Tag: covid-19

Long COVID after breakthrough SARS-CoV-2 infection

Abstract:

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear.

In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders.

The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

Source: Al-Aly, Z., Bowe, B. & Xie, Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med (2022). https://doi.org/10.1038/s41591-022-01840-0  https://www.nature.com/articles/s41591-022-01840-0 (Full text)

Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report

Abstract:

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

Source: Sabino JS, Amorim MR, de Souza WM, Marega LF, Mofatto LS, Toledo-Teixeira DA, Forato J, Stabeli RG, Costa ML, Spilki FR, Sabino EC, Faria NR, Benites BD, Addas-Carvalho M, Stucchi RSB, Vasconcelos DM, Weaver SC, Granja F, Proenca-Modena JL, Vilela MMDS. Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report. Viruses. 2022 May 13;14(5):1042. doi: 10.3390/v14051042. PMID: 35632784; PMCID: PMC9143223. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143223/ (Full text)

Neurological Sequelae of COVID-19

Abstract:

Background: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19.

The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders.

Objective: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments.

Methods: A literature review was carried out by the authors using PubMed with the search terms “COVID-19” and “Neurology”, “Neurological Manifestations”, “Neuropsychiatric Manifestations”, “Stroke”, “Encephalopathy”, “Headache”, “Guillain-Barre syndrome”, “Depression”, “Anxiety”, “Encephalitis”, “Seizure”, “Spasm”, and “ICUAW”. Another search was carried out for “Long-COVID” and “Post-Acute COVID-19” and “Neurological Manifestations” or “Neuropsychiatric Manifestations”. Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients.

Results: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

Source: Ahmad SJ, Feigen CM, Vazquez JP, Kobets AJ, Altschul DJ. Neurological Sequelae of COVID-19. J Integr Neurosci. 2022 Apr 6;21(3):77. doi: 10.31083/j.jin2103077. PMID: 35633158. https://www.imrpress.com/journal/JIN/21/3/10.31083/j.jin2103077/htm (Full text)

Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study

Abstract:

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample.

This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures).

Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006).

We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Source: Damiano RF, Neto DB, Oliveira JVR, Magalhães Santos J, Alves JVR, Guedes BF, Nitrini R, de Araújo AL, Oliveira M, Brunoni AR, Voegels RL, Bento RF, Busatto G, Miguel EC, Forlenza OV, de Rezende Pinna F; HCFMUSP COVID-19 study group. Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study. Eur Arch Psychiatry Clin Neurosci. 2022 May 28:1–9. doi: 10.1007/s00406-022-01427-3. Epub ahead of print. PMID: 35633395; PMCID: PMC9142732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142732/ (Full text)

Cardiometabolic syndrome — an emergent feature of Long COVID?

Large-scale clinical studies on the post-infectious impacts of SARS-CoV-2 have suggested that patients who have recovered from acute infection have increased risk for cardiometabolic syndrome-associated morbidities such as diabetes, chronic kidney disease and heart failure. Initial studies have taken the first steps towards unravelling the molecular processes that may be driving these findings, including the role of immune and inflammatory factors, but a comprehensive aetiology remains unclear. Given that cardiometabolic syndrome progression in patients with Long COVID may pose a significant global health and economic burden post pandemic, there is an emergent need to identify therapeutic targets and treatment options.

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Source: Frere, J.J., tenOever, B.R. Cardiometabolic syndrome — an emergent feature of Long COVID?. Nat Rev Immunol (2022). https://doi.org/10.1038/s41577-022-00739-8 (Full text)

One Year Follow-Up of COVID-19 Related Symptoms and Patient Quality of Life: A Prospective Cohort Study

Abstract:

Purpose: Globally, concerns have grown regarding the long-term effects of novel coronavirus disease (COVID-19) infection. Therefore, we evaluated the long-term course of persistent symptoms and patient quality of life.

Materials and methods: This prospective cohort study was conducted at a single tertiary university hospital from August 31, 2020 to March 29, 2021 with adult patients followed at 6 and 12 months after acute COVID-19 symptom onset or diagnosis. Clinical characteristics, self-reported symptoms, EuroQol 5 dimension 5 level (EQ5D-5L) index scores, Korean version of the Patient Health Questionnaire-9 (PHQ-9), Korean version of the Posttraumatic Stress Disorder Checklist-5 (PCL-5-K), and Generalized Anxiety Disorder-7 (GAD-7) were investigated. Symptom persistent or non-persistent groups were defined according to persistency of COVID-19 related symptoms or signs after acute COVID-19 infection, respectively.

Results: Of all 235 patients, 170 (64.6%) patients were eligible for analysis. The median age was 51 (interquartile range, 37-61) years old, and 102 patients were female (60.0%). After 12 months from acute COVID-19 infection, in total, 83 (48.8%) patients still suffered from COVID-19-related symptoms. The most common symptoms included amnesia (24.1%), insomnia (14.7%), fatigue (13.5%), and anxiety (12.9%). Among the five EQ5D-5L categories, the average value of anxiety or depression was the most predominant. PHQ-9 and PCL-5-K scores were statistically higher in the COVID-19-related symptom persistent group than the non-persistent group (p=0.001). However, GAD-7 scores showed no statistical differences between the two groups (p=0.051).

Conclusion: Neuropsychiatric symptoms were the major COVID-19-related symptoms after 12 months from acute COVID-19 infection, reducing quality of life.

Source: Kim Y, Kim SW, Chang HH, Kwon KT, Hwang S, Bae S. One Year Follow-Up of COVID-19 Related Symptoms and Patient Quality of Life: A Prospective Cohort Study. Yonsei Med J. 2022 Jun;63(6):499-510. doi: 10.3349/ymj.2022.63.6.499. PMID: 35619573. https://eymj.org/DOIx.php?id=10.3349/ymj.2022.63.6.499 (Full text)

Use of linked patient data to assess the effect of Long-COVID on system-wide healthcare utilisation

Abstract:

Background: Within the relatively early stages of the COVID-19 pandemic, there had been an awareness of the potential longer-term effects of infection (so called Long-COVID) but little was known of the ongoing demands such patients may place on healthcare services.

Objective: To investigate whether COVID-19 illness is associated with increased post-acute healthcare utilisation.

Method: Using linked data from primary care, secondary care, mental health and community services, activity volumes were compared across the 3 months preceding and proceeding COVID-19 diagnoses for 7,791 individuals, with a distinction made between whether or not patients were hospitalised for treatment. Differences were assessed against those of a control group containing individuals who had not received a COVID-19 diagnosis. All data were sourced from the authors’ healthcare system in South West England.

Results: For hospitalised COVID-19 cases, a statistically significant increase in non-elective admissions was identified for males and females <65 years. For non-hospitalised cases, statistically significant increases were identified in GP Doctor and Nurse attendances and GP prescriptions (males and females, all ages); Emergency Department attendances (females <65 years); Mental Health contacts (males and females ≥65 years); and Outpatient consultations (males ≥65 years).

Conclusion: There is evidence of an association between positive COVID-19 diagnosis and increased post-acute activity within particular healthcare settings. Linked patient-level data provides information that can be useful to understand ongoing healthcare needs resulting from Long-COVID, and support the configuration of Long-COVID pathways of care.

Source: Murch BJ, Hollier SE, Kenward C, Wood RM. Use of linked patient data to assess the effect of Long-COVID on system-wide healthcare utilisation. Health Inf Manag. 2022 May 25:18333583221089915. doi: 10.1177/18333583221089915. Epub ahead of print. PMID: 35615791. https://pubmed.ncbi.nlm.nih.gov/35615791/

Post-Acute Sequelae of SARS-CoV-2 infection (PASC) – Lessons Learned From a Coordinated Health Systems Response

Abstract:

Objective: To outline a consensus designed process for triaging and managing patients with Post COVID syndrome at the Mayo Clinic.

Patients and methods: We convened a central multidisciplinary team including members from General Internal Medicine, Occupational Medicine, Physical Medicine & Rehabilitation, Psychology, Allergy and Immunology, Infectious Disease, Pulmonology, Neurology, Cardiology, Pediatrics and Otorhinolaryngology, with membership from all the Mayo Clinic sites in Arizona, Florida, Iowa, Minnesota, and Wisconsin.

Results: Consensus recommendations were made for best practice guidelines on triaging and managing patients. Several innovations were agreed upon including a PASC specific appointment request form for data collection, a bio-registry, a bio-repository, and a PASC specific treatment program.

Conclusions: Given that each clinical site had individual clinical practices, these recommendations were implemented using different models, which may provide broad applicability to other clinical settings.

Source: Ganesh R, Vanichkachorn GS, Munipalli B, Hanson SN, Abu Dabrh AM, Croghan IT, Dawson NL, Hurt RT. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) – Lessons Learned From a Coordinated Health Systems Response. Mayo Clin Proc Innov Qual Outcomes. 2022 Jun 1. doi: 10.1016/j.mayocpiqo.2022.05.007. Epub ahead of print. PMID: 35669936; PMCID: PMC9156955. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156955/ (Full text)

Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study

Abstract:

Background: In the absence of research into therapies and care pathways for long COVID, guidance based on ’emerging experience’ is needed.

Aim: To provide a rapid expert guide for GPs and long COVID clinical services.

Design and setting: A Delphi study was conducted with a panel of primary and secondary care doctors.

Method: Recommendations were generated relating to the investigation and management of long COVID. These were distributed online to a panel of UK doctors (any specialty) with an interest in, lived experience of, and/or experience treating long COVID. Over two rounds of Delphi testing, panellists indicated their agreement with each recommendation (using a five-point Likert scale) and provided comments. Recommendations eliciting a response of ‘strongly agree’, ‘agree’, or ‘neither agree nor disagree’ from 90% or more of responders were taken as showing consensus.

Results: Thirty-three clinicians representing 14 specialties reached consensus on 35 recommendations. Chiefly, GPs should consider long COVID in the presence of a wide range of presenting features (not limited to fatigue and breathlessness) and exclude differential diagnoses where appropriate. Detailed history and examination with baseline investigations should be conducted in primary care. Indications for further investigation and specific therapies (for myocarditis, postural tachycardia syndrome, mast cell disorder) include hypoxia/desaturation, chest pain, palpitations, and histamine-related symptoms. Rehabilitation should be individualised, with careful activity pacing (to avoid relapse) and multidisciplinary support.

Conclusion: Long COVID clinics should operate as part of an integrated care system, with GPs playing a key role in the multidisciplinary team. Holistic care pathways, investigation of specific complications, management of potential symptom clusters, and tailored rehabilitation are needed.

Source: Nurek M, Rayner C, Freyer A, Taylor S, Järte L, MacDermott N, Delaney BC; Delphi panellists. Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study. Br J Gen Pract. 2021 Oct 28;71(712):e815-e825. doi: 10.3399/BJGP.2021.0265. PMID: 34607799; PMCID: PMC8510689. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510689/ (Full text)

Long COVID in children and young people: uncertainty and contradictions

AN EVOLVING PICTURE:

‘Long COVID’ describes both ongoing symptomatic COVID-19 (5–12 weeks after onset) and post-COVID-19 syndrome (≥12 weeks after onset).1 Long COVID is also a patient-preferred term2 so will be used throughout this editorial to describe symptoms lasting ≥4 weeks after an acute episode of COVID-19.

As the phenomenon of long COVID emerged and came to be recognised, including with the publication of the guideline by the National Institute for Health and Care Excellence, Scottish Intercollegiate Guideline Network, and the Royal College of General Practitioners,1 there was still limited evidence about whether children and young people could suffer with prolonged symptoms following an acute COVID-19 infection. The general opinion was still that SARS-CoV-2 was a mild infection in the young.3

Narratives emerged, however, from parents describing prolonged problems in their children, following an acute COVID- 19 infection,4 and this was borne out in the scientific literature.5

Jasmin (young person with long COVID) describes her situation: ‘I’m Jasmin. I am 11 years old and I have suffered from long COVID for over a year. I was perfectly fit and happy, and enjoyed doing sports. Having long COVID has really changed my life in many different ways. I can’t go to school much anymore, I don’t see my friends, I can’t exercise, I can’t even walk far without a wheelchair. I think that a lot of people don’t understand what the illness is and how difficult it is for me.’

The prevalence of long COVID in children is disputed. Evidence from the CLoCK study,6 which recruited a cohort of 11–17- year- olds from the general UK population between January and March 2021, gives a broad estimate. The study reported 66.5% of children had symptoms 3 months after a positive polymerase chain reaction (PCR) test, compared with 53.3% who had a negative test; 30.3% versus 16.2% had ≥3 symptoms at 3 months. The big limitation of this study was the response rate of only 13.4%. The researchers say that if this 13.4% is representative of all 11–17 year olds who have tested positive for COVID-19, over 32 000 (one in seven) young people throughout England would still have ≥3 physical symptoms 3 months later. However, if only teenagers who responded to the survey had any persisting problems and those who chose not to respond had completely recovered, this would mean a best-case scenario of 4000 cases of long COVID in children and young people.

The Office for National Statistics prevalence estimates indicate that 149 000 children and young people (aged 5–16 years) had symptoms lasting for ≥4 weeks after infection, 31 000 of whom have had symptoms for over a year.7 The impact of the Delta and Omicron waves on these figures is yet to be determined.

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Source: Carolyn A Chew-Graham, Tracy A Briggs and Binita Kane. Long COVID in children and young people: uncertainty and contradictions. British Journal of General Practice 2022; 72 (719): 253-254. DOI: https://doi.org/10.3399/bjgp22X719501  https://bjgp.org/content/72/719/253 (Full text)