⚡️We developed & performed initial validation on an amplicon-based sequencing protocol (PrimalSeq) for Monkeypox virus (MPXV).

It improves genome coverage compared to metagenomic sequencing, especially at CTs >20.

🧵 1/8 | Protocol 👉
protocols.io/view/monkeypox… It's based on a design led by @Scalene & @pathogenomenick originally for Zika virus that was adapted for SARS-CoV-2 ("ARTIC protocol") and used by labs around the world.

Our goal was for this to be plug n' play with current SARS-CoV-2 protocols. (2/8)
nature.com/articles/nprot…

🧬July-14 Connecticut #SARSCoV2 variant surveillance
@CovidCT|@CTDPH|@CDC_AMD|@YaleSPH|@Yalemed

📈BA.5 is now the dominant variant in CT (53% from 6/27-7/4), followed by BA.2 (34% & 📉) and BA.4 (11% & 📈)

🚫No detection of BA.2.75

🧵 (1/8) | Report 👉
kphamyale.shinyapps.io/variant_report/ Using a logistic regression of the daily frequencies, we predict that as of today (July-14), BA.5 is probably 80-90% in Connecticut.

BA.4 is still 📈 as it outcompetes BA.2, but will probably start to 📉 in frequency soon after BA.2 is gone. (2/8)

🧬May-19 Connecticut #SARSCoV2 variant surveillance
@CovidCT|@CTDPH|@CDC_AMD|@YaleSPH|@YaleMed

📊Sequencing last 3 weeks
➡️ BA.2.12.1 = 44% (📈 8%)
➡️ BA.2 (other lineages) = 56% (📉 7%)
➡️ BA.4/5 = 0.3% (5 total)

🧵 (1/13) | Report 👉
covidtrackerct.com/variant-survei… Omicron BA.2.12.1 is still 📈 in Connecticut as it is across most of the US. Fitting the % of sequenced cases to a logistic growth curve, we estimate that BA.2.12.1:

1⃣ is ~80% frequency today (May019)
2⃣ surpassed 50% in early May
3⃣ may reach 95% in early/mid June
(2/13)

🧬May-5 Connecticut #SARSCoV2 variant surveillance
@CovidCT|@CTDPH|@CDC_AMD|@YaleSPH|@Yalemed

Last 3 weeks
➡️BA.1.1 = 4%
➡️BA.2.12.1 = 23% (may be slowing down)
➡️BA.2 (other lineages) = 73%
➡️BA.4/BA.5 = 0% (might still be coming)

🧵 (1/9) | Report 👉
covidtrackerct.com/variant-survei… We no longer have TaqPath data from YNHH to track SGTF, but we will use our "VOC" PCR assay that detect SGTF and ORF1a target failures (ORFTF).

BA.1 = SGTF
BA.2 = ORFTF

BA.1 is barely hanging on. (2/9)

🧬 March-17 Connecticut #SARSCoV2 variant surveillance
@CovidCT | @CTDPH | @CDC_AMD | @YaleSPH | @Yalemed

📊Sequencing data last 3 weeks
BA.1/.1 = 84%📉
BA.2 = 16%📈
Delta = 0%

📊PCR data this week
BA.1/.1 = 41%📉
BA.2 = 59%📈

🧵 (1/7) | Report 👉
covidtrackerct.com/variant-survei… Based on our TaqPath PCR data (S-gene detected), we estimate that:

➡️ BA.2 is >50% in Southern Connecticut
➡️ At this rate - BA.2 will be 95% by early April
➡️ BA.2 doubling rate = 7.8 days (BA.1 in December = 3-4 days)
➡️ BA.2 ~43% more transmissible than BA.1/.1

(2/7)

Here are comparative results between 10 TaqPath S-gene detected samples tested by YNHH and with our validated VOC PCR assay. Most with our assay were actually SGTF, and looking at the YNHH results, the S-gene CTs for those were 5-7 higher than N/ORF. (5/16) We are looking into these low level spike amplification samples that should be SGTF to see if this is a lab/TaqPath assay artifact or if there is something about these BA.1 sequences. So far doesn't seem to be sequence-related. Will report (6/16)

🧬 Feb-3 Connecticut #SARSCoV2 variant surveillance
@CovidCT|@CTDPH|@CDC_AMD|@YaleSPH|@Yalemed

7 Omicron BA.2 cases detected in CT, but still remains <1%

BA.2 by sequencing last 3 weeks = 0.7% (5/709)
BA.2 by PCR last 3 days = <1%

🧵 (1/16) | Report 👉
covidtrackerct.com/variant-survei… Starting with the TaqPath PCR data:

We now estimate that Omicron BA.1 has remained at 98-100% of the daily tests for ~2 weeks. Meaning that Omicron BA.2 and Delta could only be a combined 0-2%.

This is different than our estimates from last week (2/16)

🧬 2022.01.27 Connecticut #SARSCoV2 variant surveillance
@CovidCT | @CTDPH | @CDC_AMD | @jacksonlab | @YaleSPH | @Yalemed

📊 by NGS last 3 weeks
BA.1 = 97%
BA.2 = <1%
Delta = 3%

📊 by SGTF yesterday
BA.1 = 85%
Delta/BA.2 = 15%

short 🧵 | Report 👉
covidtrackerct.com/variant-survei… We reported the first Omicron BA.2 case in Connecticut earlier in the week. We haven’t confirmed any new cases since. (2/n)

https://twitter.com/NathanGrubaugh/status/1486083856860123137?s=20

⚡️Our latest pre-print:

Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

Read it 👉
medrxiv.org/content/10.110…

🧵 (1/20) 1st, some background

@maryebushman, @BillHanage & co found that variants with ⬆️ transmissibility & partial immune escape may significantly 📈 infections even in a well-💉 population.

From an infection standpoint, this was our worse variant fear (2/20)
cell.com/cell/fulltext/…

🧬 2022.01.25 Connecticut #SARSCoV2 variant surveillance - brief report
@CovidCT | @YaleSPH | @YaleMed

⚡️We detected the first *BA.2* Omicron case in Connecticut. Sample collected on Jan-8 from Fairfield County.

Short 🧵 on this divergent Omicron lineage (1/9) BA.1 is the lineage of Omicron that caused the recent wave of infections in CT.

While BA.2 is still technically Omicron, and BA.2 shares 32 mutations with BA.1, BA.2 also has 28 unique mutations.

For perspective, BA.1 and BA.2 are almost as divergent as Delta and Alpha. (2/9)

🧬 2022.01.20 Connecticut #SARSCoV2 variant surveillance
@CovidCT | @CTDPH | @CDC_AMD | @jacksonlab | @YaleSPH | @Yalemed

📊 by NGS last 3 weeks
Omicron = 96% (all BA.1)
Delta = 4%

📊 by SGTF yesterday
Omicron = 96%
Delta = 4%

short 🧵 | Report 👉
covidtrackerct.com/variant-survei… Not much has changed for a while.

The frequency of Omicron in the community (measured by SGTF) has remained stable at 91-97% for the last 3 weeks, going back to Dec-30. These data are mostly from Fairfield and New Haven Counties. (2/8)

🧬 2022.01.06 Connecticut #SARSCoV2 variant surveillance
@CovidCT | @CTDPH | @CDC_AMD | @jacksonlab | @YaleSPH | @Yalemed

📊 by NGS last 3 weeks
Omicron = 54% (all BA.1)
Delta = 46%

📊 by SGTF yesterday
Omicron = 95%
Delta = 5%

short 🧵 | Report 👉
covidtrackerct.com/variant-survei… As of Jan-5, we estimate that Omicron (by SGTF) is 95% in outpatients primarily from Fairfield and New Haven Counties. Omicron frequency has been between 91-95% for the last 7 days, though is still slowly rising. (2/n)

🧬 2021.12.23 Connecticut #SARSCoV2 variant surveillance
@CovidCT | @CTDPH | @CDC_AMD | @jacksonlab | @YaleSPH | @Yalemed

📊 by NGS last 3 weeks
Delta = 88%
Omicron = 12%

📊 by SGTF yesterday
Delta = 26%
Omicron = 74%

short 🧵 | Report 👉
covidtrackerct.com/variant-survei… As of 12/22, we estimate by SGTF that Omicron is 74% in outpatients primarily from Fairfield and New Haven Counties. @jacksonlab is also reporting Omicron at near 50% from their outpatient testing.

I think that it’s safe to say that Omicron is now dominant in Connecticut. (2/7)

I am fortunate to have worked with the amazing @sarahcobey to write a preview for the incredible paper recently published by @maryebushman, @BillHanage, & co on the interplay between intrinsic transmissibility and immune escape on variant success. (1/16)

authors.elsevier.com/a/1eHy5L7PXf0KZ Here is a link to @maryebushman, @BillHanage et al's paper out in this issue of @CellCellPress (2/16)

cell.com/cell/fulltext/…

⚡️Yale-Connecticut #omicron update.

As of 12/20, we estimate that Omicron is now the dominant variant (56%) in outpatients tested by @YNHH.

Omicron's doubling rate of ~3.5 days is ~3x faster than Delta's during late spring/early summer.

Short 🧵 (1/5)
covidtrackerct.com/variant-survei… Our data 👆 do not represent all of Connecticut, but I expect that if Omicron is not dominant yet state-wide, it will be within days.

I'm still shocked that a variant that I first learned about on Thanksgiving (11/25) will likely be dominant in CT by Christmas (12/25)

(2/5)

⚡️We are now posting daily S-gene target failure (SGTF) data – a proxy for Omicron – from clinical testing @ynhh (Connecticut) on our website. That way I don’t need to write a thread every day 😉

📊2021.12.16 = 33% SGTF

Short 🧵 | See the data 👉
covidtrackerct.com/variant-survei… The data are located on our weekly variant report (though I will *try* to update daily). If you scroll down below the summary table, you’ll see the interactive figure. There you can find the data that underline the trends. (2/5)

🧬 12/16 Connecticut #SARSCoV2 variant surveillance
@CovidCT | @jacksonlab | @CTDPH | @YaleSPH |@Yalemed

40 sequence-confirmed Omicron cases

📊 by NGS (lags)
Delta = 95%
Omicron = 5%

📊 by SGTF
Delta = 70-88%
Omicron = 12-30%

short 🧵 | Report 👉
covidtrackerct.com/variant-survei… S-gene target failure (SGTF) data (a proxy for omicron) from yesterday took a big leap from 12% to 30%, which may end up being a bit of an outlier (noise w/ small n). Regardless, the % keeps rising fast, and we predict that Omicron will >50% in this population within days. (2/5)

12/14 Yale SGTF update

We can now track daily TaqPath tests from Yale New Haven Hospital, and of the pos tests with ORF target < 30 CT, report the fraction likely Omicron (SGTF) and Delta (non-SGTF).

From tests on Dec 13, *23/214 (9.7%)* had a SGTF
Explanation & caveats in 🧵 Our data represent a fraction of the samples tested by YNHH, and the catchment is primarily New Haven and Fairfield Counties. So they don’t represent all of Connecticut. I’ve heard from others tracking SGTFs elsewhere in the state that they are not seeing a high % yet. (2/11)

🧬 12/2 Connecticut #SARSCoV2 variant surveillance @CovidCT | @jacksonlab | @CTDPH | @YaleSPH | @Yalemed

👑Delta - 100% (614/614)

📊Top lineages
25% - AY.103
19% = AY.44
14% = AY.25
6% = AY.3
6% = AY.119

0⃣ Omicron or Delta AY.4.2

short 🧵 | Report 👉
covidtrackerct.com/variant-survei… It's all Delta so far in Connecticut, with no signs (yet) of Omicron via sequencing or PCR signatures (i.e. S-gene target failures). (2/6)

🧵 Brief update on impact of #Omicron on the CDC #SARSCov2 primers/probes that are commonly used in PCR assays in the US and abroad (1/6)

https://twitter.com/NathanGrubaugh/status/1464369814407892996

(2/6) The CDC N1 probe mismatch in Omicron is a C28311T mutation. Of the 91 B.1.1.529 sequences on GISAID:
- 48 have a T (mismatch)
- 19 have a C (exact match)
- 26 have no coverage (NNNs)

B.1.1.529 PCR detection 🧵

Like Alpha (B.1.1.7), B.1.1.529 has the spike 69-70 deletion that causes a S-gene target failure (SGTF) when using the ThermoFisher TaqPath COVID-19 assay. Because most other variants didn't have the deletion, this was helpful for tracking Alpha (1/8) Likewise, reporting SGTFs will be extremely helpful again for tracking the spread & growth of B.1.1.529, like the amazing folks in South Africa are already demonstrating (2/8)

https://twitter.com/Tuliodna/status/1463911577544011780?s=20