key: cord-256338-ovj63ith authors: bhattacharya, b.; Kumar, R.; Meena, D. V. p.; Soneja, M.; Vig, S.; Rastogi, V.; Bhatnagar, S.; Mohan, A.; Wig, N. title: SARS-CoV-2 RT-PCR profile in 298 Indian COVID-19 patients : a retrospective observational study date: 2020-06-20 journal: nan DOI: 10.1101/2020.06.19.20135905 sha: doc_id: 256338 cord_uid: ovj63ith Background: Despite being in the 5th month of pandemic, knowledge with respect to viral dynamics, infectivity and RT-PCR positivity continues to evolve. Aim: To analyse the SARS CoV-2 nucleic acid RT-PCR profiles in COVID-19 patients. Design: It was a retrospective, observational study conducted at COVID facilities under AIIMS, New Delhi. Methods : Patients admitted with laboratory confirmed COVID-19 were eligible for enrolment. Patients with incomplete details, or only single PCR tests were excluded. Data regarding demographic details, comorbidities, treatment received and results of SARS-CoV-2 RT-PCR performed on nasopharyngeal and oropharyngeal swabs, collected at different time points, was retrieved from the hospital records. Results : 298 patients were included, majority were males (75.8%) with mean age of 39.07 years (0.6-88 years). The mean duration from symptom onset to first positive RT-PCR was 4.7 days (SD 3.67), while that of symptom onset to last positive test was 17.83 days (SD 6.22). Proportions of positive RT-PCR tests were 100%, 49%, 24%, 8.7% and 20.6% in the 1st, 2nd, 3rd, 4th & >4 weeks of illness. 12 symptomatic patients had prolonged positive test results even after 3 weeks of symptom onset. Age >= 60 years was associated with prolonged RT-PCR positivity (statistically significant). Conclusion : This study showed that the average period of PCR positivity is more than 2 weeks in COVID-19 patients; elderly patients have prolonged duration of RT-PCR positivity and requires further follow up. The COVID-19 pandemic continues to affect millions of people worldwide with more than 50,000 active cases in India and around 3000 deaths. (1) Identifying potentially infectious patients and isolating them is critical in order to halt the spread of infection. As per WHO guidance all suspected cases should be screened by nucleic acid amplification tests (NAATs) such as the reverse-transcription polymerase chain reaction (RT-PCR) on upper and lower respiratory tract samples. (2) Serological assays can aid in the diagnosis of suspected COVID-19 cases but is not available as yet and routine viral culture is not recommended. Hence currently the RT-PCR assay forms the backbone of SARS-CoV-2 diagnosis. However the dynamics of viral shedding has not been fully understood. Currently as per the revised government of India guidelines asymptomatic or mildly symptomatic patients can be discharged 10 days after symptom onset and the strategy of repeat RT-PCR testing has been done away with. (3) In this retrospective study we aim to characterise the RT-PCR profiles of Indian COVID-19 patients which can further aid in defining an appropriate time for discharge or isolation of infected patients. This study was conducted at AIIMS, New Delhi, a tertiary care teaching hospital with special dedicated wards and isolation centers for COVID-19 patients. It was an observational retrospective study where all patients who were admitted with a diagnosis of COVID-19 according to the government of India guidelines between 20th March 2020 to 30th April 2020 were included. Procedure & data collection: All patients admitted, between 20th March 2020 to 30th April 2020 at AIIMS, New Delhi were screened for eligibility. Cases with laboratory confirmed diagnosis of COVID-19, made by positive SARS-CoV-2 RT-PCR on nasopharyngeal samples, were enrolled regardless of symptomatology. Patients with at least 2 SARS-CoV-2 RT-PCR reports . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 20, 2020. were noted retrospectively from hospital records. For symptomatic patients, duration will be considered from day of symptom onset, while for asymptomatic patients, duration from first RT-PCR will be considered. Patients were eligible for discharge after they became asymptomatic and had two reports with RT -PCR results as negative (tests performed at least 24 hours apart). The statistical software STATA v15.1 (STATA corp, LLC, TX, USA) was used for all statistical analysis. For testing of hypothesis two tailed test was considered and p value of less than 0.05 was considered to be statistically significant. Descriptive analysis of the data was carried out first to summarise the study population. Mean ± Standard Deviation were given for continuous variables with no extreme values. Continuous variables with extreme value(skewed) were given by Median and IQR and qualitative variables were expressed as proportion (% ). Data normality is checked by Normal probability plot and Kolmogorov -Smirnov test. For comparison of two groups Student's t test was performed and for the comparison of more than two groups one way ANOVA followed by Bonferroni correction for multiple comparisons was applied. 324 patients were eligible for enrolment, and 26 cases were excluded ( Figure 1 ). A total of 298 patients were included in the study for final analysis. 164 (55%) patients were symptomatic and 134 (45%) were asymptomatic; most symptomatic patients having mild or moderate disease as per ICMR (Indian Council of Medical Research) guidelines. (4) All the patients were managed as per ICMR guidelines and institution protocol. Three patients had severe illness and all of them succumbed to illness (they were excluded from the study as only 1 RT-PCR result was available). The mean age of our study population was 39·07 years (6 months-88 years); majority cases were males 75·8% (226) males. 39 (13·08%) patients had diabetes mellitus and 23 (7·7%) had hypertension. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 20, 2020. . https://doi.org/10.1101/2020.06.19.20135905 doi: medRxiv preprint A total of 930 RT-PCR tests were done for 298 patients, with an average of 3·12 tests per patient. 252 patients (137 symptomatic, 115 asymptomatic) had been declared as cured at the time of final analysis. A total of 90 patients had a second positive RT-PCR assay whereas the rest 208 had either repeat negative assays or repeat test results were unavailable for them. The mean duration to first positive RT-PCR from onset of symptoms was 4·7 days (1-21 days; SD 3·67); the median duration was 3 days (IQR:2-7). The mean duration from symptom onset to last positive RT-PCR was 17·83 (8-33 days; SD 6·22), median duration was 18 days (IQR 13·75-21). The percentage of positive RT-PCR tests in symptomatic patients was highest in the 1st week (100%), followed by 49%, 24%, 8·7% and 20·6% in the 2nd, 3rd, 4th week and beyond 4th week respectively ( Figure 2 ). The percentage of positive RT-PCR results following 1st RT-PCR test (regardless of symptoms ) was 50% in 1st week, followed by 28%, 10·8%, 16·2% and 6.6% in 2nd, 3rd, 4th and beyond 4th week respectively. Further analysis to look for association of age, gender, comorbidities, and symptomatology with the duration of RT-PCR positivity was done. The mean duration of positivity in age group 60 years or more, 19 -59 years and <18 years were 22·33±7·17, 17·18±5·79 and 14·75±4·85 days (p= 0·04)( Figure 3 ). The age wise distribution of median duration has been given in Table 2 . The mean period of last positive RT-PCR assay from the day of symptom onset among males and females (17·51±6·64 and 18·38±5·58 days, p=0·61), diabetics and non-diabetics (17·83±6·89 and 17·84±6·11 days,p=0·99), hypertensives and non-hypertensives (19·85±5·66 and 17·55±6·30 days, p=0.36) . The mean duration from 1st and last positive RT-PCR assays between symptomatic and asymptomatic patients were 13·01±4·63 and 13·93±5·42 days respectively; and the difference was not statistically significant with p value <0·05 (p=0·39). In asymptomatic patients, mean duration of positivity (from 1st RT-PCR) among the 3 age groups,age 60 years or more, 19 -59 years, < 18 years were 15(±6·59), 13·29 (±4·67), 10·5(±2·25) days [p value= 0·17]. The median time between 1st and last positive RT-PCR assays in the 3 age groups were 14(IQR:9-20), 12(IQR:9·25-17), and 11(IQR:9·25-12) days respectively (Table 3) . There was no statistically significant difference among diabetics and non-diabetics (14·69±6·73 and 13·12±4·57 days, p=0·29), . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 20, 2020. . https://doi.org/10.1101/2020.06.19.20135905 doi: medRxiv preprint hypertensives and non-hypertensives (13·37±4·92 and 13·2±5·22 days, p=0·91), males and females (13·6±4·86 and 12·94±5·08 days, p=0·53). Among symptomatic patients, 12 (7·3%) had positive RT-PCR beyond 21 days of symptom onset. Of these, 4 had diabetes mellitus, 3 had hypertension, and 4 were elderly i.e 60 years or above. Understanding the pathogenesis, transmission dynamics of SARS CoV-2 is important to manage the cases, stop transmission and prevent further expansion of the pandemic. Prompt identification and isolation of cases is critical in order to halt the spread of infection. This study was conducted in the initial part of pandemic in India, which, to the best of our knowledge provides the largest data on SARS-CoV-2 RNA detection in naso-pharyngeal and oro-pharyngeal samples in symptomatic or asymptomatic COVID-19 cases. As viral isolation is neither readily feasible nor available, diagnosis of viral RTIs relies upon molecular tests such as nucleic acid amplification and detection based tests. To the best of our knowledge this is the first study which provides information about the dynamic RT-PCR profile in COVID-19 cases in India. Most patients remain positive for SARS-CoV-2 after two weeks of symptom onset. Older age was associated with prolonged positivity. Patients with comorbidities and old age require special considerations from management and containment point of view. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 20, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 20, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 20, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 20, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 20, 2020. . https://doi.org/10.1101/2020.06.19.20135905 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 20, 2020. . https://doi.org/10.1101/2020.06.19.20135905 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 20, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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