Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients.

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa.

We conducted a mixed-methods study to understand current drug use practices and access to healthcare services for people who use injection drugs in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who used injection drugs within the past 6 months from KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP. None of the participants ever tested for Hepatitis C.

The Impact of the COVID-19 Pandemic on the Experiences and Operations of Sponsors of the Summer Food Service Program in Maryland, USA: A Multiphase Mixed Methods Study.

During the COVID-19 pandemic, the Summer Food Service Program (SFSP) was allowed to operate in untraditional non-summer months to ensure children did not lose access to free and reduced-priced nutritious meals when schools were mandated to close in the United States. This study assessed the impact of the pandemic on the operations and experiences of Summer Food Service Program (SFSP) sponsors in the state of Maryland during the COVID-19 pandemic in 2020 (Phase I) and 2021 (Phase II). This study used a multiphase explanatory sequential mixed methods design with qualitative prioritization. Maryland SFSP sponsors completed an online survey (Phase I: n = 27, Phase II: n = 30), and semi-structured in-depth interviews were conducted with a subset of sponsors who completed the survey (Phase I: n = 12, Phase II: n = 7). Inductive and deductive analyses were used for qualitative data, and descriptive statistics were used for quantitative data. The COVID-19 pandemic caused SFSP sponsors to change their operations. Sponsors were primarily concerned about staff safety/burnout and decreased participation. Sponsors perceived waivers implemented by the United States Department of Agriculture to be crucial in enabling them to serve meals to children during the pandemic. The findings from our study support advocacy efforts to permanently implement waivers and provide free school meals for all children.

Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure.

We have previously shown computationally that Mycolactone (MLN), a toxin produced by Mycobacterium ulcerans, strongly binds to Munc18b and other proteins, presumably blocking degranulation and exocytosis of blood platelets and mast cells. We investigated the effect of MLN on endocytosis using similar approaches, and it bound strongly to the N-terminal of the clathrin protein and a novel SARS-CoV-2 fusion protein. Experimentally, we found 100% inhibition up to 60 nM and 84% average inhibition at 30 nM in SARS-CoV-2 live viral assays. MLN was also 10× more potent than remdesivir and molnupiravir. MLN's toxicity against human alveolar cell line A549, immortalized human fetal renal cell line HEK293, and human hepatoma cell line Huh7.1 were 17.12%, 40.30%, and 36.25%, respectively. The cytotoxicity IC50 breakpoint ratio versus anti-SARS-CoV-2 activity was more than 65-fold. The IC50 values against the alpha, delta, and Omicron variants were all below 0.020 µM, and 134.6 nM of MLN had 100% inhibition in an entry and spread assays. MLN is eclectic in its actions through its binding to Sec61, AT2R, and the novel fusion protein, making it a good drug candidate for treating and preventing COVID-19 and other similarly transmitted enveloped viruses and pathogens.

Longitudinal adaptive immune responses following sequential SARS-CoV-2 vaccinations in MS patients on anti-CD20 therapies and sphingosine-1-phosphate receptor modulators.

BACKGROUND: Adequate response to the SARS-CoV-2 vaccine represents an important treatment goal in caring for patients with multiple sclerosis (MS) during the ongoing COVID-19 pandemic. Previous data so far have demonstrated lower spike-specific IgG responses following two SARS-CoV-2 vaccinations in MS patients treated with sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb) compared to other disease modifying therapies (DMTs). It is unknown whether subsequent vaccinations can augment antibody responses in these patients. OBJECTIVES: The goal of this observational study was to determine the effects of a third SARS-CoV-2 vaccination on antibody and T cell responses in MS patients treated with anti-CD20 mAb or S1P receptor modulators. METHODS: Vaccine responses in patients treated with anti-CD20 antibodies (ocrelizumab and ofatumumab) or S1P receptor modulators (fingolimod and siponimod) were evaluated before and after third SARS-CoV-2 vaccination as part of an ongoing longitudinal study. Total spike protein and spike receptor binding domain (RBD)-specific IgG responses were measured by Luminex bead-based assay. Spike-specific CD4+ and CD8+ T cell responses were measured by activation-induced marker expression. RESULTS: MS patients and healthy controls were enrolled before and following SARS-CoV-2 vaccination. A total of 31 MS patients (n = 10 ofatumumab, n = 13 ocrelizumab, n = 8 S1P) and 10 healthy controls were evaluated through three SARS-CoV-2 vaccinations. Compared to healthy controls, total spike IgG was significantly lower in anti-CD20 mAb-treated patients and spike RBD IgG was significantly lower in anti-CD20 mAb and S1P-treated patients following a third vaccination. While seropositivity was 100% in healthy controls after a third vaccination, total spike IgG and spike RBD IgG seropositivity were lower in ofatumumab (60% and 60%, respectively), ocrelizumab (85% and 46%, respectively), and S1P-treated patients (100% and 75%, respectively). Longer treatment duration, including prior treatment history, appeared to negatively impact antibody responses. Spike-specific CD4+ and CD8+ T cell responses were well maintained across all groups following a third vaccination. Finally, immune responses were also compared in patients who were vaccinated prior to or following ofatumumab treatment. Antibody responses were significantly higher in those patients who received their primary SARS-CoV-2 vaccination prior to initiating ofatumumab treatment. CONCLUSIONS: This study adds to the evolving understanding of SARS-CoV-2 vaccine responses in people with MS treated with disease-modifying therapies (DMTs) known to suppress humoral immunity. Our findings provide important information for optimizing vaccine immunity in at-risk MS patient populations.

Low Prevalence of Interferon-α Autoantibodies in People Experiencing Long COVID Symptoms.

Interferon (IFN)-specific autoantibodies have been implicated in severe COVID-19 and have been proposed as a potential driver of the persistent symptoms characterizing Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC). We report than only two of 215 SARS-CoV-2 convalescent participants tested over 394 timepoints, including 121 people experiencing Long COVID symptoms, had detectable IFN-α2 antibodies. Both had been hospitalized during the acute phase of the infection. These data suggest that persistent anti-IFN antibodies, although a potential driver of severe COVID-19, are unlikely to contribute to Long COVID symptoms in the post-acute phase of the infection.

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.

Values of COVID-19 Self-Testing among Urban and Rural South Africans: A Cross-Sectional Survey.

Self-testing for COVID-19 may be a preferable strategy for identifying SARS-CoV-2 infection among populations in low- and middle-income settings. To determine South Africans' values related to COVID-19 self-testing should it become widely available, a cross-sectional survey was administered in Durban, KwaZulu-Natal Province and the King Sabata Dalindyebo sub-district of the Eastern Cape. A 35-question survey was administered to 531 participants (268 female) in one urban and one rural setting of South Africa. Survey participants were randomly selected by household in the rural setting, while in the urban setting participants were approached in randomly selected public places. The survey assessed participants' likelihood of using and willingness to pay for a COVID-19 self-test and actions they would take following a COVID-19 self-test. The results were analysed using descriptive statistics and bivariate and multivariate regression. Overall, 93.03% of participants supported COVID-19 self-testing, 61.62% of participants were willing to pay for self-testing, and 90.15% indicated they would communicate their results if they tested positive. Rural participants were more positively associated with each of these outcomes compared with urban-based participants. Should they test positive, most participants said they would: go in-person to a health facility for counselling (76.45%), self-isolate (95.85%), notify close contacts (97.74%), and inform their employer (95.14%). COVID-19 self-testing was a preferable option for most participants, although this varied with setting and demographic characteristics. Self-testing may overcome barriers to care for South Africans, but to achieve this, policies for self-testing and delivery methods must not exacerbate individuals' underlying economic vulnerabilities.

Suicidal ideation in men during COVID-19: an examination of protective factors.

BACKGROUND: Men account for three-quarters of all suicide deaths in many Western nations including Australia. Whilst extensive research has examined risk factors for suicidal ideation and behaviour in men, protective factors remain underexplored, particularly social support, resilience and coping behaviours. Such factors are important to examine particularly in the context of COVID-19, where enforced isolation (among other negative lifestyle effects) has created widespread risk for the development of suicidal ideation. This mixed-methods study aimed to examine associations of various protective factors with suicidal ideation in men, using data from an online survey conducted during the COVID-19 pandemic. In addition, we aimed to qualitatively investigate men's self-reported protective strategies when experiencing suicidal thoughts and behaviour. METHODS: A convenience sample of 700 men (age M = 50.3 years; SD = 15.2 years) responded to an online survey including quantitative measures of suicidal ideation, planning and attempt, alongside employment and relationship status, coping, social support, resilience, and a qualitative free-text item gauging men's self-reported protective strategies. Multinomial logistic regression was applied to compare odds of sub-categories of suicide risk (ideation; planning) according to protective factors. Qualitative responses were analysed via thematic analysis. RESULTS: Men in a relationship, and those lower in emotion-focused and avoidant coping reported lower odds of suicidal ideation. Maintaining employment throughout the pandemic was protective against suicidal ideation and planning; as was greater perceived social support from friends. Greater self-reported resilience was protective against suicidal ideation and planning. Qualitative analyses led to the development of two themes: coping and connecting, reflecting men's intra- and interpersonal management strategies; and sustaining selflessness, where men's imaginings of the collateral damage of their suicidal behaviour was protective against action on suicidal thoughts or plans. CONCLUSIONS: Findings of this study speak to the nuanced roles of interpersonal connections, resilience and coping behaviours in protecting against suicidal ideation and planning in men. In addition, qualitative insights further cement men's identification with familial protector and/or provider roles as protective against suicidal action.

"I could hang up if the practitioner was a prat": Australian men's feedback on telemental healthcare during COVID-19.

The COVID-19 pandemic restrictions, uncertainties and management inconsistencies have been implicated in men's rising distress levels, which in turn have somewhat normed the uptake of telemental healthcare services (i.e., phone and/or video-conference-based therapy). Given past evidence of poor engagement with telemental health among men, this mixed-methods study examined Australian men's use of, and experiences with telemental health services relative to face-to-face care during the pandemic. A community sample of Australian-based men (N = 387; age M = 47.5 years, SD = 15.0 years) were recruited via Facebook advertising, and completed an online survey comprising quantitative items and open-response qualitative questions with the aim of better understanding men's experiences with telemental healthcare services. In total, 62.3% (n = 241) of participants reported experience with telemental health, and regression analyses revealed those who engaged with telemental health were on average younger, more likely to be gay and university educated. Men who had used telemental health were, on average, more satisfied with their therapy experience than those who had face-to-face therapy. Among those who had telemental healthcare, marginally lower satisfaction was observed among regional/rural based relative to urban men, and those who had to wait longer than 2 months to commence therapy. Qualitative findings highlighted positive aspects of telemental healthcare including comfort with accessing therapy from familiar home environments and the convenience and accessibility of telemental health alongside competing commitments and COVID-19 restrictions. Conversely, drawbacks included technical limitations such as crosstalk impeding therapeutic progress, disconnects and audio-visual lag-times and the 'impersonal' nature of telemental healthcare services. Findings broadly signal COVID-19 induced shifts norming of the use of virtual therapy services, with clear scope for improvement in the delivery of therapeutic practice using digital modalities, especially among help-seeking men.

It is time for a national strategy on equitable access to assistive technology in Canada.

The time has come to develop and implement a Canadian strategy on equitable access to Assistive Technology (AT). AT use has significant health, social, and economic benefits for people with disabilities and older people, and benefits society by assisting to mitigate the most prominent health and social challenges of our time. Our research with citizens (with/without experiences of disabilities or AT use) and system leaders across Canada determined that access is variable and inequitable, with unmet needs, restricted funding, and inefficiencies. Collaboratively, we devised a blueprint, comprising a policy vision, three priority issues to address, principles to underpin policy actions, and short- and long-term priorities, from which to build a strategy. We hope the blueprint sparks action among citizens and health leaders, especially those working across governments, sectors, and communities to promote leadership and create a cross-jurisdictional coalition to elaborate on a national strategy and action plans for moving forward.

Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq.

Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.

Reducing COVID-19 Health Inequities by Identifying Social Needs and Clinical Deterioration of Discharged Emergency Department Patients.

INTRODUCTION: The decision to discharge a patient from the hospital with confirmed or suspected coronavirus 2019 (COVID-19) is fraught with challenges. Patients who are discharged home must be both medically stable and able to safely isolate to prevent disease spread. Socioeconomically disadvantaged patient populations in particular may lack resources to safely quarantine and are at high risk for COVID-19 morbidity. METHODS: We developed a telehealth follow-up program for emergency department (ED) patients who received testing for COVID-19 from April 24-June 29, 2020 and were discharged home. Patients who were discharged with a pending COVID-19 test received follow-up calls on Days 1, 4, and 8. The objective of our program was to screen and provide referrals for health-related social needs (HRSN), conduct clinical screening for worsening symptoms, and deliver risk-reduction strategies for vulnerable individuals. We conducted retrospective chart reviews on all patients in this cohort to collect demographic information, testing results, and outcomes of clinical symptom and HRSN screening. Our primary outcome measurement was the need for clinical reassessment and referral for an unmet HRSN. RESULTS: From April 24-June 29, 2020, we made calls to 1,468 patients tested for COVID-19 and discharged home. On Day 4, we reached 67.0% of the 1,468 patients called. Of these, 15.9% were referred to a physician's assistant (PA) out of concern for clinical worsening and 12.4% were referred to an emergency department (ED) patient navigator for HRSNs. On Day 8, we reached 81.8% of the 122 patients called. Of these, 19.7% were referred to a PA for clinical reassessment and 14.0% were referred to an ED patient navigator for HRSNs. Our intervention reached 1,069 patients, of whom 12.6% required referral for HRSNs and 1.3% (n = 14) were referred to the ED or Respiratory Illness Clinic due to concern for worsening clinical symptoms. CONCLUSION: In this patient population, the demand for interventions to address social needs was as high as the need for clinical reassessment. Similar ED-based programs should be considered to help support patients' interdependent social and health needs beyond those related to COVID-19.

Course and Treatment of a Rare Neurological Sequelae After COVID-19: Miller Fisher Syndrome.

Reports of COVID-19 infection detailing its symptoms and outcomes point to its effects systemically, including that of the nervous system, such as the rare Miller Fisher syndrome (MFS). In this report, we identified a 43-year-old Caribbean man who arrived in the USA with ataxia and ascending bilateral lower extremity weakness after COVID-19 infection. Before arrival, the patient was diagnosed with Guillain-Barré syndrome (GBS). He was treated with IV methylprednisolone and a round of IV immunoglobulin (IVIG); however, he showed a minimal response. Upon admission to our ED, he had severe tachypnea and flaccid symmetrical quadriparesis combined with areflexia. Moreover, he had begun to exhibit signs of multiple cranial nerve palsies, including ophthalmoplegia and facial diplegia. Additionally, his laboratory cerebrospinal fluid (CSF) analysis was grossly normal. Therefore, he was diagnosed with MFS. Furthermore, he developed acute depression and exhibited signs of mania. The patient was treated with IV methylprednisolone and the second round of a five-day course of IVIG, resulting in marked clinical improvement. This case highlights the need for a multidisciplinary care approach in patients with MFS. It also points to the possible benefit of multiple IVIG rounds in MFS patients who do not improve after the first course.

Consensus docking and MM-PBSA computations identify putative furin protease inhibitors for developing potential therapeutics against COVID-19.

The coronavirus disease 2019 (COVID-19) is a pandemic that has severely posed substantial health challenges and claimed millions of lives. Though vaccines have been produced to stem the spread of this disease, the death rate remains high since drugs used for treatment have therapeutic challenges. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the disease, has a slew of potential therapeutic targets. Among them is the furin protease, which has a cleavage site on the virus's spike protein. The cleavage site facilitates the entry of the virus into human cells via cell-cell fusion. This critical involvement of furin in the disease pathogenicity has made it a viable therapeutic strategy against the virus. This study employs the consensus docking approach using HYBRID and AutoDock Vina to virtually screen a pre-filtered library of 3942 natural product compounds of African origin against the human furin protease (PDB: 4RYD). Twenty of these compounds were selected as hits after meeting molecular docking cut-off of - 7 kcal.mol-1, pose alignment inspection, and having favorable furin-ligand interactions. An area under the curve (AUC) value of 0.72 was computed from the receiver operator characteristic (ROC) curve, and Boltzmann-enhanced discrimination of the ROC curve (BEDROC) value of 0.65 showed that AutoDock Vina was a reasonable tool for selecting actives for this target. Seven of these hits were proposed as potential leads having had bonding interactions with catalytic triad residues Ser368, His194, and Asp153, and other essential residues in the active site with plausible binding free energies between - 189 and - 95 kJ/mol from the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations as well as favorable ADME/Tox properties. The molecules were also predicted as antiviral, anti-inflammatory, membrane permeability inhibitors, RNA synthesis inhibitors, cytoprotective, and hepatoprotective with probable activity (Pa) above 0.5 and probable inactivity values below 0.1. Some of them also have anti-influenza activity. Influenza virus has many similarities with SARS-CoV-2 in their mode of entry into human cells as both are facilitated by the furin protease. Pinobanksin 3-(E)-caffeate, one of the potential leads is a propolis compound. Propolis compounds have shown inhibitory effects against ACE2, TMPRSS2, and PAK1 signaling pathways of SARS-CoV-2 in previous studies. Likewise, quercitrin is structurally similar to isoquercetin, which is currently in clinical trials as possible medication for COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02056-1.

Consensus docking and MM-PBSA computations identify putative furin protease inhibitors for developing potential therapeutics against COVID-19

The coronavirus disease 2019 (COVID-19) is a pandemic that has severely posed substantial health challenges and claimed millions of lives. Though vaccines have been produced to stem the spread of this disease, the death rate remains high since drugs used for treatment have therapeutic challenges. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the disease, has a slew of potential therapeutic targets. Among them is the furin protease, which has a cleavage site on the virus’s spike protein. The cleavage site facilitates the entry of the virus into human cells via cell–cell fusion. This critical involvement of furin in the disease pathogenicity has made it a viable therapeutic strategy against the virus. This study employs the consensus docking approach using HYBRID and AutoDock Vina to virtually screen a pre-filtered library of 3942 natural product compounds of African origin against the human furin protease (PDB: 4RYD). Twenty of these compounds were selected as hits after meeting molecular docking cut-off of − 7 kcal.mol−1, pose alignment inspection, and having favorable furin-ligand interactions. An area under the curve (AUC) value of 0.72 was computed from the receiver operator characteristic (ROC) curve, and Boltzmann-enhanced discrimination of the ROC curve (BEDROC) value of 0.65 showed that AutoDock Vina was a reasonable tool for selecting actives for this target. Seven of these hits were proposed as potential leads having had bonding interactions with catalytic triad residues Ser368, His194, and Asp153, and other essential residues in the active site with plausible binding free energies between − 189 and − 95 kJ/mol from the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations as well as favorable ADME/Tox properties. The molecules were also predicted as antiviral, anti-inflammatory, membrane permeability inhibitors, RNA synthesis inhibitors, cytoprotective, and hepatoprotective with probable activity (Pa) above 0.5 and probable inactivity values below 0.1. Some of them also have anti-influenza activity. Influenza virus has many similarities with SARS-CoV-2 in their mode of entry into human cells as both are facilitated by the furin protease. Pinobanksin 3-(E)-caffeate, one of the potential leads is a propolis compound. Propolis compounds have shown inhibitory effects against ACE2, TMPRSS2, and PAK1 signaling pathways of SARS-CoV-2 in previous studies. Likewise, quercitrin is structurally similar to isoquercetin, which is currently in clinical trials as possible medication for COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-02056-1.

Male-Type Depression Mediates the Relationship between Avoidant Coping and Suicidal Ideation in Men.

Despite known links between men's avoidant coping behaviours (e.g., distraction, denial, substance use) and suicide risk, little research has explored the mechanisms underpinning this relationship. This study sought to examine whether male-type depression symptoms (e.g., anger, aggression, emotion suppression), assessed by the Male Depression Risk Scale, mediate the association between avoidant coping and suicide/self-harm ideation in men. Data were drawn from an online survey of a community sample of 606 Australian men (M age = 50.11 years; SD = 15.00), conducted during the COVID-19 pandemic. Mediation analyses were applied to examine the effect of male-type depression on the association between avoidant coping and suicidal/self-harm ideation, controlling for age, resilience and the experience of two psychosocial stressors during the COVID-19 pandemic (financial stress and government restrictions). Avoidant coping was associated with suicidal/self-harm ideation, r = 0.45, p < 0.001. Results supported a mediating role of male-type depression symptoms in this relationship, R2= 0.29, PM = 0.36, p < 0.001, underscoring the importance of screening for male-type depression symptoms to better identify men at risk of suicidal/self-harm ideation. Results also suggest a need to support men to develop effective coping strategies, particularly in the context of common psychosocial stressors experienced during the COVID-19 pandemic and beyond.