key: cord-0275314-as4a6bpz
authors: Gunadi,; Hakim, M. S.; Wibawa, H.; Marcellus,; Setiawaty, V.; Slamet,; Trisnawati, I.; Supriyati, E.; Khair, R. E.; Iskandar, K.; Afiahayati,; Siswanto,; Irene,; Anggorowati, N.; Daniwijaya, E. W.; Nugrahaningsih, D. A. A.; Puspadewi, Y.; Puspitarani, D. A.; Tania, I.; Vujira, K. A.; Ardlyamustaqim, M. B.; Gabriela, G. C.; Eryvinka, L. S.; Nirmala, B. C.; Geometri, E. T.; Darutama, A. A.; Kuswandani, A. A.; Lestari,; Irianingsih, S. H.; Khoiriyah, S.; Lestari, I.; Ananda, N. R.; Arguni, E.; Nuryastuti, T.; Wibawa, T.; group, Yogyakarta-Central Java COVID-19 study
title: Is the infection of the SARS-CoV-2 Delta variant associated with the outcomes of COVID-19 patients?
date: 2021-10-07
journal: nan
DOI: 10.1101/2021.10.05.21262783
sha: 61d21968a7e76f3e791c61d4c26cd76fc07b84ea
doc_id: 275314
cord_uid: as4a6bpz

Background: SARS-CoV-2 Delta variant (B.1.617.2) has been responsible for the current increase in COVID-19 infectivity rate worldwide. We compared the impact of the Delta variant and non-Delta variant on the COVID-19 outcomes in patients from Yogyakarta and Central Java provinces, Indonesia. Methods: We ascertained 161 patients, 69 with the Delta variant and 92 with the non-Delta variant. The Illumina MiSeq next-generation sequencer was used to perform the whole genome sequences of SARS-CoV-2. Results: The mean age of patients with Delta and the non-Delta variant was 27.3 +/- 20.0 and 43.0 +/- 20.9 (p=3x10-6). The patients with Delta variant consisted of 23 males and 46 females, while the patients with the non-Delta variant involved 56 males and 36 females (p=0.001). The Ct value of the Delta variant (18.4 +/- 2.9) was significantly lower than the non-Delta variant (19.5 +/- 3.8) (p=0.043). There was no significant difference in the hospitalization and mortality of patients with Delta and non-Delta variants (p=0.80 and 0.29, respectively). None of the prognostic factors was associated with the hospitalization, except diabetes with an OR of 3.6 (95% CI=1.02-12.5; p=0.036). Moreover, the patients with the following factors have been associated with higher mortality rate than patients without the factors: age [≥]65 years, obesity, diabetes, hypertension, and cardiovascular disease with the OR of 11 (95% CI=3.4-36; p=8x10-5), 27 (95% CI=6.1-118; p=1x10-5), 15.6 (95% CI=5.3-46; p=6x10-7), 12 (95% CI=4-35.3; p=1.2x10-5), and 6.8 (95% CI=2.1-22.1; p=0.003), respectively. Multivariate analysis showed that age 65 years, obesity, diabetes, and hypertension were the strong prognostic factors for the mortality of COVID-19 patients with the OR of 3.6 (95% CI=0.58-21.9; p=0.028), 16.6 (95% CI=2.5-107.1; p=0.003), 5.5 (95% CI=1.3-23.7; p=0.021), and 5.8 (95% CI=1.02-32.8; p=0.047), respectively. Conclusions: We show that the patients infected by the SARS-CoV-2 Delta variant have a lower Ct value than the patients infected by the non-Delta variant, implying that the Delta variant has a higher viral load, which might cause a more transmissible virus among humans. However, the Delta variant does not affect the COVID-19 outcomes in our patients. Our study also confirms the older age and comorbidity increase the mortality rate of COVID-19 patients.

The SARS-CoV-2 variants of concern (VOC), including Alpha, Beta, Gamma, and Delta, has 133 attracted public health authorities due to its capability on higher transmission, the possibility of 134 affecting COVID-19 severity, and the impact of the effectiveness of public health measures, 135 diagnosis, treatment, and vaccines [1, 2, 3] . SARS-CoV-2 Delta variant (B.1.617.2) has been 136 responsible for the current increase in COVID-19 infectivity rate worldwide [4, 5, 6, 7] . 137

However, our knowledge about the role of the Delta variant on the COVID-19 outcomes 138 is still very limited [8, 9] . Moreover, several prognostic factors have been associated with 139 COVID-19 illness [10, 11, 12] . Here, we compared the impact of the Delta variant and non-Delta 140 variant on the COVID-19 outcomes in patients from Yogyakarta and Central Java provinces, 141 According to previous studies, we associated the following prognostic factors with the 152 hospitalization and mortality of COVID-19 patients: sex, age, comorbidity, and smoking 153 [10, 11, 12] . 154 . 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)

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First, Single-stranded cDNA was synthesized from RNA extracted from the viral transport 157 medium of patients with COVID-19 using SuperScript™ III First-Strand Synthesis System 158 (Thermo Fisher Scientific, MA, United States). Then, the second strand was synthesized using 159 COVID-19 ARTIC v3 primer pool design by SARS-CoV-2 ARTIC Network using Phusion™ 160 We used a dataset of 250 available SARS-CoV-2 genomes extracted from GISAID from our 170 region and others (Acknowledgment Table is provided in Supp. Table 1 ) to reconstruct the 171 phylogenetic tree. Multiple nucleotide sequence alignment was performed using the MAFFT 172 program (https://mafft.cbrc.jp/alignment/server/). We used the neighbor-joining statistical 173 method with 1,000 bootstrap replications [14, 15] to construct a phylogenetic tree from 29.420 174 nucleotide length of the open reading frame (ORF) of SARS-CoV-2, followed by computation of 175 the evolutionary distances and model the rate variation among sites by the Kimura 2-parameter 176 method and the gamma distribution with estimated shape parameter (α) for the dataset, 177 . 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 October 7, 2021. and mortality. There were no significant differences in the hospitalization and mortality of 214 patients with Delta and non-Delta variants (p=0.80 and 0.29, respectively) ( Table 2) . None of the 215 prognostic factors was associated with the hospitalization, except comorbidity of diabetes with 216 the OR of 3.6 (95% CI=1.02-12.5; p=0.036) ( Table 2) . Moreover, the patients with the following 217 factors have been associated with higher mortality rate than patients without these factors: age 218 ≥ 65 years, obesity, diabetes, hypertension, and cardiovascular disease with OR of 11 (95% 219 CI=3.4-36; p=8x10 -5 ), 27 (95% CI=6.1-118; p=1x10 -5 ), 15.6 (95% CI=5.3-46; p=6x10 -7 ), 12 220 (95% CI=4-35.3; p=1.2x10 -5 ), and 6.8 (95% CI=2.1-22.1; p=0.003), respectively (Table 2) . 221 . 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 October 7, 2021. . 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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Subsequently, we performed a multivariate analysis to find an independent factor affecting the 226 COVID-19 outcomes. Multivariate analysis showed that age ≥65 years, obesity, diabetes, and 227 hypertension were strong prognostic factors for the mortality of COVID-19 patients with the OR 228 of 3.6 (95% CI=0.58-21.9; p=0.028), 16.6 (95% CI=2.5-107. 1; p=0.003), 229 p=0.021), p=0.047) , respectively. In addition, no prognostic factors 230 were associated with the hospitalization of COVID-19 patients (Table 3) . 231 We thank the Collaborator Members of the Yogyakarta-Central Java COVID-19 study group: 330

We gratefully acknowledge the authors, the originating and submitting laboratories for their 337 sequence and metadata shared through GISAID. We also thank to Besar Besar Veteriner Wates 338 (Disease Investigation Center Wates) where the virus samples were sequenced using the NGS 339 Illumina MiSeq instrument. All submitters of data may be contacted directly via www.gisaid.org. 340

The Acknowledgments Table for GISAID is reported as Supplementary Table 1 . 341 . 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 October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21262783 doi: medRxiv preprint

World Health Organization. Tracking SARS-CoV-2 variants