In a recent medRxiv* preprint report, a research group from Israel described a novel SARS-CoV-2 strain with a non-synonymous mutation in its spike glycoprotein, designated as P681H; nevertheless, its emergence has not been associated with increased infections rate, facilitated spread or vaccine evasion.

The coronavirus disease 2019 (COVID-19) is still running rampant all over the world. As of March 2021, Israel found itself amidst the third wave of the infection. This resulted in tightening the restrictions as case levels rise, despite the ongoing vaccine rollout.

One of the more salient problems is the emergence of novel SARS-CoV-2 variants that are sometimes linked with faster spread and more severe clinical presentation. This is why increasing efforts to sequence complete viral genomes are of utmost importance.

What is the P681H mutation?

Recent studies have shown that P681H mutation of the SARS-CoV-2 spike glycoprotein is becoming pervasive among viral sequences. It has been observed as early as March 2020 in samples from Hawaii and Nigeria, and is also found in the globally spreading B.1.1.7 variant.

What is known about this mutation is that it is located next to the furin cleavage site in the spike glycoprotein protein, supposedly enhancing SARS-CoV-2 transmissibility by inducing a conformational change in the aforementioned protein, following protease activity at the cell membrane.

In order to appraise the situation with this mutation in Israel, as well as its public health significance, a research group led by Dr. Neta S. Zuckerman from the Central Virology Laboratory, Israel Ministry of Health, Sheba Medical Center in Israel, decided to characterize the Israeli P618H strain, identify it in sewage samples, and conduct adequate neutralization experiments.

Sequencing efforts and neutralization experiments

Random sampling efforts and the collection of clinical samples positive for SARS-CoV-2 have been a routine endeavor in Israel since December 2020. However, in order to accurately detect new variants, a detailed bioinformatic analysis was pursued after sequencing efforts in this study.

Moreover, whole genome sequencing of samples from wastewater treatment plants in nine locations across Israel (collected once a month between August 2020 and January 2021) has also been pursued.

The neutralization potency of antibodies against the local Israeli P681H strain has been compared to the neutralization effects of other strains that are circulating in Israel with the use of Vero-E6 cells (i.e., kidney epithelial cells from an African green monkey).

A growing presence of P681H

Herein, we report 181 sequences that are part of the B.1.1.50 lineage, but form a unique local strain that harbors the P681H mutation along with additional defining mutations”, say the researchers.

The P681H strains have been found in clinical samples since November 2020, but wastewater SARS-CoV-2 sequencing effort has shown that the P681H mutation was already in Israel in October 2020. Furthermore, the frequency of this mutation increased since late December 2020 due to an increase in the B.1.1.7 variant that also carries it.

In addition, by using sera from vaccinated individuals, neutralization assays have revealed comparable neutralization properties of the sera against the P681H Israeli strain, the B.1.1.7 strain and the non-P681H strain.

Not a variant of concern

Everything said, this study has shown that the local P681H strain can be neutralized as efficiently as frequently circulating strains, which has important implications for currently used vaccines.

“As the strain was not associated with escalated infection or spread, and given that the P681H mutation is observed in additional SARS-CoV-2 strains worldwide, this emerging local variant is currently not defined as a variant of concern”, conclude study authors.

Nonetheless, ongoing monitoring of the P681H strain by routine next-generation sequencing in Israel continues, and this data may prove very valuable in our continuous battle against COVID-19.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.