Detecting anti-SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion

Abstract:

Serum-based ELISA (enzyme-linked immunosorbent assay) has been widely used to detect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, to date, no study has investigated patient urine as a biological sample to detect SARS-CoV-2 virus-specific antibodies. An in-house urine-based ELISA was developed using recombinant SARS-CoV-2 nucleocapsid protein.

The presence of SARS-CoV-2 antibodies in urine was established, with 94% sensitivity and 100% specificity for the detection of anti-SARS-CoV-2 antibodies with the urine-based ELISA and 88% sensitivity and 100% specificity with a paired serum-based ELISA. The urine-based ELISA that detects anti-SARS-CoV-2 antibodies is a noninvasive method with potential application as a facile COVID-19 immunodiagnostic platform, which can be used to report the extent of exposure at the population level and/or to assess the risk of infection at the individual level.

Source: Ludolf F, Ramos FF, Bagno FF, Oliveira-da-Silva JA, Reis TAR, Christodoulides M, Vassallo PF, Ravetti CG, Nobre V, da Fonseca FG, Coelho EAF. Detecting anti-SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion. Sci Adv. 2022 May 13;8(19):eabn7424. doi: 10.1126/sciadv.abn7424. Epub 2022 May 13. PMID: 35559681; PMCID: PMC9106288. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106288/ (Full text)

Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors

Abstract:

Background: Severe clinical pictures and sequelae of COVID-19 disease are immune mediated and characterized by a ‘cytokine storm’. Skeletal muscle has emerged as a potent regulator of immune system function. The aim of the present study is to define the prevalence of sarcopenia among COVID-19 survivors and the negative impact of sarcopenia on the post-acute COVID-19 syndrome and its related risk factors.

Methods: A total of 541 subjects recovered from COVID-19 disease were enrolled in the Gemelli Against COVID-19 Post-Acute Care between April 2020 and February 2021. They underwent a multidisciplinary clinical evaluation and muscle strength and physical performance assessment.

Results: Mean age was 53.1 years (SD 15.2, range from 18 to 86 years), and 274 (51%) were women. The prevalence of sarcopenia was 19.5%, and it was higher in patients with a longer hospital stay and lower in patients who were more physically active and had higher levels of serum albumin. Patients with sarcopenia had a higher number of persistent symptoms than non-sarcopenic patients (3.8 ± 2.9 vs. 3.2 ± 2.8, respectively; P = 0.06), in particular fatigue, dyspnoea, and joint pain.

Conclusions: Sarcopenia identified according to the EWGSOP2 criteria is high in patients recovered from COVID-19 acute illness, particularly in those who had experienced the worst clinical picture reporting the persistence of fatigue and dyspnoea. Our data suggest that sarcopenia, through the persistence of inflammation, could be the biological substrate of long COVID-19 syndrome. Physical activity, especially if associated with adequate nutrition, seems to be an important protective factor.

Source: Martone AM, Tosato M, Ciciarello F, Galluzzo V, Zazzara MB, Pais C, Savera G, Calvani R, Marzetti E, Robles MC, Ramirez M, Landi F; Gemelli Against COVID-19 Post-Acute Care Team. Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors. J Cachexia Sarcopenia Muscle. 2022 Jun 14. doi: 10.1002/jcsm.12931. Epub ahead of print. PMID: 35698920. https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12931 (Full text)

Long-Term Symptoms of COVID-19: One-Year Follow-Up Study

Abstract:

Introduction: Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome.

Methods: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States).

Results: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%).

Conclusion: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals’ attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.

Source: Shivani F, Kumari N, Bai P, et al. (June 14, 2022) Long-Term Symptoms of COVID-19: One-Year Follow-Up Study. Cureus 14(6): e25937. doi:10.7759/cureus.25937 https://www.cureus.com/articles/91406-long-term-symptoms-of-covid-19-one-year-follow-up-study (Full text)

A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study

Abstract:

Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition.

To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19.

The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide.

Source: Munblit D, Nicholson T, Akrami A, Apfelbacher C, Chen J, De Groote W, Diaz JV, Gorst SL, Harman N, Kokorina A, Olliaro P, Parr C, Preller J, Schiess N, Schmitt J, Seylanova N, Simpson F, Tong A, Needham DM, Williamson PR; PC-COS project steering committee. A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study. Lancet Respir Med. 2022 Jun 14:S2213-2600(22)00169-2. doi: 10.1016/S2213-2600(22)00169-2. Epub ahead of print. PMID: 35714658; PMCID: PMC9197249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197249/ (Full text)

The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study

Abstract:

Background: Characterizing the post-COVID health conditions is helpful to direct patients to appropriate healthcare.

Aims: To describe the presence of symptoms in COVID-19 patients within 6 months after diagnosis and to investigate the associated factors in terms of reporting symptoms.

Methods: Data of DEU-COVIMER (a telephone interview-based COVID-19 follow-up center established in a tertiary care hospital) was analyzed for SARS-CoV-2 RNA positive participants aged ≥ 18 years from November 1st, 2020, to May 31st, 2021. Symptom frequencies were stratified by demographic and clinical characteristics at one, three, and 6 months after diagnosis. With the patients who had symptoms at baseline, generalized estimating equations were applied to identify the factors associated with reporting of symptoms.

Results: A total of 5610 patients agreed to participate in the study. Symptom frequency was 37.2%, 21.8%, and 18.2% for the first, third, and sixth months. Tiredness/fatigue, muscle or body aches, and dyspnea/difficulty breathing were the most common symptoms in all time frames. In multivariate analysis, older age, female gender (odds ratio OR 1.74, 95% confidence interval 1.57-1.93), bad economic status (OR 1.37, 1.14-1.65), current smoking (OR 1.15, 1.02-1.29), being fully vaccinated before COVID-19 (OR 0.53, 0.40-0.72), having more health conditions (≥ 3 conditions, OR 1.78, 1.33-2.37), having more symptoms (> 5 symptoms, OR 2.47, 2.19-2.78), and hospitalization (intensive care unit, OR 2.18, 1.51-3.14) were associated with reporting of symptoms.

Conclusions: This study identifies risk factors for patients who experience post-COVID-19 symptoms. Healthcare providers should appropriately allocate resources prioritizing the patients who would benefit from post-COVID rehabilitation.

Source: Emecen AN, Keskin S, Turunc O, Suner AF, Siyve N, Basoglu Sensoy E, Dinc F, Kilinc O, Avkan Oguz V, Bayrak S, Unal B. The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study. Ir J Med Sci. 2022 Jun 17:1–10. doi: 10.1007/s11845-022-03072-0. Epub ahead of print. PMID: 35715663; PMCID: PMC9205653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205653/ (Full text)

Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID

Abstract:

Objective: Musculoskeletal (MSK) pain is being increasingly reported by patients as one of the most common persistent symptoms in post-COVID-19 syndrome or Long COVID. However, there is a lack of understanding of its prevalence, characteristics, and underlying pathophysiological mechanisms. The objective of this review is to identify and describe the features and characteristics of MSK pain in Long COVID patients.

Methods: The narrative review involved a literature search of the following online databases: MEDLINE (OVID), EMBASE (OVID), CINAHL, PsyclNFO, and Web of Science (December 2019 to February 2022). We included observational studies that investigated the prevalence, characteristics, risk factors and mechanisms of MSK pain in Long COVID. After screening and reviewing the initial literature search results, a total of 35 studies were included in this review.

Results: The overall reported prevalence of MSK pain in Long COVID ranged widely from 0.3% to 65.2%. The pain has been reported to be localized to a particular region or generalized and widespread. No consistent pattern of progression of MSK pain symptoms over time was identified. Female gender and higher BMI could be potential risk factors for Long COVID MSK pain, but no clear association has been found with age and ethnicity. Different pathophysiological mechanisms have been hypothesized to contribute to MSK pain in Long COVID including increased production of proinflammatory cytokines, immune cell hyperactivation, direct viral entry of neurological and MSK system cells, and psychological factors.

Conclusion: MSK pain is one of the most common symptoms in Long COVID. Most of the current literature on Long COVID focuses on reporting the prevalence of persistent MSK pain. Studies describing the pain characteristics are scarce. The precise mechanism of MSK pain in Long COVID is yet to be investigated. Future research must explore the characteristics, risk factors, natural progression, and underlying mechanisms of MSK pain in Long COVID.

Source: Khoja O, Silva Passadouro B, Mulvey M, Delis I, Astill S, Tan AL, Sivan M. Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID. J Pain Res. 2022 Jun 17;15:1729-1748. doi: 10.2147/JPR.S365026. PMID: 35747600; PMCID: PMC9212788. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212788/ (Full text)

Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2

The omicron variant of SARS-CoV-2 (PANGO B.1.1.529) spread rapidly across the world, out-competing former variants soon after it was first detected in November, 2021. According to the Our World in Data COVID-19 database, In Europe, the number of confirmed cases reported between December, 2021, and March, 2022 (omicron period) has exceeded all previously reported cases. Omicron appears to cause less severe acute illness than previous variants, at least in vaccinated populations. However, the potential for large numbers of people to experience long-term symptoms is a major concern, and health and workforce planners need information urgently to appropriately scale resource allocation.
In this case-control observational study, we set out to identify the relative odds of long-COVID (defined following the National Institute for Health and Care Excellence guidelines as having new or ongoing symptoms 4 weeks or more after the start of acute COVID-19) in the UK during the omicron period compared with the delta period. We used self-reported data from the COVID Symptom Study app. (King’s College London Research Ethics Management Application System number 18210, reference LRS-19/20-18210). Data were extracted and pre-processed using ExeTera13 (version 0.5.5).
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Source: Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet. 2022 Jun 18;399(10343):2263-2264. doi: 10.1016/S0140-6736(22)00941-2. PMID: 35717982; PMCID: PMC9212672. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00941-2/fulltext (Full text)

Self-Reported Long COVID in the General Population: Sociodemographic and Health Correlates in a Cross-National Sample

Abstract:

We aimed to gain knowledge of possible sociodemographic predictors of long COVID and whether long COVID was associated with health outcomes almost two years after the pandemic outbreak. There were 1649 adults who participated in the study by completing a cross-sectional online survey disseminated openly in Norway, the UK, the USA, and Australia between November 2021 and January 2022.

Participants were defined as having long COVID based on self-reports that they had been infected by COVID-19 and were experiencing long-lasting COVID symptoms. Logistic regression analyses were used to examine possible sociodemographic predictors, and multivariate analysis of variance was used to examine whether long COVID status was associated with health outcomes. None of the sociodemographic variables was significantly associated with reporting long COVID. Having long COVID was associated with higher levels of psychological distress, fatigue, and perceived stress. The effect of long COVID on health outcomes was greater among men than among women.

In conclusion, long COVID appeared across sociodemographic groups. People with long COVID reported worsened health outcomes compared to those who had had COVID-19 but without long-term symptoms. Men experiencing long COVID appear to be particularly vulnerable to experiencing poorer health outcomes; health services may pay extra attention to potentially unnoticed needs for support among men experiencing long COVID.

Source: Bonsaksen T, Leung J, Price D, Ruffolo M, Lamph G, Kabelenga I, Thygesen H, Geirdal AØ. Self-Reported Long COVID in the General Population: Sociodemographic and Health Correlates in a Cross-National Sample. Life (Basel). 2022 Jun 15;12(6):901. doi: 10.3390/life12060901. PMID: 35743932. https://www.mdpi.com/2075-1729/12/6/901/htm (Full text)

COVID-19 Pandemic-Revealed Consistencies and Inconsistencies in Healthcare: A Medical and Organizational View

Abstract:

The circumstances of the Coronavirus disease caused by the SARS-CoV-2 virus (COVID-19) pandemic have had a significant impact on global and national developments, affecting the existence of society in all its expressions, as well as the lives of people themselves. In the context of the pandemic, increased attention has been focused on acute measures, but the ending of the pandemic is expected as a resolution of the related healthcare problems. However, there are several indicators that the COVID-19 pandemic might induce long-term consequences for individual and public health. Some of the consequences are inferred and predictable, but there are also areas of medicine that have been indirectly affected by the pandemic, and these consequences have not yet been sufficiently explored.

This study is focused on drawing attention to some of the COVID-19 pandemic consistencies and the pandemic-revealed inconsistencies in healthcare. Content analysis and statistical analysis were applied to achieve the aim of the study. The main findings of the study address chronic disease burden (particularly, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)), healthcare governance and organizational issues, and the synergy between health policy perspectives and innovative solutions in practice.

The study provides insight into the particular healthcare issues affected by the COVID-19 pandemic, such as the increase in mortality in some diagnoses besides COVID-19 and the possible emergence of a new type of resistance-vaccine-resistance-contemporaneously supporting the identification of the tendencies and currently unnoticed indirect consistencies and inconsistencies revealed by the pandemic.

Source: Araja D, Berkis U, Murovska M. COVID-19 Pandemic-Revealed Consistencies and Inconsistencies in Healthcare: A Medical and Organizational View. Healthcare (Basel). 2022 May 31;10(6):1018. doi: 10.3390/healthcare10061018. PMID: 35742069. https://www.mdpi.com/2227-9032/10/6/1018/htm  (Full text)

Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is considered to be associated with post-viral complications and mental stress, but the role of autoimmunity also remains promising. A comparison of autoimmune profiles in chronic fatigue of different origin may bring insights on the pathogenesis of this disease.

Thirty-three patients with CFS/ME were divided into three subgroups. The first group included Herpesviridae carriers (group V), the second group included stress-related causes of chronic fatigue (distress, group D), and the third group included idiopathic CFS/ME (group I). Were evaluated thirty-six neural and visceral autoantigens with the ELISA ELI-test (Biomarker, Russia) and compared to 20 healthy donors, either without any fatigue (group H), or “healthy but tired” (group HTd) with episodes of fatigue related to job burnout not fitting the CFS/ME criteria.

β2-glycoprotein-I autoantibodies were increased in CFS/ME patients, but not in healthy participants, that alludes the link between CFS/ME and antiphospholipid syndrome (APS) earlier suspected by Berg et al. (1999). In CFS/ME patients, an increase in levels of autoantibodies towards the non-specific components of tissue debris (double-stranded DNA, collagen) was shown. Both CFS and HTd subgroups had elevated level of autoantibodies against serotonin receptors, glial fibrillary acidic protein and protein S100. Only group V showed an elevation in the autoantibodies towards voltage-gated calcium channels, and only group D had elevated levels of dopamine-, glutamate- and GABA-receptor autoantibodies, as well as NF200-protein autoantibodies.

Therefore, increased autoimmune reactions to the multiple neural antigens and to adrenal medullar antigen, but not to other tissue-specific somatic ones were revealed. An increase in autoantibody levels towards some neural and non-tissue-specific antigens strongly correlated with a CFS/ME diagnosis. Autoimmune reactions were described in all subtypes of the clinically significant chronic fatigue. Visceral complaints in CFS/ME patients may be secondary to the neuroendocrine involvement and autoimmune dysautonomia. CFS may be closely interrelated with antiphospholipid syndrome, that requires further study.

Source: Danilenko OV, Gavrilova NY, Churilov LP. Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology. Pathophysiology. 2022 May 25;29(2):187-199. doi: 10.3390/pathophysiology29020016. PMID: 35736644.  https://www.mdpi.com/1873-149X/29/2/16/htm (Full text)