Changes in sexual behavior among MSM during the spread of COVID-19 in China: results of an online survey (preprint)

Background Sexual behavior drives the transmission of sexually transmitted infections, especially among men who have sex with men (MSM). This study aims to evaluate the sexual behavior changed among MSM during the COVID-19.Methods An online survey was conducted to collect socio-demographic, sexual behavioral, and HIV testing information before and during the COVID-19. Chi-square was used to determine the behavior differences before and during the COVID-19. We identified the factors associated with sexual behavior among MSM using logistic regression.Results Totally 506 MSM participated in the survey. Compared with participants who didn't reduce the number of sexual partners (193, 38.1%), participants who reduced sexual partners (313, 61.9%) had higher values of multiple sexual partners, causal sexual partners, used condoms with causal sexual partners, and sought sexual partners using apps. Participants who reduced the number of sexual partners than before COVID-19, reported having a higher proportion of causal sexual behavior (χ2 = 21.047, p < 0.001), which means engaged in casual sex in the last three months.Conclusions The lockdown measures significantly impacted the sexual behavior of MSM. After the epidemic is over, however, we need to increase health education for MSM to reduce their high-risk sexual behaviors and protect them from STDs.

Traditional uses and pharmacological activities of Tetracera alnifolia (Wild) Drake (preprint)

Ethnopharmacological relevance: Tetracera alnifolia (Wild) Drake, is well used in traditional Guinean medicine for the treatment of infectious skin diseases. The present aim was to contribute to the valorization of Tetracera alnifolia leaves, focused on ethnomedical, biological and phytochemical investigations. Materials and methods: we conducted an ethnomedical survey across several markets of the city of Conakry to identify 39 healers. Chloroform, methanol, dichloromethane, and aqueous extracts were tested for activities against protozoa, bacteria, fungi, HIV, and SARS-CoV-2. Results: the traditional healers indicated that T. alnifolia is used in the treatment of more than 15 pathologies including Fassa (marasmus/malnutrition), Soukhou kouye (white discharge in women), and Temou bankhi (sexual weakness in men). Leaves were the most used part. The modes of preparation included decoction and powder. Data from biological activities identicatied good activities of the methanolic extract against Leishmania infantum (MIC = 8.11 g / ml) and a moderate activity on Trypanosoma brucei (MIC = 28.15 g / ml) and Staphylococcus aureus (MIC = 29.91 g/ ml), while dichloromethane extracts acted on live SARS-CoV-2 replication with up to 53.4% inhibition at 50 g/mL. Conclusion: these results explain at least in part the traditional use of T. alnifolia

Survey analysis of patient satisfaction and sexual issues in the management of vulvar lichen sclerosus (preprint)

Objective Vulvar lichen sclerosus (VLS) is an underestimated chronic disease. It can cause significant symptom burden and sexual dysfunction. This study aimed to evaluate patient satisfaction and current challenges in the management of VLS in a certified dysplasia unit, particularly during the COVID-19 pandemic.Methods This survey analyzed patients who had been diagnosed with VLS and treated at our DKG-certified dysplasia unit. The study was conducted during the COVID-19 pandemic in the Department of Gynecology and Obstetrics at the University of Aachen. The questionnaire contained 43 questions covering general treatment, diagnostic delays, psychological and sexual issues and specific questions about the COVID-19 pandemic. The questionnaire was distributed between January 2021 and September 2023.Results This study included 103 patients diagnosed with VLS who were treated at our certified dysplasia unit. Overall, 48% of the patients were satisfied with the success of the therapy. Most participants reported psychological problems (36.8%), fear of cancer (53.3%), or sexual restrictions (53.3%). Among the patients, 38% were bothered by the regular application of topical cortisone. However, 72% were willing to undergo treatment for more than 24 months. The COVID-19 outbreak in March 2020 had a significant negative impact on general VLS care from the patient’s perspective (3,83/5 before vs. 3,67/5 after; p = 0.046). There was a general request for booklets to inform and educate patients about their disease. Furthermore, the respondents demanded a telephone hotline to answer the questions and wished for follow-up visits via e-mail to cope better with their current situation.Conclusion This study highlights the need for more effective treatments for VLS and an increased awareness of psychological and sexual distress. To ensure patient well-being and satisfaction, it is imperative to offer individualized care in a team of specialists from various disciplines.

Covid-19, pelvic health and women’s voices: a descriptive study (preprint)

Objective: To examine how the pandemic affected women with pelvic dysfunction. Design: A Survey Monkey™ questionnaire on how the pandemic and Covid-19 infection affected women’s pelvic problems, exercise, and weight. A free text box captured their comments. Setting: Online questionnaire worldwide. Sample: Six hundred and forty-seven women. Results: Bladder control 265 (41%), prolapse 240 (37%), pelvic pain 40 (6%), sexual dysfunction 27 (4%), faecal incontinence 19 (3%) and other 56 (9%) were respondents’ main pelvic problems. Symptoms were unchanged for 331 (51%), worse for 243 (38%), and improved for 60 (10%). Weight was gained by 290 (45%), unchanged by 243 (38%), and lost by 114 (17%). Exercise levels were unchanged, worse, or better in 33%. Difficulty accessing medical appointments and date for surgery were experienced by 235 (36.5%) and 38 (6%) women respectively. Sixty-six (10.3%) women reported covid-19 infection: the distribution of pelvic problems and changes through the pandemic, weight and exercise patterns, and difficulty either getting a date for surgery or accessing healthcare were similar to those not contracting infection. Sexual dysfunction was the main new or worsening problem, featuring 13 women (18%). Seventy women - 16 recently delivered, and 54 with a pre-existing pelvic problem commented. Five core themes were identified. Difficulty accessing healthcare review, mental health impact and physiotherapy services especially affected delivered women, while lifestyle alterations and conservative treatment tools were more prominent in women with a pre-existing problem. Conclusions: The pandemic left many women with pelvic dysfunction without services, and this survey captures their suffering.

Initial Experience of Long-Term Prophylaxis with Lanadelumab for Hereditary Angioedema in China: a Clinical Observation of Four patients. (preprint)

Background Hereditary angioedema (HAE) is a rare genetic disorder caused by a deficiency or dysfunction of C1 esterase inhibitor (C1-INH), which leads to recurrent episodes of bradykininmediated edema. Lanadelumab is a plasma kallikrein inhibitor that is the only first line therapy for long term prophylaxis (LTP) of HAE attacks in China since 2021.Objectives To observe the clincial efficacy and safety of lanadelumab in Chinese patients with HAE in a small population of four patients.Method Four HAE patients from three academic centers in China was included. Demographic characteristics, clinical manifestions and life quality of HAE patients were recorded before and after LTP treatment of lanadelumab .The primary outcome is the attack frequence of symptoms, and disease-related work loss days. The secondary outcome is the improved life quality of patients. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL).Results Lanadelumab led to the reductions of 98.04% and 100% in attack rate and treated attack rate respectively. Three patients of four (75%) reported complete remission from attacks after starting the administration of lanadelumab. Two patients had significant improvements on AE-QoL and DLQI (both scores reduction rate were 100%) in early period of treatment (4 weeks and 2 weeks, respectively) and all the patients had significant improvement on missed work days/year (reduction rate was 100%). The efficacy of lanadelumab was stable during vaccination and infection with COVID-19. No treatment-related serious/severe treatment emergent adverse events (TEAEs) occured during the treatment of lanadelumab.Conclusions Our study first demonstrated the clinical efficacy of lanadelumab with highly safety in Chinese HAE patients. A reasonable dosage plan can ensure the stability of therapeutic effects of lanadelumab. Moreover, lanadelumab also play a protective role to prevent attack in the case of COVID-19 infection.

Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states (preprint)

COVID-19 is associated with diverse neurological abnormalities, which predict poor outcome in patients. However, the mechanisms whereby infection-induced inflammation could affect complex neuropathologies in COVID-19 are unclear. We hypothesized that microglia, the resident immune cells of brain, are centrally involved in this process. To study this, we developed an autopsy platform allowing the integration of molecular anatomy-, protein- and mRNA data sets in post-mortem mirror blocks of brain and peripheral organ samples from COVID-19 cases. Nanoscale microscopy, single-cell RNA sequencing and analysis of inflammatory and metabolic signatures revealed distinct mechanisms of microglial dysfunction associated with cerebral SARS-CoV-2 infection. We observed focal loss of microglial P2Y12R at sites of virus-associated vascular inflammation together with dysregulated microglia-vascular-astrocyte interactions, Cx3Cr1-fractalkine axis deficits and mitochondrial failure in severely affected medullary autonomic nuclei and other brain areas. Microglial dysfunction occurs at sites of excessive synapse- and myelin phagocytosis and loss of glutamatergic terminals. While central and systemic viral load is strongly linked in individual patients, the regionally heterogenous microglial reactivity in the brain correlated with the extent of central and systemic inflammation related to IL-1 / IL-6 via virus-sensing pattern recognition receptors (PRRs) and inflammasome activation pathways. Thus, SARS-CoV-2-induced central and systemic inflammation might lead to a primarily glio-vascular failure in the brain, which could be a common contributor to diverse COVID-19-related neuropathologies.

ECHOCARDIOGRAPHIC MANIFESTATIONS OF COVID 19 ILLNESS AND DEVELOPMENT OF PERSISTENT RV DYSFUNCTION AND PULMANARY HYPERTENSION AS A LONG TERM SEQUELAE OF COVID 19 ILLNESS: A STUDY AMONG PATIENTS OF SOUTH EAST ASIAN REGION (preprint)

Abstract Objectives- To study the Echocardiographic manifestations of covid 19 illness among patients admitted in our facility, Correlate MAPSE, TAPSE, PASP, CRP levels and CTSI among covid 19 patients with their 28 day outcome as survivors and non survivors and to look for evidence of residual RV dysfunction and Pulmonary hypertension using TTE after 1 year of follow-up. Study design- Prospective observational study at various medical wards and ICUs in SMS medical college and associated hospitals. Methods- 258 patients with a Covid-19 RT-PCR positive report from a throat or a nasal swab within 72 hours of admission were included in the study. Each patient underwent a complete clinical assessment and routine blood investigations including CRP levels were done. A complete transthoracic echocardiogram was done within 48 hours of admission. Patients also underwent a HRCT chest and CTSI scores were estimated. All patients were followed for a period of 28 days. The MAPSE, TAPSE, PASP, CTSI and CRP levels were then correlated with the outcome of the patient. The survivors again underwent a TTE at 1 year after their recovery from covid-19 illness to look for residual RV dysfunction by TAPSE and the development of pulmonary hypertension as measured by PASP using Bernoulli?s equation. Results-Amongst patient of covid 19 illness the MAPSE, TAPSE, PASP, CTSI and CRP levels all correlated well with outcome of patients. While most covid-19 survivors recovered from their illness yet some patients showed evidence of persistent RV dysfunction and pulmonary hypertension even after 1 year of follow up.

Assessment and Therapeutic Modulation of Heart Rate Variability: Potential Implications in Patients with COVID-19 (preprint)

Cardiac damage has been attributed to SARS-Cov-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population.

Mental and Sexual Health of Men in Times of COVID-19 Lockdown.

Due to the worldwide spread of COVID-19, some restrictions were introduced which could lead to the development of distress and somatic symptoms. This survey aimed to study the mental and sexual health of men during the COVID-19 outbreak. An online questionnaire was conducted to collect data on contact with people suspected of infection/infected with the SARS-CoV-2 virus, use of stimulants, and perceived mental and sexual health during isolation among Polish men. They were also asked to answer the Beck Depression Inventory (BDI) and the International Index of Erectile Function (IIEF-15) questionnaire. In total, 606 men with a mean age of 28.46 ± 9.17 years took part in the survey. Fear of contracting the COVID-19 infection had a negative impact on the mental health of 132 men (21.8%). Fear of the health condition of loved ones caused stress and a depressed mood in 253 men (41.7%), and media reports worsened the mental health of 185 men (30.2%). In the BDI, 71.95% of the respondents did not suffer from depressive symptoms, 17.33% were diagnosed with mild depression, 6.11% with moderate depression, and 4.62% had severe depression. The mean score in the IIEF-15 questionnaire in the erectile function domain was 22.27, orgasm-7.63, desire-8.25, satisfaction-10.17, and general satisfaction-6.84. Depressive symptoms indicated more severe sexual functioning disorders (p < 0.001). Fear, following the media, and loneliness were associated with more severe depressive and sexual disorders (p < 0.001). The libido level (p = 0.002) and frequency of sexual activity (p < 0.001) were also lower during the pandemic than before the lockdown. These data showed that the COVID-19 pandemic had a significant impact on male mental and sexual health.

The prevalence and severity of mental health problems and sexual dysfunction in hemodialysis patients before and during the COVID-19 pandemic.

INTRODUCTION: This study aimed to investigate the prevalence and severity of mental health problems and sexual dysfunction in hemodialysis patients before and during the COVID-19 pandemic. METHODS: A total of 84 hemodialysis patients were evaluated in terms of Pittsburgh Sleep Quality Index, Beck Depression Inventory, International Index of Erectile Function (IIEF-5), and Female Sexual Function Index (FSFI). RESULTS: Poor sleep quality (79.8%) and poor mental health status (62.7%) and higher likelihood of having depression (31.0 vs. 61.9%, p < 0.001) were noted. The IIEF-5 (10.5 [5-25] vs. 7.5 [5-23], p < 0.001) and FSFI (12 [4-78] vs. 6 [4-66], p < 0.001) scores were significantly decreased during the pandemic with an increase in the likelihood of having erectile dysfunction (p < 0.001). CONCLUSION: Our findings indicate high prevalence of mental health issues, an impaired quality of life and an increase in prevalence and severity of suspected depression during pandemic in hemodialysis patients along with deterioration in erectile dysfunction among males.

Rehabilitation delivery models to foster healthy ageing – a scoping review (preprint)

Background: Rehabilitation is essential to foster healthy ageing. Older adults have unique rehabilitation needs due to a higher prevalence of non-communicable diseases, susceptibility to infectious diseases like COVID-19, injuries, and mental health conditions. However, there is a limited understanding of how rehabilitation is delivered to the ageing population. To address this gap, we conducted a scoping review to describe rehabilitation delivery models used to optimise the ageing population's functioning/functional ability and foster healthy ageing. Methods: We searched Medline and Embase (January 2015 to May 2022) for primary studies published in English describing approaches to provide rehabilitation in people older than 50. Three authors screened records for eligibility and extracted data independently and in duplicate. Data synthesis included descriptive quantitative analysis of study and rehabilitation provision characteristics, and qualitative analysis to identify rehabilitation delivery models. Results: Out of 6,933 identified records, 585 articles were assessed for eligibility, and 283 studies with 69,257 participants were included. We identified six rehabilitation delivery models: outpatient (24%), telerehabilitation (22%), home (18.5%), community (16.3%), inpatient (14.6%), and eldercare (4.7%). These models often involved multidisciplinary teams (31.5%) and follow integrated care principles (30.4%). Most studies used a disease-centred approach (59.0%), while studies addressing multimorbidity (6.0%) and prevalent health problems of ageing, such as pain, low hearing and vision, or incontinence were scarce. The most frequently provided interventions were therapeutic exercises (54.1%), self-management education (40.1%), and assessment of person-centred goals (40%). Other interventions, such as assistive technology (8.1%) and environmental adaptations (7.4%) were infrequent. Conclusions: We provided a comprehensive overview of six delivery models used to provide rehabilitation to the ageing population and highlight research gaps that require further attention, including a lack of systematic assessment of functioning/functional ability, a predominance of disease-centred rehabilitation, and scarcity of programs addressing prevalent issues like pain, hearing/vision loss, fall prevention, incontinence, and sexual dysfunctions. Our research can facilitate evidence-based decision-making and inspire further research and innovation in rehabilitation and healthy ageing. Limitations of our study include reliance on published research to infer practice and not assessing model effectiveness. Future research in the field is needed to expand and validate our findings.

The Impact of COVID-19 Vaccination on the Sexual Health of Males (preprint)

The COVID-19 pandemic negatively affected the mental and sexual health of individuals, especially healthcare professionals. In this study, we aimed to investigate the changes in anxiety and sexual activity of male healthcare professionals following vaccination. This prospective cross-sectional and descriptive online survey study was conducted between July 1, 2021 and November 1, 2021, involving a total of 170 healthcare professionals. Socio-demographic characteristics, pre- and post-vaccination anxiety and sexual activity levels of the participants were compared. There was a significant increase in only intercourse times of the participants before and after vaccination (p=0.034). The Beck anxiety scale score decreased from (median: 19, min: 16, max: 47) before vaccination to (median: 17, min: 10, max: 43) after vaccination (p<0.001). Likewise, Arizona Sexual Experiences Scale scores decreased after vaccination (median: 10, min: 5, max: 20) compared to before vaccination (median: 12, min: 5, max: 18) (p<0.001). International Index of Erectile functon(IIEF) score also increased after vaccination (25.49±6.50) compared to before vaccination (24.71±7.10) (p<0.001). Orgasmic Function, Sexual Desire, Intercourse Satisfaction, Overall Satisfaction scores also improved (p=0.013, p<0.001, p=0.027, p<0.001). Mental and Sexual disorders increased with the COVID-19 pandemic. In addition to immunity, the vaccine also has positive effects on anxiety and sexual activity.

Clinical Spectrum and Outcome of Neonatal Multi-System Inflammatory Syndrome (MIS-N) - A Prospective Cohort Study. (preprint)

AIMS: To analyze the clinical spectrum in Neonates with MIS-N based on the time of presentation and also to assess the use of immunomodulator therapy in MIS-N. SUBJECTS AND METHODS: We studied 100 neonates, delivered at BLDE (DU) Shri B M Patil Medical College Hospital admitted to Level III-A NICU from JULY 2020 to MAY 2021. 98 neonates had high titers of Ig G antibodies and negative for COVID Antigen. We categorized the cohorts into EARLY MIS-N (<72 hrs) and LATE MIS-N (>72 hrs). RESULTS: 58 presented as EARLY MIS-N with Respiratory Distress in 40 (70%), cardiac dysfunction 34 (60%), PPHN 12(20%), Fever 12(20%), seizures 12(20%), encephalopathy in 6(10%), sepsis-like features 6(10%), had elevated inflammatory markers like CRP (30%), D-Dimer (70%), Ferritin (30%), cardiac biomarkers like BNP (60%), LDH (30%) and ECHO showing LV dysfunction in 50%. LATE MIS-N presented mostly with fever 28(70%), sepsis-like features 24(60%), Respiratory Distress in 16(40%), cardiac dysfunction 12 (30%), hypoglycemia 4(10%) parotitis 4(10%), had significantly elevated inflammatory markers like CRP (70%), D-Dimer (50%), Ferritin (70%), cardiac biomarkers like BNP (40%), LDH (20%) and ECHO showing LV dysfunction in 20%, dilated coronaries in 20 %, PPHN in 10%. Oxygen and respiratory support requirement was more in EARLY presenters and IVIG and steroid requirement was more in LATE presenters. CONCLUSION: We observed that maternal SARS COV2 antibodies transferred transplacentally and neonatal antibodies acquired after COVID 19 infection can cause MIS-N in neonates. The immunomodulator therapy is required in severe cases of MIS-N only.

sexual function and its associated factors in Iranians with and without a recent history of COVID-19 infection (preprint)

This study was designed to investigate the sexual function and its associated factors in Iranian women and men with and without a recent history of contracting COVID-19. This cross-sectional study was conducted with 384 individuals from August 1 to December 25, 2021, in Iran. The respondents were asked to fill out the International Index of Erectile Function (IIEF) questionnaire, the Female Sexual Function Index (FSFI) questionnaire, the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI-II), and Haj-Yahia’s questionnaire of violence against women. The results showed that mean FSFI score of female respondents was 20.39 ± 4.15. Women with a recent history of COVID-19 infection had significantly lower scores in the orgasm (P = 0.012) and satisfaction (P = 0.030) dimensions of FSFI. The mean IIEF score of male respondents was 17.79 ± 4.31. There was a significant difference between groups with and without a recent history of COVID-19 in terms of mean IIEF score and also mean scores of each dimension of IIEF (p = 0.004). Multivariate regression showed that women’s sexual function was associated with age and BDI-II score, whereas men’s sexual function was associated with the history of recent COVID-19 infection and the education level. In addition, the results suggest an increase in the prevalence of sexual dysfunction during the COVID-19 pandemic in both women and men. These results can help the country’s health policymakers to devise appropriate measures for mitigating the adverse impacts of the COVID-19 pandemic on the well-being of communities, families, and individuals.

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles (preprint)

People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+ T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.

Comparison of psycho-sexual factors and the quality of life between breastfeeding and non- breastfeeding women during the COVID-19 pandemic: A cross-sectional study (preprint)

Background According to the increased preponderance of COVID-19 and its possible effects on psychological health and quality of life (QoL), this study aimed to compare the psycho-sexual factors and the QoL between breastfeeding non-breastfeeding mothers during the COVID-19 pandemic.Method A comparative cross-sectional study was conducted through an online survey of 123 breastfeeding and 87 non-breastfeeding women referred to the gynecology clinic of Arash Hospital in Tehran from May to Jun 2020. Depression, anxiety, general health, female sexual dysfunction, QoL, Corona Disease, Anxiety, obsessions, and compulsions were assessed by an appropriate questionnaire.Result The results showed that breastfeeding women had better mental health, sexual function, and QoL (P < 0.001). The mean general health scores in breastfeeding women were significantly lower than in the non-breastfed group (21.92 ± 11.56 vs. 27.75 ± 16.09, P = 0.003). There were no statistically significant differences in marital satisfaction and Padua inventory between groups (P > 0.05). Multivariate regression analysis shows that the GHQ score of the BF group was 4.5 units higher than the non-BF group (P = 0.02) and the other variables were not significant.Conclusion This study highlights the effect of breastfeeding on the maternal mental health of mothers, especially in the coronavirus pandemic. It is possible to identify the need for more excellent psychological support in general and particularly in lactating mothers.

Neurologic sequalae of COVID-19 are determined by immunologic imprinting from previous Coronaviruses. (preprint)

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health emergency. Although SARS-CoV-2 is primarily a respiratory pathogen, extra-respiratory organs, including the central nervous system (CNS), can also be affected. Neurologic symptoms have been observed not only during acute SARS-CoV-2 infection, but also at distance from respiratory disease, also known as long-COVID or neurological post-acute sequelae of COVID-19 (neuroPASC). The pathogenesis of neuroPASC is not well understood, but hypotheses include SARS-CoV-2-induced immune dysfunctions, hormonal dysregulations, and persistence of SARS-CoV-2 reservoirs. In this study, we used a high throughput systems serology approach to dissect the humoral response to SARS-CoV-2 (and other common Coronaviruses - 229E, HKU1, NL63, OC43) in the serum and cerebrospinal fluid (CSF) from 112 infected individuals who developed or did not develop neuroPASC. Unique SARS-CoV-2 humoral profiles were observed in the CSF of neuroPASC. All antibody isotypes (IgA, IgM, IgA) and subclasses (IgA1-2; IgG1-4) were detected in serum, whereas CSF was characterized by focused IgG1 (and absence of IgM). These data argue in favor of compartmentalized brain-specific responses against SARS-CoV-2 through selective transfer of antibodies from the serum to the CSF across the blood-brain-barrier, rather than intrathecal synthesis, where more diversity in antibody classes/subclasses would be expected. Moreover, compared to individuals who did not develop post-acute neurological complications following infection (n=94), those with neuroPASC (n=18) exhibited attenuated systemic antibody responses against SARS-CoV-2, characterized by decreased capacity to activate antibody-dependent complement deposition (ADCD), NK cell activation (ADNKA) and to bind Fc{gamma} receptors. However, surprisingly, neuroPASC showed significantly expanded antibody responses to other common Coronaviruses, including 229E, HKU1, NL63, and OC43. This biased humoral activation across coronaviruses was particularly enriched in neuroPASC individuals with poor outcome, suggesting an original antigenic sin (or immunologic imprinting), where pre-existing immune responses against related viruses shape the response to current infection, as a key prognostic biomarker of neuroPASC disease. Overall, these findings point to a pathogenic role for compromised anti-SARS-CoV-2 responses in the CSF, likely resulting in incomplete virus clearance from the brain and persistent neuroinflammation, in the development of post-acute neurologic complications of SARS-CoV-2 infection.