Tag: covid-19

Clinical trials on the pharmacological treatment of long COVID: A systematic review

Abstract:

The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also known as post-acute coronavirus disease 19 (COVID-19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome.

A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022. This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVID or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction.

Most of the interventions are related to the mechanisms causing the individual symptoms. Although the six published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability. This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials.

Source: Chee YJ, Fan BE, Young BE, Dalan R, Lye DC. Clinical trials on the pharmacological treatment of long COVID: A systematic review. J Med Virol. 2022 Nov 8:e28289. doi: 10.1002/jmv.28289. Epub ahead of print. PMID: 36349400. https://pubmed.ncbi.nlm.nih.gov/36349400/

Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes

Abstract:

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as “long-COVID” or “post-COVID-19” syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge.

A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms.

Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories.

Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.

Source: Spinicci M, Graziani L, Tilli M, Nkurunziza J, Vellere I, Borchi B, Mencarini J, Campolmi I, Gori L, Giovannoni L, Amato C, Livi L, Rasero L, Fattirolli F, Marcucci R, Giusti B, Olivotto I, Tomassetti S, Lavorini F, Maggi L, Annunziato F, Marchionni N, Zammarchi L, Bartoloni A. Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes. Viruses. 2022 Oct 27;14(11):2367. doi: 10.3390/v14112367. PMID: 36366465; PMCID: PMC9698829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698829/ (Full text)

The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome

Background: Fatigue is common after viral infections, including SARS-CoV-2.1 Our purpose was to report the prevalence and impact of persistent fatigue 6 months after SARS-CoV-2 infection, considering post-exertional malaise2 and criteria for chronic fatigue syndrome.3

Methods: Since March 2020, individuals tested for SARS-CoV-2 at the Geneva University Hospitals outpatient testing center benefit from remote ambulatory follow-up (COVICARE). This study included all individuals tested between March 2020 and December 2020 and whose follow-up was at 6 months or more after their test date.

Follow-up included questions about the prevalence of symptoms (yes/no) and their severity using a Likert scale (mild, moderate, or severe). Fatigue was assessed using the Eastern Cooperative Oncology Group (ECOG) scale and the Chalder fatigue scale. The Chalder fatigue scale was scored using the 4-item Likert and the bimodal scoring schemes. A score of ≥ 4 on bimodal scoring indicated severe fatigue.

The DePaul brief questionnaire was used to identify post-exertional malaise and criteria for chronic fatigue syndrome.

The Sheehan Disability Scale was used to assess functional impairment. Reduced work capacity was defined as missing days off work or having a reduced productivity on the Sheehan disability scale.

Comorbidities were considered present if pre-existing prior to SARS-CoV-2 infection. Statistical analysis included descriptive comparisons of percentages using chi-square tests and Student’s t test.

Results: Overall, 5515 individuals participated in this study (response rate 70.7%), with 5406 participants at 6 months or more after their test date. A total of 1497 (27.7%) participants had a documented positive SARS-CoV-2 test and were ultimately included in the study. The median time for follow-up was 225 days (interquartile range 207–398). Respectively, fatigue was reported by 17.2%, post-exertional malaise by 8.2%, and the presence of criteria for chronic fatigue syndrome by 1.1% of SARS-CoV-2-positive individuals, compared to 8.9%, 3.5%, and 0.5% of SARS-CoV-2-negative individuals. Characteristics are presented in Table 1.

Out of SARS-CoV-2-positive participants with fatigue (n = 258), 35.3% had moderate to severe limitations on the ECOG scale, and 83.0% had a score ≥ 4 on the Chalder fatigue scale. The Chalder fatigue scale revealed a mean score of 19 out of 33, SD 5.4, and a mean score of 6.7 out of 11, SD 3.3 using bimodal scoring. After adjusting for age and sex, 47.7% of SARS-CoV-2-positive individuals with fatigue at 6 months or more had the frequency and severity criteria for post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome.

Individuals had a higher prevalence of insomnia, cognitive impairment, headaches, generalized pain, functional impairment, reduced work capacity, and decreased physical activity, after SARS-CoV-2 infection. The prevalence of these sequelae was adjusted for age and sex and was increasingly higher with severe fatigue, with post-exertional malaise, or when criteria for chronic fatigue syndrome were present (Fig. 1).

Discussion: Fatigue is the most common and persistent post-COVID symptom. The spectrum of fatigue severity in post-COVID individuals ranges from feeling tired to having severe fatigue, post-exertional malaise, or criteria for chronic fatigue syndrome with an increasing impact on health, functional capacity, and physical activity.

Almost half of individuals experiencing fatigue at 6 months after the infection had post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome, prompting physicians to consider pacing as a management option, in the absence of other treatment options at this stage. SARS-CoV-2 infection was positively associated with fatigue and post-exertional malaise.

Results showed that individuals with fatigue were more likely to be vaccinated. This was partially explained by the baseline distribution as older individuals and those with more comorbidities were more likely to get vaccinated.

Results compare to recent reviews showing an overlap between post-COVID condition and chronic fatigue syndrome. Our study graded post-COVID fatigue by severity in correlation with functional capacity, and showed the high prevalence of post-exertional malaise.

Limitations include the self-reported nature of this follow-up with individuals infected in 2020 and follow-up in 2021, lacking comparisons to individuals infected with other variants. Additionally, this study considered having received at least 2 doses as full vaccination, a concept that continues to evolve with time.

Physicians, employers, and insurance companies should address fatigue on a spectrum, accounting for the correlated functional impairment, decreased activity levels, and potentially poorer quality of life.

Source: Nehme M, Chappuis F, Kaiser L, Assal F, Guessous I. The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome. J Gen Intern Med. 2022 Nov 10:1–5. doi: 10.1007/s11606-022-07882-x. Epub ahead of print. PMID: 36357723; PMCID: PMC9648889. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648889/ (Full text)

 

Is SARS-CoV-2 the only cause of long-COVID?

Abstract:

Around 10% of adults infected with SARS-CoV-2 that survive a first episode of COVID-19 appear to experience long-term clinical manifestations. The signs and symptoms of this post-acute COVID-19 syndrome (PACS) include fatigue, dyspnea, joint pain, myalgia, chest pain, cough, anosmia, dysgeusia, headache, depression, anxiety, memory loss, concentration difficulties, and insomnia. These sequelae remind the constellation of clinical manifestations previously recognized as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS).

This condition has been described following distinct infectious events, mostly acute viral illnesses. In this way, the pathophysiology of PACS might overlap with mechanisms involved in other post-infectious fatigue syndromes. The risk of PACS is more frequent in women than men. Additional host genetic factors could be involved.

There is a dysregulation of multiple body organs and systems, involving the immune system, the coagulation cascade, endocrine organs, autonomic nervous system, microbiota-gut-brain axis, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, etc. Hypothetically, an abnormal response to certain infectious agents could trigger the development of postinfectious fatigue syndromes.

Source: Pintos-Pascual I, Moreno-Torres V, Ibánez-Estéllez F, Corrales-Rodriguez P, Treviño A, Corpas M, Corral O, Soriano V, de Mendoza C. Is SARS-CoV-2 the only cause of long-COVID? AIDS Rev. 2022 Nov 25. doi: 10.24875/AIDSRev.22000025. Epub ahead of print. PMID: 36427058.  https://pubmed.ncbi.nlm.nih.gov/36427058/

Post–COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients

Abstract:

Importance  Identification of long-term post–COVID-19 symptoms among hospitalized and nonhospitalized patients is needed.

Objective  To compare the presence of post–COVID-19 symptoms 2 years after acute SARS-CoV-2 infection between hospitalized and nonhospitalized patients.

Design, Setting, and Participants  A cross-sectional cohort study was conducted at 2 urban hospitals and general practitioner centers from March 20 to April 30, 2020, among 360 hospitalized patients and 308 nonhospitalized patients with acute SARS-CoV-2 infection during the first wave of the pandemic. Follow-up was conducted 2 years later.

Main Outcomes and Measures  Participants were scheduled for a telephone interview 2 years after acute infection. The presence of post–COVID-19 symptoms was systematically assessed, with particular attention to symptoms starting after infection. Hospitalization and clinical data were collected from medical records. Between-group comparisons and multivariate logistic regressions were conducted.

Results  A total of 360 hospitalized patients (162 women [45.0%]; mean [SD] age, 60.7 [16.1] years) and 308 nonhospitalized patients (183 women [59.4%]; mean [SD] age, 56.7 [14.7] years) were included. Dyspnea was more prevalent at the onset of illness among hospitalized than among nonhospitalized patients (112 [31.1%] vs 36 [11.7%]; P < .001), whereas anosmia was more prevalent among nonhospitalized than among hospitalized patients (66 [21.4%] vs 36 [10.0%]; P = .003). Hospitalized patients were assessed at a mean (SD) of 23.8 (0.6) months after hospital discharge, and nonhospitalized patients were assessed at a mean (SD) of 23.4 (0.7) months after the onset of symptoms. The number of patients who exhibited at least 1 post–COVID-19 symptom 2 years after infection was 215 (59.7%) among hospitalized patients and 208 (67.5%) among nonhospitalized patients (P = .01). Among hospitalized and nonhospitalized patients, fatigue (161 [44.7%] vs 147 [47.7%]), pain (129 [35.8%] vs 92 [29.9%]), and memory loss (72 [20.0%] vs 49 [15.9%]) were the most prevalent post–COVID-19 symptoms 2 years after SARS-CoV-2 infection. No significant differences in post–COVID-19 symptoms were observed between hospitalized and nonhospitalized patients. The number of preexisting medical comorbidities was associated with post–COVID-19 fatigue (odds ratio [OR], 1.93; 95% CI, 1.09-3.42; P = .02) and dyspnea (OR, 1.91; 95% CI, 1.04-3.48; P = .03) among hospitalized patients. The number of preexisting medical comorbidities (OR, 3.75; 95% CI, 1.67-8.42; P = .001) and the number of symptoms at the onset of illness (OR, 3.84; 95% CI, 1.33-11.05; P = .01) were associated with post–COVID-19 fatigue among nonhospitalized patients.

Conclusions and Relevance  This cross-sectional study suggested the presence of at least 1 post–COVID-19 symptom in 59.7% of hospitalized patients and 67.5% of nonhospitalized patients 2 years after infection. Small differences in symptoms at onset of COVID-19 were identified between hospitalized and nonhospitalized patients. Post–COVID-19 symptoms were similar between hospitalized and nonhospitalized patients; however, lack of inclusion of uninfected controls limits the ability to assess the association of SARS-CoV-2 infection with overall and specific post–COVID-19 symptoms 2 years after acute infection. Future studies should include uninfected control populations.

Source: Fernández-de-las-Peñas, Martín-Guerrero, Hernández-Barrera. Post–COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients. November 15, 2022. doi:10.1001/jamanetworkopen.2022.42106 (Full text)

Association between long COVID symptoms and employment status

Abstract:

Background: Symptoms of Coronavirus-19 (COVID-19) infection persist beyond 2 months in a subset of individuals, a phenomenon referred to as long COVID, but little is known about its functional correlates and in particular the relevance of neurocognitive symptoms.

Method: We analyzed a previously-reported cohort derived from 8 waves of a nonprobability-sample internet survey called the COVID States Project, conducted every 4-8 weeks between February 2021 and July 2022. Primary analyses examined associations between long COVID and lack of full employment or unemployment, adjusted for age, sex, race and ethnicity, education, urbanicity, and region, using multiple logistic regression with interlocking survey weights.

Results: The cohort included 15,307 survey respondents ages 18-69 with test-confirmed COVID-19 at least 2 months prior, of whom 2,236 (14.6%) reported long COVID symptoms, including 1,027/2,236 (45.9%) reporting either ‘brain fog’ or impaired memory. Overall, 1,418/15,307 (9.3%) reported being unemployed, including 276/2,236 (12.3%) of those with long COVID and 1,142/13,071 (8.7%) of those without; 8,228 (53.8%) worked full-time, including 1,017 (45.5%) of those with long COVID and 7,211 (55.2%) without. In survey-weighted regression models, presence of long COVID was associated with being unemployed (crude OR 1.44, 95% CI 1.20-1.72; adjusted OR 1.23, 95% CI 1.02-1.48), and with lower likelihood of working full-time (crude OR 0.73, 95% CI 0.64-0.82; adjusted OR 0.79, 95% CI 0.70 -0.90). Among individuals with long COVID, the presence of cognitive symptoms — either brain fog or impaired memory — was associated with lower likelihood of working full time (crude OR 0.71, 95% CI 0.57-0.89, adjusted OR 0.77, 95% CI 0.61-0.97).

Conclusion: Long COVID was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. Presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to respond to long COVID, and particularly the associated neurocognitive symptoms.

Source: Kristin Lunz Trujillo, Roy H Perlis, Alauna Safarpour, Mauricio Santillana, Katherine Ognyanova, James Druckman, David Lazer. Association between long COVID symptoms and employment status. medRxiv 2022.11.17.22282452; doi: https://doi.org/10.1101/2022.11.17.22282452 (Full text available as PDF file)

HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms

Abstract:

Due to the wide scope and persistence of COVID-19´s pandemic, post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. SARS-CoV-2, in line with other infectious agents, has the capacity to activate dormant human endogenous retroviral sequences ancestrally integrated in human genomes (HERVs). This activation was shown to relate to aggravated COVID-19 patient´s symptom severity.

Despite our limited understanding of how HERVs are turned off upon infection clearance, or how HERVs mediate long-term effects when their transcription remains aberrantly on, the participation of these elements in neurologic disease, such as multiple sclerosis, is already settling the basis for effective therapeutic solutions. These observations support an urgent need to identify the mechanisms that lead to HERV expression with SARS-CoV-2 infection, on the one hand, and to answer whether persistent HERV expression exists in post-COVID-19 condition, on the other.

The present study shows, for the first time, that the HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Moreover, increased anti-SARS-CoV-2 immunoglobulins in post-COVID-19 condition, particularly high anti-SARS-CoV-2 immunoglobulin levels of the E isotype (IgE), seem to strongly correlate with deteriorated patient physical function (r=-0.8057, p<0.01).

These results indicate that HERV-W ENV antigenemia and anti-SARS-CoV-2 IgE serology should be further studied to better characterize post-COVID-19 condition pathogenic drivers potentially differing in subsets of patients with various symptoms. They also point out that such biomarkers may serve to design therapeutic options for precision medicine in post-COVID-19 condition.

Source: Giménez-Orenga K, Pierquin J, Brunel J, Charvet B, Martín-Martínez E, Perron H, Oltra E. HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms. Front Immunol. 2022 Oct 27;13:1020064. doi: 10.3389/fimmu.2022.1020064. PMID: 36389746; PMCID: PMC9647063.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647063/ (Full text)

Co-Ultramicronized Palmitoylethanolamide/Luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome

Abstract:

Objective: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI).

Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI.

Methods: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700mg + 70mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity.

Results: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected.

Conclusions: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients.

Significance: This study confirms altered physiology of the motor cortex in long Covid and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Source: Viviana Versace, Paola Ortelli, Sabrina Dezi, Davide Ferrazzoli, Alessia Alibardi, Ilenia Bonini, Michael Engl, Roberto Maestri, Martina Assogna, Valentina Ajello, Elke Pucks-Faes, Leopold Saltuari, Luca Sebastianelli, Markus Kofler, Giacomo Koch. Co-Ultramicronized Palmitoylethanolamide/Luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome. Clinical Neurophysiology, 2022, ISSN 1388-2457, https://doi.org/10.1016/j.clinph.2022.10.017. https://www.sciencedirect.com/science/article/pii/S1388245722009385 (Full text)

 

The role of gut microbiota in etiopathogenesis of long COVID syndrome

To the editor.

COVID-19, a novel infectious disease caused by SARS-CoV-2 first emerged on November 17, 2019 had a high fatality rate and affected millions of people around the world [1]. The involvement of lung gut axis and the identification of viral RNA in feces of infected patients has drawn attention to a possible fecal-oral transmission route of SARS-CoV-2 [2].

Recent research shows a potential connection between long-term COVID-19 and dysbiosis of the gut flora. Long COVID-19 infection or post-acute COVID-19 syndrome is seen after weeks or months after the initial COVID-19 infection is characterized by complications and lingering symptoms such as fatigue, muscle weakness, and sleeplessness. Up to 3 out of 4 individuals report at least one symptom six months after recovering from COVID-19 infection, making it a relatively prevalent condition [3]. Long COVID may develop as a result of a heightened immune response, cell damage, or physiological effects of COVID-19 infection.

The gut microbiome, the billions of bacteria, fungus, and other microbes that live in the digestive tract, has been linked to COVID-19 severity and may possibly have an impact on the healing process, according to a growing body of research [4]. Researchers at the Chinese University of Hong Kong’s Center for Gut Microbiota Research discovered a clue in 2020.

When compared to healthy controls, persons with COVID-19 had unique changes in their gut microbiota, or the population of bacteria that live in their gut [5]. Early reports from Wuhan suggested that 2–10% of COVID-19 patients experienced gastrointestinal (GI) symptoms, such as diarrhoea, however a recent meta-analysis found that up to 20% of patients with COVID-19 had GI symptoms. SARS-CoV-2 virus was found in anal swabs and stool samples in over half of COVID-19 patients, suggesting that the digestive tract could be an extrapulmonary location for virus multiplication and activity [6, 7].

Read the rest of this article HERE.

Source: Kaushik P, Kumari M, Singh NK, Suri A. The role of gut microbiota in etiopathogenesis of long COVID syndrome. Horm Mol Biol Clin Investig. 2022 Nov 1. doi: 10.1515/hmbci-2022-0079. Epub ahead of print. PMID: 36317311. https://www.degruyter.com/document/doi/10.1515/hmbci-2022-0079/html (Full text)

Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study

Abstract:

Objective: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID.

Design: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages.

Setting: Israeli general practice.

Subjects: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and ,936 without a history of SARS-CoV-2 infection.

Main outcome measures: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms.

Results: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness.

Conclusion: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.

Key Points

Long-COVID has emerged as a significant health problem with a serious impact on normal daily function• Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.• Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.• Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.

Source: Adler L, Gazit S, Pinto Y, Perez G, Mizrahi Reuveni M, Yehoshua I, Hoffman R, Azuri J, Patalon T. Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study. Scand J Prim Health Care. 2022 Oct 31:1-8. doi: 10.1080/02813432.2022.2139480. Epub ahead of print. PMID: 36314555. https://www.tandfonline.com/doi/full/10.1080/02813432.2022.2139480 (Full text)