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)

Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation

Abstract:

Background: Subclinical myocardial dysfunction may exist in post-COVID-19 patients and may carry significance in long term.

Methodology: Subjects of long-COVID-19 with historically and radiologically significant pulmonary involvement (without documented cardiac involvement) were evaluated on outpatient follow-up echocardiographically when they had disproportionate shortness of breath (SOB), fatigue, or high pulse rate as perceived by the physicians. The common acute-phase symptoms were noted and scored retrospectively. The assessment included spirometry and measurement of chronic obstructive pulmonary disease (COPD) assessment test (CAT) score with measurement of the left ventricular (LV) and right ventricular (RV) free wall global longitudinal strain as an adjunct to routine two-dimensional and Doppler echocardiography and spirometry. The results were evaluated statistically with respect to the history of hospitalization.

Results: The hospitalized (n = 15) and nonhospitalized (n = 10) patients were demographically similar. However, the nonhospitalized patients had higher total symptom score (p = 0.03), anosmia (p = 0.017), and ageusia (p = 0.0019). At follow-up (>3 months of acute illness), the nonhospitalized patients had a better CAT score (p = 0.04), higher change in max pulse rate (p = 0.03), and higher forced expiratory volume in 1 second (FEV1) (p = 0.002), tricuspid annular plane systolic excursion (TAPSE) (p = 0.02), and left ventricular global longitudinal strain (LVGLS) (-17.15 ± 1.19 vs -13.11 ± 1.91) (p = 0.0001). Overall, the two groups formed distinct clusters. The LVGLS and the maximum pulse rate difference in the two chair test (2CT) seem to contribute maximally to the variance between the two groups in multivariate analysis.

Conclusion: The subclinical myocardial dysfunction persisting in post-COVID patients (without suspected cardiac affection and lower neuroinflammatory symptoms in the acute phase) with significant pulmonary affection needs further evaluation. They demonstrate a higher max pulse rate difference in the 2CT. This real-world observation demands further investigations.

Source: Bhattacharyya P, Sengupta S, De A, Mukherjee S, Paul M, Dey D. Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation. J Assoc Physicians India. 2022 Nov;70(11):11-12. doi: 10.5005/japi-11001-0147. PMID: 37355939. https://japi.org/article/files/JAPI0147_p18-22_compressed.pdf (Full text)

Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2

Abstract:

Long COVID is a well-known complication to COVID-19 that affect millions of people worldwide and causes wide range of symptoms. We present a rare case of a previously diagnosed follicular lymphoma patient, who had a long COVID with persistent negative SARS-CoV-2 antibodies and required an aggressive antiviral treatment.

Source: Tayar E, Isber R, Isber N. Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2. Heliyon. 2023 Jun;9(6):e17149. doi: 10.1016/j.heliyon.2023.e17149. Epub 2023 Jun 21. PMID: 37378376; PMCID: PMC10284434. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284434/ (Full text)

Etiopathogenic theories about long COVID

Abstract:

The main etiopathogenic theories of long coronavirus disease (COVID) are listed and a conjunction of them is carried out with the objective of deciphering the pathophysiology of the entity, finally the main lines of treatment existing in real life are discussed (Paxlovid, use of antibiotics in dysbiosis, triple anticoagulant therapy, temelimab).

Source: Del Carpio-Orantes L. Etiopathogenic theories about long COVID. World J Virol. 2023 Jun 25;12(3):204-208. doi: 10.5501/wjv.v12.i3.204. PMID: 37396704; PMCID: PMC10311581. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311581/ (Full text)

Long COVID and possible preventive options

Abstract:

Most of the people who suffered from COVID-19 fully recovered, but approximately 10–20% of them developed a wide variety of symptoms after they recover from their initial illness. Long COVID can develop at any patient; however, several studies suggest that the development of Long Covid syndrome may be linked to severity of acute illness.

Some of the risk factors are hospitalization (with mechanical ventilation), Intensive Care Unit admission, age (over 50 years), gender (female) and comorbidities. Since the precise mechanism of Long COVID has not been clarified, neither the management of Long COVID-19 syndrome has been solved yet.

Promising results have been published with vaccines as they effectively reduced the risk of Long COVID; however, other data suggest that vaccination results only partial protection in the post-acute phase of the disease. Recently, the orally effective antiviral agents (Paxlovid, molnupiravir) are preferred for outpatient management, and they highly reduce the progression of mild-to-moderate COVID-19 to severe one, and consequently, might reduce the development of Long COVID. Finally, recently, several clinical trials are in progress with either dietary supplements or drugs with different mechanisms of action.

Additional information on the precise mechanisms, risk factors of Long COVID may result in successful preventive and therapeutic management of Long Covid 19 syndrome.

Source: Sebők S, Gyires K. Long COVID and possible preventive options. Inflammopharmacology. 2023 Jun 21. doi: 10.1007/s10787-023-01204-1. Epub ahead of print. PMID: 37344737. https://link.springer.com/article/10.1007/s10787-023-01204-1 (Full text)

Oligosaccharides as Potential Regulators of Gut Microbiota and Intestinal Health in Post-COVID-19 Management

Abstract:

The COVID-19 pandemic has had a profound impact worldwide, resulting in long-term health effects for many individuals. Recently, as more and more people recover from COVID-19, there is an increasing need to identify effective management strategies for post-COVID-19 syndrome, which may include diarrhea, fatigue, and chronic inflammation. Oligosaccharides derived from natural resources have been shown to have prebiotic effects, and emerging evidence suggests that they may also have immunomodulatory and anti-inflammatory effects, which could be particularly relevant in mitigating the long-term effects of COVID-19.

In this review, we explore the potential of oligosaccharides as regulators of gut microbiota and intestinal health in post-COVID-19 management. We discuss the complex interactions between the gut microbiota, their functional metabolites, such as short-chain fatty acids, and the immune system, highlighting the potential of oligosaccharides to improve gut health and manage post-COVID-19 syndrome. Furthermore, we review evidence of gut microbiota with angiotensin-converting enzyme 2 expression for alleviating post-COVID-19 syndrome.

Therefore, oligosaccharides offer a safe, natural, and effective approach to potentially improving gut microbiota, intestinal health, and overall health outcomes in post-COVID-19 management.

Source: Cheong KL, Chen S, Teng B, Veeraperumal S, Zhong S, Tan K. Oligosaccharides as Potential Regulators of Gut Microbiota and Intestinal Health in Post-COVID-19 Management. Pharmaceuticals (Basel). 2023 Jun 9;16(6):860. doi: 10.3390/ph16060860. PMID: 37375807; PMCID: PMC10301634. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10301634/ (Full text)

Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up

Abstract:

Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry.

In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization.

The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome.

Source: Babicki M, Kapusta J, Pieniawska-Śmiech K, Kałuzińska-Kołat Ż, Kołat D, Mastalerz-Migas A, Jankowski P, Chudzik M. Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up. Viruses. 2023 Jun 13;15(6):1370. doi: 10.3390/v15061370. PMID: 37376668; PMCID: PMC10304551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304551/ (Full text)

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

Abstract:

Long COVID, also known for post-acute sequelae of COVID-19, describes the people who have the signs and symptoms that continue or develop after the acute COVID-19 phase. Long COVID patients suffer from an inflammation or host responses towards the virus approximately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an uncharacterized duration.

Anyone infected with COVID-19 before could experience long-COVID conditions, including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early. People with long COVID may experience health problems from different types and combinations of symptoms over time, such as fatigue, dyspnea, cognitive impairments, and gastrointestinal (GI) symptoms (e.g., nausea, vomiting, diarrhea, decreased or loss of appetite, abdominal pain, and dysgeusia). The critical role of the microbiome in these GI symptoms and long COVID were reported in clinical patients and experimental models.

Here, we provide an overall view of the critical role of the GI tract and microbiome in the development of long COVID, including the clinical GI symptoms in patients, dysbiosis, viral-microbiome interactions, barrier function, and inflammatory bowel disease patients with long COVID. We highlight the potential mechanisms and possible treatment based on GI health and microbiome. Finally, we discuss challenges and future direction in the long COVID clinic and research.

Source: Zhang J, Zhang Y, Xia Y, Sun J. Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19. Genes Dis. 2023 Jun 19. doi: 10.1016/j.gendis.2023.03.034. Epub ahead of print. PMID: 37362775; PMCID: PMC10278891. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278891/ (Full text)

In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting

Abstract:

In vitro, ACE2 translocates to the nucleus to induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor of nuclear ACE2 (NACE2i) inhibits viral replication two days after SARS-CoV-2 infection. Moreover, the peptide also prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles.

NACE2i treatment increases the levels of the active histone mark, H3K27ac, restores host translation in infected hamster bronchiolar cells, and leads to an enrichment in methylated ACE2 in hamster bronchioles and lung macrophages, a signature associated with virus protection. In addition, ACE2 methylation is increased in myeloid cells from vaccinated patients and associated with reduced SARS-CoV-2 spike protein expression in monocytes from individuals who have recovered from infection.

This protective epigenetic scarring of ACE2 is associated with a reduced latent viral reservoir in monocytes/macrophages and enhanced immune protection against SARS-CoV-2. Nuclear ACE2 may represent a therapeutic target independent of the variant and strain of viruses that use the ACE2 receptor for host cell entry.

Source: Tu WJ, Melino M, Dunn J, McCuaig RD, Bielefeldt-Ohmann H, Tsimbalyuk S, Forwood JK, Ahuja T, Vandermeide J, Tan X, Tran M, Nguyen Q, Zhang L, Nam A, Pan L, Liang Y, Smith C, Lineburg K, Nguyen TH, Sng JDJ, Tong ZWM, Chew KY, Short KR, Le Grand R, Seddiki N, Rao S. In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting. Nat Commun. 2023 Jun 27;14(1):3680. doi: 10.1038/s41467-023-39341-4. PMID: 37369668; PMCID: PMC10300102. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300102/ (Full text)

Interventions to support mental health in people with long COVID: a scoping review

Abstract:

Introduction: Long COVID (LC) is a multisystem disease with symptoms lasting weeks or months beyond the acute COVID-19 infection. Several manifestations are reported by people with LC, including effects on mental health, with varying degrees of psychological distress and disturbances to daily activities. Research conducted to identify effective interventions to support mental health among people with LC has been limited by the breadth and scope of studies.

Aim: This review aims to identify interventions being tested to support mental health of people with LC.

Methods: A scoping review was conducted by searching five databases for articles published between January 2020 and early October 2022 to identify research evaluating interventions focused on improving mental health symptoms associated with LC. Results from all sources were checked for eligibility by two reviewers, and agreements were resolved by discussion. Gray literature and reference list of included studies and relevant reviews were scrutinised to identify any additional studies. Data extraction was conducted by one reviewer and checked by another reviewer for accuracy.

Results: Of the 940 studies identified, 17 were included, the design of which varied but included mainly case studies (n = 6) and clinical trials (n = 5). Several interventions were described, ranging from single interventions (e.g., pharmacologic) to more holistic, comprehensive suites of services (pharmacologic and non-pharmacologic). Several mental health outcomes were measured, mostly anxiety and depression. All included studies were reported to be associated with improvements in participants’ mental health outcomes.

Conclusion: This scoping review identified studies reporting on a variety of interventions to support mental health among people with LC. Although positive changes were reported by all studies, some were case studies and thus their findings must be interpreted with caution. There is a need for more research to be conducted to identify the impact of interventions on mental health of people with LC.

Source: Al-Jabr H, Hawke LD, Thompson DR, Clifton A, Shenton M, Castle DJ, Ski CF. Interventions to support mental health in people with long COVID: a scoping review. BMC Public Health. 2023 Jun 20;23(1):1186. doi: 10.1186/s12889-023-16079-8. PMID: 37340400; PMCID: PMC10280822. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280822/ (Full text)