ObjectiveThe prevalence of mental distress has been noted in shelter hospitals set up for COVID-19. Potential risk demographic and hospitalization factors were screened. We also aimed to determine whether humanistic care established in the shelter hospital was effective in ameliorating mental distress.MethodsA cross-sectional observational survey-based single-centered study was conducted from 28th April to 5th May 2022 during the COVID-19 pandemic in Shanghai. Asymptomatic adult inpatients and those with mild symptoms were recruited for this study, and humanistic care measures were carried out by the administrative office according to the Work Program on Psychological Assistance and Social Work Services at the Shelter Hospital launched on 5th March 2020. Symptoms of mental distress, such as reported stress, anxiety, depression, and insomnia were measured using the Chinese Stress Response Questionnaire-28, the Chinese version of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index-7, respectively.ResultsIn total, 1,246 out of 9,519 inpatients, including 565 (45.35%) women and 681 (54.65%) men, with a median age of 36 years responded to the survey. The overall prevalence of stress, anxiety, depression, and insomnia in inpatients was 94 (7.54%), 109 (8.75%), 141 (11.32%), and 144 (11.56%), respectively. Mental distress was aggravated by COVID-19-related symptoms, comorbidities, and prolonged hospital stays. A stable internet connection was the most effective measure to reduce stress and depression. Offering inpatient with study or work facilitations, and mental health education help to ameliorate anxiety and depression. Organizing volunteering was a potential protective factor against stress.ConclusionHumanistic care is crucial and effective for protecting against mental distress, which should be emphasized in shelter hospitals.