Tag: women vs men

Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19

Abstract:

Background: The pandemic has highlighted and exacerbated health inequities in both acute coronavirus disease 2019 (COVID-19) and its longer-term sequelae. Given the heterogeneity in definitions of long COVID and the lack of centralized registries of patients with the disease, little is known about the differential prevalence among racial, ethnic, and sex subgroups. This study examines long COVID among Black, White, Asian, and Hispanic Americans and evaluates differences in the associated cognitive symptomology.

Method: Data from four releases of the Census Bureau’s Household Pulse Survey detailing COVID-19 incidence and the duration and type of symptoms among a nationally representative sample of adults from June 1, 2022, through October 17, 2022, were combined. Binary logistic regression assessed the relative likelihood of long COVID among those who had been diagnosed COVID between racial, ethnic, and sex subgroups. Among those reporting long COVID, differences in the prevalence of difficulty understanding and difficulty remembering were assessed. Empirical models accounted for household, regional, vaccination, and insurance differences between respondents. Two-stage selection models were applied to test the robustness of the results.

Results: Among respondents who tested positive for COVID-19, Blacks (OR=1.097, CI=1.034-1.163), females (OR=1.849, CI=1.794-1.907), and Hispanics (OR=1.349, CI=1.286-1.414) were more likely to experience long COVID (symptoms lasting for 3 months or longer) compared to Whites, males, and non-Hispanics respectively. However, those with private health insurance (OR=0.634, CI=0.611-0.658) and who received the COVID vaccine (OR=0.901, CI=0.864-0.94) were less likely to have endured COVID symptoms than their counterparts. Symptoms of long COVID varied significantly between population subgroups. Compared to Whites, Blacks were more likely to have trouble remembering (OR=1.878, CI=1.765-1.808) while Hispanics were more likely to report difficult understanding (OR=1.827, CI=1.413, 2.362). Females, compared to males, were less likely to experience trouble understanding (OR=0.664, CI=0.537, 0.821), but more likely to report trouble remembering (OR=1.34, CI=1.237, 1.451).

Conclusions: Long COVID is more prevalent among Blacks, Hispanics, and females, but each group appears to experience long COVID differently. Therefore, additional research is needed to determine the best method to treat and manage this poorly understood condition.

Source: Jacobs MM, Evans E, Ellis C. Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19. J Natl Med Assoc. 2023 Feb 13:S0027-9684(23)00025-1. doi: 10.1016/j.jnma.2023.01.016. Epub ahead of print. PMID: 36792456; PMCID: PMC9923441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923441/ (Full text)

Characteristics associated with physical functioning and fatigue in patients with chronic fatigue syndrome (CFS): secondary analyses of a randomized controlled trial

Abstract

Objective: This study aimed to explore associations at the group level between patient characteristics at baseline and the outcomes of physical functioning and fatigue in patients with chronic fatigue syndrome (CFS) participating in a randomized controlled trial on cognitive behavioural therapy (CBT).

Methods/design: Consecutively, 236 adult participants fulfilling the Centres for Disease Control and Prevention (CDC) 1994 criteria for CFS were randomly allocated to either 16 weeks of standard CBT, 8 weeks of Interpersonal CBT or a treatment as usual control group. In secondary analyses we investigated how gender, age, pain, anxiety, depression, memory and VO2max at baseline were associated with physical function and fatigue before and after treatment, controlling for the CBT-interventions and the baseline levels of the outcome measures.

For the two groups receiving CBT, a 1-year follow-up analysis was also done. Bivariate and multivariable linear regression was used to explore the targeted associations.

Results: At baseline, less pain (p < .001) and higher VO2max (p = 0.014) were associated with better physical function, while better memory (p = 0.001) and fewer depressive symptoms (p = 0.017) were associated with less fatigue. Better memory and physical function at baseline (p = 0.015 and p < .001, respectively) and male gender (p = 0.003) were associated with higher physical function post-intervention.

Male gender (p = 0.010) was associated with higher physical function at 1-year follow-up. Fatigue severity at baseline was the only variable associated with follow up scores for fatigue (p < .001).

Conclusion: Our findings show that fatigue and physical function were associated with different types of characteristics at baseline, indicating a heterogeneity among CFS patients.

Source: Merethe Eide Gotaas, Tormod Landmark, Anne S. Helvik & Egil A. Fors (2023) Characteristics associated with physical functioning and fatigue in patients with chronic fatigue syndrome (CFS): secondary analyses of a randomized controlled trial, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2175521 https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2175521 (Full text)

Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients

Abstract:

Introduction: The coronavirus disease (COVID) 2019 pandemic remains a great challenge for the healthcare system. The widely reported prolonged signs and symptoms resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (Long-COVID) require medical care. The aim of the study was to assess factors, including lifestyle variables, related to the course of COVID-19 infection and to assess their impact on prolonged symptoms in non-hospitalized patients with COVID-19.

Methods: A total of 1,847 (637 men and 1,210 women) non-hospitalized participants of the STOP-COVID registry of the PoLoCOV-Study who, following the COVID-19, underwent check-up examinations at the cardiology outpatient clinic were included in the analysis.

Results: The study participants (median age 51 [41-62] years) were evaluated at 13.4 (8.4-23.6) weeks following the diagnosis of COVID-19. Female sex (odds ratio [OR] 1.46 [95% CI 1.19-1.78]), body mass index (BMI; per 1 kg/m2: 1.02 [1.00-1.04]), hypertension (1.39 [1.07-1.81]), asthma (1.55 [1.06-2.27]), stress or overworking (1.54 [1.25-1.90]), and nightshift work (1.51 [1.06-2.14]) were independently related to the severity of symptoms during acute phase of the COVID-19 infection. The Long-COVID syndrome was independently related to the female sex (1.42 [1.13-1.79]), history of myocardial infarction (2.57 [1.04-6.32]), asthma (1.56 [1.01-2.41]), and severe course of the acute phase of the COVID-19 infection (2.27 [1.82-2.83]).

Conclusion: Female sex, BMI, asthma, hypertension, nightshifts, and stress or overworking are significantly related to the severity of the acute phase of the COVID-19 infection, while female sex, asthma, history of myocardial infarction, and the severity of symptoms in the acute phase of COVID-19 are the predictors of Long-COVID in non-hospitalized patients. We did not find an independent relation between Long-COVID and the studied lifestyle factors.

Source: Pływaczewska-Jakubowska M, Chudzik M, Babicki M, Kapusta J, Jankowski P. Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients. Front Med (Lausanne). 2022 Oct 24;9:1036556. doi: 10.3389/fmed.2022.1036556. PMID: 36353225; PMCID: PMC9637668. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637668/ (Full text)

Sex-dependent characteristics of Neuro-Long-COVID: Data from a dedicated neurology ambulatory service

Abstract:

“Long-COVID” is a clinical entity that consists of persisting post-infectious symptoms that last for more than three months after the onset of the first acute COVID-19 symptoms. Among these, a cluster of neurological persisting symptoms defines Neuro-Long-COVID. While the debate about the pathogenesis of Long-COVID is still ongoing, sex differences have been individuated for both the acute and the chronic stage of the infection.

We conducted a retrospective study describing sex differences in a large sample of patients with Neuro-Long-COVID. Demographic and clinical data were collected in a specifically designed Neuro-Long-Covid outpatient service. Our sample included 213 patients: 151 were females and 62 were males; the mean age was similar between females (53 y, standard deviation 14) and males (55 y, standard deviation 15); no significant differences was present between the demographic features across the two groups.

Despite the prevalence of the specific chronic symptoms between male and females showed no significant differences, the total number of females accessing our service was higher than that of males, confirming the higher prevalence of Neuro-Long-COVID in female individuals. Conversely, a worse acute phase response in males rather than females was confirmed by a significant difference in the rates of acute respiratory symptoms (p = 0.008), dyspnea (p = 0.018), respiratory failure (p = 0.010) and the consequent need for ventilation (p = 0.015), together with other acute symptoms such as palpitations (p = 0.049), headache (p = 0.001) and joint pain (p = 0.049).

Taken together, these findings offer a subgroup analysis based on sex-dependent characteristics, which can support a tailored-medicine approach.

Source: Michelutti M, Furlanis G, Buoite Stella A, Bellavita G, Frezza N, Torresin G, Ajčević M, Manganotti P. Sex-dependent characteristics of Neuro-Long-COVID: Data from a dedicated neurology ambulatory service. J Neurol Sci. 2022 Jul 28;441:120355. doi: 10.1016/j.jns.2022.120355. Epub ahead of print. PMID: 35994869; PMCID: PMC9328838. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328838/ (Full text)

Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection

Abstract:

Prospective cohort studies following individuals from acute infections have documented a prevalent post-infective fatigue state meeting diagnostic criteria for chronic fatigue syndrome (CFS) – that is, a post-infective fatigue syndrome (PIFS). The Dubbo Infection Outcomes Study (DIOS) was a prospective cohort following individuals from acute infection with Epstein-Barr virus (EBV), Ross River virus (RRV), or Q fever through to assessment of caseness for CFS designated by physician and psychiatrist assessments at 6 months. Previous studies in DIOS have revealed that functional genetic polymorphisms in both immunological (pro- and anti-inflammatory cytokines) and neurological (the purinergic receptor, P2X7) genes are associated with both the severity of the acute infection and subsequent prolonged illness.

Principal components analysis was applied to self-report data from DIOS to describe the severity and course of both the overall illness and concurrent mood disturbance. Associations between demographics and acute infection characteristics, with prolonged illness course as well as the PIFS outcome were examined using multivariable statistics. Genetic haplotype-driven functional variations in the neuropeptide Y (NPY) gene previously shown to be associated with brain responses to stress, and to trait anxiety were also examined as predictors.

The sample included 484 subjects (51% female, median age 32, IQR 19-44), of whom 90 (19%) met diagnostic criteria for CFS at 6 months. Participants with greater overall illness severity and concurrent mood disturbance in the acute illness had a more prolonged illness severity (HR = 0.39, 95% CI: 0.34-0.46, p < 0.001) and mood disturbance (HR = 0.36, 95% CI: 0.30-0.42, p < 0.001), respectively. Baseline illness severity and RRV infection were associated with delayed recovery.

Female gender and mood disturbance in the acute illness were associated with prolonged mood disturbance. Logistic regression showed that the odds of an individual being diagnosed with PIFS increased with greater baseline illness severity (OR = 2.24, 95% CI: 1.71-2.94, p < 0.001). There was no association between the NPY haplotypes with overall illness severity or mood disturbance either during the acute illness phase or with prolonged illness (p > 0.05). Severe acute infective illnesses predicted prolonged illness, prolonged mood disturbance and PIFS. These factors may facilitate early intervention to manage both PIFS and mood disturbances.

Source: Sandler CX, Cvejic E, Valencia BM, Li H, Hickie IB, Lloyd AR. Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection. Front Neurol. 2022 Jul 25;13:935442. doi: 10.3389/fneur.2022.935442. PMID: 35959390; PMCID: PMC9359311. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359311/ (Full text)

Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Australian primary care patients: only part of the story?

Abstract:

Background: ME/CFS is a disorder characterized by recurrent fatigue and intolerance to exertion which manifests as profound post-exertional malaise. Prevalence studies internationally have reported highly variable results due to the 20 + diagnostic criteria. For Australia, the prevalence of ME/CFS based on current case definitions is unknown.

Objectives: To report prevalence of ME/CFS in patients aged ≥ 13 years attending Australian primary care settings for years 2015-2019, and provide context for patterns of primary care attendance by people living with ME/CFS.

Methodology: Conducted in partnership with the Patient Advisory Group, this study adopted a mixed methods approach. De-identified primary care data from the national MedicineInsight program were analyzed. The cohort were regularly attending patients, i.e. 3 visits in the preceding 2 years. Crude prevalence rates were calculated for years 2015-2019, by sex, 10-year age groups, remoteness and socioeconomic status. Rates are presented per 100,000population (95% confidence intervals (CI)). Qualitative data was collected through focus groups and in-depth 1:1 interview.

Results: Qualitative evidence identified barriers to reaching diagnosis, and limited interactions with primary care due to a lack of available treatments/interventions, stigma and disbelief in ME/CFS as a condition. In each year of interest, crude prevalence in the primary care setting ranged between 94.9/100,000 (95% CI: 91.5-98.5) and 103.9/100,000 population (95%CI: 100.3-107.7), equating to between 20,140 and 22,050 people living with ME/CFS in Australia in 2020. Higher rates were observed for age groups 50-59 years and 40-49 years. Rates were substantially higher in females (130.0-141.4/100,000) compared to males (50.9-57.5/100,000). In the context of the qualitative evidence, our prevalence rates likely represent an underestimate of the true prevalence of ME/CFS in the Australian primary care setting.

Conclusion: ME/CFS affects a substantial number of Australians. Whilst this study provides prevalence estimates for the Australian primary care setting, the qualitative evidence highlights the limitations of these. Future research should focus on using robust case ascertainment criteria in a community setting. Quantification of the burden of disease can be used to inform health policy and planning, for this understudied condition.

Source: Orji N, Campbell JA, Wills K, Hensher M, Palmer AJ, Rogerson M, Kelly R, de Graaff B. Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Australian primary care patients: only part of the story? BMC Public Health. 2022 Aug 9;22(1):1516. doi: 10.1186/s12889-022-13929-9. PMID: 35945527. https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-022-13929-9 (Full text)

COVID-19 Infection: Its Lingering Symptoms in Adults

Abstract:

Background: Recent studies showed that a significant percentage of people who recovered from coronavirus disease 2019 (COVID-19) had lingering symptoms. Among patients diagnosed with COVID-19 infection, studies showed persistent symptoms both in patients hospitalized and in outpatient settings. In the studies done in the outpatient setting involving mild to moderate COVID-19 patients, there were significant variations regarding the exact percentage of people with lingering symptoms. Also, in the outpatient setting, not many studies were done on COVID-19 patients that assessed risk factors for having lingering symptoms. Given that a large percentage of people infected with COVID-19 infection do not get hospitalized, it is imperative that this lacuna be filled. We believe knowing the details of long-term symptoms of COVID-19 infection both from prevalence and predictors point of view, could allow the physicians, healthcare system and community to better prepare for managing and following these patients.

Materials and methods: Our study period was within 12 months after the first documented case of COVID-19 occurred in the State of Alabama. Our study population included patients who were diagnosed with a documented case of COVID-19 in this time period and were under the care of a single primary care provider at an ambulatory clinic. Among 80 patients who had documented COVID-19, three left the practice, two declined to participate in the study and three were deceased (two due to COVID-19 and one for other reasons). Therefore, the study population constituted 72 patients. A questionnaire was mailed to all 72 patients to see how many of them had symptoms three months and beyond of having COVID-19 infection. A chart review was conducted for the study participants to assess for “Comorbid conditions”, health conditions that were considered conclusively high risk for acute COVID-19 infection by US Center for Disease Control and Prevention (CDC).

Results: Fifty-three patients responded to the questionnaire; 27 patients (50.9%) reported lingering symptoms beyond three months of diagnosis with COVID-19 infection. The three most common symptoms reported were fatigue (56%), brain fog (48%), and shortness of breath (41%). The results also showed that women are more likely than men to have lingering symptoms. “Elderly” (≥65 years) patients were as likely as 18-64 years old patients to have lingering symptoms and the presence of one or more of the “Comorbid conditions” does not have any bearing on the occurrence of lingering symptoms.

Conclusion: Future studies should be done in a larger population to assess the findings that our study showed regarding “elderly” age and the presence of one or more “comorbid conditions” being independent variables of the occurrence of prolonged COVID-19 symptoms. We recommend studies be done assessing the prevalence and predictors for the long-term effects of the COVID-19 infection. This knowledge could help in preventing those long-term symptoms from occurring in the first place and also in preparing the patient, the physician and the community in managing the outcomes effectively.

Source: Yellumahanthi DK, Barnett B, Barnett S, Yellumahanthi S. COVID-19 Infection: Its Lingering Symptoms in Adults. Cureus. 2022 May 4;14(5):e24736. doi: 10.7759/cureus.24736. PMID: 35677013; PMCID: PMC9166577. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166577/ (Full text)

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Infectious pathogens are implicated in the etiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) because of the occurrence of outbreaks of the disease. While a number of different infectious agents have been associated with the onset of ME/CFS, the identity of a specific organism has been difficult to determine in individual cases. The aim of our study is to survey ME/CFS subjects for evidence of an infectious trigger and/or evidence of immune dysregulation via serological testing of plasma samples for antibodies to 122 different pathogen antigens.
Immune profiles were compared to age-, sex-, and BMI-matched controls to provide a basis for comparison. Antibody levels to individual antigens surveyed in this study do not implicate any one of the pathogens in ME/CFS, nor do they rule out common pathogens that frequently infect the US population. However, our results revealed sex-based differences in steady-state humoral immunity, both within the ME/CFS cohort and when compared to trends seen in the healthy control cohort.
Source: O’Neal AJ, Glass KA, Emig CJ, Vitug AA, Henry SJ, Shungu DC, Mao X, Levine SM, Hanson MR. Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Proteomes. 2022; 10(2):21. https://doi.org/10.3390/proteomes10020021 https://www.mdpi.com/2227-7382/10/2/21/htm (Full text)

Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain

Abstract:

The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn, direct investigations using rodent and human preclinical pain models have been lacking.

Here, we discovered that in the Freund’s adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator brain-derived neurotrophic factor (BDNF) failed to downregulate inhibitory signalling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B and pGluN2B) in female rats, resulting in no effect of ex vivo brain-derived neurotrophic factor on synaptic NMDAR responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans.

As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in superficial dorsal horn neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain neuronal phenotype, with BDNF driving a coupling between disinhibition and NMDAR potentiation in adult lamina I neurons following the prepubescent elimination of sex hormones in females. This discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment for pain in both sexes.

Source: Dedek A, Xu J, Lorenzo LÉ, Godin AG, Kandegedara CM, Glavina G, Landrigan JA, Lombroso PJ, De Koninck Y, Tsai EC, Hildebrand ME. Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain. Brain. 2022 Apr 29;145(3):1124-1138. doi: 10.1093/brain/awab408. PMID: 35323848; PMCID: PMC9050559. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9050559/ (Full text)

Novel genes and sex differences in COVID-19 severity

Abstract:

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5×10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3×10-22 and p = 8.1×10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4×10-8).

In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7×10-8) and ARHGAP33 (p = 1.3×10-8), respectively.

The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1×10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE.

We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Source: Cruz R, Almeida SD, Heredia ML, Quintela I, Ceballos FC, Pita G, Lorenzo-Salazar JM, González-Montelongo R, Gago-Domínguez M, Porras MS, Castaño JAT, Nevado J, Aguado JM, Aguilar C, Aguilera-Albesa S, Almadana V, Almoguera B, Alvarez N, Andreu-Bernabeu Á, Arana-Arri E, Arango C, Arranz MJ, Artiga MJ, Baptista-Rosas RC, Barreda-Sánchez M, Belhassen-Garcia M, Bezerra JF, Bezerra MAC, Boix-Palop L, Brion M, Brugada R, Bustos M, Calderón EJ, Carbonell C, Castano L, Castelao JE, Conde-Vicente R, Cordero-Lorenzana ML, Cortes-Sanchez JL, Corton M, Darnaude MT, De Martino-Rodríguez A, Campo-Pérez V, Bustamante AD, Domínguez-Garrido E, Luchessi AD, Eirós R, Sanabria GME, Fariñas MC, Fernández-Robelo U, Fernández-Rodríguez A, Fernández-Villa T, Gil-Fournier B, Gómez-Arrue J, Álvarez BG, Quirós FGB, González-Peñas J, Gutiérrez-Bautista JF, Herrero MJ, Herrero-Gonzalez A, Jimenez-Sousa MA, Lattig MC, Borja AL, Lopez-Rodriguez R, Mancebo E, Martín-López C, Martín V, Martinez-Nieto O, Martinez-Lopez I, Martinez-Resendez MF, Martinez-Perez Á, Mazzeu JA, Macías EM, Minguez P, Cuerda VM, Silbiger VN, Oliveira SF, Ortega-Paino E, Parellada M, Paz-Artal E, Santos NPC, Pérez-Matute P, Perez P, Pérez-Tomás ME, Perucho T, Pinsach-Abuin ML, Pompa-Mera EN, Porras-Hurtado GL, Pujol A, León SR, Resino S, Fernandes MR, Rodríguez-Ruiz E, Rodriguez-Artalejo F, Rodriguez-Garcia JA, Ruiz-Cabello F, Ruiz-Hornillos J, Ryan P, Soria JM, Souto JC, Tamayo E, Tamayo-Velasco A, Taracido-Fernandez JC, Teper A, Torres-Tobar L, Urioste M, Valencia-Ramos J, Yáñez Z, Zarate R, Nakanishi T, Pigazzini S, Degenhardt F, Butler-Laporte G, Maya-Miles D, Bujanda L, Bouysran Y, Palom A, Ellinghaus D, Martínez-Bueno M, Rolker S, Amitrano S, Roade L, Fava F, Spinner CD, Prati D, Bernardo D, Garcia F, Darcis G, Fernández-Cadenas I, Holter JC, Banales JM, Frithiof R, Duga S, Asselta R, Pereira AC, Romero-Gómez M, Nafría-Jiménez B, Hov JR, Migeotte I, Renieri A, Planas AM, Ludwig KU, Buti M, Rahmouni S, Alarcón-Riquelme ME, Schulte EC, Franke A, Karlsen TH, Valenti L, Zeberg H, Richards B, Ganna A, Boada M, Rojas I, Ruiz A, Sánchez P, Real LM; SCOURGE Cohort Group; HOSTAGE Cohort Group; GRA@CE Cohort Group, Guillen-Navarro E, Ayuso C, González-Neira A, Riancho JA, Rojas-Martinez A, Flores C, Lapunzina P, Carracedo Á. Novel genes and sex differences in COVID-19 severity. Hum Mol Genet. 2022 Jun 16:ddac132. doi: 10.1093/hmg/ddac132. Epub ahead of print. PMID: 35708486.  https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddac132/6607933  (Full text available as PDF file)