key: cord-0898927-by4gqlst
authors: Tani‐Sassa, Chihiro; Iwasaki, Yumi; Ichimura, Naoya; Nagano, Katsutoshi; Takatsuki, Yuna; Yuasa, Sonoka; Takahashi, Yuta; Nakajima, Jun; Sonobe, Kazunari; Nukui, Yoko; Takeuchi, Hiroaki; Tanimoto, Kousuke; Tanaka, Yukie; Kimura, Akinori; Tohda, Shuji
title: Viral loads and profile of the patients infected with SARS‐CoV‐2 Delta, Alpha, or R.1 variants in Tokyo
date: 2021-12-02
journal: J Med Virol
DOI: 10.1002/jmv.27479
sha: 87402ec67165f1cd2bc604ff945018a13de19e36
doc_id: 898927
cord_uid: by4gqlst

The rapid spread of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) became a serious concern worldwide in summer 2021. We examined the copy number and variant types of all SARS‐CoV‐2‐positive patients who visited our hospital from February to August 2021 using polymerase chain reaction (PCR) tests. Whole genome sequencing was performed for some samples. The R.1 variant (B.1.1.316) was responsible for most infections in March, replacing the previous variant (B.1.1.214); the Alpha (B.1.1.7) variant caused most infections in April and May; and the Delta variant (B.1.617.2) was the most prevalent in July and August. There was no significant difference in the copy numbers among the previous variant cases (n = 29, median 3.0 × 10(4) copies/µl), R.1 variant cases (n = 28, 2.1 × 10(5) copies/µl), Alpha variant cases (n = 125, 4.1 × 10(5) copies/µl), and Delta variant cases (n = 106, 2.4 × 10(5) copies/µl). Patients with Delta variant infection were significantly younger than those infected with R.1 and the previous variants, possibly because many elderly individuals in Tokyo were vaccinated between May and August. There was no significant difference in mortality among the four groups. Our results suggest that the increased infectivity of Delta variant may be caused by factors other than the higher viral loads. Clarifying these factors is important to control the spread of Delta variant infection.

The rapid spread of the Delta variant (B.1.617.2) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a serious problem worldwide in summer 2021. 1 We previously reported that the R.1 variant (the sublineage Information on SARS-CoV-2 variants and patient numbers is provided by the Tokyo Metropolitan Institute of Public Health, 3 

To determine the SARS-CoV-2 variant for each patient, we used melting curve analysis of PCR products. Viral RNA was purified from the swab samples that were positive for SARS-CoV-2, using the EZ1 

The difference in copy numbers and ages among the four types of variant cases was evaluated using the Steel-Dwass test. The difference in the rate of intensive care unit (ICU) admission and mortality was evaluated using the χ 2 test. The variant types from 20 samples could not be determined as variant screening PCR did not produce any PCR products; this is probably because the samples had a very small copy number F I G U R E 1 Sequential transition of four types of variant cases determined by PCR-based melting curve analysis. Untyped bar represents the samples of which variant type was not determined because of that the PCR products were not generated probably due to small copy number. PCR, polymerase chain reaction (data not shown). Untyped samples (shown as Untyped bar in Figure 1 ) were excluded from the following analysis.

The clinical profiles of the 288 patients enrolled are shown in Table 1 . Comparing the age of each variant group, there was no significant difference between Delta and Alpha cases. However, the Delta variant cases were significantly younger than the R.1 variant cases (p = 5 × 10 −5 ) and the previous strain cases (p = 6 × 10 −7 ).

As an indicator of increased severity, the rates of admission to the intensive care unit (ICU) were compared among the four groups. The rate of ICU admission for previous strain cases was significantly higher than that of Delta variant cases (p = 0.022). There were no significant differences among the other variant pairs. With regard to mortality, no significant difference was found between any pair of groups.

The distribution of viral loads as copy numbers in the swabsoaked samples is shown in Figure 2 . There was no significant difference in copy number among the four variant groups. We could not find a clear relationship between copy number and severity ( Figure 2-upper panel) and between copy number and generation ( Figure 2-lower panel) . The copy numbers of patients who died in the Delta variant group seemed high compared with the numbers of those who did not die, however, this finding could not be confirmed as only three patients died in this group.

The Delta variant has attracted attention for its increased transmissibility. 1 Viral load is thought to be one of the factors that causes increased transmissibility. Li et al. reported that the viral load of Delta variants was more than a thousand times higher than that of the Wuhan strain in the initial wave of 2020 in China. 5 Ong et al. also reported that the Delta variant was associated with lower PCR cycle threshold values compared with the wild-type in Singapore. 6 Because we had no patients with the Wuhan strains in early 2020, we could not compare the viral load between the Delta variant cases and the Wuhan strain cases.

Contrary to these reports, our data showed that the viral loads of the Delta variant cases were no higher than those of the other variant cases. It should be noted that our data may be biased because our 

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Viral loads and profile of the patients infected with SARS-CoV-2 Delta, Alpha, or R.1 variants in Tokyo

Nagano, Yuta Takahashi, Sonoka Yuasa, Yuna Takatsuki, Jun Nakajima, and Kazunari Sonobe. Performed WGS: Hiroaki Takeuchi, Kousuke Tanimoto, Yukie Tanaka, and Akinori Kimura. Analyzed data: Naoya Ichimura and Shuji Tohda. Wrote the paper: Shuji Tohda.

The data and protocol of RT-PCR are available from the corresponding author upon request.

http://orcid.org/0000-0002-5689-9858Shuji Tohda http://orcid.org/0000-0002-2642-5459