one-year recovery following hospitalisation in the UK: a prospective observational study.

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/

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)