Treatment of Brain Fog of Long COVID Syndrome: A Hypothesis

Abstract:

The emergence of the SARS-CoV-2 (COVID-19) virus has exacted a significant toll on the global population in terms of fatalities, health consequences, and economics. As of February 2023, there have been almost 800 million confirmed cases of the disorder reported to the WHO [1], although the actual case-positive rate is estimated to be much higher.

While many cases recover, the mortality rate associated with the illness is about 1% (based on the WHO data). Most patients experience the illness as a mild to moderate disorder and recover without significant sequelae. However, as the COVID-19 pandemic has continued, there has emerged a significant group of COVID-19 survivors who experience persistent symptoms beyond the acute course of the illness.

As many as one in eight patients report persistent symptoms 90 to 150 days after the initial infection [2]. These so-called Long COVID or post-COVID syndrome patients are mostly drawn from those who were hospitalised for the disorder, but both non-hospitalised and vaccinated subjects may also experience the syndrome [3]. While an agreed definition of Long COVID is yet to be settled, a multiplicity of symptoms affecting most major organ systems has been reported in patients.

Common Long COVID symptoms include fatigue, dyspnoea, headaches, myalgia, anosmia, dysgeusia, cognitive symptoms, and mental disorders such as depression and anxiety [4]. It is estimated that approximately a third of patients with Long COVID exhibit either fatigue, cognitive impairment, or both up to 12 weeks after a confirmed diagnosis of COVID-19 [5].

Source: Norman TR. Treatment of Brain Fog of Long COVID Syndrome: A Hypothesis. Psychiatry International. 2023; 4(3):242-245. https://doi.org/10.3390/psychiatryint4030024 https://www.mdpi.com/2673-5318/4/3/24 (Full text)

Prevalence of Post-Acute COVID-19 Sequalae and Average Time to Diagnosis Among Persons Living With HIV

Abstract:

Aims: The aims of this meta-analysis were to assess: the prevalence of Post-Acute COVID-19 sequalae in HIV positive patients; average time of diagnosis; and meta-regress for possible moderators of PACS.
Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database to get the best relevant results. These included Medline indexed journals; PubMed Central; NCBI Bookshelf and publishers’ Web sites in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included “long COVID-19 or post-acute COVID-19 syndrome/sequalae”, “persons living with HIV or HIV. The criteria for inclusion were published clinical articles reporting HIV in association with long COVID-19, further, the average time to an event of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Egger’s tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The review/trial was PROSPERO registered (CRD42022328509).
Results: A total of 43 studies reported post-acute COVID-19 syndrome. Of those, five reported post-acute COVID-19 sequalae in PLHIV. Prevalence of post-acute COVID-19 sequalae was 43.1% (95% CI 20.5% to 68.9%) in persons living with HIV (PLWH). The average time to PACS diagnosis was 4 months at 64% [0.64 (95% CI 0.230, 0.913) (P < 0.0000), I2= 93%] and at one year to PACS diagnosis was at 70 %, however with non-significant correlation (P > 0.05). On comorbidities, asthenia was associated with PACS at 17.6 % [0.176 (95% CI 0.067, 0.385) (P = 0.008), I2= 86%] while fatigue at 82%, however not related with PACS event incidence (P < 0.05). Americas, Asian and European regions showed PACS events rates of 82%, 43% and 19 % respectively (P<0.05) relative to HIV infection.
Conclusion: PACS prevalence in PLWH was 43% occurring at an average time of 4 months at 64% and 70 % at 12 months however non-significant with PACS. Asthenia was significantly associated with PACS at 17.6 % while fatigue at 82%, however not related with PACS event incidence. Americas recorded the highest PACS event rates in PLWH.
Source: Muthuka, J.; Nyamai, E.; Onyango, C.; Oluoch, K.; Nabaweesi, R. Prevalence of Post-Acute COVID-19 Sequalae and Average Time to Diagnosis Among Persons Living With HIV. Preprints 2023, 2023081633. https://doi.org/10.20944/preprints202308.1633.v1 https://www.preprints.org/manuscript/202308.1633/v1 (Full text available as PDF file)

Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022

Abstract:

Objective To characterise Long COVID in a highly vaccinated population infected by Omicron.

Design Follow-up survey of persons testing positive for SARS-CoV-2 in Western Australia, 16 July-3 August 2022.

Setting Community

Participants 22,744 persons with COVID-19 who had agreed to participate in research at the time of diagnosis were texted a survey link 90 days later; non-responders were telephoned. Post stratification weights were applied to responses from 11,697 (51.4%) participants, 94.0% of whom had received >= 3 vaccine doses.

Main outcome measures Prevalence of ‘Long COVID’ – defined as reporting new or ongoing COVID-19 illness-related symptoms or health issues 90 days post diagnosis; associated health care utilisation, reductions in work/study and risk factors were assessed using log-binomial regression.

Results 18.2% (n=2,130) of respondents met case definition for Long COVID. Female sex, being 50-69 years of age, pre-existing health issues, residing in a rural or remote area, and receiving fewer vaccine doses were significant independent predictors of Long COVID (p < 0.05). Persons with Long COVID reported a median of 6 symptoms, most commonly fatigue (70.6%) and difficulty concentrating (59.6%); 38.2% consulted a GP and 1.6% reported hospitalisation in the month prior to the survey due to ongoing symptoms. Of 1,778 respondents with Long COVID who were working/studying before their COVID-19 diagnosis, 17.9% reported reducing/discontinuing work/study.

Conclusion 90 days post Omicron infection, almost 1 in 5 respondents reported Long COVID symptoms; 1 in 15 of all persons with COVID-19 sought healthcare for associated health concerns >=2 months after the acute illness.

The known The prevalence of Long COVID varies widely across studies conducted in diverse settings globally (range: 9%-81%).

The new In a highly vaccinated population (94% with >=3 vaccine doses), almost 20% of persons infected with the SARS-CoV-2 Omicron variant reported symptoms consistent with Long COVID 90 days post diagnosis. Long COVID was associated with sustained negative impacts on work/study and a substantial utilisation of GP services 2-3 months after the acute illness; however, ED presentations and hospitalisations for Long COVID were rare.

The implications GP clinics play a significant role in managing the burden of Long COVID in Australia.

Source: Mulu Woldegiorgis, Gemma Cadby, Sera Ngeh, Rosemary Korda, Paul Armstrong, Jelena Maticevic, Paul Knight, Andrew Jardine, Lauren Bloomfield, Paul Effler. Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022.

A retrospective cohort analysis leveraging augmented intelligence to characterize long COVID in the electronic health record: A precision medicine framework

Abstract:

Physical and psychological symptoms lasting months following an acute COVID-19 infection are now recognized as post-acute sequelae of COVID-19 (PASC). Accurate tools for identifying such patients could enhance screening capabilities for the recruitment for clinical trials, improve the reliability of disease estimates, and allow for more accurate downstream cohort analysis.

In this retrospective cohort study, we analyzed the EHR of hospitalized COVID-19 patients across three healthcare systems to develop a pipeline for better identifying patients with persistent PASC symptoms (dyspnea, fatigue, or joint pain) after their SARS-CoV-2 infection. We implemented distributed representation learning powered by the Machine Learning for modeling Health Outcomes (MLHO) to identify novel EHR features that could suggest PASC symptoms outside of typical diagnosis codes. MLHO applies an entropy-based feature selection and boosting algorithms for representation mining. These improved definitions were then used for estimating PASC among hospitalized patients.

30,422 hospitalized patients were diagnosed with COVID-19 across three healthcare systems between March 13, 2020 and February 28, 2021. The mean age of the population was 62.3 years (SD, 21.0 years) and 15,124 (49.7%) were female.

We implemented the distributed representation learning technique to augment PASC definitions. These definitions were found to have positive predictive values of 0.73, 0.74, and 0.91 for dyspnea, fatigue, and joint pain, respectively.

We estimated that 25 percent (CI 95%: 6-48), 11 percent (CI 95%: 6-15), and 13 percent (CI 95%: 8-17) of hospitalized COVID-19 patients will have dyspnea, fatigue, and joint pain, respectively, 3 months or longer after a COVID-19 diagnosis. We present a validated framework for screening and identifying patients with PASC in the EHR and then use the tool to estimate its prevalence among hospitalized COVID-19 patients.

Source: Strasser ZH, Dagliati A, Shakeri Hossein Abad Z, Klann JG, Wagholikar KB, Mesa R, Visweswaran S, Morris M, Luo Y, Henderson DW, Samayamuthu MJ; Consortium for Clinical Characterization of COVID-19 by EHR (4CE); Omenn GS, Xia Z, Holmes JH, Estiri H, Murphy SN. A retrospective cohort analysis leveraging augmented intelligence to characterize long COVID in the electronic health record: A precision medicine framework. PLOS Digit Health. 2023 Jul 25;2(7):e0000301. doi: 10.1371/journal.pdig.0000301. PMID: 37490472; PMCID: PMC10368277. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368277/ (Full text)

Post COVID-19 symptoms are common, also among young adults in the general population

Abstract:

Post coronavirus disease-19 (post COVID-19) is mainly studied in clinical populations and less is known about post COVID-19 in a young general population. The aim of the study is to investigate the prevalence and symptoms of post COVID-19 and its potential risk factors in young adults.

Participants from the Swedish population-based birth cohort BAMSE were included (n = 2022, mean age 26.5 years). Post COVID-19 was assessed through a questionnaire and defined as symptoms after confirmed COVID-19 (registry-based or self-reported positive test) lasting for ≥ 2 months. In total, 681 participants had had confirmed COVID-19. Among them, 112 (16.5%) fulfilled the definition of post COVID-19 (17.8% in females, 14.5% in males, p = 0.26).

The most common post COVID-19 symptoms were altered smell and taste (68.8%), dyspnea (33.7%) and fatigue (30.4%). Overall, no major risk factors for post COVID-19 were identified except for being bedbound during COVID-19. However, asthma and rhinitis were associated with the post COVID-19 symptom dyspnea, migraine with altered smell and taste, and lower self-rated health with fatigue. In conclusion, post COVID-19 symptoms are common, also among young adults in the general population. Although not life-threatening, it could have a considerable impact on public health due to the high prevalence and long-term symptoms.

Source: Mogensen I, Ekström S, Hallberg J, Georgelis A, Melén E, Bergström A, Kull I. Post COVID-19 symptoms are common, also among young adults in the general population. Sci Rep. 2023 Jul 12;13(1):11300. doi: 10.1038/s41598-023-38315-2. PMID: 37438424; PMCID: PMC10338459. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338459/ (Full text)

Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection

Abstract:

Although “post-COVID-19 syndrome” (PCS) is reported to be common even in non-hospitalized individuals, long-term information on symptom burden, healthcare needs, utilization, and satisfaction with healthcare is scarce. The objectives of this study were to describe symptom burden, healthcare utilization and experiences with the healthcare offered for PCS in a German sample of non-hospitalized persons 2 years after SARS-CoV-2 infection.

Individuals with past COVID-19 confirmed by positive polymerase chain reaction testing were examined at the University Hospital of Augsburg from 4 November 2020 to 26 May 2021 and completed a postal questionnaire between 14 June 2022 and 1 November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS.

Of the 304 non-hospitalized participants (58.2% female, median age 53.5), 210 (69.1%) had a PCS. Among these, 18.8% had slight to moderate functional limitations. Participants with PCS showed a significantly higher utilization of healthcare and a large proportion complained about lacking information on persistent COVID-19 symptoms and problems finding competent healthcare providers.

The results indicate the need to optimize patient information on PCS, facilitate access to specialized healthcare providers, provide treatment options in the primary care setting and improve the education of healthcare providers.

Source: Kirchberger I, Meisinger C, Warm TD, Hyhlik-Dürr A, Linseisen J, Goßlau Y. Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection. Viruses. 2023 Jun 5;15(6):1326. doi: 10.3390/v15061326. PMID: 37376625; PMCID: PMC10303962. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303962/ (Full text)

Long- COVID and general health status in hospitalized COVID-19 survivors

Abstract:

Despite advances in clinical research, the long-term effects of COVID-19 on patients are not clear. Many studies revealed persistent long-term signs and symptoms. In a survey study, 259 hospitalized confirmed COVID-19 patients between 18 and 59 years were interviewed. Demographic characteristics and complaints were studied through telephone interviews. Any patient-reported symptoms that continued or developed from 4 weeks up to 12 weeks after the onset of the disease were recorded only if they did not exist prior to infection.

The 12-Item General Health Questionnaire was used for screening and assessing mental symptoms and psychosocial well-being. The mean age of participants was 43.8 ± 9.9 years. About 37% had at least one underlying disease. 92.5% showed ongoing symptoms that the most prevalent complications were hair loss (61.4%), fatigue (54.1%), shortness of breath (40.2%), altered smell (34.4%), and aggression (34.4%), respectively. In terms of factors affecting patients’ complaints, there were significant differences between age, sex, and underlying disease with long-remaining complications. This study shows a high rate of long COVID-19 conditions that should be considered by physicians, policymakers, and managers.

Source: Mohtasham-Amiri, Z., Keihanian, F., Rad, E.H. et al. Long- COVID and general health status in hospitalized COVID-19 survivors. Sci Rep 13, 8116 (2023). https://doi.org/10.1038/s41598-023-35413-z (Full study)

Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group

Abstract:

Background: There is limited data on the prevalence and risk factors for long COVID and few prospective studies with appropriate control groups and adequate sample sizes. We performed a prospective study to determine the prevalence and risk factors for long COVID.

Methods: We recruited individuals aged ≥15 years who were clinically suspected of having an acute SARS-CoV-2 infection from September 2020 to April 2021. We collected nasopharyngeal swabs three to five days following symptom onset for analysing using reverse transcriptase polymerase chain reaction (RT-PCR). We also collected clinical and sociodemographic characteristics from both SARS-CoV-2 positive and negative participants using structured questionnaires. We followed-up the participants via telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life.

Results: We followed 814 participants (412 COVID-19 positive and 402 COVID-19 negative persons). Most (n = 741/814) had mild symptoms. Both groups had similar sociodemographic and clinical characteristics, except for the hospitalization rate (15.8% in the COVID-19 positive vs 1.5% in the COVID-19 negative group). One month after disease onset, 122/412 (29.6%) individuals in the COVID-19 positive (long COVID) and 24 (6%) in the COVID-19 negative group reported residual symptoms. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms in the acute phase. Compared to recovered individuals, older age and having more than five symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID, with 57 (55.9%) reporting an impact in at least one dimension of the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) questionnaire.

Conclusions: In this prospective study consisting predominantly of individuals with mild disease, the persistence of symptoms after an acute respiratory illness was associated with a diagnosis of COVID-19. Polysymptomatic acute disease and older age were risk factors for long COVID.

Source: Cazé AB, Cerqueira-Silva T, Bomfim AP, de Souza GL, Azevedo AC, Brasil MQ, Santos NR, Khouri R, Dan J, Bandeira AC, Cavalcanti LP, Barral-Netto M, Barral A, Barbosa CG, Boaventura VS. Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group. J Glob Health. 2023 May 12;13:06015. doi: 10.7189/jogh.13.06015. PMID: 37166260; PMCID: PMC10173895. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173895/ (Full text)

A Review of Neurological Symptoms in Long COVID and Clinical Management

Abstract:

Long COVID is a clinical diagnosis generally referring to the persistence or development of new symptoms, affecting multiple organ systems after SARS-CoV-2 COVID-19 infection. Long COVID is thought to affect ∼20% of people after infection, including all age ranges and severity of infection. Fatigue, postexertional malaise, and respiratory and cardiac symptoms are commonly described. Neurological symptoms such as cognitive changes, sensory disturbances, headaches, and dysautonomia are common as well. The underlying pathophysiology remains unclear but immune dysregulation, autoimmunity, persistent viral reservoirs, and microvascular dysfunction have been implicated. As there are no tests at this time to diagnose long COVID, work-up should be focused on assessing reversible or treatable causes of symptoms. Furthermore, no treatments for long COVID currently exist, and management remains focused on a multimodal approach and symptom management, with many people showing improvement in symptoms over time.

Source: Navis A. A Review of Neurological Symptoms in Long COVID and Clinical Management. Semin Neurol. 2023 Apr 17. doi: 10.1055/s-0043-1767781. Epub ahead of print. PMID: 37068519. https://pubmed.ncbi.nlm.nih.gov/37068519/

Employment outcomes of people with Long Covid symptoms: community-based cohort study

Abstract:

Background Evidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and subsequent employment outcomes.

Methods This was an observational, longitudinal study using a pre-post design. We included UK COVID-19 Infection Survey participants who completed questionnaires on Long Covid from 3 February 2021 to 30 September 2022 when they were aged 16 to 64 years and not in full-time education. We used conditional logit modelling to explore the time-varying relationship between Long Covid status ≥12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting ≥4 weeks.

Results Of 206,299 included participants (mean age 45 years, 54% female, 92% white), 15% were ever inactive in the labour market and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks (adjusted odds ratio (aOR): 1.45; 95% CI: 1.17 to 1.81) or 40 to <52 weeks (1.34; 1.05 to 1.72) post-infection. Compared with pre-infection, reporting Long Covid was also associated with increased odds of long-term absence 18 to <24 weeks (1.40; 1.04 to 1.90) and 24 to <30 weeks (1.45; 1.03 to 2.04) post-infection, but not beyond 30 weeks. Combining with official statistics on Long Covid prevalence, our estimates translate to 27,000 (95% CI: 6,000 to 47,000) working-age adults in the UK being inactive because of their Long Covid symptoms in July 2022.

Conclusions Long Covid is likely to have contributed to reduced levels of participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.

Source: Daniel Ayoubkhani, Francesco Zaccardi, Koen B. Pouwels, A. Sarah Walker, Donald Houston, Nisreen A. Alwan, Josh Martin, Kamlesh Khunti, Vahé Nafilyan. Employment outcomes of people with Long Covid symptoms: community-based cohort study.
medRxiv 2023.03.21.23287524; doi: https://doi.org/10.1101/2023.03.21.23287524 https://www.medrxiv.org/content/10.1101/2023.03.21.23287524v1.full-text (Full text)