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Jun 1 55 tweets 17 min read
Study shows that COVID-19 was present in five U.S. states in December 2019, even before the first reported case in China

#SARSCoV2_timeline #Fall2019 #Winter2019 #serology #US news-medical.net/news/20210621/…
Serologic Testing of US Blood Donations to Identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)–Reactive Antibodies: December 2019–January 2020

Clinical Infectious Diseases, Vol. 72, Iss. 12, 15 June 2021

academic.oup.com/cid/article/72…

#SARSCoV2_timeline #Winter2019 Sridhar V Basavaraju,  Monica E Patton,  Kacie Grimm, Mohamm
“Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China, in December 2019, with subsequent worldwide spread.

The first US cases were identified in January 2020.” … Methods To determine if SARS-CoV-2–reactive antibodies
“Methods

To determine if SARS-CoV-2–reactive antibodies were present in sera prior to the first identified case in the United States on 19 January 2020, residual archived samples from…”
“… 7389 routine blood donations collected by the American Red Cross from

13 December 2019 to 17 January 2020 from donors resident in 9 states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin)…”
“…were tested at the Centers for Disease Control and Prevention for anti–SARS-CoV-2 antibodies.”
“Specimens reactive
by pan-immunoglobulin (pan-Ig) enzyme-linked immunosorbent assay (ELISA) against the
full spike protein were tested by

IgG and
IgM ELISAs,
microneutralization test,
Ortho total Ig S1 ELISA, and receptor-binding domain/ACE2 blocking activity assay.”
“Results

Of the 7389 samples, 106 were reactive by pan-Ig.

Of these 106 specimens, 90 were available for further testing.” Results Of the 7389 samples, 106 were reactive by pan-Ig. Of
“Eighty-four of 90 had neutralizing activity,

1 had S1 binding activity, and

1 had receptor-binding domain/ACE2 blocking activity >50%,

suggesting the presence of anti–SARS-CoV-2–reactive antibodies.

Donations with reactivity occurred in all 9 states.”
“Conclusions

These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to 19 January 2020.
“The study was approved by the American Red Cross Institutional Review Board. Data for this report were collected as part of public health emergency response and determined by the CDC Office of the Associate Director for Science to not require additional CDC [IRB] review.“ METHODS  Ethical Considerations  The study was approved by t
academic.oup.com/cid/article/72…

Blood Donor Sample Description

Whole blood or blood products intended for transfusion are collected from volunteer donors in either fixed collection sites or as part of mobile collection drives.” Donors are questioned regarding travel outside of the United
“All blood donors are subjected to medical and social history questionnaires to ascertain risk factors associated with transfusion-transmissible infectious diseases, such as HIV.”
“Donors are questioned regarding travel outside of the United States and are deferred for travel to malaria-affected areas. SARS-CoV-2 risk-based donor deferral for travel to China was not implemented until February 2020.”
“As part of the donation evaluation, donors undergo a basic physical examination, which includes temperature, blood pressure, and heart rate measurements. Persons presenting to donate blood with signs or symptoms consistent with bacterial or viral respiratory infections,…”
“…including influenza, are deferred and instructed to return for donation once symptoms have resolved. Serum specimens from all blood donations are tested for infectious-disease markers as required by the Food and Drug Administration.”
“Archived, residual serum specimens from routine donations collected by the American Red Cross from 13 December 2019 to 17 January 2020 from donors resident in California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington,& Wisconsin were sent to CDC…” Archived, residual serum specimens from routine donations co
“Laboratory Methods

Once at CDC, sera were screened using a pan-immunoglobulin (pan-Ig) enzyme-linked immunosorbent assay (ELISA) against the pre-fusion stabilized ectodomain of the spike protein (S) that includes both S1 and S2 domains.” Laboratory Methods  Once at CDC, sera were screened using a
“To ensure high-throughput screening capability, initial screening did not include background correction.”
“Initial reactive specimens, defined as having an optical density (OD) of 0.5 or greater in the screening ELISA (tested at a 1:100 dilution), were then confirmed by reflex testing at 1:100 and 1:400 dilutions using the same ELISA with background correction.”
“Specimens were considered confirmed reactive if there was a signal to threshold ratio of 1 or greater at a background-corrected OD of 0.4.

At a background-corrected OD of 0.4 with serum diluted 1:100, specificity of this assay is 99.3% …and sensitivity is 96%…”
“When paired sera from…[PCR]–confirmed infections with
other common coronaviruses were tested,

4 of 42 exhibited increasing signal between the acute and convalescent timepoints, but all were below the assay cutoff.”
“ Isotype-specific tests were performed using the same ELISA technique, but with IgG- or IgM-specific secondary antibody.”

academic.oup.com/cid/article/72…
“Confirmed-reactive specimens were further tested using a microneutralization test with live SARS-CoV-2 USA-WA1/2020, SARS-CoV-1 S1 pan-Ig ELISA, & a surrogate neutralization assay that measures the ability of sera to block the interaction between the S receptor-binding domain…” Confirmed-reactive specimens were further tested using a mic
“…(RBD) and the cellular receptor ACE2. For microneutralization, sera were serially diluted 2-fold between 1:20 and 1:640, incubated with virus for 30 minutes at 37°C, and used to inoculate Vero CCL-81 cells.”
“After 5 days, cells were fixed and stained with formalin–crystal violet to observe live/dead cells. The highest dilution at which sera blocked viral infection was determined to be the neutralizing titer, with more than 40 designated as positive.”
“For the Ortho ELISA and surrogate neutralization assays, the manufacturers’ instructions were followed.”

Statistical Analyses  Descriptive analyses were performed to
Table 1. Total Number of Samples Tested, That Were Reactive, With Positive Microneutralization and Surrogate Neutralization, and Reactive for the S1 Ortho Test

Specimens collected
🟢12/13-16/2019
&
🔵12/30/2019 - 1/17/2020
are summarized separately.

academic.oup.com/view-large/264…

pdf Table 1. Total Number of Samples Tested, Number of Samples T
academic.oup.com/view-large/264…

“Figure 1.
Combined results of confirmatory tests from 90 spike-reactive routine blood donations collected in 9 US states between [12/13/2019 & 1/17/2020]. Each line indicates a single serum that was already confirmed to bind SARS-CoV-2 spike by ELISA.” Combined results of confirmatory tests from 90 spike-reactiv…Higher numbers indicate more neutralizing activity. The s
“RESULTS

Serum specimens were sent to CDC for anti–SARS-CoV-2 testing from 7389 unique donations (Table 1).

Of these, 106 (1.4%) were confirmed reactive by the pan-Ig S ELISA screen

and then a confirmatory assay with background correction (Table 1).” …During validation of the assay, 3 of 519 true-negative se
“These confirmed-reactive sera included

39 of 1912 (2.0%) donations collected between
13 and 16 December 2019

from residents of California (23/1912) and Oregon or Washington (16/1912).”
“Sixty-seven confirmed-reactive (67/5477, 1.2%) donations
were collected between

30 December 2019 and 17 January 2020

from residents of
Massachusetts (18/5477), Wisconsin or Iowa (22/5477), Michigan (5/5477), and Connecticut or Rhode Island (33/5477).”
“During validation of the assay,

[❓]
3 of 519 true-negative sera
had reactivities above the signal: threshold cutoff of 1 ranging from 1.46 to 2.11.

These true-negative sera were collected from healthy adults between 2016 and 2019 (n=377),…”
“…patients with
suspected Hantavirus between
2016 and 2019 (n=101),

HIV-positive individuals between 2011 and 2012 (n=10),

hepatitis B–positive individuals between 2011 & 2012 (n=10),

or hepatitis C–positive individuals between 2011 and 2012 (n=10).”
“True positive sera from 99 patients with PCR-confirmed COVID-19 collected more than 10 days post–symptom onset ranged from 0.11 to 6.99, with a median of 6.10 & a standard deviation of 1.91.”
“Of the 106 confirmed-reactive sera, 67 had threshold cutoffs between 1.0 & 2.11, which is within the same range of true-negative sera that were above the assay cutoff.”
“In contrast, 32 & 4 had threshold cutoffs of 2.12–4.08 & greater than 4.30, respectively, well above the true-negative sera that tested above cutoff limits.”
“Of the 106 confirmed-reactive specimens, 90 were available for further testing. …using isotype-specific spike protein ELISAs,
Ortho pan-Ig S1 assay, microneutralization tests, and a surrogate neutralization assay that detects the ability of sera to block RBD binding to ACE2.” By the Ortho S1 pan Ig assay, 1 reactive serum sample had a
“Of the 90 sera tested by microneutralization, 84 had an endpoint titer greater than 40. When the anti–spike protein isotype responses were examined, 39 of the 90 had both S-reactive IgG & IgM (43.3%),…”
“…8 were IgM positive but IgG negative, 29 were IgG positive but IgM negative, and the remaining 14 were just positive using a pan-Ig secondary.”
“By the Ortho S1 pan Ig assay, 1 reactive serum sample had a signal-to-threshold cutoff of 1.89 (with a retest of 1.10), and by surrogate neutralization 21 sera exhibited 20–30% inhibition, 1 at 45% inhibition, and 1 at 71% inhibition.”
“When results in all tests were compared by individual specimen, there was not an obvious pattern of specimens with higher signals in ELISA, surrogate neutralization, or live virus microneutralization tests clustering together (Figure 1),…”
“…indicating that each donation had a unique pattern of test results.

These data might indicate that there is no clear delineation between potentially cross-reactive specimens and those that were obviously from SARS-CoV-2–infected individuals.”
“The mean age of repeat reactive donors was 52 years (range, 16–95 years).

More donations occurred among males than females
(55.1% male specimens from 13–16 December 2019;
53.6% male specimens from 30 December 2019 and 17 January 2020).” The mean age of repeat reactive donors was 52 years (range,
“The proportion of reactive donations was
higher among males than females among donations from

13–16 December 2019
(2.6%…males, 1.4%…females)

and from

30 December 2019–
17 January 2020
(1.1%…males, 0.7%…females).”
“Among donations collected in California, Washington, and Oregon,
the proportion of reactive donations was
higher among donors aged 40 years or older.”

academic.oup.com/cid/article/72…
“Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in All of Us Research Program Participants, 2 January to 18 March 2020”

6/15/2021

#SARSCoV2_timeline #Winter2019 #Winter2020 #Spring2020 #serology #NIH
academic.oup.com/cid/article/74…

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#epidemiological_dynamics
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I can’t reply on the other thread, anymore. @OnTapPhysio
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A Danger for Our Democracies
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thedailybeast.com/what-made-the-…
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Definition of catatonic symptoms
#Negativism
Apparently motiveless resistance to instructions or to attempts to move/examine the patient. Contrary behavior, does the opposite of the instruction

#Automatic_obedience Exaggerated cooperation w/the examiner’s request, or repeated movements that are requested once
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S. Table 2. Prospective studies…: benzodiazepines, electroconvulsive therapy (ECT) antipsychotics ncbi.nlm.nih.gov/pmc/articles/P…
ncbi.nlm.nih.gov/pmc/articles/P…

Panel 1A.
Catatonia checklist

Psychomotor Activity
Observation:
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Abnormal •Grimacing •stereotypy •mannerism •posturing •perseveration

Decreased •Stupor •ambitendency •staring Observation: agitation/excitement , impulsivity, Combativene
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