key: cord-0848477-72icd7zc authors: Kute, Vivek B.; Meshram, Hari Shankar; Navadiya, Vijay V.; Chauhan, Sanshriti; Patel, Dev D.; Desai, Sudeep N.; Shah, Nauka; Dave, Ruchir B.; Banerjee, Subho; Engineer, Divyesh P.; Patel, Himanshu V.; Rizvi, Syed Jamal; Mishra, Vineet V. title: Consequences of the first and second COVID‐19 wave on kidney transplant recipients at a large Indian transplant centre date: 2021-08-21 journal: Nephrology (Carlton) DOI: 10.1111/nep.13961 sha: 65edf27f5c6bfd97dfa190b8df2ef10e605faa0c doc_id: 848477 cord_uid: 72icd7zc BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID‐19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single‐centre retrospective study of 259 KTRs with COVID‐19 to compare first wave (March 15–December 31 2020, n = 157) and second wave (April 1–May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p‐value .04) and also included paediatric patients (0 vs. 5.9%; p‐value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p‐value .007); COVID‐19 positive patients had less frequent cough (32 vs. 13.8%; p‐value .001), fever was less frequent (58 vs. 37%; p‐value .001), and we observed fewer co‐morbidities (11 vs. 20.6%; p‐value .04). The percentages of neutrophils (77 vs. 83%; p‐value .001) and serum ferritin (439 vs. 688; p‐value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p‐value .0001). Hydroxychloroquine (11 vs. 0%; p‐value .0001) and tocilizumab (7 vs. 0%; p‐value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p‐value .0001) and remdesivir (47 vs. 65%; p‐value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p‐value .01) and ICU admissions (20 vs. 37.2%; p‐value .002) were more frequent during second wave. The 28‐day mortality rate (9.6 vs. 10%; p‐value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID‐19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre. intensive care admission was more frequent during the second wave of infection although mortality rates were similar in both waves. The timeline of COVID-19 waves varied amongst different geographic regions of the world and even in different geographic areas/states within the country. In India, the first wave commenced in March 2020 with cases started dropping in September 2020 till December 2020, India faced its COVID-19 second wave from March to June 2021. 1 On May 1 2021, India reported more than 400 000 new daily COVID-19 cases. 2 Several recent reports detail India's COVID-19 emergency during the second wave 3,4,5 with COVID-19 management depending on location, resources and disease burden under very limited healthcare resources. 6, 7, 8, 9 Several differences have been reported between the first and second waves, with a lower proportion of severe cases and younger patients, including children 10 affected by the second wave. [11] [12] [13] [14] [15] [16] [17] [18] Likewise, data comparing the characteristics of the infection in kidney transplant recipients (KTR) between two COVID-19 waves are scarce. 19, 20, 21 There are reports on the effects of the first wave on KTR in India; 22, 23, 24, 25 however, there are no data currently available on the effects of the second wave from India. 26, 27 Immunosuppressive regimens for KTR with COVID-19 and management protocols have been reported in our previous publication of KTR with COVID-19 in the first wave. 22, 23 Policy change (or change to management/follow-up off transplant recipients) between first and second waves: Table 1 shows the differences in the management protocol of first and second wave. The second wave was less severe but more contagious and has been linked to a more pronounced burden on the healthcare system with a limited number of hospital beds and deficit in ICU beds and oxygen supply. It is worth noting that with experience learned during the first wave, the second wave has been encountered more prepared with more knowledge about the disease to trained health care workers who were mostly vaccinated and less concerned about acquiring COVID-19. Hospitals had adequate availability of personal protective equipment, better drug availability (e.g., plasma therapy and remdesevir), more enhanced bed capacity, more ICU/ventilator beds and better telemedicine utilization. During the second wave, there was easy access to RT-PCR laboratory testing with rapid turnaround time, home care medical teams, markedly reduced costs for testing, reduced treatment cost, better knowledge about COVID-19, better access to health care due to mini-lockdowns, night curfews, and micro containments instead of national lockdown, and access to vaccines, which led to lower death rates. These measures applied for better management of patients in the second wave compared to the first one. Social distancing, hand wash, mask/face cover and covid appropriate behaviour helped to prevent infection rate outside the hospital. Statistical analysis: Statistical analysis was performed using the Statistical Package for Social Science (SPSS) version 17.0 (SPSS Inc., Chicago, IL). Continuous data are presented as median and interquartile ranges (IQR) and mean ± SD, and student's t tests were used to compare two groups. Categorical data were compared using the χ2 test or Fisher's exact test. Statistical significance was set at p < .05. Of the 259 KTRs with COVID-19 during both waves, 157 (60.6%) corresponded to the first wave and 102 (39.4%) to the second wave. We .015 .002 versus 1 Age group in years, n (%) <18 0 (0) 6 (5.9) .003 0 (0) 6 (6.5) .003 .21 34 (24) 17 (18.5) .33 5 (34) 1 (10) .34 Blood group distribution, n (%) A 37 (24) 20 (19.6) .53 34 (24) 19 (20.7) .63 3 (20) 1 (10) . .85 3 (20) 1 (10) .62 .71 versus 1 Obstructive uropathy 10 (6) 6 (5.9) .22 13 (9) 12 (13) . .85 3 (20) 1 (10) .62 .08 8 (5) 12 (13) .057 3 (20) 2 (20) 3.4 | Management and outcome of the cohort in the two waves Table 4 shows a detailed analysis of immune modulation, treatment and outcomes comparing waves one and two. Patients who did not require any oxygen support were more common in the second wave and four had suboptimal response and three died due to COVID-19. 28 We had around 400 chronic kidney disease patients on haemodialysis .12 8 (5) 11 (12) .09 3 (20) 2 (20) .73 .01 versus .8 Note: Bold indicates statistically significant value. Abbreviations: hsCRP, high-sensitive C reactive protein; IL-6, interleukin-6; LDH, lactate dehydrogenase; PCT, procalcitonin; S.G.P.T.: aspartate transferase; TCL: total leucocyte count. T A B L E 4 Comparing COVID-19 severity, treatment and outcome of kidney transplant recipients with COVID-19 in the two waves .0001 15 (100) 10 ( .38 3 (20) 3 (30) .65 .04 versus .057 .0001 15 (100) 10 (100) .0001 .0023 12 (80) 2 (20) .005 . .0001 .0001 3 (30) .052 N/A versus .37 Nitazoxanide 0 (0) .0001 0 (0) .0001 Favipiravir 36 (22) 12 (11.8) .032 32 (22) 10 (10.8) .02 4 (27) 2 (20) 1 .52 versus .33 Tofacitinib 0 (0) 8 (7.9) .0005 0 (0) .0001 0 (0) 3 (30) . .004 18 (12) 2 (2.2) .003 3 (20) 1 (10) . Overall, intensive care admissions were more frequent during the second wave (n = 38, 37.2% vs. n = 31, 20%; p-value .002). The 28-day mortality rates (n = 15, 9.6% vs. n = 10, 10%; p-value 1) were comparable. Interestingly, the incidence of mucormycosis (n = 2, 1.3% vs. n = 10, 10%; p-value .01) was disproportionately higher during the second. During the first wave, older age was associated with higher mortality (p-value .002 vs. 1). Sex did not affect the mortality rate. (neutrophil-to-lymphocyte ratio, C-reactive protein, LDH, IL-6, urea and d-dimer) as predictors of severe COVID-19 in both waves. 16 In our study, we identified IL6 level, LDH and allograft dysfunction as predictors of mortality in both waves. The overall patient mortality rates were 11.6 and 14.5% in hospi- less pneumonia and received less frequently anti-COVID-19 treatment in the second wave, and the overall mortality was lower but similar in critical patients. 20 The observed high-case fatality in the elderly transplant recipients could be due to age-associated comorbidities. 30 Our study had findings similar to this analysis of the Spanish Registry. 20 The interaction between age and time post-kidney transplant should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination. The recent study from European transplant centre described similar mortality rates in both waves, which is similar to our report. 31 In their report, there was no difference in clinical spectrum except the significant high number of cases being managed as outpatients in the second wave. Older age and chronic graft dysfunction was associated with mortality similar to our study. has not yet started in India, and more vigilance is needed to prevent a future COVID-19 surge in this population. Limitations: A single-centre study was a limiting factor. The low rate of asymptomatic or mild patients is likely an under-reported. There is no facility available for virological sequencing and testing of mutant strains of COVID-19 in resource-limited settings. We reported mainly hospitalized patients, and thus conclusions may not be broadly applicable to all asymptomatic patients and those diagnosed and managed in the outpatient setting and multicentre studied are required to validate our findings for the entire country. There was no difference in the mortality between the two waves. Mortality in KTRs with COVID-19 (10%) was higher than that in nonimmunosuppressed patients (1.2%) in our study. India's massive COVID surge puzzles scientists The Lancet. 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Tullius, MD, PhD, Harvard Medical School, Boston. The authors of this manuscript have no conflicts of interest to disclose. All authors participated equally in research design, the writing of the article, the performance of the research, the data collection, the data analysis, data interpretation and all authors approved the version for publication and agreed to be accountable for all aspects of the work. Vivek B. Kute https://orcid.org/0000-0002-0002-2854Hari Shankar Meshram https://orcid.org/0000-0001-9148-8168Subho Banerjee https://orcid.org/0000-0001-8231-9987