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ORIGINAL ARTICLE
Year : 2022  |  Volume : 49  |  Issue : 3  |  Page : 294-297

Risk factors for cessation of viral RNA shedding in COVID-19 patients


1 Department of Community Medicine, HBTMC and Dr. RN Cooper Hospital, Mumbai, Maharashtra, India
2 Department of Community Medicine, HBTMC and Dr. RN Cooper Hospital; Seven Hills Dedicated COVID Hospital, Mumbai, Maharashtra, India

Date of Submission29-Jun-2021
Date of Acceptance25-Aug-2021
Date of Web Publication27-Dec-2022

Correspondence Address:
Dr. Smita Santosh Chavhan
Department of Community Medicine, HBTMC and Dr. RN Cooper Hospital, U 15, Bhaktivedanta Swami Rd, JVPD Scheme, Juhu, Mumbai - 400 056, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.jss_87_21

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  Abstract 


Objectives: Our study aimed to evaluate the risk factors for the cessation of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) RNA detection in a cohort of inpatients of laboratory-confirmed coronavirus disease 2019 (COVID-19) cases. Materials and Methods: This was a hospital-based, cross-sectional study. All COVID-19 patients positive on the reverse transcription polymerase chain reaction (RTPCR) test of nasopharyngeal samples who were admitted in this Dedicated COVID Hospital (DCH) from April to June 2020 were included in this study. The deceased patients were excluded.Cessation of Viral RNA Shedding (CVS) was considered to have been achieved on the date of the first negative SARS-CoV-2 RTPCR result out of the two consecutive negative SARS-CoV-2 PCR results on nasopharyngeal swabs taken 24 h apart. Results: Of the 4632 COVID-19 patients, 3307 (71.4%) patients achieved CVS. Patients had a median (IQR) time from positive to negative PCR of 16 (11–23) days. In multivariate cox regression analysis, age group 41 − 60 years (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63–0.91), age >60 years (HR [CI] = 0.63 [0.53–0.78]), female sex (HR [CI] = 1.08 [1.01-1.16]), cancer (HR [CI] = 1.87 [1.03–3.41]) were the independent risk factors for cessation of viral shedding. Conclusion: Patients older than 40 years, male patients were shedding viral RNA for more duration and can be considered for the isolation for a longer duration.

Keywords: Comorbidities, COVID-19, polymerase chain reaction testing, SARSCo-V-2, tertiary care hospital, virus shedding


How to cite this article:
Dhikale PT, Chavhan SS, Adsul BB, Gokhale CN, Ingale AR, Kinge KV. Risk factors for cessation of viral RNA shedding in COVID-19 patients. J Sci Soc 2022;49:294-7

How to cite this URL:
Dhikale PT, Chavhan SS, Adsul BB, Gokhale CN, Ingale AR, Kinge KV. Risk factors for cessation of viral RNA shedding in COVID-19 patients. J Sci Soc [serial online] 2022 [cited 2023 Jan 31];49:294-7. Available from: https://www.jscisociety.com/text.asp?2022/49/3/294/365183




  Introduction Top


The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. On 25/06/2021, India has 3 crores (16.8% of the worlds) COVID-19 cases.[1] The COVID dedicated facilities in India were divided into three types, namely COVID Care Center, Dedicated COVID Health Center, and Dedicated COVID Hospital (DCH).[2]

The clinical presentation of COVID-19 is heterogeneous. The World Health Organization (WHO) has given a case definition for a confirmed case of COVID-19 as any individual with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms. This has led to reliance on reverse transcription-polymerase chain reaction (RTPCR) for the diagnosis and management of COVID-19.[3],[4]

Initially, the WHO recommendations for discharge from isolation required two negative RT-PCR results on sequential samples taken at least 24 h apart.[5] It was later revised allowing discharge without retesting.[6] The Ministry of Health and Family Welfare also modified the COVID-19 discharge policy from time to time aligned with the WHO guidelines and the 3 tier COVID-19 facilities.[7] Better understanding of transmission risk among individuals with different comorbidities and sociodemographic variables will help in the refinement of discharge criteria.[6] The published data about the association of comorbidities to RTPCR from India are scarce.

Objectives

We aimed to evaluate the risk factors for the cessation of SARS-CoV-2 RNA detection in a cohort of inpatients of laboratory-confirmed COVID-19 cases.


  Materials and Methods Top


Study setting

This study was done in a large DCH in a metro city.[8] All the patients were receiving the standard management as per the guidelines for the management of COVID-19 patients.[9],[10] Nasopharyngeal samples were taken for all the patients. The accredited laboratory doing the RTPCR tests was following all required standards. The laboratory was using Thermo KingFisher for extraction. QIAgility-QIAGEN for Master Mix, Quantstudio for PCR amplification.

Study design and population

This was a hospital-based, cross-sectional study. All COVID-19 patients positive on RTPCR test of nasopharyngeal samples who were admitted in this DCH from April to June 2020 were included in this study. The deceased patients were excluded to capture those who achieved viral RNA clearance. Suspected cases of COVID-19 whose RTPCR never came positive were excluded. The information regarding socio-demographic data, date of onset of symptoms, reports of the swab, duration of stay, comorbidities, etc., were collected retrospectively from hospital records. Follow-up throat-swab specimens were obtained at intervals of 4 ± 2 days. Cessation of viral RNA shedding (CVS) was considered to have been achieved on the date of the first negative SARS-CoV-2 RTPCR results of the two consecutive negative SARS-CoV-2 RTPCR results on nasopharyngeal swabs collected at least 24 hours apart. Permission from the Institute Ethics Committee was taken. Full confidentiality of respondent's information was maintained.

Statistical analysis

Data entry was done by using Microsoft Excel version 2010, and statistical analysis was done using IBM SPSS Statistics for Windows, version 22 (IBM, Bangalore, Karnataka). The Chi-square test was used to test the sex differences in COVID-19 patients. To explore the risk factors associated with viral shedding Kaplan–Meier analysis, Log-rank test, and Cox regression analysis were used. The risk factors were entered in the model using the “Enter” selection method. The level of significance was fixed at 0.05.


  Results Top


The 4632 COVID-19 patients who were admitted to this DCH from April to June 2020 and who were successfully discharged were included in the study. Of these 3307 (71.4%) patients achieved CVS. As shown in [Figure 1], Patients had a median (IQR) time from positive to negative PCR of 16 (11–23) days. The median (IQR) duration of hospital stay of COVID-19 patients was 12 (8–17) days. Demographics and comorbidities are summarized in [Table 1]. The median (IQR) age of the patients was 47 (34–58) years. Majority of the patients 3196 (69%) were male. The common comorbidities were hypertension (22.8%), diabetes mellitus (21.2%), cardiovascular diseases (CVD) (4.3%), chronic kidney diseases (3.4%), chronic lung diseases (CLD) (1.3%), and cancer (0.3%). [Table 2] depicts the risk factors associated with cessation of viral RNA shedding. In [Figure 2] the Kaplan–Meier curves shows the proportion of SARS-CoV-2 RNA-positive patients.
Figure 1: Box plot of median time to cessation of viral RNA shedding from symptom onset by risk factors

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Table 1: Clinical characteristics of patients with coronavirus disease 2019

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Table 2: Risk factors associated with cessation of viral ribonucleic acid shedding

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Figure 2: Kaplan–Meier curve of negative polymerase chain reaction test results after symptom onset

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Univariate Cox regression analysis showed that age group 41–60 years (P = 0.002), age >60 years (P < 0.001), female sex (P = 0.04), diabetes (P = 0.02), hypertension (P < 0.001), and CVDs (P = 0.006) were found to be significantly associated with cessation of viral shedding (CVS).

In multivariate Cox regression analysis age group 41–60 years (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63–0.91), age >60 years (HR [CI] = 0.63 [0.53–0.78]), female sex (HR [CI] = 1.08 [1.01–1.16]), cancer (HR [CI] = 1.87 [1.03–3.41]) were independently associated with prolonged viral shedding. [Figure 3], [Figure 4], [Figure 5] depicts Kaplan-Meier curves of factors which were significant in multivariate Cox regression.
Figure 3: Kaplan-Meier curves between different age group patients (Log-rank P < 0.001)

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Figure 4: Kaplan–Meier curves between male and female patients. (Log-rank P = 0.036)

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Figure 5: Kaplan–Meier curves between cancer and noncancer patients. (Log-rank P = 0.135)

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  Discussion Top


In this study, we described the clinical risk factors for prolonged viral shedding in patients with COVID-19. Patients had a median time from positive to negative PCR of 16 days. This was similar to two studies in China.[11],[12] In our study, the range of viral shedding was 3 − 63 days. In a review article, the range of viral shedding was similar.[13]

In our study female sex, younger age (0 − 40 years) and cancer patients showed a shorter duration of viral shedding. The sex-related difference in the duration of viral RNA shedding was consistent with the findings of two previous studies, this can be due to sex-specific immune response.[12],[14] In a study in China, old age people was found to shed the virus for a longer duration of time which was similar to our study.[15] A study from China found patients with CVD had prolonged viral shedding than other patients; we had similar findings in univariate analysis but not in the multivariate analysis.[16] A study from the USA found patients with asthma had prolonged viral shedding than other patients, but we did not find such association with CLD.[14] In a study of critically ill COVID-19 patients, Diabetic patients had prolonged viral shedding than other patients. We had similar findings in univariate analysis but not in the multivariate analysis.[17]

The specificity of RTPCR is very good. A systematic review of the RTPCR test reported its false-negative rates between 2% and 29% (equating to the sensitivity of 71%–98%).[18] In a study of critically ill COVID-19 patients, the association of the first negative RT-PCR with a second negative result was 96.7%.[17] The discharge should be governed by viral shedding, clinical scenario, guidelines, infectivity, and patient-related factors.

Limitations

There can be false-negative results of RTPCR. Furthermore, RTPCR tests can detect nonviable viruses, so the viral RNA shedding may not equate to the persistence of the infectious virus.


  Conclusion Top


The patients older than 40 years, male patients are shedding viral RNA for more duration and can be considered for isolation for a longer duration.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Report of COVID-19 Cases. Medical Education and Drugs Department. Public Health Department. Government of Maharashtra; 25 June 2021.  Back to cited text no. 1
    
2.
Ministry of Health and Family Welfare Directorate General of Health Services EMR Division. Guidance document on appropriate management of suspect/confirmed cases of COVID-19. Available from: https://www.mohfw.gov.in/pdf/FinalGuidanceonMangaementofCovidcasesversion 2.pdf. [Last accessed on 2021 Sep 24].  Back to cited text no. 2
    
3.
World Health Organization. Global Surveillance for Human Infection with Novel Coronavirus (2019-nCoV). Interim Guidance. Available from: https://apps.who.int/iris/bitstream/handle/10665/330857/WHO-2019-nCoV-SurveillanceGuidance-2020.3-eng.pdf?sequence=1&isAllowed=y. [Last accessed on 2020 Jan 31].  Back to cited text no. 3
    
4.
World Health Organization. Public Health Surveillance for COVID-19 Interim Guidance. Available from: https://apps.who.int/iris/bitstream/handle/10665/333752/WHO-2019-nCoV-SurveillanceGuidance-2020.7-eng.pdf?sequence=1&isAllowed=y.[Last accessed on 2020 Aug 07].  Back to cited text no. 4
    
5.
World Health Organization. Laboratory Testing of Human Suspected Cases of Novel Coronavirus (nCOV) Infection (Interim Guidance). Available from: https://apps.who.int/iris/bitstream/handle/10665/330676/9789240000971-eng.pdf?sequence=1&isAllowed=y. [Last accessed on 2021 Sep 24].  Back to cited text no. 5
    
6.
World Health Organization. Criteria for Releasing COVID-19 Patients from Isolation. Available from: https://www.who.int/news-room/commentaries/detail/criteria-for-releasing-covid-19-patients-from-isolation. [Last accessed on 2020 Jun 17].  Back to cited text no. 6
    
7.
Ministry of Health and Family Welfare, Government of India. Revised Discharge Policy for COVID-19. Available from: https://www.mohfw.gov.in/pdf/ReviseddischargePolicyforCOVID19.pdf. [Last accessed on 2021 Sep 24].  Back to cited text no. 7
    
8.
Kumbhar M, Chavhan S, Adsul B. Seven Hills Dedicated COVID Hospital. Mumbai: Municipal Corporation of Greater Mumbai; 2020. p. 44.  Back to cited text no. 8
    
9.
Ministry of Health and Family Welfare, Government of India. Directorate General of Health Services (EMR Division). Guidelines on Clinical Management of COVID – 19. Available from: https://www.mohfw.gov.in/pdf/GuidelinesonClinicalManagementofCOVID1912020.pdf. [Last accessed on 2021 Sep 24].  Back to cited text no. 9
    
10.
Ministry of Health and Family Welfare, Government of India. Directorate General of Health Services (EMR Division) CLINICAL MANAGEMENT PROTOCOL: COVID-19. Available from: https://www.mohfw.gov.in/pdf/ClinicalManagementProtocolforCOVID19.pdf. [Last accessed on 2021 Sep 24].  Back to cited text no. 10
    
11.
Wu Y, Guo C, Tang L, Hong Z, Zhou J, Dong X, et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol 2020;5:434-5.  Back to cited text no. 11
    
12.
Feng Z, Li J, Yao S, Yu Q, Zhou W, Mao X, et al. Clinical factors associated with progression and prolonged viral shedding in COVID-19 patients: A multicenter study. Aging Dis 2020;11:1069-81.  Back to cited text no. 12
    
13.
Karia R, Nagraj S. A review of viral shedding in resolved and convalescent COVID-19 patients. SN Compr Clin Med 2020;3:1-10.  Back to cited text no. 13
    
14.
Xu K, Chen Y, Yuan J, Yi P, Ding C, Wu W, et al. Factors associated with prolonged viral RNA shedding in patients with COVID-19. Clin Infect Dis 2020;71:799-806.  Back to cited text no. 14
    
15.
Corsini Campioli C, Cano Cevallos E, Assi M, Patel R, Binnicker MJ, O'Horo JC. Clinical predictors and timing of cessation of viral RNA shedding in patients with COVID-19. J Clin Virol 2020;130:104577.  Back to cited text no. 15
    
16.
Fu Y, Han P, Zhu R, Bai T, YiJ, Zhao X, et al. Risk factors for viral RNA shedding in COVID-19 patients. Eur Resp J 2020;56:2086-95.  Back to cited text no. 16
    
17.
Buetti N, Trimboli P, Mazzuchelli T, Lo Priore E, Balmelli C, Trkola A, et al. Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients. Endocrine 2020;70:454-60.  Back to cited text no. 17
    
18.
Arevalo-Rodriguez I, Buitrago-Garcia D, Simancas-Racines D, Zambrano-Achig P, Del Campo R, Ciapponi A, et. al. False-negative results of initial RT-PCR assays for COVID-19: a systematic review. PloS one. 2020;15:e0242958.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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