Clinical Symptom Influence on The Time of Nucleic Acid Conversion to Negative in COVID-19 Patients with SARS-CoV-2 Omicron Variant: A Retrospective Observational Study

doi:10.21203/rs.3.rs-4938608/v1

Background

The duration for COVID-19 patients to achieve a negative nucleic acid test result is influenced by various factors. This study aimed to explore the influences of clinical symptoms of COVID-19 on the time required for nucleic acid test results to become negative.

Methods

This retrospective study enrolled a total of 486 participants infected with COVID-19 who were aged ≥ 18 years and hospitalized at Shanghai Lingang Make-shift Hospital between April 10, 2022, and May 20, 2022. The clinical data included patient demographics, clinical symptoms, and the time of nucleic acid conversion to negative, all assessed using a cross-sectional study method.

Results

This study included COVID-19 patients with a median age of 38, comprising 66.0% males and 34.0% females. Multiple linear regression analyses demonstrated a significant positive correlation between the time of nucleic acid conversion to negative and the clinical symptoms of throat pain among patients with COVID-19 (β = 0.845, 95% CI: 0.123–1.567, P ≤ 0.05). Logistic regression analysis showed that throat pain had a significant negative effect on the 7-day negative nucleic acid conversion rate (OR = 0.586, 95%CI:0.390–0.880, P ≤ 0.01), as did diarrhea(OR = 0.541, 95%CI = 0.295–0.989, P ≤ 0.05).

Conclusion

The varying clinical symptoms influence the time to negative nucleic acid test results in COVID-19 patients, indicating that these symptoms should receive special attention in clinical treatment to optimize therapy and shorten recovery time.

clinical symptoms

COVID-19

SARS-CoV-2 omicron variant

the time to negative nucleic acid test

seven-day conversion rate to negative

The COVID-19 pandemic has significantly affected global health and economies ^1–5. SARS-CoV-2, the novel coronavirus responsible for COVID-19, primarily spreads through respiratory droplets, leading to lung infections⁶.Despite advancements in vaccines and treatments, diagnosing and managing COVID-19 remain challenging. Infected individuals are categorized based on illness severity: asymptomatic, mild, moderate, or severe. Patients with mild-to-moderate COVID-19 typically display mild clinical symptoms but risk progressing to severe disease if not properly managed ⁷. Therefore, it is crucial to control disease progression in patients with mild-to-moderate COVID-19.

Nucleic acid testing, which mainly detects the presence of viral genomic components, is most commonly recommended to detect novel coronaviruses. By collecting DNA or RNA from patient samples, laboratories can use the polymerase chain reaction (PCR) to amplify and test specific genetic sequences of viruses. This highly sensitive and specific method allows for quick and accurate diagnosis of infections caused by the novel coronavirus^8–12. During hospitalization, achieving a negative SARS-CoV-2 RNA test is crucial for discharge criteria. Previous results have indicated that the time of nucleic acid conversion to negative(TNACN ) varies among individuals, influenced by factors, such as age, sex, vaccination status, underlying medical conditions, immune response strength, viral load, and lymphocyte count^13–18. Additionally, treatment and clinical management can impact the results of negative nucleic acid tests^19–25.

Clinical symptoms play a crucial role in the progression of COVID-19, serving as important indicators of patients' subjective experiences and disease severity²⁶. Understanding the relationship between these symptoms and the transition to negative nucleic acid tests is essential for optimizing treatment strategies and predicting disease outcomes. Research indicates that the time to negative COVID-19 nucleic acid tests is significantly prolonged in patients experiencing fever or nausea²⁷. Xiaowen Hu et al. identified age over 45 and chest tightness as independent risk factors for COVID-19 ²⁸. Additionally, patients with digestive symptoms had a longer interval from symptom onset to viral clearance (P < 0.001) and had a higher likelihood of testing positive for the virus in fecal samples (P = 0.033) compared to those with respiratory symptoms²⁹. However, the correlation between nucleic acid conversion time and clinical symptoms in patients with mild or moderate COVID-19 remains unclear.

This study aimed to investigate the relationship between the clinical symptoms of COVID-19 patients and the time of nucleic acid conversion to negative, analyzing the factors influencing this transition time. By collecting clinical data and laboratory test results from patients, we will analyze the type and duration of symptoms that patients experience after infection with the novel coronavirus and the trends between these symptoms and nucleic acid test results. Additionally, we will consider factors (e.g., age, sex, and underlying diseases) to explore their impact on the nucleic acid-negative time. Through this study, will reveal the correlation between the time of nucleic acid conversion to negative and clinical symptoms in mild COVID-19 patients, providing a new scientific basis for personalized treatment plans, predicting rehabilitation, and prevention and control measures.

This retrospective study collected clinical data of patients hospitalized at Shanghai Lingang Makeshift Hospital from April 10, 2022, to May 20, 2022, using a cross-sectional study design. This study protocol was approved by the Ethics Committee of Zhongda Hospital, Southeast University (approval No. 2022ZDSYLL222-P01). However, informed consent was waived due to the nature of retrospective analysis.

Inclusion and exclusion criteria

The inclusion criteria were as follows: (i) diagnosed with light or asymptomatic COVID-19 in the Lingang Shelter Hospital; (ii) aged ≥ 18 years; and (iii) were available to complete the questionnaire. The exclusion criteria were: (i) with serious cardiovascular or cerebrovascular diseases; (ii) with severe diseases affecting the liver, kidneys, blood, or immune system; or (iii) with a history of major surgery.

Clinical characteristics collection

Patient data on general conditions and clinical symptoms were collected by attending physicians within 24 hours of admission using a standardized questionnaire. All doctors involved in data collection received pre-unified training. Upon discharge of the patient, their data is collected through the background system, including age, sex, body mass index (BMI), smoking status, vaccination status, underlying conditions, medication history, clinical symptoms, and the timing of nucleic acid test results turning negative. According to the U.S. Centers for Disease Control and Prevention (CDC) guidelines, smokers are those who have smoked at least 100 cigarettes and continue to smoke. In contrast, nonsmokers are those who have smoked < 100 cigarettes ³⁰. Vaccination status was categorized as unvaccinated (no doses of the COVID-19 vaccine) or vaccinated (having received one, two, or three doses). Clinical symptoms encompassed common respiratory symptoms (e.g., fever, cough, nasal congestion, chest tightness, bitter taste, shortness of breath, dry mouth, headache, runny nose, and throat pain), and systemic symptoms such as fatigue, excessive sweating, muscle pain, palpitations, loss of appetite, gastrointestinal reactions, and insomnia. Used drugs refer to those that have been used related antiviral drugs, immune-enhancing drugs and traditional Chinese medicines to treat COVID-19, and unused medicines are those that have not been used that could affect recovery from COVID-19.

Outcome follow up

The study focused on two main outcomes: the duration of nucleic acid conversion and the seven-day conversion rate. Nucleic acid results were obtained through pharyngeal swab testing. The time of nucleic acid conversion to negative is measured from the day the patient initially tested positive for nucleic acid, with the endpoint being the first day on which two consecutive negative nucleic acid results are observed.

Statistical analysis

The statistical analysis was conducted by employing SPSS 23.0 software. Categorical data were reported as frequencies (%), while continuous data were presented as mean ± standard deviation (χ ± s). Descriptive statistics were employed to summarize the general data. To examine the relationship between clinical symptoms and the time of nucleic acid conversion to negative, we utilized t-tests, and multiple regression analysis. We used pearson's Chi-square test and binary logistic regression modeling to explore the association between patients' clinical symptoms and the 7-day negative conversion rates. These analytical techniques calculated compute odds ratios and 95% confidence intervals (CIs). The nucleic acid negative time of ≤ 7 days was coded as 1, and > 7 days was 0. The potential confounding factors include age, sex, BMI, smoking status, underlying health conditions, vaccination status, and medication use. Statistical significance was determined with a threshold of P < 0.05.

As of May 20, 2022, a total of 544 COVID-19 patients were initially identified as potentially eligible for the study. However, 38 patients could not have their nucleic acid conversion time to negative status determined due to being transferred to other makeshift or designated hospitals. Additionally, six patients were excluded due to age restrictions, and 14 because of incomplete information. Consequently, 486 patients were included in the final analysis.

Demographic characteristics

This study involved 486 patients affected with the COVID-19 Omicron variant. Among them, 66.0% were men, and their median age was 38 years. Asymptomatic patients accounted for 11.32%, and symptomatic patients accounted for 88.68%. The median BMI was 23.34. A total of 153 (31.5%) patients had a history of smoking, and 333 (68.5%) had no history of smoking. Among the patients, 75 individuals, representing 15.4% of the total cohort, had a history of chronic disease. However, 454 patients (93.4%) had received vaccination, and 254 patients (52.26%) were undergoing drug therapy (Figure 1).

Association between the time of nucleic acid conversion to negative and the clinic symptoms

The t-tests results showed that patients with chronic diseases, throat pain, and muscle pain symptoms had a longer time of nucleic acid conversion to negative (P ≤0.05 or P ≤0.01, Table 1). These findings suggest that the time of nucleic acid conversion to negative may be related to chronic disease, throat pain, and muscle pain symptoms in patients.

Significant variables from the t-tests, including chronic diseases, throat pain, and muscle soreness, were taken as independent variables, while the time of nucleic acid conversion to negative were considered dependent variables for the linear regression analysis. As shown in table 2, the chronic diseases significantly positively affect the time of nucleic acid conversion to negative (β= 1.170,95% CI=0.262–2.079，P = 0.012< 0.05) , the throat pain significantly positively affect the time of nucleic acid conversion to negative (β= 0.845,95% CI=0.123–1.567, P = 0.022< 0.05). The muscular soreness did not impact the number of days when nucleic acids turned negative（P＞0.05, Table 2 and Figure 2).

Relationship Between Clinical Symptoms and the 7-Day Negative Nucleic Acid Conversion Rate (NNACR) in COVID-19 Patients

Pearson's Chi-square test and Fisher's exact probability test were employed to examine differences between the study groups. The analysis revealed significant correlations between the 7-day NNACR and factors, such as cough, dry pharynx, sore pharynx, dry mouth, diarrhea, vaccination, and drug use (P < 0.05) (Table 3 and Figure 3).

Significant variables identified through the Pearson Chi-square test such as cough, dry pharynx, sore throat, dry mouth, diarrhea, vaccination status, and drug use were considered as independent variables. The 7-day negative conversion rate of nucleic acid was used as the dependent variable for logistic regression analysis (the independent variable screening method was forward LR stepwise method). After automatic identification by the model, the remaining 3 items, including vaccination, throat pain and diarrhea, were finally included in the model. As shown in figure 4, the vaccination had a significant negative effect on the 7-day NNACR (P = 0.004 < 0.01). Throat pain had a significant negative effect on the 7-day NNACR (P = 0.010 < 0.05), as did diarrhea (P = 0.046 < 0.05) (Figure 4

In this work, we focused on the COVID-19 patients with Omicron variant strain at Shanghai Lingang Makeshift Hospital to explore the correlation between their symptoms and the time required for nucleic acid negativity. The results showed that symptoms of throat pain were often accompanied by a significantly prolonged negative time for COVID-19 nucleic acids, and there was a significant correlation between the two. Furthermore, the 7-day NNACR was significantly lower in patients presenting with both throat pain and diarrhea, underscoring the impact of different symptoms on the nucleic acid negative conversion timeline.

The global SARS-CoV-2 pandemic has presented significant challenges to human health. Nucleic acid detection is the primary method of diagnosing COVID-19 infection ^8–12. The time of nucleic acid conversion to negative has become an important indicator of disease progression, patient recovery, and public health decision-making. This " time of nucleic acid conversion to negative" is defined as the interval from the first positive test to the first negative result. Research indicates that this period varies based on individual differences and disease severity, typically ranging from 1 to 3 weeks. However, various factors can affect this process, resulting in different lengths of time for nucleic acids to turn negative. Studies have found that the length of time for COVID-19 to become negative is closely related to the viral load, patient age, underlying diseases, health status, treatment measures, and living environment. Patients with a higher initial viral load usually take longer to clear the virus from the body¹⁸, thus prolonging the nucleic acid transition to a negative state. Older patients have relatively weak immune function, resulting in a slower virus clearance rate and a prolonged nucleic acid transition time. Children and young people generally recover faster with shorter nucleic acid transition times ⁷. Patients with chronic conditions like diabetes, hypertension, cardiovascular disease ⁷, or immune deficiencies tend to experience longer durations before achieving negative nucleic acid test results. The early use of antiviral drugs and effective symptomatic treatment can significantly shorten the negative nucleic acid transition time ^22–25. The strength of an individual's immune system directly affects the viral clearance rate. An immune overreaction (such as a cytokine storm) may lead to a severe inflammatory response ¹⁷, prolonging the negative nucleic acid transition time. Additionally, good nutritional support, a healthy lifestyle, and vaccination are conducive to the normal functioning of the immune system ⁷, shortening the negative nucleic acid time. In clinical practice, developing a personalized treatment plan based on each patient's unique conditions is essential. This approach helps accelerate the negative conversion of nucleic acids, minimizes the risk of transmission, and ensures the health and well-being of the patient.

According to clinical observations and research, the symptoms of COVID-19 are diverse and show individual differences and complexities. This work focuses on the symptoms of COVID-19 patients to gain insight into the clinical manifestations and the COVID-19 characteristics. Respiratory symptoms are prevalent among COVID-19 patients, which include sore throat, headache, nasal congestion, runny nose, dry cough, dyspnea, and chest tightness. Additionally, digestive symptoms such as nausea, vomiting, and diarrhea are also relatively common ^31–34. These symptoms may have resulted from an inflammatory response caused by a virus invading the intestine ³⁵. Additionally, some patients with COVID-19 experience muscle soreness, fatigue, taste loss, abnormal taste, and excessive sweating. Previous studies have shown a correlation between fever, gastrointestinal symptoms, chest tightness, and negative nucleic acid transition time in patients ^27–28.

Fever is the predominant symptom observed in patients with SARS-CoV-2 ^36,37. Studies have indicated that fever might serve as a clinical marker for poor prognosis, as it is associated with the release of inflammatory mediators by the body during febrile episodes ^38,39. These inflammatory mediators can induce tissue damage and organ dysfunction by promoting the production of toxic oxygen derivatives. This suggests that individuals infected with SARS-CoV-2 who experience fever may have an extended time to achieve negative nucleic acid test results ^40,41. Several studies have discovered that the angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is present in both the upper and lower gastrointestinal tracts, with expression levels nearly 100 times higher than those in respiratory organs ^42,43. Patients exhibiting digestive symptoms often have higher concentrations of intestinal viruses ^44, which can lead to damage to the intestinal mucosa. Ya Yang et al²⁷ observed that digestive symptoms, including nausea and diarrhea, were associated with an extended duration of nucleic acid conversion to negative in COVID-19 patients.

This study showed that throat pain symptoms often experience a significantly prolonged negative time for COVID-19 nucleic acid transition, and there is a significant correlation between the two. Additionally, patients with throat pain and diarrhea had a significantly lower rate of negative transformation 7 days after COVID-19. Throat pain commonly arises from the release of inflammatory mediators in the airway triggered by SARS-CoV-2 infection, which impacts the sensory nerves in the throat tissue ⁴⁵. This indicates more severe upper respiratory tract inflammation ^46,47 and slower disease recovery. Moreover, The symptom of throat pain can impact a patient’s ability to eat and rest properly, potentially compromising their immune system’s effectiveness against the virus. This could account for the observation that COVID-19 patients experiencing throat pain symptoms often require a longer time to achieve a negative nucleic acid test result. Additionally, diarrhea is a frequently observed symptom in COVID-19 infections. Its occurrence indicates that the virus not only affects the respiratory system but may also invade the digestive tract ³⁵, increasing the complexity and scope of the infection and thus prolonging the negative nucleic acid time. Diarrhea can lead to fluid and electrolyte imbalances and intestinal flora disorders, weakening the immune system's function and reducing the body's efficiency in fighting viruses. This condition is often accompanied by diarrhea, which may further reduce the body's natural immune defenses. Therefore, it usually takes longer for COVID-19 patients with diarrheal symptoms to achieve a negative nucleic acid transition. Treating patients with throat pain and diarrhea may be an effective strategy to accelerate the negative nucleic acid transformation process in COVID-19 patients. Therefore, in clinical practice, it is crucial to closely monitor and intervene in patients' symptoms, particularly those that have a significant impact on the time it takes for nucleic acid tests to return negative. Effective treatment measures should be taken to improve patients' cure rate and recovery speed.

This study had limitations. First, it was conducted during an outbreak primarily driven by the Omicron BA.5.2 variant of the coronavirus, which means the research focused exclusively on this specific strain. Consequently, the effects of other COVID-19 variants on clinical symptoms and outcomes are not addressed by this study. Second, only asymptomatic and mild patients were admitted to the Shanghai Lingang Makeshift Hospital, while ordinary and severe patients were treated in designated hospitals. Therefore, we could not evaluate the correlation between clinical symptoms and nucleic acid-negative times in normal and severely ill patients. Third, due to the retrospective observational study design, our inferences may be prone to residual confounding bias.

Future research should include clinical trials focusing on various COVID-19 strains, involving larger sample sizes, extended time periods, and multiple geographic regions. These studies could offer deeper insights into how clinical symptoms influence the negative conversion of COVID-19 nucleic acids, thereby providing a more comprehensive reference and guidance for the diagnosis and treatment of COVID-19 patients.

This study explored how various symptoms are related to the time required for nucleic acid test results to turn negative in COVID-19 patients with Omicron variant, specifically at the Shanghai Lingang Makeshift Hospital. The results showed that patients with the symptom of throat pain tended to experience a longer negative nucleic acid transition, with a significant correlation between the two. Additionally, patients experiencing throat pain and diarrhea exhibited a markedly lower rate of negative nucleic acid conversion within 7 days. These findings underscore the impact of various clinical symptoms on the duration of negative nucleic acid conversion in COVID-19 patients. They suggest that addressing these symptoms with heightened attention in clinical practice could help optimize treatment strategies and potentially accelerate patient recovery.

Ethics approval and consent to participate: This study was approved by the Ethics Commission for Clinical Research at Zhongda Hospital, Southeast University, registered under Approval No. 2022ZDSYLL222-P01. The research adhered to the principles outlined in the Declaration of Helsinki, ensuring the confidentiality of all patient information. Informed consent was waived due to the nature of the study as a retrospective study.

Consent publication:Not applicable.

Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interest: The authors declare that they have no competing interests.

Funding: This study was funded by National Key R&D Program of China (grant number 2022YFC2304600), National Natural Science Foundation of China (grant number 82272235), Jiangsu Province Key research and development Program (Social Development) Special Project (grant number BE2021734), Jiangsu Province Traditional Chinese and Western Medicine Collaborative Flagship Hospital Construction Project (grant number CZXM-ZK-33), National Traditional Chinese and Western Medicine Flagship Department Construction Project - Intensive Care Medicine (grant number CZXM-ZK-46).

Authors’ contribution: Hui Feng conceived and designed the study. Hui Feng performed the main data collection and analyses under supervision of Xiang Hong and Shanhu Qiu and Shaolei Ma. Hui Feng wrote the draft of the manuscript. Yingzi Huang gives overall direction to the work. All authors have contributed to, seen, and approved the final, submitted version of the manuscript.

Acknowledgements:We sincerely thank all the participants for their cooperation in this study. Additionally, we would like to express our deep appreciation to the heads of Lingang Shelter Hospital for their unwavering support.

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Table 1 T-tests results of the correlation between the TNACN and the clinic symptoms of COVID-19 persons

Variables		No. Of Cases (%)	TNACN（d）	t	P
Sex	Men	321 (66.05%)	6.61±3.94	0.22	0.829
	Women	165 (33.95%)	6.53±3.28
Age	<60 years	445 (91.56%)	6.53±3.72	-1.01	0.313
	≥60 years	41 (8.44%)	7.15±3.82
Smoking	Without	333 (68.52%)	6.75±3.83	1.45	0.147
	With	153 (31.48%)	6.22±3.48
BMI	<28 kg/m2	423 (87.04%)	6.59±3.82	0.14	0.890
	≥28 kg/m2	63 (12.96%)	6.52±3.07
Chronic Disease	Without	411 (84.57%)	6.42±3.68	-2.27	0.023*
	With	75 (15.43%)	7.48±3.86
Vaccination	without	32 (6.58%)	7.41±3.97	-1.29	0.197
	with	454 (93.42%)	6.53±3.71
Drug usage	without	232 (47.74%)	6.38±4.33	1.17	0.244
	with	254 (52.26%)	6.78±3.07
Fever	without	264 (54.32%)	6.33±3.91	-1.67	0.095
	with	222 (45.68%)	6.89±3.47
Weak	without	319 (65.64%)	6.48±3.96	-0.86	0.392
	with	167 (34.36%)	6.78±3.23
Sweatiness	without	312 (64.20%)	6.49±3.97	-0.74	0.457
	with	174 (35.80%)	6.75±3.24
Cough	without	180 (37.04%)	6.19±4.40	-1.77	0.077
	with	306 (62.96%)	6.81±3.25
Pharyngoxerosis	without	320 (65.84%)	6.46±3.97	-1.03	0.305
	with	166 (34.16%)	6.83±3.21
Itchy throat	without	333 (68.52%)	6.40±3.75	-1.59	0.112
	with	153 (31.48%)	6.98±3.65
Throat pain	without	321 (66.05%)	6.26±3.50	-2.68	0.008**
	with	165 (33.95%)	7.21±4.07
Bitter taste	without	390 (80.25%)	6.56±3.83	-0.30	0.762
	with	96 (19.75%)	6.69±3.28
Dry mouth	without	380 (78.19%)	6.47±3.80	-1.27	0.205
	with	106 (21.81%)	6.99±3.44
Chest distress and shortness of breath	without	423 (87.04%)	6.53±3.84	-0.84	0.401
	with	63 (12.96%)	6.95±2.85
Inappetence	without	403 (82.92%)	6.56±3.84	-0.34	0.735
	with	83 (17.08%)	6.71±3.13
Abdominal distension	without	466 (95.88%)	6.55±3.77	-0.88	0.381
	with	20 (4.12%)	7.30±2.41
Constipation	without	446 (91.77%)	6.56±3.74	-0.43	0.67
	with	40 (8.23%)	6.83±3.59
Diarrhea	without	435 (89.51%)	6.49±3.80	-1.64	0.102
	with	51 (10.49%)	7.39±2.89
Palpitation	without	470 (96.71%)	6.58±3.71	-0.18	0.857
	with	16 (3.29%)	6.75±4.31
Nasal obstruction	without	334 (68.72%)	6.49±3.98	-0.85	0.399
	with	152 (31.28%)	6.80±3.11
Rhinorrhea	without	358 (73.66%)	6.55±3.95	-0.34	0.736
	with	128 (26.34%)	6.68±3.03
Sleep disorders	without	418 (86.01%)	6.52±3.83	-0.99	0.322
	with	68 (13.99%)	7.00±3.01
Nausea and vomiting	without	457 (94.03%)	6.51±3.75	-1.75	0.08
	with	29 (5.97%)	7.76±3.23
Muscular soreness	without	365 (75.10%)	6.39±3.45	-1.99	0.048*
	with	121 (24.90%)	7.17±4.42
Headache	without	328 (67.49%)	6.50±3.98	0.69	0.489
	with	158 (32.51%)	6.75±3.14
Asymptomatic	without	431 (88.68%)	6.70±3.61	1.57	0.121
	with	55 (11.32%)	5.71±4.47

^** P ≤0.01, ^*P≤0.05； TNACN: the time of nucleic acid conversion to negative.

Table 2 The multiple regression analysis results on the correlation between the clinical symptoms and the time of nucleic acid conversion to negative in COVID-19 patients

Variables	β	95% CI	P
Chronic Disease	1.170	0.262–2.079	0.012*
Throat pain	0.845	0.123–1.567	0.022*
muscular soreness	0.578	-0.215–1.370	0.154

*P≤0.05, **P≤0.01, ***P ≤ 0.001

Table 3 Pearson's Chi-square test (cross-analysis) results of the relationship between clinical symptoms and the 7-day NNACR in COVID-19 patients

Variables		7-day NNACR		χ2	p
		＞7ds	≤7ds
Sex	Men	106 (33.02)	215 (66.98)	0.004	0.948
	Women	54 (32.73)	111 (67.27)
Age	<60 years	142 (31.91)	303 (68.09)	2.445	0.118
	≥60 years	18 (43.90)	23 (56.10)
Smoking	Without	115 (34.53)	218 (65.47)	1.246	0.264
	With	45 (29.41)	108 (70.59)
BMI	<28 kg/m2	139 (32.86)	284 (67.14)	0.006	0.941
	≥28 kg/m2	21 (33.33)	42 (66.67)
Chronic Disease	Without	128 (31.14)	283 (68.86)	3.814	0.051
	With	32 (42.67)	43 (57.33)
Vaccination	without	142 (31.28)	312 (68.72)	8.442	0.004**
	with	18 (56.25)	14 (43.75)
Drug usage	without	95 (37.40)	159 (62.60)	4.835	0.028*
	with	65 (28.02)	167 (71.98)
Fever	without	78 (29.55)	186 (70.45)	2.983	0.084
	with	82 (36.94)	140 (63.06)
Weakness	without	99 (31.03)	220 (68.97)	1.497	0.221
	with	61 (36.53)	106 (63.47)
Sweatiness	without	94 (30.13)	218 (69.87)	3.08	0.079
	with	66 (37.93)	108 (62.07)
Cough	without	46 (25.56)	134 (74.44)	7.025	0.008**
	with	114 (37.25)	192 (62.75)
Pharyngoxerosis	without	92 (28.75)	228 (71.25)	7.384	0.007**
	with	68 (40.96)	98 (59.04)
Itchy throat	without	102 (30.63)	231 (69.37)	2.514	0.113
	with	58 (37.91)	95 (62.09)
Throat pain	without	91 (28.35)	230 (71.65)	8.953	0.003**
	with	69 (41.82)	96 (58.18)
Bitter taste	without	130 (33.33)	260 (66.67)	0.151	0.697
	with	30 (31.25)	66 (68.75)
Dry mouth	without	115 (30.26)	265 (69.74)	5.577	0.018*
	with	45 (42.45)	61 (57.55)
Chest distress and shortness of breath	without	136 (32.15)	287 (67.85)	0.877	0.349
	with	24 (38.10)	39 (61.90)
Inappetence	without	132 (32.75)	271 (67.25)	0.03	0.863
	with	28 (33.73)	55 (66.27)
Abdominal distension	without	150 (32.19)	316 (67.81)	2.755	0.097
	with	10 (50.00)	10 (50.00)
Constipation	without	145 (32.51)	301 (67.49)	0.414	0.52
	with	15 (37.50)	25 (62.50)
Diarrhea	without	135 (31.03)	300 (68.97)	6.686	0.010**
	with	25 (49.02)	26 (50.98)
Palpitation	without	152 (32.34)	318 (67.66)	2.185	0.139
	with	8 (50.00)	8 (50.00)
Nasal obstruction	without	106 (31.74)	228 (68.26)	0.679	0.41
	with	54 (35.53)	98 (64.47)
Rhinorrhea	without	114 (31.84)	244 (68.16)	0.716	0.398
	with	46 (35.94)	82 (64.06)
Sleep disorders	without	131 (31.34)	287 (68.66)	3.386	0.066
	with	29 (42.65)	39 (57.35)
Nausea and vomiting	without	147 (32.17)	310 (67.83)	1.98	0.159
	with	13 (44.83)	16 (55.17)
Muscular soreness	without	113 (30.96)	252 (69.04)	2.558	0.11
	with	47 (38.84)	74 (61.16)
Headache	without	106 (32.32)	222 (67.68)	0.167	0.683
	with	54 (34.18)	104 (65.82)
Asymptomatic	without	143 (33.18)	288 (66.82)	0.114	0.736
	with	17 (30.91)	38 (69.09)

*P ≤ 0.05, **P ≤ 0.01, ***P≤0.001；7-Day NNACR：7-Day Negative Nucleic Acid Conversion Rate；

No competing interests reported.

Clinical Symptom Influence on The Time of Nucleic Acid Conversion to Negative in COVID-19 Patients with SARS-CoV-2 Omicron Variant: A Retrospective Observational Study

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Inclusion and exclusion criteria

Clinical characteristics collection

Outcome follow up

Statistical analysis

Results

Discussion

CONCLUSION

Declarations

References

Tables

Additional Declarations

Status:

Version 1