Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2

doi:10.21203/rs.3.rs-1980808/v1

Download PDF

Research Article

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2

https://doi.org/10.21203/rs.3.rs-1980808/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

To explore the risk factors associated with the viral shedding time in the elder Chinese patients infected with SARS-CoV-2 omicron.

Methods

Participants infected with SARS-CoV-2 omicron were enrolled in a retrospective study, and divided into two groups according to the shedding time of omicron [≥ 10 days, "late clearance group" and < 10 days, "early clearance group"].

Results

180 patients were enrolled in the study (88 early, 92 late), with a median time of viral shedding was 10 days and a mean age of 77.02 years. When comparing patients between either group, prolonged SARS-CoV-2 omicron shedding was associated with old age (P = 0.007), unvaccinated (P = 0.001), delayed admission to hospital after illness onset (P = 0.001), D-dimer (P = 0.003) and methylprednisolone treatment (P = 0.048). In the multivariable analysis, vaccinated [OR], 0.319 [95% CI, 0.130–0.786], P = 0.013), paxlovid (OR, 0.259 [95% CI, 0.104–0.643], P = 0.004), and time from onset to admission (OR, 1.802 [95% CI, 1.391–2.355], P = 0.000) were significantly associated with viral clearance.

Conclusions

The older age, methylprednisolone therapy, and D-dimer were associated with prolonged duration of omicron viral shedding. The time from onset to hospitalization, unused paxlovid and unvaccinated were independent risk factors in patients infected with SARS-CoV-2 omicron.

viral shedding time

SARS-CoV-2

Omicron

factors

Coronavirus Disease 2019 (COVID-19) was identified in January 2020 and has been swept by human‑to‑human transmission ^{[1, 2]}. Five variants of concern (VOC) have been identified so far, namely Alpha, Beta, Gamma, Delta, and Omicron variants designated by the World Health Organization (WHO) ^{[3, 4]}. The rapid spread of the omicron variant was first identified on November 24, 2021, and became the predominant variant, posing a severe threat worldwide ^{[5, 6]}. Compared to DNA viruses, RNA viruses have a higher mutation ^[7]. During the COVID-19 pandemic ^{[8, 9]}, researchers indicated that the variant of omicron is the most mutated strain in the midst of SARS-CoV-2 variants, which may help the virus evade infection-blocking antibodies ^[7]. These mutations will affect the characteristics of the SARS-CoV-2 omicron, including infectivity, immune escape, viral shedding time, and outcome. Data showed that the infectivity of SARS-CoV-2 omicron variants 10-fold higher than that of the original virus, but they were less likely to be admitted and require ICU level care ^[10]. In addition, reinfection was observed approximately 10 times more frequently than in the Delta variant ^{[11, 12]}. Therefore, omicron will significantly impact the therapeutic effect of COVID-19 drugs, immunity secondary to vaccination or prior infection, infectivity, and outcome ^[13].

In 2022, a wave of COVID-19 rapidly appeared in shanghai, China. After comparing the genomes of viruses, it was found that the genomes of the infected viruses in Shanghai belong to the Omicron BA.2.2 ^{[14, 15,]}. Zhang et al. found that the total cases in Shanghai were higher while the severity rate and mortality was lower, similar to other countries ^[5]. Moreover, studies of people infected with omicron variant suggested that older age might potentially predict mortality and severity ^{[16, 17]}.

Understanding the kinetics of infectious viral shedding to possible transmission risk is crucial to guiding infection prevention and control strategies ^[18]. Therefore, it is essential to understand the shedding time of the variant of omicron since it is a crucial factor in the guidance of decisions about isolation precaution and antiviral treatment ^{[19, 20]}. Through a retrospective cohort study, including 59 hospitalized patients with COVID-19, the elderly was independently associated with long-term virus shedding ^[21]. Another study demonstrated that sex, corticosteroid, and Delayed admission is an independent risk factor for prolonged virus shedding time in COVID-19 patients ^[22]. However, whether these findings are also applicable to the omicron variants is still unclear. Up to June 24, 2022, we have used the search terms ("Omicron") and ("shedding time") and ("prolonged") to search PubMed and found no relevant articles. In short, the relationship between omicron viral shedding time and risk factors has not been fully clarified. Hence, this study aimed to evaluate the characteristics of viral shedding time with older patients infected with omicron and identify risk factors influencing the duration of viral shedding.

Patients enrollment

361 participants with confirmed SARS-CoV-2 Omicron BA.2.2 admitted to the Ninth People Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled for analysis. (Fig. 1). Participants were diagnosed with SARS-CoV-2 according to the guidelines of China (version 9). The earliest patient was admitted on April 23, 2020.

According to the characteristics of SARS-CoV-2 omicron, older patients are a risk factor for exacerbation of the disease. Hence, this study was aim to explore the occurrence of the viral shedding in older patients infected with omicron variants. Inclusion criteria: 1) Ct value<35 for both ORF1ab and N gene; 2) age ≥ 60. According to the criteria, 180 patients were enrolled. Among all patients, the viral shedding time of 88 patients was within 10 days, and that of 92 patients was over 10 days.

This trial received approval from the Ethics Committee of the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (No. SH9H-2022-T112-2) and registered at the Chinese Clinical Trial Registry (ChiCTR2200060700).

Trial procedures

This retrospective cohort study was designed to assess the time of virus shedding in elderly participants infected with SARS-CoV-2 omicron (Fig. 1).

Patients whose viral shedding time was less than 10 days were included in the early viral clearance group, and patients whose viral shedding time was more than or equal to 10 days were included in the late viral clearance group. Clinical characteristics and treatment of patients were collected using electronic medical records. The clinical characteristics were as follows: 1) age, mean; 2) cycle threshold value (CT. N and ORF); 3) time from onset to enrollment in patients; 4) gender; 5) condition at admission; 6) vaccine status; 7) comorbidity; 8) first symptoms; 9) laboratory indicators 10) time from the first admission to the negative testing; 11) viral shedding time. The treatment of patients was as follows: 1) medication; 2) auxiliary breathing; 3) whether to enter ICU.

Definition

Nucleic acid negative test is recognized as viral shedding (two consecutive, Ct value༞35 for the ORF and N gene) and was quantified by RT-PCR ^[5]. The time to viral shedding was from the first positive nucleic acid test to successive negative detection. Time from onset to patient enrollment was considered the time from the first positive nucleic acid test to the date of first hospitalization ^{[23, 24]}.

Conditions at admission were included: 1) asymptomatic cases; 2) mild cases; 3) moderate cases; 4) severe cases, according to Chinese guidelines (version 9). Charlson comorbidity index is a widely used complication scoring system involving 17 diseases ^[25]. Medication is the therapeutic drugs used during hospitalization, including paxlovid, anticoagulation, methylprednisolone, and Chinese medicine. Assisted breathing includes nasal tube oxygen inhalation, mask oxygen inhalation, ventilator oxygen inhalation, and ECMO.

Statistical analysis

Categorical variables were described as numbers (%), and continuous variables were described as median (IQR) or mean (Standard Deviation, SD). Continuous variables were compared with the Mann-Whitney U test or Student's t test, and categorical variables were compared by the χ² test or Fisher's exact tests. Logistic regression was employed to analysis risk factors, adjusted odds ratio (OR and 95%CI were calculated. P-values < 0.05 were considered statistically significant). The different rate of negative nucleic acid test between-group was compared by the Kaplan-Meier method with a log-rank test.

Characteristics of participants in this trial

The study included 180 older participants infected with the variants of omicron. Among 180 participants, the median time of viral shedding was 10 days, and 104 (57.78%) were female with the mean age was 77.02. Among all patients, the median time from onset to enrollment was 1 day (1–3 days), and the viral shedding time was 10 days (8–12 days). Most patients were mild cases, and only 1 case (0.56%) was diagnosed as severe cases. Among the 180 patients, 56 (31.11%) were vaccinated, and 124 (68.89%) were unvaccinated. During hospitalization, 174 (96.67%) patients were treated with traditional Chinese medicine, followed by 134 (74.44%) patients treated with paxlovid. In addition, 28 (15.56%) patients needed nasal catheter assisted oxygen inhalation during hospitalization.

Risk factors for the viral shedding

The purpose of this study was to observe the virus shedding time of elderly patients infected with SARS-CoV-2 omicron. Then, Participants were further divided into two groups; one was the viral shedding time＜10 days (n = 88), and another was the viral shedding time ≥ 10 days (n = 92). Clinical characteristics, epidemiological, treatment, laboratory indicators, and outcomes were compared between either (Table 1). No significant differences were found in the Ct value, or sex, between either group. Variables with statistical significance (P < 0.05) between two groups, including age (75.05 vs. 78.91, P = 0.007), vaccinated [38 (43.18%) vs. 18 (19.57%), P = 0.001)], D-dimer (0.48 vs. 0.97, P = 0.030), time from onset to enrollment (1 vs. 3, P = 0.001) and time from the first day admission to the negative testing (6.18 vs. 8.7, P = 0.001). Compared with the late viral clearance group, the early viral clearance group had more patients using paxlovid [74 (84.09%) vs. 60 (65.22), P = 0.004). However, patients who used methylprednisolone were higher in the late viral clearance group than in the early [6 (6.81%) vs. 15 (16.30%), P = 0.048)]. In addition, the ratio of severe cases at first hospitalization in the late group was higher than that in the early group (0% vs. 1.09%), but no significant differences were found in the condition at admission. Moreover, we found that the mean of Charlson was higher in the late viral clearance group (0.76 vs. 1.09, P = 0.051).

Table 1

Comparison of clinical characteristics and treatment responses between groups with different viral shedding time
Characteristics	Total N = 180	Viral shedding time		P-value	P-value*
Characteristics	Total N = 180	＜10 days N = 88	≥ 10days N = 92	P-value	P-value*
Age, mean (SD), year	77.02 (9.74)	75.05 (9.73)	78.91 (9.42)	0.007	0.008
CT.N, mean (SD) ^a	28.80 (2.87)	28.50 (2.91)	29.06 (2.82)	0.196	0.254
CT.ORF, mean (SD)	28.18 (3.36)	27.72 (3.43)	28.71 (3.24)	0.047	0.076
Time from onset to enrollment in patients, median (IQR), day ^b	1 (1–3)	1 (1–2)	3 (1–5)	< 0.001	< 0.001
Time from the first day treatment to the negative testing, mean (SD), day	7.47 (2.65)	6.18 (1.35)	8.7 (2.99)	< 0.001	< 0.001
Sex				0.515	-
Male, n (%)	76 (42.22%)	35 (39.77%)	41 (44.57%)
Female, n (%)	104 (57.78%)	53 (60.23%)	51 (55.43%)
Condition at admission ^c				0.150	-
Asymptomatic cases, n (%)	12 (6.67%)	9 (10.23%)	3 (3.26%)
mild cases, n (%)	142 (78.89%)	67 (76.13%)	75 (81.52%)
moderate cases, n (%)	25 (13.89%)	12 (13.63%)	13 (14.13%)
severe cases, n (%)	1 (0.56%)	0 (0.00%)	1 (1.09%)
Vaccine				< 0.001	-
Unvaccinated, n (%)	124 (68.89%)	50 (56.82%)	74 (80.43%)
vaccinated, n (%)	56 (31.11%)	38 (43.18%)	18 (19.57%)
Comorbidity
Hypertension, n (%)	110 (61.11%)	53 (60.23%)	57 (61.96%)	0.812	-
Diabetes, n (%)	41 (22.78%)	15 (17.05%)	26 (28.26%)	0.073	-
Coronary artery disease, n (%)	32 (17.78%)	19 (21.59%)	13 (14.13%)	0.205	-
Charlson, median(IQR)^d	1 (0–1)	1(0–1)	1 (0–2)	0.051	0.101
First symptoms
Fever n (%)	84 (46.67%)	43 (48.86%)	41 (45.05%)	0.610	-
Fatigue, n (%)	45 (25%)	24 (27.27%)	21 (22.83%)	0.491	-
Cough, n (%)	141 (78.33%)	66 (75%)	75 (81.52%)	0.288	-
Expectoration, n (%)	109 (60.56%)	52 (59.09%)	57 (61.96%)	0.694	-
runny nose, n (%)	56 (31.11%)	24 (27.27%)	32 (34.78%)	0.277	-
Sore throat, n (%)	64 (35.56%)	39 (44.32%)	25 (27.17%)	0.016	-
Laboratory indicators
WBC, mean (SD), /L)	4.95 (1.48)	4.71 (1.40)	5.18 (1.52)	0.850	0.064
L, mean (SD), /L	1.32 (0.57)	1.25 (0.45)	1.39 (0.65)	0.124	0.163
ALT, median (IQR), U/L	17 (12.25-25)	21.78 (13-27.5)	22.15 (12–25)	0.336	0.230
AST, median (IQR), U/L	26.50 (22–33)	27 (21.5–34)	30.40 (23–33)	0.823	0.547
Prothrombin time, mean (SD), s	10.98 (0.82)	10.98 (0.8)	10.98 (0.84)	0.711	0.841
APTT, mean (SD), s	29.43 (3.20)	29.09 (2.83)	29.76 (3.50)	0.230	0.117
Fibrinogen, mean (SD), g/dL	3.20 (0.78)	3.09 (0.63)	3.30 (0.89)	0.016	0.174
Fibrinogen＜2, n (%)	29 (16.11%)	9 (10.23%)	20 (21.74%)	0.07	-
D-dimer, mean (SD), mg/L	0.43 (0.26–0.79)	0.48 (0.21–0.64)	0.97 (0.28–0.99)	＜0.001	0.003
D-dimer＞0.5, n (%)	72 (40%)	27 (30.68%)	45 (48.91%)	0.030	-
CRP, mean (SD), mg/L	5.44 (2.28–13.8)	8.49 (2.07–10.94)	13.9 (2.36–15.17)	0.05	0.229
CRP＞10, n (%)	56 (31.11%)	24 (27.27%)	32 (34.78%)	0.345	-
Treatment
Nasal duct, n (%)	28 (15.56%)	12 (13.64%)	16 (17.39%)	0.487	-
Paxlovid, n (%)	134 (74.44%)	74 (84.09%)	60 (65.22%)	0.004	-
Anticoagulation, n (%)	32 (17.78%)	11 (12.50%)	21 (22.83%)	0.070	-
Methylprednisolone, n (%)	21 (11.67%)	6 (6.81%)	15 (16.30%)	0.048	-
Chinese medicine, n (%)	174 (96.67%)	86 (97.73%)	88 (95.65%)	0.438	-
* Indicated U test. ^a Real-time PCR Ct value. ^b Time from onset to enrollment in patients, including the time of initial symptoms or the first positive nucleic acid. ^c According to WHO criteria. ^d Charlson comorbidity index.

Factors associated with the shedding time

Variables with statistical significance (P < 0.05) between two groups, including vaccination status, age, time from onset to enrollment, use of paxlovid, use of methylprednisolone, D-dimer, and Charlson, were tested. The results showed that the vaccinated (OR, 0.319 [95% CI, 0.130–0.786], P = 0.013), used paxlovid (OR, 0.259 [95% CI, 0.104–0.643], P = 0.004), time from onset to enrollment (OR, 1.802 [95% CI, 1.391–2.355], P = 0.000), and D-dimer (OR, 2.005 [95% CI, 0.975–4.121], P = 0.059) were independent factors associated with the time of viral shedding (Table 2). Kaplan Meier curve analysis indicated the cumulative viral negative proportion was higher in patients admitted to hospital within 3 days after the first nucleic acid positive (P = 0.0001; Fig. 2A). Moreover, patients in the vaccinated group had a higher probability of faster virus shedding than the unvaccinated group (P = 0.0001, Fig. 2B). SARS-CoV-2 omicron clearance was delayed in participants who did not use paxlovid during hospitalization compared with those who used paxlovid (P = 0.006, Fig. 2C).

Table 2

Multivariable analyses of factors associated with duration of viral shedding time
Variable	Multivariable analysis
Variable	Odds ratio (OR)	95% CI	P-value
Age	1.024	0.983–1.067	0.246
Vaccinated	0.319	0.130–0.786	0.013
Time from onset to enrollment in patients, days	1.802	1.391–2.355	0.000
Paxlovid	0.259	0.104–0.643	0.004
Methylprednisolone	2.390	0.713–8.016	0.158
D-dimer	2.005	0.975–4.121	0.059
Charlson	1.288	0.928–1.787	0.130

Clinical characteristics related to Paxlovid and vaccination status

There were 56 patients vaccinated, and 124 were unvaccinated (Table 3). We did not found significant difference after compared to the two groups. However, the time from the first-day admission to the negative testing was prolonged in the unvaccinated group (7.85 vs. 6.62, P = 0.004). During our study, 134 patients were treated with paxlovid, and 46 patients were not used. Participant characteristics were similar between the two groups (Table 3). Not using paxlovid group and using paxlovid group was significantly associated with the time from the first-day admission to the negative testing (8.26 vs. 7.19, P = 0.018).

Table 3

Comparison of clinical characteristics between groups of vaccine status or paxlovid status.
Parameters	Vaccine status			Paxlovid
Parameters	Unvaccinated N = 124	Vaccinated N = 56	P-value	Unused N = 46	Used N = 134	P-value
Age, mean (SD), year	78.79 (9.73)	73.11 (8.61)	< 0.001	77.20 (9.99)	76.96 (9.69)	0.889
Sex			0.156			0.216
Male, n (%)	48 (38.71%)	28 (50%)		23 (50%)	53 (39.55%)
Female, n (%)	76 (61.29%)	28 (50%)		23 (50%)	81 (60.45%)
Condition at admission			0.696			0.675
Asymptomatic cases, n (%)	9 (7.26%)	4 (7.14%)		2 (4.35%)	11 (8.21%)
mild cases, n (%)	102 (82.26%)	49 (87.50%)		39 (84.78%)	112 (83.58%)
moderate cases, n (%)	12 (9.68%)	3 (5.36%)		5 (10.87%)	10 (7.46%)
severe cases, n (%)	1 (0.81%)	0		0	1 (0.75%)
CT.N, mean (SD)	28.79 (2.94)	28.79 (2.74)	0.996	29.20 (2.73)	28.65 (2.91)	0.259
CT.ORF, mean (SD)	28.32 (3.39)	28.03 (3.32)	0.592	28.79 (3.17)	28.04 (3.41)	0.191
Time from onset to enrollment in patients, median (IQR), day	1 (1-3.25)	1 (1–2)	0.340	2 (1–4)	1 (1–3)	0.169
Charlson, median(IQR)^d	1 (0–1)	0 (0-1.25)	0.310	1 (0–2)	1(0–1)	0. 843
WBC, mean (SD), /L)	4.93 (1.48)	5 (1.48)	0.796	5.22 (1.57)	4.86 (1.43)	0.151
L, mean (SD), /L	1.30 (0.90–1.70)	1.25 (1-1.60)	0.960	1.30 (1-1.70)	1.20 (0.90–1.60)	0.478
D-dimer, mean (SD), mg/L	0.45 (0.28–0.79)	0.37 (0.21–0.64)	0.092	0.47 (0.27–0.83)	0.42 (0.25–0.75)	0.212
WB＜4.0, n (%)	34 (27.42%)	14 (25%)	0.734	9 (19.57%)	39 (29.10%)	0.207
L＞1.0, n (%)	41 (33.06%)	17 (30.36%)	0.719	14 (30.43%)	44 (32.84%)	0.764
D-dimer＞0.5, n (%)	55 (44.35%)	17 (30.91%)	0.091	21 (45.65%)	51 (38.35%)	0.384
CRP＞10, n (%)	34 (27.42%)	22 (40%)	0.094	15 (32.61%)	41 (30.83%)	0.822
Viral shedding time, mean (SD), day	10.76 (3.34)	8.95 (2.53)	< 0.001	11.48 (3.08)	9.75 (3.15)	0.002
Time from the first day treatment to the negative testing, mean (SD), day	7.85 (2.85)	6.62 (1.92)	0.004	8.26 (2.78)	7.19 (2.56)	0.018

There are few investigation of the omicron variant shedding time. To the best of our knowledge, this retrospective trial aims to evaluate the risk factors associated with the time of viral shedding in the elder Chinese participants infected with omicron (age ≥ 60). We found that age, methylprednisolone therapy, longer time from onset to admission and D-dimer were associated with prolonged viral shedding. Moreover, results indicated that time from onset to hospitalization, unused paxlovid, and unvaccinated were independent risk factors in patients infected with omicron (Table 2).

Many mutation changes were found across the omicron, significantly impacting the immunity secondary to vaccination or prior infection and the efficacy of therapeutic drugs ^[13]. Unvaccinated patients had a longer viral shedding time than vaccinated patients with SARS-CoV-2 omicron in our study [38 (43.18%) vs. 18 (19.57%)]. This observation may demonstrate that the vaccine has a role in accelerating the virus shedding of elderly patients infected with omicron. The findings are consistent with a prospective, observational study, which indicated that the vaccine, especially the booster vaccination, remains effective in preventing severe-stage progression and improving prognosis in patients infected with omicron ^[26]. Like this research, Fan et al. proposed that the vaccine can provide effective protection against the variants of omicron, although there will be a percentage of breakthrough infections ^[27]. However, our results only show that the vaccine can shorten the viral shedding time in this population. It can not be explained whether it can improve the severe disease rate and reduce the infection rate.

In previous research, a study to observe the factors associated with viral shedding among a cohort of COVID-19 patients indicated that male participants had longer viral shedding and more severe symptoms than females infected with COVID-19 ^[28]. Unlike their results, we found no difference between gender and viral shedding time in patients with omicron. This result is consistent with a recent study ^[29]. Among the 180 patients, the mean age was 77.02 years. We found that older age could prolonged duration of viral shedding. It might be related to age-related comorbidities that may result in prolonged viral shedding ^[30]. In the analysis of complications, we found differences in charlson comorbidity index between either group, but there was no significant difference in hypertension, diabetes, or chronic lung disease between them. We considered that the reason for this phenomenon is that the patients we included are older, so the proportion of patients with complications is higher than the average level. Therefore, the impact of a single comorbidity is relatively weak. We also found that a long time from onset to admission could also prolonged duration of viral shedding.

The surprising immune evasion ability of the omicron variant may bring many challenges to specific drug ^[31]. Paxlovid, an oral drug, has received the FDA's emergency use authorization for treating COVID-19 patients. The efficacy of paxlovid in elderly patients infected with the omicron variant is still unclear. By analyzing the usage of paxlovid between the two groups, we found that the early viral clearance group used paxlovid more frequently than the late group. Our results also suggested that paxlovid can significantly reduce the nucleic acid shedding time. In addition, unused paxlovid was an independent risk factor for the nucleic acid shedding. To best know the efficacy of paxlovid in SARS-CoV-2 omicron, many clinical studies are still needed. Used of methylprednisolone was found to prolonged viral shedding time, but it was not an independent risk factor. Previous studies also demonstrated that corticosteroid uses prolonged the viral shedding time in SARS-CoV-2 patients ^[32]. Another research reported that the treatment of low-dose corticosteroid does not delay the viral shedding time ^[33]. Therefore, the immunosuppressive effect of methylprednisolone may lead to the prolongation of the viral shedding time. However, this does not deny the therapeutic effect of methylprednisolone in COVID-19.

There are several limitations of this study. 1) Our trial is a single study with small sample size; 2) We adopted to explore the risk factors associated with the viral shedding time, but not everyone was diagnosed on the first day; 3) There is no specific distinction in this article as to whether to vaccinate the booster vaccine. 4) Participants were only patients aged 60. Thus, the results presented in the manuscript can only represent this part of the population but not all patients infected with omicron; 5) This article only shows that the vaccine still has an effective on the viral shedding time of omicron, but it can not explain whether it can improve the severe condition and reduce the transmission of omicron; 6) This study can only explain the relationship between paxlovid and the viral shedding time, but can not explain the effective on the severe rate and mortality. With a larger sample, future trials may further help to clarify the risk factors associated with the viral shedding time in the elder Chinese patients infected with SARS-CoV-2 omicron.

This study demonstrated that age, D-dimer, methylprednisolone, and longer time from onset to enrollment could prolonged duration of viral shedding in older people infected with omicron. Moreover, time from onset to hospitalization, unused paxlovid, and unvaccinated were independent risk factors in patients infected with omicron associated with viral shedding. Therefore, symptomatic patients with omicron should be hospitalized promptly and the indications for methylprednisolone therapy strictly controlled. In addition, the efficacy of paxlovid and vaccination in SARS-CoV-2 omicron should be further improved.

COVID-19: Coronavirus Disease 2019; VOC: variants of concern; WHO: World Health Organization; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; FDA: Food and Drug Administration

Availability of data and materials

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

Ethics approval and consent to participate

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Contributors

W.Z., X.J., X.Y., Z.D., W.W., Z.S., W.Z., J.C., X.Y and Y.L. collected the epidemiological and clinical data. J.X. and Y.L. were responsible for enrollment and clinical monitoring. X.Y., W.C., Z.D., X.J. and Y.L. were responsible for the distribution and storage of medicines. W.Z., J.C., W.C., X.Y., Y.L. and X.J. were responsible for statistical data. X.Y., W.Z., X.J., X.Y., J.C., J.X. and Y.L. drafted the manuscript. J.C. and Y.L. were responsible for funding, study conception and design, revising and submitting the final manuscript.

Acknowledgments

We respectfully thank all patients enrolled in this study. This work was supported by the Fund for talent construction and scientific research of the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. None of the individuals received compensation for their contribution.

Role of the Funder/Sponsor

The funding agencies had no role in the study design and clinical medications; collection, analysis, and interpretation of the data; preparation, written, review, or approval of the manuscript.

O'Neill L, Chumbler NR. Risk Factors for COVID-19 Hospitalization in School-Age Children. Health services research and managerial epidemiology. 2022;9:23333928221104677.
Qin Z, Sun Y, Zhang J, Zhou L, Chen Y, Huang C. Lessons from SARS–CoV–2 and its variants (Review). Molecular medicine reports. 2022;26(2).
Zhang J, Chen N, Zhao D, Zhang J, Hu Z, Tao Z. Clinical Characteristics of COVID-19 Patients Infected by the Omicron Variant of SARS-CoV-2. Frontiers in medicine. 2022;9:912367.
Guo Y, Han J, Zhang Y, He J, Yu W, Zhang X, et al. SARS-CoV-2 Omicron Variant: Epidemiological Features, Biological Characteristics, and Clinical Significance. Frontiers in immunology. 2022;13:877101.
Shen Y, Ai J, Lin N, Zhang H, Li Y, Wang H, et al. An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants. Emerging microbes & infections. 2022;11(1):1518–23.
SARS-CoV-2 B.1.1.529 (Omicron) Variant - United States, December 1–8, 2021. MMWR Morbidity and mortality weekly report. 2021;70(50):1731-4.
Tian D, Sun Y, Xu H, Ye Q. The emergence and epidemic characteristics of the highly mutated SARS-CoV-2 Omicron variant. Journal of medical virology. 2022;94(6):2376–83.
Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215–20.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271 – 80.e8.
Fall A, Eldesouki RE, Sachithanandham J, Paul Morris C, Norton JM, Gaston DC, et al. A Quick Displacement of the SARS-CoV-2 variant Delta with Omicron: Unprecedented Spike in COVID-19 Cases Associated with Fewer Admissions and Comparable Upper Respiratory Viral Loads. medRxiv: the preprint server for health sciences. 2022.
Özüdoğru O, Bahçe YG, Acer Ö. SARS CoV-2 reinfection rate is higher in the Omicron variant than in the Alpha and Delta variants. Irish journal of medical science. 2022:1–6.
Islam MR, Hossain MJ. Detection of SARS-CoV-2 Omicron (B.1.1.529) variant has created panic among the people across the world: What should we do right now? Journal of medical virology. 2022;94(5):1768–9.
Kannan S, Shaik Syed Ali P, Sheeza A. Omicron (B.1.1.529) - variant of concern - molecular profile and epidemiology: a mini review. European review for medical and pharmacological sciences. 2021;25(24):8019–22.
Wang L, Cheng G. Sequence analysis of the emerging SARS-CoV-2 variant Omicron in South Africa. Journal of medical virology. 2022;94(4):1728–33.
Kawaoka Y, Uraki R, Kiso M, Iida S, Imai M, Takashita E, et al. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2. Research square. 2022.
Li M, Liu Q, Wu D, Tang L, Wang X, Yan T, et al. Association of COVID-19 Vaccination and Clinical Severity of Patients Infected with Delta or Omicron Variants - China, May 21, 2021-February 28, 2022. China CDC weekly. 2022;4(14):293–7.
Smith DJ, Hakim AJ, Leung GM, Xu W, Schluter WW, Novak RT, et al. COVID-19 Mortality and Vaccine Coverage - Hong Kong Special Administrative Region, China, January 6, 2022-March 21, 2022. China CDC weekly. 2022;4(14):288–92.
Cogliati Dezza F, Oliva A, Cancelli F, Savelloni G, Valeri S, Mauro V, et al. Determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection. Diagnostic microbiology and infectious disease. 2021;100(2):115347.
Zhou M, Yu FF, Tan L, Zhu YD, Ma N, Song LJ, et al. Clinical characteristics associated with long-term viral shedding in patients with coronavirus disease 2019. American journal of translational research. 2020;12(10):6954–64.
Yan D, Liu XY, Zhu YN, Huang L, Dan BT, Zhang GJ, et al. Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection. The European respiratory journal. 2020;56(1).
Zhou C, Zhang T, Ren H, Sun S, Yu X, Sheng J, et al. Impact of age on duration of viral RNA shedding in patients with COVID-19. Aging. 2020;12(22):22399–404.
Hu F, Yin G, Chen Y, Song J, Ye M, Liu J, et al. Corticosteroid, oseltamivir and delayed admission are independent risk factors for prolonged viral shedding in patients with Coronavirus Disease 2019. The clinical respiratory journal. 2020;14(11):1067–75.
Fox-Lewis A, Fox-Lewis S, Beaumont J, Drinković D, Harrower J, Howe K, et al. SARS-CoV-2 viral load dynamics and real-time RT-PCR cycle threshold interpretation in symptomatic non-hospitalised individuals in New Zealand: a multicentre cross sectional observational study. Pathology. 2021;53(4):530–5.
Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. Jama. 2020;324(5):460–70.
Charlson ME, Carrozzino D, Guidi J, Patierno C. Charlson Comorbidity Index: A Critical Review of Clinimetric Properties. Psychotherapy and psychosomatics. 2022;91(1):8–35.
Feng Q, Wang Z, Yu H, Shi L, Xu L. [Analysis of clinical characteristics of 362 vaccinated or unvaccinated patients infected by novel coronavirus Omicron variant]. Zhonghua wei zhong bing ji jiu yi xue. 2022;34(5):459–64.
Fan Y, Li X, Zhang L, Wan S, Zhang L, Zhou F. SARS-CoV-2 Omicron variant: recent progress and future perspectives. Signal transduction and targeted therapy. 2022;7(1):141.
Xu K, Chen Y, Yuan J, Yi P, Ding C, Wu W, et al. Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19). Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020;71(15):799–806.
Bennasrallah C, Zemni I, Dhouib W, Sriha H, Mezhoud N, Bouslama S, et al. Factors associated with a prolonged negative conversion of viral RNA in patients with COVID-19. International journal of infectious diseases: IJID : official publication of the International Society for Infectious Diseases. 2021;105:463–9.
Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. The Journal of infection. 2020;80(6):e14-e8.
Rössler A, Riepler L, Bante D, von Laer D, Kimpel J. SARS-CoV-2 Omicron Variant Neutralization in Serum from Vaccinated and Convalescent Persons. The New England journal of medicine. 2022;386(7):698–700.
Hu Z, Li S, Yang A, Li W, Xiong X, Hu J, et al. Delayed hospital admission and high-dose corticosteroids potentially prolong SARS-CoV-2 RNA detection duration of patients with COVID-19. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2021;40(4):841–8.
Fang X, Mei Q, Yang T, Li L, Wang Y, Tong F, et al. Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19. The Journal of infection. 2020;81(1):147–78.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Introduction

Methods

Patients enrollment

Trial procedures

Definition

Statistical analysis

Results

Characteristics of participants in this trial

Risk factors for the viral shedding

Factors associated with the shedding time

Clinical characteristics related to Paxlovid and vaccination status

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1