Pathogenic human coronaviruses such as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent MERS indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared to age matched females. The degree of sex-bias to SARS-CoV infection increased with advancing age such that middle-aged mice showed much more pronounced differences compared to young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages (IMMs) and neutrophils in the lungs of male mice and depletion of IMMs partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.

The Middle East Respiratory Syndrome-coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived but the virus-specific T cell response has not been addressed in MERS patients. Here, we obtained PBMCs and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4 and CD8 T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT50) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4 but not CD8 T cell responses; patients with higher PRNT50 and CD4 T cell responses had longer ICU stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8 T cell responses comparable to those of the whole cohort. There were no correlations between age, disease severity, co-morbidities and virus-specific CD8 T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.

Background: Coronavirus disease 2019 (COVID-19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID-19 severity. Objective: To compare outcomes in hospitalized adults with severe COVID-19 treated with standard prophylactic versus intermediate dose enoxaparin. Methods: We conducted a multi-center, open-label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID-19 and admitted to an intensive care unit (ICU) and/ or had laboratory evidence of coagulopathy. Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weightadjusted dose enoxaparin. The primary outcome was all-cause mortality at 30 days.Secondary outcomes included arterial or venous thromboembolism and major bleeding.Results: A total of 176 patients (99 males and 77 females) underwent randomization. In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30-1.45; P = .31 by Chi-square test). Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33-1.37; P = .28). Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm. Conclusion:In hospitalized adults with severe COVID-19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.

The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.

Study Objective: Among a comprehensive range of frontline emergency department health care personnel, we assessed symptoms of anxiety and burnout, specific coronavirus disease 2019 (COVID-19) work-related stressors, and risk for posttraumatic stress disorder (PTSD). We also determined whether COVID-19 serologic testing of HCP decreased their self-reported anxiety.Methods: In a prospective cohort study from May 13, 2020, to July 8, 2020, we used electronic surveys to capture participant self-reported symptoms before and after serologic testing for anti-SARS-CoV-2 immunoglobulin G antibodies. Participants were physicians, nurses, advanced practice providers, and nonclinical ED personnel at 20 geographically diverse United States EDs. We evaluated these domains: 1) the effects of the COVID-19 pandemic on overall stress and anxiety; 2) COVID-19-related work stressors; 3) burnout; and 4) PTSD risk (measured using the Primary Care-PTSD Screen for DSM-5, a 5-item screening instrument in which a score of 3 signifies high risk for PTSD). We also assessed perceptions of whether results of COVID-19 antibody testing decreased participants' self-reported anxiety.Results: Of 1,606 participants, 100% and 88% responded to the baseline and follow-up surveys, respectively. At baseline, approximately half (46%) reported symptoms of emotional exhaustion and burnout from their work, and 308 (19.2%, 95% confidence interval [CI] 17.3% to 21.1%) respondents screened positive for increased PTSD risk. Female respondents were more likely than males to screen positive (odds ratio [OR] 2.03, 95% CI 1.49 to 2.78). Common concerns included exposing their family and the health of coworkers diagnosed with COVID-19. After receiving antibody test results, 54% (95% CI 51.8 to 56.7) somewhat agreed, agreed, or strongly agreed that knowledge of their immune status had decreased their anxiety. A positive serology result indicating prior SARS-CoV-2 infection was associated with a higher likelihood of reporting decreased anxiety (2.83, 95% CI 1.37 to 5.83). Conclusion:Symptoms of anxiety and burnout were prevalent across the spectrum of ED staff during the COVID-19 pandemic. One-fifth of ED personnel appeared to be at risk for PTSD. Increased provision of serologic testing may help to mitigate anxiety.