1  Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide. COVID-19 is highly contagious and can result in acute respiratory distress, multiple organ failure, or death in severe cases (Huang et al., 2020a, Wang et al., 2020, Yang et al., 2020, Zhang et al., 2020). The reported mortality rate of COVID-19 is lower than that of severe acute respiratory syndrome (SARS) (Donnelly et al., 2003), or Middle East respiratory syndrome (MERS) (Ahmed, 2017). However, the number of patients needing urgent critical care is remarkably larger than previous outbreaks of SARS or MERS, which could lead to a critical shortage of intensive care unit (ICU) beds and specialized medical and nursing personnel, and, consequently, result in the collapse of local health care systems. Thus, timely and appropriate dynamic monitoring and treatment for non-ICU inpatients is urgent and necessary to reduce the risk of patients becoming critically ill and requiring ICU care.
Patients with COVID-19 typically present a decrease in absolute lymphocyte count (ALC) (Huang et al., 2020a, Wang et al., 2020). The dynamic profile of total circulating lymphocytes indicated that a continuous and sustained decrease in the ALC is closely associated with disease aggravation and death in COVID-19 patients (Wang et al., 2020, Zhou et al., 2020). Indeed, lymphopenia was associated with increased disease severity in COVID-19 (Tan et al., 2020). In addition, the neutrophil-to-lymphocyte ratio (NLR) can also serve as a simple complementary indicator to predict clinical severity and prognosis, and is an independent risk factor for mortality in patients with COVID-19 (Lagunas-Rangel, 2020, Qin et al., 2020, Liu et al., 2020). These studies indicate that promoting recovery from lymphopenia and slowing the deterioration based on an increased NLR may reduce the need for ICU care and improve the prognosis of patients with COVID-19.
To date, no specific drugs have been shown to be effective in alleviating lymphopenia in patients with COVID-19. Sleep is a physiological and behavioral process required for survival and plays an important role in metabolism and immune system homeostasis (Besedovsky et al., 2019, Haspel et al., 2020, Mukherjee et al., 2015); indeed, sleep and immunity are bidirectionally linked (Besedovsky et al., 2019). Sleep disturbance impairs innate and adaptive immune responses and activates inflammation, with an increase in circulating inflammatory cytokines due to disruption of the circadian rhythms (Haack et al., 2007, Irwin, 2015, Vgontzas et al., 2004). Short-term sleep deprivation is associated with compromised natural killer cell activity in the blood (Fondell et al., 2011). Disruption of the circadian rhythm of sleep, shorter sleep duration, or poor quality of sleep could increase susceptibility to upper respiratory infections (Cohen et al., 2009, Loef et al., 2019, Patel et al., 2012, Prather et al., 2015). In fact, septic patients with frequently disrupted sleep have higher mortality rates (Huang et al., 2014). Sleep impairment occurs frequent in patients with COVID-19 (Liguori et al., 2020), which may be due to isolated environment without family member’ companion, physical discomfort caused by the illness, or psychological factor (fear, anxiety, helplessness and/or depression, etc.) (Guo et al., 2020). However, there are currently no reports of the effects of sleep quality during hospitalization on immune function recovery and prognosis in patients with COVID-19. In tour study, we aimed to describe the effects of self-reported sleep quality on recovery from lymphopenia, deterioration based on an increased NLR, and clinical outcomes in hospitalized patients with COVID-19.