Exploring the Trajectory Recovery Curve of the number of Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study

Abstract:

Objective: This multicenter study investigated the recovery curve of the number of post-COVID symptoms in previously hospitalized survivors by using an exponential decay model and mosaic plots.

Methods: Patients hospitalized during the first wave of the pandemic (from March 10 to May 31, 2020) due to COVID-19 from five hospitals in Madrid (Spain) were scheduled for two telephone interviews at two follow-ups with a five-month period in between and were asked about the presence of post-COVID symptoms. The total number of post-COVID symptoms was monitored. Clinical features, symptoms at hospital admission, and hospitalization data were collected from medical records.

Results: A total of 1,593 COVID-19 survivors were assessed 8.4 (T1) and 13.2 (T2) months after hospitalization. The mean number of post-COVID symptoms was 2.6 (SD 2.0) at T1 and 1.5 (SD 1.4) at T2. The trajectory curve showed a decrease prevalence trend. The analysis also revealed that 985 (61.8%) subjects reported a greater number (T1>T2), 549 (34.5%) equal number (T1 =T2) and 59 (3.7%) lower number (T1<T2) of post-COVID symptoms in the first (T1: 8.4 months) in comparison with the second (T2: 13.2 months) assessment.

Conclusion: Current trajectory analysis revealed an overall decrease in the tendency in the number of post-COVID symptoms throughout the two years after the infection.

Source: Fernández-de-Las-Peñas C, Martín-Guerrero JD, Cancela-Cilleruelo I, Moro-López-Menchero P, Rodríguez-Jiménez J, Pellicer-Valero OJ. Exploring the Trajectory Recovery Curve of the number of Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study. Int J Infect Dis. 2022 Feb 9:S1201-9712(22)00083-2. doi: 10.1016/j.ijid.2022.02.010. Epub ahead of print. PMID: 35150911; PMCID: PMC8826603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826603/ (Full text)

Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity?

Dear editor,

We have read with great interest the review article by Sapkota et al. which has been recently published in the Clinical Rheumatology journal dealing with long COVID []. In this paper, the authors reported the symptoms and immunological findings of patients who were infected from severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2). These symptoms and laboratory features share similarities with those of patients suffering from autoimmune rheumatic diseases (ARDs). They concluded that long COVID is a mimicker of ARDs and needs to be excluded to ensure a correct diagnosis [].

Recently, we reported a patient who contracted SARS-CoV-2 infection and developed an erosive seronegative arthritis six months after infection []. Musculoskeletal, cutaneous, and other systemic manifestations, along with the presence of autoantibodies, are frequently observed in these patients. On the other hand, SARS-CoV-2 may trigger autoimmune responses and the development of de-novo manifestations of ARDs, as in our patient []. The pathogenesis of these phenomena is not well defined. One hypothesis implies the presence of autoantibodies against interferon (IFN) type-I, or inborn errors in the type-I IFN immunity []. Another hypothesis is that SARS-CoV-2 might trigger autoimmune responses through molecular mimicry []. Several viruses have been implicated as possible etiological factors for the development of ARDs, mostly systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and others. Between viruses Epstein-Barr virus (EBV) is implicated in the pathogenesis of the above disorders []. Indeed, EBV can trigger immune responses through molecular mimicry and is a polyclonal activator of B-cells and increases the production of rheumatoid factor (RF). Several studies suggested that molecular mimicry is a possible mechanism responsible for the development of ARDs in SARS-CoV-2 infection []. Thus, SARS-CoV-2 may trigger autoimmunity and the possible development of the de novo manifestations of ARDs.

Read the full article HERE.

Source: Drosos AA, Pelechas E, Voulgari PV. Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity? Clin Rheumatol. 2022 Feb 11:1–2. doi: 10.1007/s10067-022-06092-4. Epub ahead of print. PMID: 35147823; PMCID: PMC8831874. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831874/ (Full text)

Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection

Abstract:

Postacute sequelae of SARS-CoV2 (PASC) infection is an emerging global health crisis, variably affecting millions worldwide. PASC has no established treatment. We describe 2 cases of PASC in response to opportune administration of over-the-counter antihistamines, with significant improvement in symptoms and ability to perform activities of daily living. Future studies are warranted to understand the potential role of histamine in the pathogenesis of PASC and explore the clinical benefits of antihistamines in the treatment of PASC.

Source: Melissa D. Pinto, Natalie Lambert, Charles A. Downs, Heather Abrahim, Thomas D. Hughes, Amir M. Rahmani, Candace W. Burton, Rana Chakraborty. Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection. The Journal for Nurse Practitioners, 2022, ISSN 1555-4155, https://doi.org/10.1016/j.nurpra.2021.12.016.
https://www.sciencedirect.com/science/article/pii/S155541552100547X  (Full text)

Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review

Abstract:

Background: Long COVID-19 may affect patients after hospital discharge.

Aims: This study aims to describe the burden of the long-term persistence of clinical symptoms in COVID-19 patients.

Methods: We conducted a systematic review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The PubMed and Google Scholar databases were searched for studies that included information on the prevalence of somatic clinical symptoms lasting at least 4 weeks after the onset of a PCR- or serology-confirmed diagnosis of COVID-19. The prevalence of persisting clinical symptoms was assessed and risk factors were described when investigated. Psychological symptoms and cognitive disorders were not evaluated in this study.

Results: Thirty-seven articles met the inclusion criteria. Eighteen studies involved in-patients only with a duration of follow-up of either less than 12 weeks, 12 weeks to 6 months, or more. In these studies, fatigue (16-64%), dyspnea (15-61%), cough (2-59%), arthralgia (8-55%), and thoracic pain (5-62%) were the most frequent persisting symptoms. In nineteen studies conducted in a majority of out-patients, the persistence of these symptoms was lower and 3% to 74% of patients reported prolonged smell and taste disorders. The main risk factors for persisting symptoms were being female, older, having comorbidities and severity at the acute phase of the disease.

Conclusion: COVID-19 patients should have access to dedicated multidisciplinary healthcare allowing a holistic approach. Effective outpatient care for patients with long-COVID-19 requires coordination across multiple sub-specialties, which can be proposed in specialized post-COVID units.

Source: Nguyen NN, Hoang VT, Dao TL, Dudouet P, Eldin C, Gautret P. Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review. Eur J Clin Microbiol Infect Dis. 2022 Feb 10:1–31. doi: 10.1007/s10096-022-04417-4. Epub ahead of print. PMID: 35142947; PMCID: PMC8830952. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830952/ (Full text)

Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study

Abstract:

Background: We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11-17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status.

Methods: In this national cohort study, adolescents aged 11-17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192).

Findings: 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4-31·7) for the test-positive group and 19·3% (17·7-21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35-1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15-17 years than those aged 11-14 years, and in those with lower pretest physical and mental health.

Interpretation: Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship.

Funding: UK Department of Health and Social Care, in their capacity as the National Institute for Health Research, and UK Research and Innovation.

Source: Stephenson T, Pinto Pereira SM, Shafran R, de Stavola BL, Rojas N, McOwat K, Simmons R, Zavala M, O’Mahoney L, Chalder T, Crawley E, Ford TJ, Harnden A, Heyman I, Swann O, Whittaker E; CLoCk Consortium, Ladhani SN. Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study. Lancet Child Adolesc Health. 2022 Feb 7:S2352-4642(22)00022-0. doi: 10.1016/S2352-4642(22)00022-0. Epub ahead of print. PMID: 35143770; PMCID: PMC8820961. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820961/  (Full text)

Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (LongCOVIDKidsDK): a national, cross-sectional study

Abstract:

Background: Many adolescents have been affected by the COVID-19 pandemic either directly by being infected with the virus or indirectly by lockdowns and restrictions influencing normal living. We aimed to investigate health, including symptoms of long COVID, in adolescents (aged 15-18 years) who tested positive for SARS-CoV-2 compared with a control group.

Methods: LongCOVIDKidsDK was a national, cross-sectional study carried out in Denmark, which included SARS-CoV-2-positive adolescents and matched controls. All Danish adolescents aged 15-18 years with a positive SARS-CoV-2 test during the period Jan 1, 2020, to July 12, 2021, and a control group matched (1:4) by age and sex were sent a survey from July 20, 2021. Participants had until Sept 15, 2021, to respond. Symptoms associated with COVID-19, school attendance, and health-related quality of life were investigated using ancillary questions and validated questionnaires (Paediatric Quality of Life Inventory [PedsQL] and Children’s Somatic Symptoms Inventory-24 [CSSI-24]). Statistical analyses included descriptive statistics and logistic regression. This study is registered at ClinicalTrials.gov, NCT04786353.

Findings: 24 315 adolescents with a positive SARS-CoV-2 test (case group) and 97 257 matched controls were invited to participate. 3013 matched controls were excluded because of suspected SARS-CoV-2 infection. 6630 (27·3%) responded in the case group and 21 640 (22·3%) responded and were eligible to participate in the control group. Across both groups, median age was 17·6 years (IQR 16·4-18·5), 16 277 (57·6%) of 28 270 responders were female, and 11 993 (42·4%) were male. Participants in the case group had greater odds of having at least one long COVID symptom lasting at least 2 months compared with the control group (3159 [61·9%] vs 12 340 [57·0%], odds ratio 1·22 [95% CI 1·15-1·30]; p<0·0001). Participants in the case group reported significantly lower symptom scores (ie, less somatic distress) on the CSSI-24 than in the control group: mean 10·7 (SD 11·4, median 7·0 [IQR 2·0-15·0]) versus 11·9 (10·6, 9·0 [4·0-17·0]; p<0·0001). Participants in the case group had better quality of life scores on the PedsQL than in the control group: physical functioning mean score 88·7 (SD 13·9, median 93·8 [IQR 84·4-100·0]) versus 86·5 (14·3, 90·6 [81·3-96·9]; p<0·0001); emotional functioning 77·1 (20·3, 80·0 [65·0-95·0]) versus 71·7 (21·4, 75·0 [60·0-90·0]; p<0·0001); social functioning 93·1 (12·5, 100·0 [90·0-100·0]) versus 88·4 (16·2, 95·0 [80·0-100·0]; p<0·0001); and school functioning 66·9 (22·5, 65·0 [60·0-85·0]) versus 62·9 (22·1, 65·0 [50·0-80·0]; p<0·0001). More participants in the case group than in the control group reported 16 or more sick days (1205 [18·2%] vs 2518 [11·6%]; p<0·0001) and 16 or more days of school absence (695 [10·5%] vs 1777 [8·2%]; p<0·0001).

Interpretation: Participants with SARS-CoV-2-positive tests had more long-lasting symptoms and sick leave, whereas participants in the control group had more short-lasting symptoms and worse quality of life. Knowledge of long COVID in adolescents is important to guide clinical recognition and management of this condition.

Funding: AP Møller and Chastine McKinney Møller Foundation.

Source: Kikkenborg Berg S, Dam Nielsen S, Nygaard U, Bundgaard H, Palm P, Rotvig C, Vinggaard Christensen A. Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (LongCOVIDKidsDK): a national, cross-sectional study. Lancet Child Adolesc Health. 2022 Feb 7:S2352-4642(22)00004-9. doi: 10.1016/S2352-4642(22)00004-9. Epub ahead of print. PMID: 35143771; PMCID: PMC8820960.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820960/  (Full text)

Long covid: “Holistic” approach is best, given range of symptoms, say researchers

New research on long covid in adults and children supports the multidisciplinary approach to clinical care that is being provided at long covid clinics in England, experts have said.

“Long covid seems to be a condition where multiple symptoms are very common,” said Terence Stephenson, Nuffield professor of child health at the UCL Great Ormond Street Institute of Child Health in London, told a Science Media Centre briefing.

“I think the services that have been set up in England for young people do address that. They are holistic and comprehensive in their approach, rather than addressing single organs or single problems,” said Stephenson, who is the lead author of the Children and Young People with Long Covid (Clock) study, published in Lancet Adolescent and Child Health.1 “If you have a mixture of symptoms of headache, cough, and dizziness, you probably want to go to a service that can deal with you holistically with all your symptoms,” he added.

There are currently around 80 long covid clinics in England that take referrals from primary care for adults or children who are experiencing a range of symptoms that might include brain fog, anxiety, depression, breathlessness, and fatigue.

Read the rest of this article HERE.

Source: Iacobucci G. Long covid: “Holistic” approach is best, given range of symptoms, say researchers. BMJ. 2022 Feb 8;376:o336. doi: 10.1136/bmj.o336. PMID: 35135781. https://www.bmj.com/content/376/bmj.o336.long (Full text)

Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19

Abstract:

Objective: A subset of individuals with coronavirus disease 2019 (COVID-19) appears to develop persisting cognitive and medical symptoms. Research in the acute stages of illness, generally utilizing cognitive screening measures or case reports, suggests presence of deficits in attention and executive function. This observational study investigated cognitive functioning among individuals with persistent cognitive complaints about 5.5 months after COVID-19 infection.

Methods: Patients with polymerase chain reaction confirmed COVID-19 and persistent cognitive complaints underwent comprehensive in-person neuropsychological evaluations. Patients with prior neurological disorders were excluded. When diagnosed, 40% required hospitalization, 15% were in an intensive care unit, 10% needed mechanical ventilation, and 10% experienced delirium.

Results: This sample was predominately women (90%), White non-Hispanic (70%), with average education of 15 years. Mild cognitive deficits were seen on tests involving attention and processing speed or executive function. Seventy percent of patients were diagnosed with a mood disorder prior to COVID-19 infection. At the time of testing, 35%-40% endorsed moderate to severe mood symptoms and 85% noted significant fatigue as measured by the Fatigue Severity Scale.

Conclusions: The pattern of cognitive deficits, although mild, is consistent with prior research at the acute stage of the illness. These findings suggest that psychological factors and other persisting symptoms (e.g., sleep, fatigue) may play a significant role in subjective cognitive complaints in patients with persisting complaints post COVID-19 who did not require intensive treatment. These patients would likely benefit from resources to manage persisting or new mood symptoms and compensatory strategies for the cognitive inefficiencies they experience.

Source: Krishnan K, Miller AK, Reiter K, Bonner-Jackson A. Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19. Arch Clin Neuropsychol. 2022 Feb 5:acac004. doi: 10.1093/arclin/acac004. Epub ahead of print. PMID: 35136912. https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acac004/6522998 (Full text)

Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial

Abstract:

Background: Given the absence of effective medical treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the testing of a new intervention that may ameliorate potentially pathologic levels of oxidative stress, sympathetic arousal, and inflammation may yield symptomatic improvements.

Objective: To explore in a pilot study, the possible beneficial effect of molecular hydrogen (H2) for the symptoms and functional limitations of ME/CFS.

Methods: Twenty-three subjects were randomized to H2 or active placebo which involved drinking up to five glasses daily of hydrogen-enriched water or placebo water for 28 days. Assessments included: (i) self-report fatigue, physical function, and stress; (ii) salivary C-Reactive Protein (inflammation), Uric Acid (antioxidant status), and Alpha-Amylase (sympathetic function); and (iii) heart rate variability (parasympathetic activity). Data were analysed with Wilcoxon rank-sum tests.

Results: Completion rate for the primary outcome measure of fatigue severity was 100% for the 11 hydrogen participants and 91.7% (n = 11) for placebo participants. No significant changes were found on self-report or biological variables in the active vs. placebo treatment conditions. A small, but significant reduction in fatigue was found in the placebo condition. Adverse effects led to treatment discontinuation in 27.2% of H2 subjects. All severe- and moderate-intensity effects were found in the active treatment condition. Adverse effects were not significantly associated with any demographic or symptom variable.

Conclusions: Therapeutic molecular hydrogen did not yield improvement on any biological or symptom measure in individuals with ME/CFS. Dosage reduction might benefit any future trial of hydrogen therapy in this illness.

Source: Fred Friedberg & Dennis Choi (2022) Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2038519

Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID: Postexertional Symptom Exacerbation is an Abnormal Response to Exercise/Activity

Prolonged symptoms after infection with the novel coronavirus 2019 (SARS-COV-2) are an emerging challenge to individual patients, society, and clinicians. In a previous post on the JOSPT Blog, we identified several lessons from research and clinical practice in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that are important lessons for long COVID. The purpose of this post is to discuss the phenomenon of postexertional symptom exacerbation (PESE) and its clinical identification to recognize the potential onset of long COVID.

Data from a large international web-based patient survey indicate substantial symptom overlap between postacute SARS-COV-2 infection (long COVID) and ME/CFS at 6 months following the onset of first symptoms. Three quarters of respondents noted disabling fatigue and over half noted cognitive dysfunction.4 A unique finding of this survey was that 75% of respondents noted PESE, which is a worsening of symptoms after activity/exercise.4 PESE is foundational to the diagnosis of ME/CFS and it is common with long COVID.4,5 This observation suggests we can further extend lessons from ME/CFS to develop our understanding of long COVID.

Read the rest of this article HERE.

Source: Todd E. Davenport Staci R. Stevens Jared Stevens Christopher R. Snell J. Mark Van Ness. Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID: Postexertional Symptom Exacerbation is an Abnormal Response to Exercise/Activity. Published online on February 2, 2022 https://doi.org/10.2519/jospt.blog.20220202