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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 7  |  Issue : 1  |  Page : 16-20

COVID-19 viral clearance patterns in patients with kidney disease: Study from tertiary care in South India


Department of Nephrology, Gandhi Medical College, Secunderabad, Telangana, India

Date of Submission10-Jan-2021
Date of Acceptance23-Jan-2021
Date of Web Publication21-Oct-2021

Correspondence Address:
Dr. Manjusha Yadla
Department of Nephrology, Gandhi Medical College, Secunderabad - 500 071, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrnm.jrnm_2_21

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  Abstract 


Aim: The aim of this study was to analyze the viral clearance patterns in COVID-positive patients with kidney disease. Patients and Methodology: This is a single-center observational study with demographic and clinical details of all the patients with renal insufficiency referred for COVID infection management. Results: Of total admissions of 250 patients with renal insufficiency, data were analyzed in those who were discharged from the hospital. Of 250 patients, 108 died and the data of 142 patients were analyzed. The mean duration of viral clearance was 27.5 days, with a range being <3 weeks to 45 days. The mean number of days for viral clearance in acute kidney injury (AKI) was 22.5 days, chronic kidney disease (CKD)-5D was 25.2 days and in transplant recipients 23.4 days. The maximum number of patients cleared the virus in the 4th week and near-complete viral was achieved by the end of the 6th week. Factors such as age, type of renal insufficiency such as AKI/CKD, presence of comorbidities like diabetes, severity of COVID disease, and presence of multiorgan involvement were not associated with viral clearance. Conclusion: In patients with kidney disease, weekly viral clearance was maximum in the 4th week. Moreover, cumulative viral clearance was 99% by the end of the 6th week.

Keywords: Clearance, COVID-19, kidney


How to cite this article:
Yadla M, Anupama K V, Ahmed T. COVID-19 viral clearance patterns in patients with kidney disease: Study from tertiary care in South India. J Renal Nutr Metab 2021;7:16-20

How to cite this URL:
Yadla M, Anupama K V, Ahmed T. COVID-19 viral clearance patterns in patients with kidney disease: Study from tertiary care in South India. J Renal Nutr Metab [serial online] 2021 [cited 2021 Dec 8];7:16-20. Available from: http://www.jrnm.in/text.asp?2021/7/1/16/328958




  Introduction Top


With the onset of pandemic due to SARS-CoV-2019, research regarding understanding the virus, its mode of spread, and therapeutic interventions improved over the last 8 months. The presence of COVID infection is diagnosed based on reverse transcription-polymerase chain reaction (RT-PCR) of a nasopharyngeal swab. The patient is said to be cleared off the virus if the RT-PCR of the nasopharyngeal swab is negative. In the general population, viral clearance patterns were reported to vary depending on the severity of infection. It was reported that in mild infection, virus would clear by day 10 in 90% of the patients, and in patients with severe infection, virus would clear after a prolonged period.[1]

Viral clearance is of significance in immunocompromised patients such as patients with kidney disease, on dialysis, transplant recipients, and also in treatment areas such as dialysis units where patients are in contact with each other and with health-care workers for a duration of 12–14 h per week. Spread from asymptomatic patients is of major concern in closely working areas. It is imperative to have good isolation and surveillance methods for near effective containment of the infection. It is also not clear as to how many days an immunocompromised patient needs to be under isolation.

The primary aim of the study is to determine the number of days for a negative nasopharyngeal swab-RT PCR from symptom onset/day of admission in patients with kidney disease.

The secondary aim of the study is to analyze the probable factors influencing the viral clearance.


  Patients and Methodology Top


Our hospital was designated COVID center in February 2020, thus enabling all the positive cases to be referred to our center. Our state has 40 government dialysis centers and multiple private standalone dialysis centers. An estimate of 10,000 dialysis population exists in the newly formed state with a population of 3 crores.

All COVID-positive dialysis patients were referred to our center for admission. Admitted patients were discharged only after the nasopharyngeal swab for SARS CoV 2019 was negative. This was due to the following reasons: lack of COVID isolation in each dialysis unit, logistics of travel of an average of 50–100 km to the nearest dialysis center in few patients, social stigma, lack of availability of isolated room in the house, and presence of small children at home.

Testing strategy

Our policy was to the Swab-RT PCR every 4th day after 10th day of admission till the report is negative. Patients were discharged only if the RT-PCR on the nasopharyngeal swab was negative. In the earlier months of the pandemic (till July), a patient was declared negative based on two consecutive negative reports and in later months, it was based on ne negative report. Many patients were asymptomatic from the 7th day to the 10th day. Very few of local city-dwellers opted for home quarantine on the 10th day. These patients were advised to come for regular dialysis in dedicated transport and were sent back to their respective units after the negative swab.

Treatment strategy

All patients admitted were RT-PCR positive on the nasopharyngeal swab for SARS-CoV-2019. All of them were treated with azithromycin, modified hydroxychloroquine done (in initial months) and steroids, low molecular weight heparin (if saturation was < 95%) n, and antiviral therapy with remdesivir if severe infection and in 1st week of admission (remdesivir was given for patients admitted from mid-August).

Dialysis strategy

All the patients were given thrice-weekly dialysis or twice weekly dialysis as per the schedule in the dedicated COVID dialysis center. Critically ill patients were given bedside dialysis or sustained low-efficiency dialysis.


  Results Top


Of the total number of 250 admissions at the time of analysis, there were 108 deaths and 142 dialysis patients' data were analyzed.

The baseline characteristics of 142 patients are tabulated in [Table 1].
Table 1: Baseline characteristics of all patients

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All the patients had resolution of symptoms between 5 and 10 days. All the patients waiting for negative nasal swab reports were asymptomatic.

Viral clearance on the nasopharyngeal swab was observed at a median of 27.5 days. Maximum virological clearance was achieved between 20 and 35 days [Figure 1]. On weekly viral clearance analysis, 31 patients cleared in the 3rd week, 81 patients in the 4th week, 18 patients in the 5th week, and 7 patients in the 6th week [Figure 2]. Almost all the patients cleared virus by the end of the 6th week (99.2%). Cumulative viral clearance was 21% at the end of the 3rd week, 84% by the end of the 4th week, and 94% by the 5th week [Figure 3]. The mean number of days for viral clearance in patients with acute kidney injury (AKI) was 22 days and in those on dialysis was 25.2 days, and in transplant recipients' duration for negative RT-PCR was 23.4 days.
Figure 1: Weekly clearance pattern of COVID-19

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Figure 2: Cumulative viral clearance pattern of COVID-19

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Figure 3: Day-wise viral clearance pattern

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On further analysis of factors influencing the early viral clearance (<27.5 vs. >27.5 days), it was observed that men cleared earlier and those with hypertension cleared before 27.5 days, both of which are only observations and may not give a strong clinical implication. Other factors such as age, diabetes, anemia, thrombocytopenia, and usage of steroids did not influence the viral clearance [Table 2].
Table 2: Factors associated with early viral clearance

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  Discussion Top


In December 2019, the first case of COVID infection was diagnosed in Wuhan, China. In India, the first case of COVID SARS-CoV-2019 was diagnosed on January 30, 2020 and in our state, it was on March 1, 2020. With the infection spreading wide and far, our state had seen the spike from mid-June till late September.

The Centers for Disease Control (CDC) recommends for most persons with COVID-19 illness, isolation, and precautions to be discontinued 10 days after symptom onset and resolution of fever for at least 24 h, without the use of fever-reducing medications, and with the improvement of other symptoms.[2] CDC further recommends in those patients with severe immunocompromised states, the role of testing strategy could be considered before discontinuation of isolation and precautions.[2] Patients with kidney disease are immunocompromised and hence in addition to the disappearance of symptoms, the testing strategy also may be used for discontinuation of isolation measures.

In a study by Zhou et al., it was observed that the median time of viral shedding persisted up to 20 days in the general population with COVID infection. In this study, patients with kidney disease were <1%.[3] In a study by Fontana et al. in 37 maintenance dialysis patients, survivors (8/37 patients) showed positive RT-PCR at a median time of 19 days.[4]

When to consider a kidney patient/dialysis patient, completely cured of virus is extremely important. The concept of isolation discontinuation is important in patients with chronic kidney disease, those on dialysis, and organ transplant recipients. In those on maintenance hemodialysis, it is pertinent to know the duration of isolation and the time for discontinuation of isolation measures. Many units dialyze the patients for a period of 2 weeks in isolation or may refer to COVID designated dialysis centers. Fontana et al. suggested that dialysis patients should be under strict isolation and surveillance measures for a period >14 days to avoid any further infection in dialysis units.[4]

COVID infection is thought to be severe in patients with renal insufficiency. Literature regarding the viral clearance or viral shedding in patients with kidney disease or practice guidelines in dialysis patients to contain the infection or prevent transmission in dialysis units is sparse.[5],[6],[7],[8],[9] In a recent meta-analysis., it was observed that many studies done were single center based and the guidelines; policies recommended were based on their experience and observations.[10] Containing the infection and prevention of transmission is possible with the knowledge of the active viral shedding period. In the general population, it is well known that viral load is maximum at symptom onset and would decline over a period of 3 weeks. It may be understood that in patients with kidney disease, viral shedding may be prolonged beyond 3 weeks due to their immune status. Long-term shedders in the general population are not hospitalized underling the significance of low levels of community transmission. Such a scenario may not be extrapolated to the dialysis population as they are at risk population, visiting the center frequently; high probability of coming in contact with asymptomatic infected patients/personnel is a common phenomenon.

It is understood that viral clearance is expected to be delayed in patients with kidney disease and much more prolonged in those on dialysis. The viral shedding patterns and the recovery from the replication-competent virus in patients with kidney disease are not known. With the limitation of the strategies for detection of replication-competent virus, it is logical to depend on RT-PCR testing to identify the viral clearance, though positive RT-PCR can occur due to actively replicating virus or dead virus.

It is interesting to note that none of the renal insufficiency patients had viral clearance before 2 weeks. Viral clearance was observed only from the beginning of 3rd week. With the RT-PCR being negative in 99.9% of patients at the end of the 6th week, it is understood that a complete viral clearance in the respiratory tract may be achieved by 42–43 days in patients with kidney disease. The number of patients clearing per week slowly increased in the 3rd week reached the peak in the 4th week with a drop in numbers during the 5th and 6th [Figure 3]. Around 60% of the patients achieved viral clearance in the 4th week and cumulative viral clearance at the end of the 4th week was 81%.

It was observed that the maximum number of patients would clear the virus off in week 4. Near 100% viral clearance was achieved by week 6. Although RT-PCR was done only once to label a negative patient, we did not readmit any discharged patient with positive RT-PCR report for the continuation of dialysis or for management of symptoms. Patients of kidney disease who were referred from all across the state were treated in our center till the RT-PCR of the nasopharyngeal swab is negative. The duration of hospital stay in our cohort was between 15 and 45 days. This is due to various logistical reasons including the inability to travel from home in a dedicated transport to the COVID dialysis center, lack of available COVID isolation machine in the nearest dialysis center, insufficient space in the house to stay in room isolation, children and elderly in the family, and social stigma.

This is the first observational study in more than 142 renal patients trying to analyze the probable viral clearance patterns. Of 142 patients, 97 are maintenance dialysis population, 25 are acute kidney injury, 15 patients are acute on chronic kidney disease, and five patients are renal transplant recipients. No difference in the median duration of viral clearance was observed between AKI, chronic kidney disease-5D, and transplant recipients (22, 25.2, and 23.4 days, respectively).

This study has an important implication in dialysis units wherein there is no clear directive as to how long to dialyze COVID-positive patients in isolation. At present, in certain centers, COVID-positive patients are being dialyzed in isolation till they become asymptomatic, which may be between 7 and 10 days. It is understood that transmission in dialysis areas is worrisome due to closed units, proximity of patients, AC to maintain the temperature, movement of large number of patients in and out of the unit, compromised physical distancing during cannulation/decannulation, etc., Although the organizational shortcomings and logistic shortcomings prevailed, it was imperative to support all the COVID-infected patients till the achievement of viral clearance. It was also observed in our cohort that the presence of comorbidities, steroid usage, and severity of illness was not associated with early viral clearance.


  Conclusion Top


In our single-center study, it was observed that (1) maximum viral clearance was achieved in the 4th week in patients with kidney disease. (2) COVID-infected dialysis patients may be dialyzed in isolation for a period of a minimum of 4 weeks to maximum of 6 weeks.

Limitations

Our study has several limitations. First, the small number of the study population may not reflect the viral patterns in large. Second, RT-PCR was done only once in the latter months due to certain limitations

Implication

This study suggests the technical and organizational planning strategies for COVID isolation in the upcoming dialysis units with the isolation facility should ensure their available for about a period of 6 weeks per patient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020;20:656-7.  Back to cited text no. 1
    
2.
Duration of Isolation and Precautions for Adults with COVID; 2020. Available from: https://www.cdc.gov'coronavirus'2019-ncov'updated. [Last accessed on 2020 Oct 19].  Back to cited text no. 2
    
3.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.  Back to cited text no. 3
    
4.
Fontana F, Giaroni F, Frisina M, Alfano G, Mori G, Lucchi L, et al. SARS-CoV-2 infection in dialysis patients in northern Italy: A single-centre experience. Clin Kidney J 2020;13:334-9.  Back to cited text no. 4
    
5.
Basile C, Combe C, Pizzarelli F, Covic A, Davenport A, Kanbay M, et al. Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres. Nephrol Dial Transplant 2020;35:737-41.  Back to cited text no. 5
    
6.
Kliger AS, Silberzweig J. Mitigating risk of COVID-19 in dialysis facilities. Clin J Am Soc Nephrol 2020;15:707-9.  Back to cited text no. 6
    
7.
Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int 2020;97:824-8.  Back to cited text no. 7
    
8.
Burgner A, Ikizler TA, Dwyer JP. COVID-19 and the inpatient dialysis unit: Managing resources during contingency planning pre-crisis. Clin J Am Soc Nephrol 2020;15:720-2.  Back to cited text no. 8
    
9.
Li J, Xu G. Lessons from the experience in Wuhan to reduce risk of COVID-19 infection in patients undergoing long-term hemodialysis. Clin J Am Soc Nephrol 2020;15:717-9.  Back to cited text no. 9
    
10.
Akbarialiabad H, Kavousi S, Ghahramani A, Bastani B, Ghahramani N. COVID-19 and maintenance hemodialysis: A systematic scoping review of practice guidelines. BMC Nephrol 2020;21:470.  Back to cited text no. 10
    


    Figures

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

  [Table 1], [Table 2]



 

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