Sleep and wake impairment in patients with SARS-CoV2 infection.

To the Editor,

The 2019 novel Coronavirus Disease (COVID-19) is unquestionably a worldwide life-threatening condition causing severe acute respiratory distress [1]; however, pauci-symptomatic or non-severe forms of pneumonia currently represent the more frequent manifestations of the infection [2]. In this pandemic contest, clinicians should be aware of the possibility that extra-pulmonary symptoms may happen in patients with non-severe respiratory form of COVID-19; specifically, neurological symptoms merit clinical attention and appropriate treatments in order to reduce the patients' disease burden [3,4].

Our NeuroCOVID-19 group performed a prospective observational study focused on the occurrence of subjective neurological symptoms in hospitalized patients with a non-severe respiratory form of COVID-19 [4]. Here, we present data deriving from a secondary analysis of the previous study with the aims to emphasize and deepen the frequency of sleep and wake impairment in patients with SARS-CoV2 infection and their relationships with the other neurological symptoms, white blood cells (WBC), C-reactive protein (CRP), and days of hospitalization.

A total of 103 patients with SARS-CoV2 infection were included in the study. Among them, 51 patients reported sleep impairment and 34 patients complained daytime sleepiness (Table 1 ). Furthermore, only 11 patients concurrently reported sleep impairment and daytime sleepiness. Considering patients with sleep impairment, they had higher CRP serum levels, more frequent dysgeusia, headache, and dizziness, and more concomitant neurological symptoms than patients without sleep alteration (Table 1). As regard patients with daytime sleepiness, they were more frequently female and presented higher CRP serum levels, lower WBC, more frequent confusion and muscle ache and, generally, more concomitant neurological symptoms than patients without daytime sleepiness.

Table 1

Demographic, clinical, laboratory, and neurological data of patients with SARS-CoV2 infection.

	Sleep Impairment		P Value	Daytime Sleepiness		P Value
	Yes(N = 51)	No(N = 52)		Yes(N = 34)	No(N = 69)
Sex (F, M)	18, 33	26, 26	NS	21, 13	23, 46	0,006
Age (Mean ± SD)	56,71 ± 12,76	54 ± 14,88	NS	52,1 ± 15,76	56,18 ± 13,36	NS
CRP (Mean ± SD)	32,15 ± 45,97	14,05 ± 26,14	0,021	25,56 ± 40,74	16,78 ± 30,67	0,039
WBC (x109/L) (Mean ± SD)	9,71 ± 7,82	7,97 ± 5,31	NS	6.19 ± 1.61	9.96 ± 7.37	0,033
Neutrophil, count (Mean ± SD)	5,85 ± 4,51	5,91 ± 5,6	NS	3,95 ± 1,95	7 ± 6,15	NS
Lymphocyte, count (Mean ± SD)	3,15 ± 7,57	1,57 ± 0,69	NS	1,55 ± 0,74	2,4 ± 5,43	NS
Neutrophil, %WB (Mean ± SD)	0,65 ± 0,22	0,66 ± 0,16	NS	0,61 ± 0,15	0,68 ± 0,2	NS
Lymphocyte, %WB (Mean ± SD)	0,24 ± 0,21	0,24 ± 0,12	NS	0,26 ± 0,13	0,22 ± 0,17	NS
Days of Hospitalization (Mean ± SD)	7,69 ± 7,13	8,53 ± 8,6	NS	6,12 ± 6,03	9,26 ± 8,78	NS
Temperature (Mean ± SD)	36,61 ± 0,84	36,51 ± 0,61	NS	36,54 ± 0,69	36,54 ± 0,69	NS
Hyposmia n	43	16	NS	15	23	NS
Dysgeusia n	52	18	0,032	18	27	NS
Auditory Dysfunction n	2	1	NS	1	1	NS
Headache n	49	17	0,033	17	25	NS
Confusion n	28	8	NS	13	10	0,004
Dizziness n	34	9	0,035	11	16	NS
Numbness/Paresthesia n	4	2	NS	2	2	NS
Fatigue n	36	12	NS	7	22	NS
Daytime Sleepiness n	24	20	NS	NA	NA	NA
Sleep Impairment n	NA	NA	NA	12	35	NS
Muscle Ache n	26	20	NS	16	17	0,013
Depression n	39	16	NS	12	24	NS
Anxiety n	34	17	NS	15	20	NS
N Symptoms (Mean ± SD)	5,3 ± 2,17	3,03 ± 2,48	0,0001	5,12 ± 2,45	3,18 ± 2,45	0,001

Abbreviations: F, female; M, male; n, number; SD, standard deviation; NS, not significant; NA, not admitted; WBC, white blood cells; CRP, C-reactive protein.

Based on the results of this secondary analysis, it appears evident that sleep and wake impairment are common complaints in patients with COVID-19. Quite many patients did not concurrently report both symptoms; thus, it is possibly to hypothesize different causal pathological mechanisms. In fact, intrinsic properties of the virus, as well as the immune and inflammatory responses, may cause both sleep and wake impairment; however, also hospitalization per se may damage sleep and alter wake in patients with SARS-CoV2 infection [4,5].

Considering the high number of patients with COVID-19 and the increasing number of non-severe respiratory illness due to SARS-CoV2 infection, this secondary investigation highlights the importance of monitoring and treating neurological symptoms in patients with COVID-19 in order to reduce the burden of the disease. Moreover, whether a better sleep quality can improve disease severity and reduce the time to recovery needs to be studied in a longitudinal follow-up investigation. Finally, with this very preliminary observation, we suggest further studies specifically identifying sleep and wake problems in patients with COVID-19 and highlighting the opportunity to perform studies with validated questionnaires and scales, or polysomnography, to better characterize sleep impairment in patients with SARS-CoV2 infection. Moreover, considering the neurotrophic properties of the virus, longitudinal follow-up should be planned to monitor the occurrence of future sleep disorders triggered by the infection.