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.

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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)

Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus

Abstract:

Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias.

Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease.

In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.

Source: Raman B, Bluemke DA, Lüscher TF, Neubauer S. Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus. Eur Heart J. 2022 Feb 18:ehac031. doi: 10.1093/eurheartj/ehac031. Epub ahead of print. PMID: 35176758. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac031/6529562 (Full text)

Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study

Abstract:

Objective: Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19.

Methods: Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1-C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed.

Results: We analysed 121 mild COVID-19 cases (mean age =45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%;p = 0.008). PCS affected 35.8% of women and 20.8% of men (p = 0.07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS, and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP in range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87;p = 0.013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4- to 5-fold increased risk of prevalent PCS. A man with CRP in range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10- to 17-fold increased risk of prevalent PCS.

Conclusions: The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.

Source: Maamar M, Artime A, Pariente E, Fierro P, Ruiz Y, Gutiérrez S, Tobalina M, Díaz-Salazar S, Ramos C, Olmos JM, Hernández JL. Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study. Curr Med Res Opin. 2022 Feb 15:1-26. doi: 10.1080/03007995.2022.2042991. Epub ahead of print. PMID: 35166141.  https://pubmed.ncbi.nlm.nih.gov/35166141/

Lessons from Long COVID: working with patients to design better research

The perspectives of people with lived experience of any condition being researched must actively inform the research questions asked and the way in which we go about answering them. The experience of Long Covid gives a contemporary example of how working together with patients is integral to medical research.

When ‘Long COVID’ emerged as a concept in Spring 2020, it was those with lived experience of the disease who gave it its name and characterized it to the world, initially through use of social media1. Even though chronic illness induced by viral infection is not a new phenomenon, awareness of this potential outcome of the COVID-19 pandemic was entirely absent from public messaging, even at a time when large numbers of people were becoming infected with SARS-CoV-2.

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Source: Alwan, N.A. Lessons from Long COVID: working with patients to design better research. Nat Rev Immunol (2022). https://doi.org/10.1038/s41577-022-00692-6  (Full text)

Long-COVID: A growing problem in need of intervention

Summary:

The number of people who have survived COVID-19 is overwhelming – official figures approach half a billion (https://covid19.who.int). Thus, any long-term consequences in COVID-19 survivors could have a huge impact on public health and on healthcare services in the coming months and years, with potentially 100 million individuals affected.

Source: Bjørn Blomberg, Rebecca Jane Cox, Nina Langeland. Long-COVID: A growing problem in need of intervention. Cell Reports Medicine, 2022, 100552, ISSN 2666-3791. https://doi.org/10.1016/j.xcrm.2022.100552. (Full text)

‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19

Abstract:

Objective: To explore the lived experience of ‘brain fog’-the wide variety of neurocognitive symptoms that can follow COVID-19.

Design and setting: A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up.

Method: 50 participants were recruited from a previous qualitative study of the lived experience of long COVID-19 (n=23) and online support groups for people with persistent neurocognitive symptoms following COVID-19 (n=27). In remotely held focus groups, participants were invited to describe their neurocognitive symptoms and comment on others’ accounts. Individuals were followed up by email 4-6 months later. Data were audiotaped, transcribed, anonymised and coded in NVIVO. They were analysed by an interdisciplinary team with expertise in general practice, clinical neuroscience, the sociology of chronic illness and service delivery, and checked by people with lived experience of brain fog.

Results: Of the 50 participants, 42 were female and 32 white British. Most had never been hospitalised for COVID-19. Qualitative analysis revealed the following themes: mixed views on the appropriateness of the term ‘brain fog’; rich descriptions of the experience of neurocognitive symptoms (especially executive function, attention, memory and language), accounts of how the illness fluctuated-and progressed over time; the profound psychosocial impact of the condition on relationships, personal and professional identity; self-perceptions of guilt, shame and stigma; strategies used for self-management; challenges accessing and navigating the healthcare system; and participants’ search for physical mechanisms to explain their symptoms.

Conclusion: These qualitative findings complement research into the epidemiology and mechanisms of neurocognitive symptoms after COVID-19. Services for such patients should include: an ongoing therapeutic relationship with a clinician who engages with their experience of neurocognitive symptoms in its personal, social and occupational context as well as specialist services that include provision for neurocognitive symptoms, are accessible, easily navigable, comprehensive and interdisciplinary.

Source: Callan C, Ladds E, Husain L, Pattinson K, Greenhalgh T. ‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19. BMJ Open. 2022 Feb 11;12(2):e056366. doi: 10.1136/bmjopen-2021-056366. PMID: 35149572; PMCID: PMC8844964. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844964/ (Full text)

Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study

Abstract:

Objective: To characterize the risk of persistent and new clinical sequelae in adults aged ≥65 years after the acute phase of SARS-CoV-2 infection.

Design: Retrospective cohort study.

Setting: UnitedHealth Group Clinical Research Database: deidentified administrative claims and outpatient laboratory test results.

Participants: Individuals aged ≥65 years who were continuously enrolled in a Medicare Advantage plan with coverage of prescription drugs from January 2019 to the date of diagnosis of SARS-CoV-2 infection, matched by propensity score to three comparison groups that did not have covid-19: 2020 comparison group (n=87 337), historical 2019 comparison group (n=88 070), and historical comparison group with viral lower respiratory tract illness (n=73 490).

Main outcome measures: The presence of persistent and new sequelae at 21 or more days after a diagnosis of covid-19 was determined with ICD-10 (international classification of diseases, 10th revision) codes. Excess risk for sequelae caused by infection with SARS-CoV-2 was estimated for the 120 days after the acute phase of the illness with risk difference and hazard ratios, calculated with 95% Bonferroni corrected confidence intervals. The incidence of sequelae after the acute infection was analyzed by age, race, sex, and whether patients were admitted to hospital for covid-19.

Results: Among individuals who were diagnosed with SARS-CoV-2, 32% (27 698 of 87 337) sought medical attention in the post-acute period for one or more new or persistent clinical sequelae, which was 11% higher than the 2020 comparison group. Respiratory failure (risk difference 7.55, 95% confidence interval 7.18 to 8.01), fatigue (5.66, 5.03 to 6.27), hypertension (4.43, 2.27 to 6.37), memory difficulties (2.63, 2.23 to 3.13), kidney injury (2.59, 2.03 to 3.12), mental health diagnoses (2.50, 2.04 to 3.04), hypercoagulability 1.47 (1.2 to 1.73), and cardiac rhythm disorders (2.19, 1.76 to 2.57) had the greatest risk differences compared with the 2020 comparison group, with similar findings to the 2019 comparison group. Compared with the group with viral lower respiratory tract illness, however, only respiratory failure, dementia, and post-viral fatigue had increased risk differences of 2.39 (95% confidence interval 1.79 to 2.94), 0.71 (0.3 to 1.08), and 0.18 (0.11 to 0.26) per 100 patients, respectively. Individuals with severe covid-19 disease requiring admission to hospital had a markedly increased risk for most but not all clinical sequelae.

Conclusions: The results confirm an excess risk for persistent and new sequelae in adults aged ≥65 years after acute infection with SARS-CoV-2. Other than respiratory failure, dementia, and post-viral fatigue, the sequelae resembled those of viral lower respiratory tract illness in older adults. These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus.

Source: Cohen K, Ren S, Heath K, Dasmariñas MC, Jubilo KG, Guo Y, Lipsitch M, Daugherty SE. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ. 2022 Feb 9;376:e068414. doi: 10.1136/bmj-2021-068414. PMID: 35140117; PMCID: PMC8828141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828141/ (Full text)

ESCMID rapid guidelines for assessment and management of long COVID

Abstract:

Scope: The aim of these guidelines is to provide evidence-based recommendations for assessment and management of individuals with persistent symptoms after acute COVID-19 infection, and provide a definition for this entity, termed “long COVID”.

Methods: We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design.

Recommendations: Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high quality prospective clinical studies/trials, including a control group, to further evaluate assessment and management of individuals with persistent symptoms of COVID-19.

Source: Yelin D, Moschopoulos CD, Margalit I, Gkrania-Klotsas E, Landi F, Stahl JP, Yahav D. ESCMID rapid guidelines for assessment and management of long COVID. Clin Microbiol Infect. 2022 Feb 16:S1198-743X(22)00092-1. doi: 10.1016/j.cmi.2022.02.018. Epub ahead of print. PMID: 35182760; PMCID: PMC8849856. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849856/ (Full text)

Neurological manifestations of long-COVID syndrome: a narrative review

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data.

The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae.

In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.

Source: Stefanou M-I, Palaiodimou L, Bakola E, et al. Neurological manifestations of long-COVID syndrome: a narrative review. Therapeutic Advances in Chronic Disease. January 2022. doi:10.1177/20406223221076890 https://journals.sagepub.com/doi/full/10.1177/20406223221076890 (Full text)

Lessons from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome for Long COVID Part 4: Heart Rate Monitoring to Manage Postexertional Symptom Exacerbation

The physiology underlying postexertional symptom exacerbation (PESE) is abnormal in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and likely long COVID. Activity pacing approaches appear warranted to accommodate the unusual physiological deficits of PESE.

The Rationale for Heart Rate Monitoring

Similar to people living with ME/CFS,7 people living with long COVID have reported finding activity pacing to be helpful. This idea is reflected in current safe rehabilitation guidelines for this condition.8 PESE is challenging to self-manage because of the variability in onset, duration, and nature from person to person.2,6 Social stigma associated with PESE may lead people to overexert to meet the demands of their daily tasks. This stigma may be exacerbated by people telling patients that “it’s all in their head” or they “just need to exercise.” Variability and stigma, in turn, make it difficult to identify important activity triggers in the early stages of learning to manage PESE.

PESE is characterized by aerobic system dysfunction. Pacing based on heart rate can help the patient avoid the dysfunctional aerobic system by keeping their activity intensity at a level anaerobic metabolism will dominate. Heart rate monitoring (HRM) provides an element of predictive potential for the patient to understand when their activities exceed physiological limits and eventually may result in PESE. In this post, we will discuss activity pacing to manage PESE that is based on HRM.

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 Part 4: Heart Rate Monitoring to Manage Postexertional Symptom Exacerbation. Published online on February 23, 2022. https://doi.org/10.2519/jospt.blog.20220223 (Full text)