Tag: long covid diagnosis

How methodological pitfalls have created widespread misunderstanding about long COVID

Key messages:

  • The existing epidemiological research on long COVID has suffered from overly broad case definitions and a striking absence of control groups, which have led to distortion of risk.

  • The unintended consequences of this may include, but are not limited to, increased societal anxiety and healthcare spending, a failure to diagnose other treatable conditions misdiagnosed as long COVID and diversion of funds and attention from those who truly suffer from chronic conditions secondary to COVID-19.

  • Future research should include properly matched control groups, sufficient follow-up time after infection and internationally-established diagnostic or inclusion and exclusion criteria.

Source: Høeg TB, Ladhani S, Prasad V. How methodological pitfalls have created widespread misunderstanding about long COVID. BMJ Evid Based Med. 2023 Sep 25:bmjebm-2023-112338. doi: 10.1136/bmjebm-2023-112338. Epub ahead of print. PMID: 37748921. https://ebm.bmj.com/content/early/2023/08/10/bmjebm-2023-112338 (Full text)

SARS-CoV-2-Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19

Abstract:

Background and objectives: Millions of Americans were exposed to SARS-CoV-2 early in the pandemic but could not get diagnosed with COVID-19 due to testing limitations. Many have developed a postviral syndrome (PVS) including neurologic manifestations similar to those with postacute sequelae of SARS-CoV-2 infection (Neuro-PASC). Owing to those circumstances, proof of SARS-CoV-2 infection was not required for evaluation at Northwestern Medicine’s Neuro COVID-19 clinic. We sought to investigate clinical and immunologic findings suggestive of SARS-CoV-2 exposure in patients with PVS.

Methods: We measured SARS-CoV-2-specific humoral and cell-mediated immune responses against Nucleocapsid and Spike proteins in 29 patients with PVS after suspected COVID-19, 32 confirmed age-matched/sex-matched Neuro-PASC (NP) patients, and 18 unexposed healthy controls. Neurologic symptoms and signs, comorbidities, quality of life, and cognitive testing data collected during clinic visits were studied retrospectively.

Results: Of 29 patients with PVS, 12 (41%) had detectable humoral or cellular immune responses consistent with prior exposure to SARS-CoV-2. Of 12 PVS responders (PVS+), 75% harbored anti-Nucleocapsid and 50% harbored anti-Spike responses. Patients with PVS+ had similar neurologic symptoms as patients with NP, but clinic evaluation occurred 5.3 months later from the time of symptom onset (10.7 vs 5.4 months; p = 0.0006). Patients with PVS+ and NP had similar subjective impairments in quality of life measures including cognitive function and fatigue. Patients with PVS+ had similar results in objective cognitive measures of processing speed, attention, and executive function and better results in working memory than patients with NP.

Discussion: Antibody and T-cell assays showed evidence of prior SARS-CoV-2 exposure in approximately 40% of the PVS group. Three-quarters of patients with PVS+ had detectable anti-Nucleocapsid and one-half anti-Spike responses, highlighting the importance of multitargeted COVID-19 immunologic evaluation and the limitations of commercially available diagnostic tests. Despite their persistent symptoms, lack of COVID-19 diagnosis likely delayed clinical care in patients with PVS. Our data suggest that millions of Americans presenting with PVS resembling Neuro-PASC were indeed exposed to SARS-CoV-2 at the beginning of the pandemic, and they deserve the same access to care and inclusion in research studies as patients with NP with confirmed COVID-19 diagnosis.

Source:Orban ZS, Visvabharathy L, Perez Giraldo GS, Jimenez M, Koralnik IJ. SARS-CoV-2-Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19. Neurol Neuroimmunol Neuroinflamm. 2023 Aug 23;10(6):e200159. doi: 10.1212/NXI.0000000000200159. PMID: 37612134; PMCID: PMC10448973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448973/ (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)

Post-COVID cognitive dysfunction: current status and research recommendations for high risk population

Abstract:

Post-COVID cognitive dysfunction (PCCD) is a condition in which patients with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, usually three months from the onset, exhibit subsequent cognitive impairment in various cognitive domains, and cannot be explained by an alternative diagnosis.

While our knowledge of the risk factors and management strategy of PCCD is still incomplete, it is necessary to integrate current epidemiology, diagnosis and treatment evidence, and form consensus criteria to better understand this disease to improve disease management. Identifying the risk factors and vulnerable population of PCCD and providing reliable strategies for effective prevention and management is urgently needed.

In this paper, we reviewed epidemiology, diagnostic markers, risk factors and available treatments on the disease, formed research recommendation framework for vulnerable population, under the background of post-COVID period.

Source: Quan M, Wang X, Gong M, Wang Q, Li Y, Jia J. Post-COVID cognitive dysfunction: current status and research recommendations for high risk population. Lancet Reg Health West Pac. 2023 Jul 5;38:100836. doi: 10.1016/j.lanwpc.2023.100836. PMID: 37457901; PMCID: PMC10344681. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344681/ (Full text)

Long COVID: An approach to clinical assessment and management in primary care

Abstract:

Long COVID is an emerging public health threat, following swiftly behind the surges of acute infection over the course of the COVID-19 pandemic. It is estimated that there are already approximately 100 million people suffering from Long COVID globally, 0.5 million of whom are South African, and for whom our incomplete understanding of the condition has forestalled appropriate diagnosis and clinical care. There are several leading postulates for the complex, multi-mechanistic pathogenesis of Long COVID. Patients with Long COVID may present with a diversity of clinical phenotypes, often with significant overlap, which may exhibit temporal heterogeneity and evolution.

Post-acute care follow-up, targeted screening, diagnosis, a broad initial assessment and more directed subsequent assessments are necessary at the primary care level. Symptomatic treatment, self-management and rehabilitation are the mainstays of clinical care for Long COVID. However, evidence-based pharmacological interventions for the prevention and treatment of Long COVID are beginning to emerge. This article presents a rational approach for assessing and managing patients with Long COVID in the primary care setting.

Source: Perumal R, Shunmugam L, Naidoo K. Long COVID: An approach to clinical assessment and management in primary care. S Afr Fam Pract (2004). 2023 Jun 23;65(1):e1-e10. doi: 10.4102/safp.v65i1.5751. PMID: 37427773; PMCID: PMC10331047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331047/ (Full text)

Persistent serum protein signatures define an inflammatory subcategory of long COVID

Abstract:

Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute SARS-CoV-2 infection. The aetiologies may include persistent inflammation, unresolved tissue damage or delayed clearance of viral protein or RNA, but the biological differences they represent are not fully understood. Here we evaluate the serum proteome in samples, longitudinally collected from 55 PASC individuals with symptoms lasting ≥60 days after onset of acute infection, in comparison to samples from symptomatically recovered SARS-CoV-2 infected and uninfected individuals.

Our analysis indicates heterogeneity in PASC and identified subsets with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), appear to be the most differentially enriched signaling pathways, distinguishing a group of patients characterized also by a persistent neutrophil activation signature.

These findings help to clarify biological diversity within PASC, identify participants with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance, including a protein panel that we propose as having diagnostic utility for differentiating inflammatory and non-inflammatory PASC.

Source: Talla, A., Vasaikar, S.V., Szeto, G.L. et al. Persistent serum protein signatures define an inflammatory subcategory of long COVID. Nat Commun 14, 3417 (2023). https://doi.org/10.1038/s41467-023-38682-4 https://www.nature.com/articles/s41467-023-38682-4 (Full text)

Identification and diagnosis of long COVID-19: A scoping review

Abstract:

Long COVID-19 (LC-19) is a condition that has affected a high percentage of the population that recovered from the initial disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LC-19 diagnosis is currently poorly defined because of its variable, multisystem, episodic symptoms, and lack of uniformity in the critical time points associated with the disease. Considering the number of cases, workers’ compromised efficiency or inability to return to their duties can affect organizations and impact economies. LC-19 represents a significant burden on multiple levels and effectively reduces quality of life. These factors necessitate the establishment of firm parameters of diagnoses to provide a foundation for ongoing and future studies of clinical characteristics, epidemiology, risk factors, and therapy.

In this scoping review, we conducted a literature search across multiple publication sites to identify papers of interest regarding the diagnosis of LC-19. We identified 225 records of interest and categorized them into seven categories. Based on our findings, there are only 11 original papers that outline the diagnostic process in detail with little overlap. This scoping review highlights the lack of consensus regarding the definition and, thereby, the LC-19 diagnosis processes. Due to no clear directive and considering the many unknowns surrounding the natural history of the disease and further recovery/sequelae from COVID-19, continued discussion and agreement on a definition/diagnosis will help future research and management of these patients.

Source: Srikanth S, Boulos JR, Dover T, Boccuto L, Dean D. Identification and diagnosis of long COVID-19: A scoping review. Prog Biophys Mol Biol. 2023 May 12;182:1-7. doi: 10.1016/j.pbiomolbio.2023.04.008. Epub ahead of print. PMID: 37182545; PMCID: PMC10176974. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176974/ (Full text)

How do German General Practitioners Manage Long-/Post-COVID? A Qualitative Study in Primary Care

Abstract:

Background: Many patients with ongoing complaints after a SARS-CoV-2 infection are treated in primary care. Existing medical guidelines on how to diagnose and treat Long-/Post-COVID are far from being comprehensive. This study aims to describe how German general practitioners (GPs) deal with this situation, what problems they experience when managing such patients, and how they solve problems associated with the diagnosis and treatment of Long-/Post-COVID.
Methods and Findings: We conducted a qualitative study and interviewed 11 GPs. The most commonly described symptoms were ongoing fatigue, dyspnea, chest tightness and a decrease in physical capacity. The most common way to identify Long-/Post-COVID was by exclusion. Patients suffering from Long-/Post-COVID were generally treated by their GPs and rarely referred. A very common non-pharmacological intervention was to take a wait-and-see approach and grant sick leave. Other non-pharmacological interventions included lifestyle advices, physical exercise, acupuncture and exercises with intense aromas. Pharmacological treatments focused on symptoms, like respiratory symptoms or headaches. Our study’s main limitations are the small sample size and therefore limited generalizability of results.
Conclusions: Further research is required to develop and test pharmaceutical and non-pharmaceutical interventions for patients with Long-/Post-COVID. In addition, strategies to prevent the occurrence of Long-/Post-COVID after an acute infection with SARS-CoV-2 have to be developed. The routine collection of data on the diagnosis and management of Long-/Post-COVID may help in the formulation of best practices. It is up to policymakers to facilitate the necessary implementation of effective interventions in order to limit the huge societal consequences of large groups of patients suffering from Long-/Post-COVID.
Source: Bachmeier BE, Hölzle S, Gasser M, van den Akker M. How do German General Practitioners Manage Long-/Post-COVID? A Qualitative Study in Primary Care. Viruses. 2023; 15(4):1016. https://doi.org/10.3390/v15041016 https://www.mdpi.com/1999-4915/15/4/1016 (Full text)

Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis

Abstract:

The question of COVID-19 and long-COVID-19 course in children remains unsolved. This infection in children, which is associated with COVID-19, can vary from asymptomatic to systemic damage of various systems. Multisystem inflammatory syndrome in children, associated with SARS-CoV-2 (MIS-C), is a serious condition in children and adolescents after experiencing COVID-19.
Published data on MIS-C have indicated that the inflammation can be registered in the gastrointestinal tract (60–100%), as well as in cardiovascular (80%), nervous (29–58%), and respiratory (21–65%) systems. However, with the changing characteristics of SARS-CoV-2, the manifestations of COVID-19 and long-COVID-19 in children have also been changing. Currently, there is no clear understanding of the development of severe COVID-19 and MIS-C in children, especially after being exposed to patients with COVID-19.
We presented two new clinical courses of multisystem inflammatory syndrome in children with severe multisystem damage after close contact to relatives with COVID-19 or long-COVID-19. Thus, high-risk children, who are positive for SARS-CoV-2 infection after contact with COVID-19 patients, should be clinically managed during the first few months. The identification of the disease complexity requires the involvement of neurologists, cardiologists, and other specialists.
Source: Vasichkina E, Kofeynikova O, Fetisova S, Starshinova AY, Sheyanova E, Vershinina T, Ryzhkov A, Skripnik A, Alekseeva D, Nechaeva E, Glushkova A, Kudlay D, Pervunina T, Starshinova A. Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis. Life. 2023; 13(3):781. https://doi.org/10.3390/life13030781 https://www.mdpi.com/2075-1729/13/3/781 (Full text)

Understanding Long COVID Syndrome: An Up to the Minute Fret

Abstract:

The Severe Acute Respiratory Syndrome Corona Virus 2 (SARSCoV-2) virus-induced corona virus disease 2019 (COVID-19) has had a global spread. Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) rst emerged in Wuhan, China, in December 2019, and the infection spread rapidly across the world. The disease caused by the virus was named corona virus disease in 2019, and was declared a global pandemic by the World Health Organization (WHO) in March 2020. While the symptoms are mild or moderate in most patients, severe pneumonia can develop in 15%, and Acute Respiratory Distress Syndrome (ARDS), septic shock, and multiple organ failure in 5%. A comprehensive strategy for precautions includes hand washing, social distancing, isolation and mask-wearing. Besides, vaccines play an essential role in preventing the spread.

Long COVID or long-haul COVID (also known as post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS) is a condition characterized by long-term health problems persisting or appearing after the typical recovery period of COVID-19. Although studies into long COVID are under way, as of May 2022 there is no consensus on the definition of the term.

Long COVID has been described as having the potential to affect nearly every organ system, causing further conditions (sequelae) including respiratory system disorders, nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, musculoskeletal pain, and anemia. The most commonly reported symptoms of long COVID are fatigue and memory problems. Many other symptoms have also been reported, including malaise, headaches, shortness of breath, anosmia (loss of smell), parosmia (distorted smell), muscle weakness, low-grade fever, and cognitive dysfunction. Overall, it is considered by default to be a diagnosis of exclusion.

Source: Gomes, Richmond. (2023). Understanding Long COVID Syndrome: An Up to the Minute Fret. 04. 1-7.  https://www.researchgate.net/publication/369037934_Understanding_Long_COVID_Syndrome_An_Up_to_the_Minute_Fret (Full text)