A Suicide Attempt Multicomponent Intervention Treatment (SAMIT Program): Study Protocol for a Multicentric Randomised Controlled Trial (preprint)

Background: Suicide has become a first-order public health concern, especially following the negative impact of COVID-19 on the mental health of the general population. Few studies have analyzed the effects of early psychotherapeutic interventions on subjects who have attempted suicide, and even fewer have focused on those hospitalized in non-psychiatric units after a medically serious suicide attempt (MSSA). The main aim of this study is to describe the protocol designed to evaluate the effectiveness of individual psychological treatment for patients hospitalized after an MSSA. The secondary objectives of the study are: 1) to evaluate the impact on quality of life and other psychosocial variables of patients with a recent MSSA who receive early psychological intervention; 2) to analyze the biological, psychological, and clinical impact of early psychotherapeutic treatment on subjects hospitalized after an MSSA. Methods: An experimental, controlled, and randomized trial will be conducted with patients over 16 years of age admitted to two general hospitals. The case intervention group will enroll for 8-sessions of individual psychotherapy, Suicide Attempts Multi-component Intervention Treatment (SAMIT), combining Dialectical Behaviour Therapy (DBT), Mentalization-Based Therapy (MBT), and Narrative approaches, while the control group will receive a treatment-as-usual intervention (TAU). Longitudinal assessment will be conducted at baseline (before treatment), post-treatment, and 3, 6, and 12 months after. The main outcome variable will be re-attempting suicide during follow-up. Discussion: Some psychotherapeutic interventions, usually implemented in outpatient, have proven to be effective in preventing suicidal behaviours. The combination of some of these may be a powerful treatment for preventing future SA in patients hospitalised after an MSSA, which is the most severely suicidal subgroup. Moreover, assessment of the biological, clinical and psychometric impact of this new intervention on patients during the first year after the attempt may help understand some of the multi-level factors associated with the effectiveness of psychotherapeutic interventions in MSSAs. The prevalence of high suicide rates requires the design of effective psychological interventions for their prevention, and also in order to design new pharmacological and psychological treatments.

Hybrid immunity improves the immune response after fourth Covid-19 vaccine dose in individuals with medical conditions predisposing to severe Covid-19 (preprint)

BackgroundData on Covid-19 booster vaccinations and subsequent infections on immune responses in the immunocompromised is limited. We studied antibody responses after the fourth dose and subsequent breakthrough infection to define patient groups benefiting most from boosters. MethodsIn Finland, fourth vaccine (booster) doses were first recommended for severely immunocompromised individuals, whom we invited to participate in 2022. We assessed spike protein specific IgG antibody levels and neutralizing antibodies (NAb) against the ancestral and Omicron BA.1 strains one month after the fourth dose from 488 adult participants and compared to the levels of 35 healthy controls after 3 doses. We used Bayesian generalized linear modelling to assess factors explaining antibody concentrations after the fourth dose. We assessed vaccine-induced and hybrid immunity six months after the last vaccine dose. ResultsChronic kidney disease (CKD) and immunosuppressive therapy (IT) were identified as factors explaining sub-optimal antibody responses. The proportion of participants with a normal antibody response and NAbs were significantly lower in CKD patients as compared to controls. By the 6-month sampling one third of the participants became infected, which enhanced antibody levels notably in most immunocompromised participants. ConclusionsImpaired antibody responses, especially NAbs against the Omicron lineage, predict limited protection in individuals with CKD, and highlight the need for alternative pharmaceutical preventive strategies. Vaccination strategies should take into account development of robust hybrid immunity responses also among the immunocompromised.

Impact of Covid-19 on the management of patients with metastatic melanoma.

The Covid-19 pandemic created new uncertainties in the management of metastatic melanoma patients. In particular, the impact of immunotherapy, targeted therapy, or chemotherapy on the risk of Sars-CoV-2 infection and severity was debated. In this study, we analyzed all patients with metastatic melanoma receiving therapy who developed Covid-19 between February 2020 and February 2022. We retrospectively collected demographic data, cancer-specific parameters, melanoma treatment regimen, comorbidities and Covid-19-specific parameters in these patients. Of the 350 patients with metastatic melanoma, 25 had Covid-19. The median age at the time of Covid-19 diagnosis was 66 years (range 36-86), 10 patients were female, and 15 patients were male. The treatment regimen during infection was immunotherapy in 12 cases, followed by targeted therapy (n = 8), chemotherapy (n = 2), and TVEC injections, follow-up and palliative therapy in 1 case each. The severity was mild in 17 patients and 8 had a moderate to critical course. Patients with a severe Covid-19 course were often older and had more comorbidities than patients with a mild infection. Many of the patients had a mild Covid-19 course despite having metastatic melanoma and systemic therapy. We therefore recommend continuing systemic therapy whenever possible, even in such exceptional situations as the Covid-19 pandemic.

Uptake of same-day initiation of HIV treatment in Malawi, South Africa, and Zambia: the SPRINT retrospective cohort study (preprint)

ABSTRACT Introduction Since 2017 global guidelines have recommended “same-day initiation” (SDI) of antiretroviral treatment (ART) for patients considered ready for treatment on the day of HIV diagnosis. Many countries in sub-Saharan Africa have incorporated a SDI option into national guidelines, but uptake of SDI is not well documented. We estimated average time to ART initiation at 12 public healthcare facilities in Malawi, 5 in South Africa, and 12 in Zambia. Methods We sequentially enrolled patients who were eligible to start ART between January 2018 and June 2019 and reviewed their medical records from the point of HIV treatment eligibility (HIV diagnosis or first HIV-related interaction with the clinic) to the earlier of treatment initiation or 6 months. We estimated the proportion of patients initiating ART at their original healthcare facilities on the same day or within 7, 14, 30, or 180 days of baseline, stratified by country and gender. Results We enrolled 826 patients in Malawi, 534 in South Africa, and 1,984 in Zambia. 88% of patients in Malawi, 57% in South Africa, and 91% in Zambia were offered and accepted SDI. In Malawi, most patients who did not receive SDI had also not initiated ART ≤ 6 months. In South Africa, an additional 13% of patients initiated ≤ 1 week, but 21% still had no record of initiation ≤ 6 months. Among those who did initiate within 6 months in Zambia, most started ≤ 1 week. There were no major differences by gender. Both WHO Stage III/IV and tuberculosis symptoms were associated with delays in ART initiation. Discussion As of 2020, uptake of same-day ART initiation was widespread, if not nearly universal, in Malawi and Zambia but was considerably less common in South Africa. Limitations of the study include pre-COVID-19 data that do not reflect pandemic adaptations and potentially missing data for Zambia. South Africa may be able to increase overall ART coverage by reducing numbers of patients who do not initiate ≤ 6 months. Registration Clinicaltrials.gov NCT04468399 (Malawi), NCT04170374 (South Africa), and NCT04470011 (Zambia).

Survival and late effects of hematopoietic cell transplantation in patients with thalassemia major.

In this retrospective study, we evaluated long-term survival and late effects in 137 patients affected by thalassemia major (TM) who received an allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 10.1 years. After a median follow-up of 30 years, 114 (83.2%) patients are living and 108 (78.8%) are cured. The cumulative incidence of nonrelapse mortality and thalassemia recurrence was 9.5% at 1 year and 10.2% at 39 years respectively. The 39-years cumulative incidence of overall survival and disease-free survival were 81.4% and 74.5%. One hundred twenty-three patients who survived more than 2 years after HCT were evaluated for late effects concerning hematological disorders, iron burden, growth, obesity, diabetes mellitus, thyroid and gonadal function, eye, heart, liver, lung, kidney, gastrointestinal, neurologic and psychiatric system, osteoarticular system, secondary solid cancer (SSC), performance status, and Covid-19 infection. Fertility was preserved in 21 males whose partners delivered 34 neonates and 25 females who delivered 26 neonates. Fifteen cases of SSC were diagnosed for a 39-year cumulative incidence of 16.4%. HCT represents a definitive cure for the majority of TM patients at the price, however, of a non-negligible early and late mortality which in the long run affects survival and disease-free survival.

Fluid Overload is Associated with Poor Prognosis in Hospitalized Patients with Covid-19 and Acute Kidney Injury (preprint)

Introduction: Acute kidney injury (AKI) has been associated with adverse outcomes among hospitalized patients with Covid-19. Although pre-pandemic data of patients with AKI has shown that volume overload is significantly associated with mortality and need for Renal Replacement Therapy (RRT), the association with worst outcomes among patients with AKI and Covid-19 has not been studied. Thus, the purpose of the study was to evaluate the effect of fluid overload in AKI with progression of the disease and mortality among patients hospitalized with Covid-19. Methods Observational retrospective cohort study that included volume balances, clinical and biochemical data of 412 hospitalized patients with Covid-19 and AKI. Univariate and Cox regression analyses were used to evaluate the association of fluid overload with 28-day mortality, AKI stage 3 and RRT. Results The mean age of the subjects was 55 ± 15 years, 64.1% were women, 69.7% developed AKI at any stage, 47.2% had diabetes, 31.4% had hypertension, and only 4.5% had chronic kidney disease. Likewise, the 28-day mortality was 20.4%, 43.3% patients required mechanical ventilation, 22.3% developed AKI stage 3, and 9.5% needed RRT. The median of global fluid overload was 1441cc (-489 to 3736), and 59.7% had a global fluid overload of > 1000 cc at discharge. After Cox regression analysis the risk for 28-day mortality, AKI stage 3 and RRT was HR = 3.014 (1.573–5.777), 3.159 (1.708–5.840), and 3.607 (1.128–11.539), respectively (p 

Metastatic testicular choriocarcinoma presenting as eyelid swelling and ptosis.

A 34-year-old man presented with an 8-day history of swelling and ptosis affecting the right upper eyelid. An MRI scan showed right superior rectus enlargement. Histology of an incisional biopsy of the muscle demonstrated metastatic choriocarcinoma to the orbit, positive for pan-cytokeratins, beta-HCG and GATA3. Possible primary sites included testis. An ultrasound of the testes identified bilateral testicular masses, highly suspicious for primary testicular malignancy. A CT scan of the chest, abdomen and pelvis identified disseminated metastatic disease conferring a poor prognostic germ cell tumour. The overall interpretation was of disseminated testicular choriocarcinoma and the patient is currently undergoing intensive chemotherapy.

Evolution of a Systematic Approach to Smoking Cessation in Ontario's Regional Cancer Centres.

Smoking cessation after a cancer diagnosis can significantly improve a person's prognosis, treatment efficacy and safety, and quality of life. In 2012, Cancer Care Ontario (now part of Ontario Health) introduced a Framework for Smoking Cessation, to be implemented for new ambulatory cancer patients at the province's 14 Regional Cancer Centres (RCCs). Over time, the program has evolved to become more efficient, use data for robust performance management, and broaden its focus to include new patient populations and additional data collection. In 2017, the framework was revised from a 5As to a 3As brief intervention model, along with an opt-out approach to referrals. The revised model was based on emerging evidence, feedback from stakeholders, and an interim program evaluation. Results showed an initial increase in referrals to cessation services. Two indicators (tobacco use screening and acceptance of a referral) are routinely monitored as part of Ontario Health's system-wide performance management approach, which has been identified as a key driver of change among RCCs. Due to the COVID-19 pandemic, many RCCs reported a decrease in these indicators. RCCs that were able to maintain a high level of smoking cessation activities during the pandemic offer valuable lessons, including the opportunity to swiftly leverage virtual care. Future directions for the program include capturing data on cessation outcomes and expanding the intervention to new populations. A focus on system recovery from COVID-19 will be paramount. Smoking cessation must remain a core element of high-quality cancer care, so that patients achieve the best possible health benefits from their treatments.

Timing and Duration of Axillary Lymph Node Swelling After COVID-19 Vaccination: Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 vaccination is now performed in most of the world to limit the spread of the disease. The first mRNA vaccine was approved in clinical settings and has specific side effects including axillary lymph node swelling, which can be misdiagnosed as breast cancer metastasis. The timing of axillary lymph node swelling and its duration are unclear. Here, we present a Japanese case and review of the existing literature. CASE REPORT: We report the case of a 67-year-old woman with breast calcification. She had regular follow ups in our hospital for this calcification and received ultrasonography of the breast and axilla at every visit. She visited 6 months before having her COVID-19 vaccination, and 7 days and 6 months after the first COVID-19 vaccination. She had a swollen axillary lymph node 7 days after the first vaccination, which although it was improved, remained for 6 months. CONCLUSION: Axillary lymph node swelling occurred 7 days after vaccination and remained up to 6 months after it.

The impact of an immuno-oncology service at a regional cancer centre based in the north west of the UK.

This article discusses the implementation and development of a centralised immuno-oncology service. As the indications and licensing of oncological immune checkpoint inhibitors (ICIs) expanded rapidly, they brought with them increasing challenges. The article evaluates the impact of an immuno-oncology service, focusing on the following areas: admission rates due to immune-related adverse events (irAEs), number of bed days occupied due to immunotherapy toxicity and the incidence of Grade 3 and 4 (severe and life-threatening) irAEs. The article will also give an overview of patients requiring acute and subsequent management of toxicity as a percentage of the overall patients commenced on immunotherapy. The ultimate aim of the article is to highlight the importance of toxicity management and the overall benefits of a immuno-oncology service. The article will also discuss the impact of COVID-19 on the immuno-oncology service, highlighting the ways in which the team has adapted to the current environment to ensure high standards of patient care have been maintained.

An uncommon case of metastatic myxofibrosarcoma presenting with elbow and hip masses.

Myxofibrosarcoma frequently recurs locally but rarely metastasizes. Herein, we describe an elderly woman who had myxofibrosarcoma of the right elbow that went untreated during the COVID-19 pandemic. She subsequently presented with two large tumors ulcerating through the skin of her right elbow and left hip.

Scottish COVID CAncer iMmunity Prevalence (SCCAMP) - a longitudinal study of patients with cancer receiving active anti-cancer treatment during the COVID-19 pandemic (preprint)

Background Cancer and systemic anti-cancer treatment (SACT) have been identified as possible risk factors for infection and related severe illness associated with SARS-CoV-2 virus as a consequence of immune suppression. The Scottish COVID CAncer iMmunity Prevalence (SCCAMP) study aims to characterise the incidence and outcomes of SARS-Cov-2 infection in patients undergoing active anti-cancer treatment during the COVID-19 pandemic and their antibody response following vaccination. Patients and Methods Eligible patients were those attending secondary care for active anti-cancer treatment for a solid tumour. Blood samples were taken for total SARS-CoV-2 antibody assay (Siemens) at baseline and after 1.5, 3, 6 and 12 months. Data on COVID-19 infection, vaccination, cancer type, treatment and outcome was obtained from routine electronic health records. Results The study recruited 766 eligible participants between 28th May 2020 and 31st October 2021. The median age was 62.7 years, and 66.5% were female. Most received cytotoxic chemotherapy (79%), with the remaining 14% receiving immunotherapy and 7% receiving another form of anti-cancer therapy (radiotherapy, other systemic anti-cancer treatment). 48 (6.3%) tested positive for SARS-CoV-2 by PCR during the study period. The overall infection rate matched that of the age-matched local general population until May 2021, after which population levels appeared higher. Antibody testing detected additional evidence of infection prior to vaccination, taking the total number to 58 (7.6%). There was no significant difference in SARS-CoV-2 PCR positive test rates based on type of anti-cancer treatment. Mortality proportion was similar between those who died within 90 days of a positive SARS-CoV-2 PCR and those with no positive PCR (10.4% vs 10.6%). Death from all causes was lowest among vaccinated patients, and of the patients who had a positive SARS-CoV-2 PCR at any time, all of those who died during the study period were unvaccinated. Multivariate analysis correcting for age, gender, socioeconomic status, comorbidities and number of previous medications revealed that vaccination was associated with a significantly lower infection rate regardless of treatment with chemotherapy or immunotherapy with hazard ratios of 0.307 (95% CI 0.144-0.6548) or 0.314 (95% CI 0.041-2.367) in vaccinated patients respectively. Where antibody data was available, 96.3% of patients successfully raised SARS-CoV-2 antibodies at a time point after vaccination. This was unaffected by treatment type. Conclusion SCCAMP provides real-world evidence that patients with cancer undergoing SACT have a high antibody response and protection from SARS-CoV-2 infection following COVID-19 vaccination.

Impact of the COVID-19 Pandemic on Treatment Patterns for Patients With Metastatic Solid Cancer in the United States.

BACKGROUND: The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic's impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. METHODS: We used an electronic health record-derived longitudinal database curated via technology-enabled abstraction to identify 14 136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at approximately 280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. RESULTS: The adjusted probability of treatment within 30 days of diagnosis was similar across periods (January-March 2019 = 41.7%, 95% confidence interval [CI] = 32.2% to 51.1%; April-July 2019 = 42.6%, 95% CI = 32.4% to 52.7%; January-March 2020 = 44.5%, 95% CI = 30.4% to 58.6%; April-July 2020 = 46.8%, 95% CI= 34.6% to 59.0%; adjusted percentage-point difference-in-differences = 1.4%, 95% CI = -2.7% to 5.5%). Among 5962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences = 1.6%, 95% CI = -2.6% to 5.8%). There was no meaningful effect modification by cancer type, race, or age. CONCLUSIONS: Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not affect TTI or treatment selection for patients with metastatic solid cancers.

Effect of Single Session Receptive Music Therapy on Anxiety and Vital Parameters in Hospitalized Covid-19 Patients: A Randomized Controlled Trial. (preprint)

Hospitalized COVID-19 patients are vulnerable to different degrees of stress disorders as well as depression, anxiety and fear. The aim of this study was to evaluate the feasibility of introducing Music therapy (MT) on site with Covid-19 patients and investigating the immediate effects a single session has on anxiety, heart rate (HR), oxygen saturation (O2Sat) and satisfaction compared to standard care. A randomized controlled trial of 40 patients was conducted. Participants were assigned to control group (CG) or the MT group (MG). MG received an individual single session of music therapy in presence. CG received standard care. MG and CG were subjected to identical measurements (pre-during-post) of the parameters STAI-Y, HR and O2Sat. Participants in MG were asked to fill in an optional open-ended question concerning their experience with MT. Significant difference in anxiety levels between scores in MG and CG (34.50 (23.25 - 40.00) vs 45.00(38, 25 - 54.00); p = 0.000) was observed. MG compared to CG had statistically significantly higher values of O2Sat (97.50 (96.25 - 99.00) versus 96.00 (96.00- 98.00); p = 0.026). Results show the feasibility of introducing MT as a supporting complementary/non-pharmacological intervention on site in Covid-19 patients. A single session of MT improves O2Sat and can significantly reduce anxiety.

The Delivery of Nitric Oxide in the Cardiovascular System: Implication for Clinical Diagnosis and Therapy (preprint)

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of Coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in cardiovascular system, the clinical applications centered on the NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process based on the clinical images and mathematical modeling to assess the endothelial function and vulnerability of atherosclerotic plaque. Then, the emerging bioimaging technologies that have the potential to directly measure the arterial NO concentration were discussed, including the Raman spectroscopy and electrochemical sensor. Aside from the diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the inhaled NO therapy to treat the pulmonary hypertension and COVID-19, stem cell therapy and NO-releasing platform to treat endothelial dysfunction and atherosclerosis.

Characteristics and Outcomes of Frail Patients with COVID-19 Admitted to ICU: An Individual Patient Data Meta-Analysis (preprint)

Purpose: Frailty is often used in clinical decision-making for patients with COVID-19, yet studies have found variable influence of frailty on outcomes in those admitted to the intensive care unit (ICU). In this individual patient data meta-analysis, we evaluated the characteristics, and outcomes of frail patients admitted to ICU with COVID-19. Methods: : We contacted the corresponding authors of sixteen eligible studies published between December 1 st 2019 and February 28 th 2021 reporting the clinical frailty scale (CFS) in patients with confirmed COVID-19 admitted to ICU. Individual patient data was obtained from 7 studies. We classified patients as non-frail (CFS=1-4) or frail (CFS=5-8). The primary outcome was hospital mortality. We also compared the use of mechanical ventilation (MV) and the proportion of ICU bed-days between frailty categories. Results: : Of the 2001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and sequential organ failure assessment (SOFA) score, CFS ≥4, use of MV, vasopressors, renal replacement therapy and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in frail patients (65.2% vs. 41.8%; p<0.001), with adjusted mortality increasing with a rising CFS score beyond 3. Younger and non-frail patients were more likely to receive MV. Frail patients spent less time on MV (median days [IQR] 9 [5-16] vs. 11 [6-18]; p=0.012) and accounted for only 12.3% of total ICU bed-days. Conclusion: Frail patients with COVID-19 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with non-frail patients. Frail patients receiving MV were at greater risk of death than non-frail patients. Systematic review registration: Registration protocol in PROSPERO (CRD42020224255).

Impact of Long-term Systemic Corticosteroid Therapy on Immune Response to the Influenza Vaccine: A Review of the Literature—How about COVID-19 Vaccine (preprint)

Corticosteroids have been widely applied in the treatment of various diseases, and patients exposed to corticosteroid therapy are at higher risk of infections, including the influenza, than others. Influenza vaccination are recommended for patients treated with steroids, while its efficacy and safety may be influenced by the immunosuppression induced by steroids. Therefore, we conducted an updated literature review of immune responses against influenza virus on patients treated with systemic corticosteroids to assess whether patients receiving long-term glucocorticoid therapy have developed an adequate antibody response. Findings from this review assume that influenza vaccine works safely and efficiently among patients with long-term systemic corticosteroid therapy at a low dose, 10mg/day might be a boundary value. Further studies are needed.

SARS-CoV-2 antibody responses in patients with aggressive haematological malignancies (preprint)

The development of antibody responses to SARS-CoV-2 is an indicator of seroprevalence and may afford protection from infection. It has been presumed that antibody responses to SARS-CoV-2 will be impaired in patients with aggressive haematological malignancy (PHM) due to underlying immunological dysfunction caused by malignancy or systemic anti-cancer treatment (SACT), placing them at increased risk. Here we analysed longitudinal serum samples from ten hospitalised PHM with aggressive disease and on SACT, collected up to 103 days post-onset of COVID-19 symptoms. We found that the majority (8/9) of PHM with confirmed SARS-CoV-2 infection seroconverted and developed antibodies to the major SARS-CoV-2 antigens (S1 and N) with most (6/8) produced neutralising antibody responses. Furthermore, the dynamics of antibody responses were broadly similar to that reported for the general population, except for a possible delay to seroconversion. Our finding that PHM on SACT can make functional antibody responses to SARS-CoV-2 has important implications for patient management and serological monitoring of SARS-CoV-2 in high-risk groups.

Estrogen and COVID-19 symptoms: associations in women from the COVID Symptom Study (preprint)

Background: Men and older women have been shown to be at higher risk of adverse COVID-19 outcomes. Animal model studies of SARS-CoV and MERS suggest that the age and sex difference in COVID-19 symptom severity may be due to a protective effect of the female sex hormone estrogen. Females have shown an ability to mount a stronger immune response to a variety of viral infections because of more robust humoral and cellular immune responses. Objectives: We sought to determine whether COVID-19 positivity increases in women entering menopause. We also aimed to identify whether premenopausal women taking exogenous hormones in the form of the combined oral contraceptive pill (COCP) and post-menopausal women taking hormone replacement therapy (HRT) have lower predicted rates of COVID-19, using our published symptom-based model. Design: The COVID Symptom Study developed by Kings College London and Zoe Global Limited was launched in the UK on 24th March 2020. It captured self-reported information related to COVID-19 symptoms. Data used for this study included records collected between 7th May - 15th June 2020. Main outcome measures: We investigated links between COVID-19 rates and 1) menopausal status, 2) COCP use and 3) HRT use, using symptom-based predicted COVID-19, tested COVID-19, and disease severity based on requirement for hospital attendance or respiratory support. Participants: Female users of the COVID Symptom Tracker Application in the UK, including 152,637 women for menopause status, 295,689 for COCP use, and 151,193 for HRT use. Analyses were adjusted for age, smoking and BMI. Results: Post-menopausal women aged 40-60 years had a higher rate of predicted COVID (P=0.003) and a corresponding range of symptoms, with consistent, but not significant trends observed for tested COVID-19 and disease severity. Women aged 18-45 years taking COCP had a significantly lower predicted COVID-19 (P=8.03E-05), with a reduction in hospital attendance (P=0.023). Post-menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P=2.22E-05) for HRT users alone. Conclusions: Our findings support a protective effect of estrogen on COVID-19, based on positive association between predicted COVID-19 and menopausal status, and a negative association with COCP use. HRT use was positively associated with COVID-19 symptoms; however, the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential comorbidities. Trial registration: The App Ethics has been approved by KCL ethics Committee REMAS ID 18210, review reference LRS-19/20-18210