Comparing surveyed adults with long COVID and those with just a positive test helps put COVID into perspective

Abstract:

Introduction Among adults who test positive for COVID-19, some develop long COVID (symptoms lasting ≥3 months), and some do not. We compared 3 groups on selected measures to help determine strategies to reduce COVID impact.

Methods Using Stata and data for 385,617 adults from the 2022 Behavioral Risk Factor Surveillance System, we compared adults reporting long COVID, those with just a positive test, and those who never tested positive, on several health status and risk factor measures plus vaccination rates (data for 178,949 adults in 29 states).

Results Prevalence of just COVID was 26.5% (95% CI 26.2-26.8) and long COVID was 7.4% (7.3-7.6). Compared with adults with just COVID those with long COVID had worse rates for 13 of 17 measures of chronic disease, disability, and poor health status, while those with just COVID had the best results for 15 of the 17 measures among all 3 groups. The 5 risk factors (obesity, diabetes, asthma, cardiovascular disease, and COPD) previously associated with COVID deaths, increased long COVID but not just COVID rates, which were highest among younger and higher income adults. Adults with long COVID had the highest rate among the 3 groups for any COVID risk factors and data from 29 states showed they had the lowest rates for ≥3 vaccine doses of 35.6%, vs. 42.7% and 50.3% for those with just a positive test, and neither, respectively. Vaccination with ≥3 vaccines vs. <3 reduced long COVID rates by 38%, and just COVID rates by 16%.

Conclusions Results show the seriousness of long COVID vs. just a positive test and that increasing vaccine coverage by targeting adults with risk factors shows promise for reducing COVID impact.

Source: Mary L. AdamsJoseph Grandpre. Comparing surveyed adults with long COVID and those with just a positive test helps put COVID into perspective.

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)

Does Pre-existing Diabetes Correlate with Long COVID-19 in Europe? Evidence from the Analysis of the Survey of Health, Ageing and Retirement in Europe’s Corona Surveys

Abstract:

Background. A substantial proportion of those infected with COVID-19 are presenting with persistent symptoms, referred to as long COVID-19. Emerging evidence suggests that the presence of pre-existing chronic conditions, such as diabetes, may increase the risk of long COVID-19. Objectives. To investigate whether having pre-existing diabetes increases the risk of developing long COVID-19 in the population of middle-aged and older adults (≥50 years old) in Europe, while assessing if this relationship can be accounted for or is modified by the known long COVID-19 and diabetes risk factors (age, sex, hospitalization, pre-existing hypertension, and weight status).

Methods. A population-based longitudinal prospective study involving a sample of respondents aged 50 years and older () with probable or confirmed COVID-19 infection from 27 countries that participated in both waves 7 and 8 of the Survey of Health, Ageing and Retirement in Europe and its 2020 and 2021 Corona Surveys. Logistic regression modeling was performed.

Results. Overall, 66.8% of the respondents affected by COVID-19 infection reported at least one long COVID-19 symptom; 55.2% were female, and the average age was 64.6 years; 13.2% had pre-existing diabetes. Respondents with pre-existing diabetes had significantly higher odds of developing long COVID-19, compared to those without diabetes (; 95% ). This relationship remained significant (; 98% ) after adjusting for sex ( for females; 95% ), hospitalization for COVID-19 illness (; 95% ), pre-existing hypertension (; 95% ), and overweight (; 95% ) and obese (; 95% ) weight status. The effect of pre-existing diabetes on the risk of long COVID-19 is moderated by age; it was highest at the age of 50 (; 95% ), and then, it declined with age.

Conclusions. There is a relationship between pre-existing diabetes and long COVID-19, even after controlling for literature-based confounding factors, with age having a moderating effect on this relationship.

Source: Sarah Cuschieri, Piotr Wilk, “Does Pre-existing Diabetes Correlate with Long COVID-19 in Europe? Evidence from the Analysis of the Survey of Health, Ageing and Retirement in Europe’s Corona Surveys”, Journal of Diabetes Research, vol. 2024, Article ID 7459628, 7 pages, 2024. https://doi.org/10.1155/2024/7459628 https://www.hindawi.com/journals/jdr/2024/7459628/ (Full text)

Role of Ferroptosis in the Progression of COVID-19 and the Development of Long COVID

Abstract:

Objectives: To examine the role of ferroptosis on the pathogenesis and progression of COVID-19.

Materials and methods: A total of 127 patients who were hospitalized for COVID-19 were categorized into two groups according to the intensity of oxygen therapy (high-flow or low-flow). Clinical characteristics, laboratory parameters, plasma markers, and peripheral blood mononuclear cell (PBMC) markers were measured at baseline and one or two weeks after treatment. Telephone follow-up was performed 3 months after discharge to assess long COVID.

Results: Patients receiving high-flow oxygen therapy had greater levels of neutrophils; D-dimer; C reactive protein; procalcitonin; plasma protein levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL-17, and acyl-CoA synthetase long-chain family member 4 (ACSL4); and PBMC mRNA level of TNF-α; but had lower levels of lymphocytes and plasma glutathione peroxidase 4 (GPX4). There were negative correlations of plasma GPX4 and cystine/glutamate transporter-11 (SLC7A11) with TNF-α, IL-6, and IL-17, and positive correlations of ACSL4 with inflammatory markers in plasma and PBMCs. The plasma levels of TNF-α, IL-6, IL-17, and ACSL4 were significantly lower after treatment than at baseline, but there were higher post-treatment levels of lymphocytes, GPX4, and SLC7A11. Patients with long COVID had a lower baseline level of plasma SLC7A11.

Conclusion: Ferroptosis is activated during the progression of COVID-19, and a low baseline level of a ferroptosis marker (SLC7A11) may indicate an increased risk for long COVID-19. Ferroptosis has potential as a clinical indicator of long COVID and as a therapeutic target.

Source: Zhao W, Wang S, Han Y, Zhang H, Cao J, Dong S, Li D, Lei M, Liu C, Gao Y. Role of Ferroptosis in the Progression of COVID-19 and the Development of Long COVID. Curr Med Chem. 2024 Jan 3. doi: 10.2174/0109298673281662231208102354. Epub ahead of print. PMID: 38310391. https://pubmed.ncbi.nlm.nih.gov/38310391/

Association of vaccine status, reinfections, and risk factors with Long COVID syndrome

Abstract:

The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to determine the prevalence of Long COVID syndrome within a population of Northeastern Mexico, correlating it with patients’ comorbidities, number of COVID-19 reinfection, and vaccination status. Employing an observational cross-sectional approach, we administered a comprehensive questionnaire covering medical history, demographics, vaccination status, COVID-related symptoms, and treatment.

Our participant cohort included 807 patients, with an average age of 41.5 (SD 13.6) years, and women accounting 59.3% of the cohort. The follow-up was 488 (IQR 456) days. One hundred sixty-eight subjects (20.9%) met Long COVID criteria. Long COVID-19 was more prevalent when subjects had reinfections (p = 0.02) and less frequent when they had a complete vaccination scheme (p = 0.05).

Through logistic regression, we found that male gender (OR 0.5, p ≤ 0.001), blood types of AB- (OR 0.48, p = 0.003) and O- (OR 0.27, p ≤ 0.001) in comparison with A+ and two doses of vaccines (OR 0.5, p = 006) to be protective factors against Long COVID; while higher BMI (OR 1.04, p = 0.005) was a risk factor.

We saw that the prevalence of Long COVID was different within vaccinated patients and specific blood types, while being female and a higher BMI were associated with an increased risk of having long-COVID.

Source: Romero-Ibarguengoitia ME, Rodríguez-Torres JF, Garza-Silva A, Rivera-Cavazos A, Morales-Rodriguez DP, Hurtado-Cabrera M, Kalife-Assad R, Villarreal-Parra D, Loose-Esparza A, Gutiérrez-Arias JJ, Mata-Porras YG, Ojeda-Salazar DA, Sanz-Sánchez MA, González-Cantú A, Azzolini E, Rescigno M. Association of vaccine status, reinfections, and risk factors with Long COVID syndrome. Sci Rep. 2024 Feb 2;14(1):2817. doi: 10.1038/s41598-024-52925-4. PMID: 38307886; PMCID: PMC10837423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10837423/ (Full text)

Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection

Abstract:

Many patients surviving SARS-CoV-2 infection suffer from long-term symptoms (long COVID or post COVID) such as shortness of breath, fatigue, loss of taste or smell and cognitive deterioration. However, few data are available concerning blood cell counts and haematological parameters during the post-COVID period.

We analysed haematological data from 83 patients previously admitted to the internal medicine unit of our institution because of symptomatic SARS-CoV-2 infection; all data were obtained within 1-12 months from disease onset. A control group of 70 apparently healthy, age- and sex-matched COVID-19 negative individuals was assessed for comparison. Blood cell counts improved in the post-COVID period, but 81% of patients had persistent abnormalities, compared with 50% in the control group, p < 0.001.

Most common haematological findings included anaemia (40%), reduced lymphocyte (43%) or eosinophil counts (38%) and low IgM memory B cells and correlated with advanced age, number of chronic comorbidities, female gender, altered renal function, reduced baseline Hb and procalcitonin concentrations and increased RDW. Data on lymphocytes and IgM memory B cells show that impaired immune responses may persist for up to one year in the post-COVID period, possibly contributing to long-term symptoms, especially in female patients.

Source: Bergamaschi G, Barteselli C, Calabretta F, Lenti MV, Merli S, Rossi CM, Di Sabatino A. Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection. Intern Emerg Med. 2024 Jan;19(1):125-133. doi: 10.1007/s11739-023-03459-6. Epub 2023 Nov 24. PMID: 38001354. https://pubmed.ncbi.nlm.nih.gov/38001354/

Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults

Abstract:

Background: The impact of vaccination prior to infection on postacute sequelae of coronavirus disease 2019 (COVID-19, PASC), also known as long COVID, remains unclear. Here we assess the protective effect of vaccination on long COVID in a community-based setting.

Methods: The Immunity Associated with SARS-CoV-2 (IASO) study is an ongoing prospective cohort of working adults that began in October 2020. Participants are actively followed for severe acute respiratory syndrome coronavirus 2 infection. We compared the prevalence of symptoms and symptom severity in vaccinated compared to unvaccinated cases. Our primary definition of long COVID was the presence of symptoms at 90 days postinfection; 30 days postinfection was also examined.

Results: Overall, by 90 days postinfection, 13% of cases had long COVID, with 27% of unvaccinated cases and 8% of vaccinated cases reporting long COVID (relative risk [RR], 0.31 [95% confidence interval {CI}, .22–.42]). Vaccination was also associated with significantly lower average severity scores at all timepoints (eg, relative severity at 90 days postinfection: −2.70 [95% CI, −1.68 to −3.73]). In the pre-Omicron era, 28% of unvaccinated cases and 18% of vaccinated cases reported long COVID (P = .07), and vaccinated cases reported less severe symptoms including less difficulty breathing (P = .01; 90-day RR, 0.07).

Conclusions: Vaccinated cases had lower prevalence of long COVID and reduced symptom severity.

Source: Hannah E Maier, Theresa Kowalski-Dobson, Ashley Eckard, Carmen Gherasim, David Manthei, Alyssa Meyers, Dawson Davis, Kevin Bakker, Kathleen Lindsey, Zijin Chu, Lauren Warsinske, Matthew Arnold, Anna Buswinka, Emily Stoneman, Riccardo Valdez, Aubree Gordon, Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults, Open Forum Infectious Diseases, Volume 11, Issue 2, February 2024, ofae039, https://doi.org/10.1093/ofid/ofae039 https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofae039/7585852 (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)

Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe

Abstract:

Background: Research on Long COVID risk factors is ongoing. High body mass index (BMI) may increase Long COVID risk, yet no evidence has been established regarding sex differences in the relationship between BMI and the risk of Long COVID. Investigating the nature of this relationship was the main objective of this study.

Methods: A population-based prospective study involving a sample of respondents aged 50 years and older (n = 4004) from 27 European countries that participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe’s (SHARE) Corona Surveys and in Waves 7 and 8 of the main SHARE survey. Logistic regression models were estimated to produce unadjusted and adjusted estimates of the sex differences in the relationship between BMI and Long COVID.

Results: Linear relationship for females, with probability of Long COVID increasing with BMI (68% at BMI = 18, 93% at BMI = 45). Non-linear relationship for males, with probability of Long COVID of 27% at BMI = 18, 68% at BMI = 33, and 40% at BMI = 45. Relationships remained significant after adjusting for known Long COVID risk factors (age and COVID-19 hospitalization), presence of chronic diseases, and respondents’ place of residence.

Conclusion: Sex differences appear to play an important role in the relationship between BMI and risk of Long COVID. Overall, females were more likely to have Long COVID, regardless of their BMI. Males at the higher end of the BMI spectrum had a lower risk of Long COVID as opposed to their female counterparts. Sex-specific research is recommended for better understanding of Long COVID risk factors.

Source: Wilk P, Stranges S, Cuschieri S. Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe. Int J Obes (Lond). 2024 Jan 29. doi: 10.1038/s41366-024-01477-8. Epub ahead of print. PMID: 38287094. https://pubmed.ncbi.nlm.nih.gov/38287094/