Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study

Abstract:

Objective: To define macro symptoms of long COVID and to identify predictive factors, with the aim of preventing the development of the long COVID syndrome.

Design: A single-centre longitudinal prospective cohort study conducted from May 2020 to October 2022.

Setting: The study was conducted at Luigi Sacco University Hospital in Milan (Italy). In May 2020, we activated the ARCOVID (Ambulatorio Rivalutazione COVID) outpatient service for the follow-up of long COVID.

Participants: Hospitalised and non-hospitalised patients previously affected by COVID-19 were either referred by specialists or general practitioners or self-referred.

Intervention: During the first visit, a set of questions investigated the presence and the duration of 11 symptoms (palpitations, amnesia, headache, anxiety/panic, insomnia, loss of smell, loss of taste, dyspnoea, asthenia, myalgia and telogen effluvium). The follow-up has continued until the present time, by sending email questionnaires every 3 months to monitor symptoms and health-related quality of life.

Primary and secondary outcome measures: Measurement of synthetic scores (aggregation of symptoms based on occurrence and duration) that may reveal the presence of long COVID in different clinical macro symptoms. To this end, a mixed supervised and empirical strategy was adopted. Moreover, we aimed to identify predictive factors for post-COVID-19 macro symptoms.

Results: In the first and second waves of COVID-19, 575 and 793 patients (respectively) were enrolled. Three different post-COVID-19 macro symptoms (neurological, sensorial and physical) were identified. We found significant associations between post-COVID-19 symptoms and (1) the patients’ comorbidities, and (2) the medications used during the COVID-19 acute phase. ACE inhibitors (OR=2.039, 95% CI: 1.095 to 3.892), inhaled steroids (OR=4.08, 95% CI: 1.17 to 19.19) and COVID therapies were associated with increased incidence of the neurological macro symptoms. Age (OR=1.02, 95% CI: 1.01 to 1.04), COVID-19 severity (OR=0.42, 95% CI: 0.21 to 0.82), number of comorbidities (OR=1.22, 95% CI: 1.01 to 1.5), metabolic (OR=2.52, 95% CI: 1.25 to 5.27), pulmonary (OR=1.87, 95% CI: 1.10 to 3.32) and autoimmune diseases (OR=4.57, 95% CI: 1.57 to 19.41) increased the risk of the physical macro symptoms.

Conclusions: Being male was the unique protective factor in both waves. Other factors reflected different medical behaviours and the impact of comorbidities. Evidence of the effect of therapies adds valuable information that may drive future medical choices.

Source: Borgonovo F, Lovaglio PG, Mariani C, Berta P, Cossu MV, Rizzardini G, Vittadini G, Capetti AF. Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study. BMJ Open. 2024 Feb 6;14(2):e075185. doi: 10.1136/bmjopen-2023-075185. PMID: 38320835; PMCID: PMC10860093. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860093/ (Full text)

High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study

Abstract:

The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections.

The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection.

In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC.

In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.

Source: Villa A, Milito C, Deiana CM, Gambier RF, Punziano A, Buso H, Bez P, Lagnese G, Garzi G, Costanzo G, Giannuzzi G, Pagnozzi C, Dalm VASH, Spadaro G, Rattazzi M, Cinetto F, Firinu D. High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study. J Clin Immunol. 2024 Feb 6;44(2):59. doi: 10.1007/s10875-024-01656-2. PMID: 38319477; PMCID: PMC10847195. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847195/ (Full text)

COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children

Abstract:

In children, the factors that influence COVID-19 disease and its medium- and long-term effects are little known. Our investigation sought to evaluate the presence of comorbidity factors associated with respiratory long COVID manifestations in children and to study ultrasound abnormalities following SARS-CoV-2 infection. Children, who arrived at the ‘Respiratory Diseases of Pediatric Interest Unit’ at the Department of Woman, Child, and General and Specialized Surgery of the University of Campania ‘Luigi Vanvitelli’, were selected during the timeframe from September 2021 to October 2022.
The children were diagnosed with a SARS-CoV-2 infection that occurred at least one month before the visit. All patients followed a COVID-19 follow-up protocol, developed by the Italian Society of Pediatric Respiratory Diseases (SIMRI), which included: collection of data regarding SARS-CoV-2 illness and history of known respiratory and allergic diseases; physical examination; BMI assessment; baseline spirometry and after bronchodilation test; six-minute walking test; and lung ultrasound (LUS).
In a cohort of 104 participants with respiratory long COVID symptoms (64.7% male, average age 8.92 years), 46.1% had fever with other symptoms, and 1% required hospitalization. BMI analysis showed 58.4% of the cohort was overweight. The LUS was positive in 27.0% of cases. A significant BMI association was observed with COVID-19 symptoms and LUS score (p-value < 0.05). No associations were found with asthma or atopy.
Source: Indolfi C, Klain A, Dinardo G, D’Addio E, Ferrara S, Decimo F, Ciprandi G, Tosca MA, Miraglia del Giudice M. COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children. Children. 2024; 11(2):166. https://doi.org/10.3390/children11020166 https://www.mdpi.com/2227-9067/11/2/166 (Full text)

Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study

Abstract:

Background: Adults and children can develop post-Covid-19 condition (PCC) (also referred to as Long Covid). However, existing evidence is scarce, partly due to a lack of a standardised case definition, short follow up duration, and heterogenous study designs, resulting in wide variation of reported outcomes. The primary aim of this study was to characterise risk factors for PCC and longitudinal rates of recovery in a cohort of children and young people using a standardised protocol.

Methods: We performed a prospective “disease-based” cohort study between 01/02/2020 to 31/10/2022 including children aged 0-18 years old, with a previous diagnosis of Covid-19. Children with microbiologically confirmed SARS-CoV-2 infection, were invited for an in-clinic follow-up assessment at a paediatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12- and 18-months post-onset). PCC was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. The statistical association between categorical variables was obtained by Chi-squared tests or Fisher’s exact tests. Multivariable logistic regressions are presented using odds ratios (OR) and 95% confidence interval (CI). Survival analysis was conducted using the Kaplan-Meier method.

Findings: 1243 children were included, median age: 7.5 (4-10.3) years old; 575 (46.3%) were females. Of these, 23% (294/1243) were diagnosed with PCC at three months post-onset. Among the study population, 143 patients remained symptomatic at six months, 38 at 12 months, and 15 at 18 months follow up evaluation. The following risk factors were associated with PCC: >10 years of age (OR 1.23; 95% CI 1.18-1.28), comorbidities (OR 1.68; 95% CI 1.14-2.50), and hospitalisation during the acute phase (OR 4.80; 95%CI 1.91-12.1). Using multivariable logistic regression, compared to the Omicron variant, all other variants were significantly associated with PCC at 3 and 6 months. At least one dose of vaccine was associated with a reduced, but not statistically significant risk of developing PCC.

Interpretation: In our study, acute-phase hospitalisation, pre-existing comorbidity, being infected with pre-Omicron variants and older age were associated with a higher risk of developing PCC. Most children recovered over time, but one-in-twenty of those with PCC at three months reported persistent symptoms 18 months post-Sars-CoV-2 infection. Omicron infection was associated with shorter recovery times. We did not find a strong protective effect of vaccination on PCC development. Although our cohort cannot be translated to all Italian children with PCC as more nationwide studies are needed, our findings highlight the need of new strategies to prevent and treat pediatric PCC are needed.

Funding: This study has been funded by Pfizer non-competitive grant, granted to DB (# 65925795).

Source: Morello R, Mariani F, Mastrantoni L, De Rose C, Zampino G, Munblit D, Sigfrid L, Valentini P, Buonsenso D. Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study. EClinicalMedicine. 2023 May;59:101961. doi: 10.1016/j.eclinm.2023.101961. Epub 2023 Apr 14. PMID: 37073325; PMCID: PMC10101848. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00138-4/fulltext (Full text)

Self-reported olfactory and gustatory dysfunctions in COVID-19 patients: a 1-year follow-up study in Foggia district, Italy

Abstract:

Background: From the initial stages of the pandemic in early 2020, COVID-19-related olfactory and gustatory dysfunctions have been widely reported and are emerging as one of the most frequent long-term sequelae of SARS-CoV-2 infection. However, data regarding the long-term recovery of the sense of smell and taste are lacking. This study aimed to characterize the evolution up to one year after the diagnosis of self-reported olfactory and gustatory dysfunctions in COVID-19 cases.

Methods: Based on the data of the active surveillance platform of the Apulia region, Italy, we selected the residents of Foggia district who were confirmed positive for SARS-CoV-2 from March 1st to June 16th, 2020, and home-quarantined with paucisymptomatic-to-mild clinical presentation. Self-reported olfactory and gustatory dysfunctions were recorded at baseline through a survey of dichotomous questions. The evolution of these symptoms at approximately one year was prospectively assessed via telephone by the validated sino-nasal outcome test 22 (SNOT-22, Italian version).

Results: Among the 1,175 COVID-19 cases notified in the Foggia district during the first epidemic wave, 488 had paucisymptomatic-to-mild clinical presentation. Of these, 41.2% (n = 201, 95% confidence interval [CI] 36.8-45.7%) reported at least one sensory dysfunction. A total of 178 to 201 (88.5%) patients agreed to participate in the follow-up survey. According to the SNOT-22 results, the persistence of a sensory dysfunction was observed in the 29.8% (n = 53, 95% CI 23.2-37.1%) of them. Particularly, loss of smell persisted in 25.8% (n = 46, 95% CI 19.6-32.9%), loss of taste in 21.3% (n = 38, 95% CI 15.6-28.1%), loss of both in 17.4% (n = 31, 95% CI 12.2-23.8%) of participants in the follow-up. The rates of full recovery increased over time: from 59% at 30 days to 71.9% at 90 days for the sense of smell; from 61.3% at 30 days to 74.7% at 90 days for the sense of taste.

Conclusions: The persistence of COVID-19-related olfactory and gustatory dysfunctions up to 12 months after the disease onset in a noteworthy proportion (approximately 3 out of 10) of patients with paucisymptomatic-to-mild clinical presentation deserves further investigations due to its possible pathophysiological implications and impact on the quality of life.

Source: Fortunato F, Martinelli D, Iannelli G, Milazzo M, Farina U, Di Matteo G, De Nittis R, Ascatigno L, Cassano M, Lopalco PL, Prato R. Self-reported olfactory and gustatory dysfunctions in COVID-19 patients: a 1-year follow-up study in Foggia district, Italy. BMC Infect Dis. 2022 Jan 22;22(1):77. doi: 10.1186/s12879-022-07052-8. PMID: 35065619; PMCID: PMC8783175. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783175/ (Full text)

Cardiovascular characteristics of chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) commonly exhibit orthostatic intolerance. Abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli was previously described in numerous studies. The aim of the current study was to describe cardiological and clinical characteristics of Italian patients with CFS. All of the patients were of Caucasian ethnicity and had been referred to our center, the Cardiology Department of the University Hospital of Pavia (Pavia, Italy) with suspected CFS.

A total of 44 patients with suspected CFS were included in the present study and the diagnosis was confirmed in 19 patients according to recent clinical guidelines. The characteristics at baseline of the population confirm findings from various previous reports regarding the prevalence in females with a female to male ratio of 4:1, the age of onset of the pathology and the presence of previous infection by the Epstein-Barr virus, cytomegalovirus and other human herpesviruses.

Despite the current data indicating that the majority of the cardiological parameters investigated are not significantly different in patients with and without CFS, a significant association between the disease and low levels of blood pressure was identified. Other pilot studies revealed a higher prevalence of hypotension and orthostatic intolerance in patients with CFS. Furthermore, many of the CFS symptoms, including fatigue, vertigo, decreased concentration, tremors and nausea, may be explained by hypotension.

Source: Sara Bozzini, Andrea Albergati, Enrica Capelli, Lorenzo Lorusso, Carmine Gazzaruso, Gabriele Pelissero, Colomba Falcone. Cardiovascular characteristics of chronic fatigue syndrome. Biomedical Reports. Published online on: November 28, 2017     https://doi.org/10.3892/br.2017.1024 https://www.spandidos-publications.com/10.3892/br.2017.1024

Chronic fatigue syndrome: Features of a population of patients from northern Italy

Abstract:

In this study we analyzed the clinical features of a population of Italian patients with chronic fatigue syndrome (CFS) diagnosed according to the CDC-1994 criteria. The aim was to investigate CFS patients and their relatives, in order to search for events related to the onset of the disease and to identify correlations with other diseases. The analysis was carried out by examining medical records belonging to 82 patients suffering from the syndrome. The documentation was collected between 2008 and 2011 and provided by the non-profit Italian organization AMCFS (Associazione Malati di CFS). The influence of gender on the age of onset and association with potential risk factors were investigated in patients and in their relatives. From the results a significant correlation between the age of onset and autoimmunity was observed.

© The Author(s) 2015.

 

Source: Capelli E, Lorusso L, Ghitti M, Venturini L, Cusa C, Ricevuti G. Chronic fatigue syndrome: Features of a population of patients from northern Italy. Int J Immunopathol Pharmacol. 2015 Mar;28(1):53-9. Doi: 10.1177/0394632015572074. https://www.ncbi.nlm.nih.gov/pubmed/25816406

 

An Italian study on health-related quality of life and fatigue in patients with chronic fatigue syndrome and patients with chronic HCV virus infection: similarities and differences

Abstract:

Severe fatigue and a significantly reduced health-related quality of life (HRQoL) have been described in patients with chronic fatigue syndrome (CFS) in comparison with patients affected by chronic hepatitis C (CHC) and other chronic medical conditions. We examined 39 CFS and 49 CHC patients to explore whether fatigue and a poor HRQoL represent a greater medical and social problem in CFS than in CHC.

The severity of fatigue and the HRQoL were assessed using the Fatigue Impact Scale (FIS) and the Health Status Questionnaire Short Form-36 (SF-36), respectively. The statistical analysis showed both a higher score of fatigue and a lower HRQoL in CFS than in CHC patients. Furthermore, in CHC patients the FIS evaluation showed a significantly reduced score of the psychosocial domain in comparison with the other domains. Multivariate linear regression analysis revealed female gender as the most important positive variable in chronic hepatitis C patients for total score of FIS.

In conclusion, CFS was associated with a severe and disabling fatigue and an impaired HRQOL. In particular, both fatigue and all aspects of HRQOL perceived by CFS patients were significantly impaired compared to CHC patients. Consequently, management of fatigue should be considered a priority in order to improve HRQOL in CFS patients. In CHC patients the impact of fatigue on HRQoL was less significant than in CFS patients, even though the FIS evaluation showed a significant impairment of the psychosocial domain.

 

Source: Racciatti D, Gorgoretti V, Sepede G, Gambi F, Pizzigallo E. An Italian study on health-related quality of life and fatigue in patients with chronic fatigue syndrome and patients with chronic HCV virus infection: similarities and differences. Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):673-81. https://www.ncbi.nlm.nih.gov/pubmed/21978699

 

Demographic and clinical aspects of an Italian patient population with chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of this study was to investigate demographic and clinical aspects of a group of Italian patients with Chronic Fatigue Syndrome (CFS) which have not yet been described, in order to compare them with International literature, and to better define certain clinical aspects of the syndrome with respect to the Fukuda et al. case definition.

METHODS: A detailed questionnaire was sent to patients with certified CFS diagnosed in a referral center and the data were collected two weeks later.

RESULTS AND CONCLUSIONS: Besides persistent fatigue, a clinical syndrome with infectious, neurological and rheumatological characteristics is outlined from the data. Demographic characteristics of Italian patients are very similar to those described in international literature. Therapy has yet to be validated with evidence-based studies in Italy. Studies on the prevalence of CFS in Italy are lacking and would be useful to better define the syndrome in this Mediterranean population.

 

Source: Carlo-Stella N, Cuccia M. Demographic and clinical aspects of an Italian patient population with chronic fatigue syndrome. Reumatismo. 2009 Oct-Dec;61(4):285-9. http://www.reumatismo.org/index.php/reuma/article/view/reumatismo.2009.285/440 (Full article)

 

Chronic fatigue syndrome: a review

Abstract:

Chronic fatigue syndrome is a relatively unknown and underdiagnosed entity in Italy where its epidemiology remains uncertain, as well as its etiology, although it causes important disability in those affected. Classification criteria by Fukuda are available to diagnose the syndrome. Its epidemiology indicates that it is probably more frequent in Northern countries and it is described in Gulf War veterans. Etiological hypotheses include infectious diseases, immunology and neurology. Among these hypotheses sickness behavior mimes certain aspects of this syndrome and is characterized by a cytokine imbalance in the central nervous system and in the periphery. There are no valid therapies available at the moment. In the laboratory of Immunogenetics, we are constituting a biological bank of the syndrome to study the immunogenetic aspects of the disease in the hope of elucidating some of the obscure areas of its etiopathogenesis.

 

Source: Carlo-Stella N, Lorusso L, Candura SM, Cuccia M. Chronic fatigue syndrome: a review. Recenti Prog Med. 2004 Nov;95(11):546-52; quiz 560. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/15598093