Wednesday, March 31, 2021

CDC:Updated COVID Variant Map & Growth Trends By State


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For the first 11 months of 2020, COVID variants were viewed as primarily of academic interest. While thousands had been identified - with the exception of the D614G `European' variant which emerged in early 2020 that appeared to have increased transmissibility over the `Asian' lineage  - none had demonstrated any truly `game changing' qualities. 

For the most part, COVID appeared functionally stable over most of 2020, despite some anecdotal reports from places like South Africa.   

In mid-December, just as the first COVID vaccines were rolling out, the UK Health Secretary Announced A New COVID Variant - now dubbed B.1.1.7 - was rapidly gaining ground in Southeast England, and initial estimates suggested it was 30%-40% more transmissible than the `wild type' COVID that had circulated for most of 2020. 

Since then, we've seen evidence that this B.1.1.7 variant is not only more transmissible, it also causes more severe illness, and carries a 67% higher mortality risk (see Eurosurveillance: Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England).

It has also spread globally (see CDC map below), and has now been reported in nearly 100 countries. 


Since then other variants of concern (VOCs) have emerged and have been identified, including B.1.351, P.1, B.1.427, and B.1.429 - along with a small number of variants of interest VOIs (including B.1.526, B.1.527, and P.2) - all of which continue to evolve and spread globally.

Overnight the CDC updated their COVID Variant Map, and their breakdown of variants by states.  Once again Florida leads the nation with 2351 B.1.1.7 variants detected, along with 49 P.1 variants, and 15 B.1.351.   Michigan and California come in second and third. 


All of these number are substantial undercounts and should be viewed as representing trends, not actual conditions on the ground. 

Variant Proportions in the U.S.
Updated Mar. 31, 2021

CDC’s national genomic surveillance program identifies new and emerging SARS-CoV-2 variants to determine implications for COVID-19 diagnostics, treatments, or vaccines authorized for use in the United States. Monitoring the spread of emerging variants in the United States relies on widespread, rapid sequencing. To accelerate sequencing in the United States, CDC has contracted with commercial diagnostic laboratories, and, in partnership with the Association of Public Health Laboratories (APHL), has implemented the National SARS-CoV-2 Strain Surveillance (NS3) program to provide a comprehensive and population-based US surveillance system.

Based on these data, sequences with similar genetic changes associated with important epidemiological and biological events are grouped into lineages*, and the proportion of lineages circulating in the United Stated are tracked and characterized to determine if they are considered variants of concern (VOC) or variants of interest (VOI). Most of the lineages identified through genomic surveillance do not fall into either of these categories. These data, along with data from many other sources, are used to inform national and state public health actions related to variants.

*A viral lineage is a group of viruses defined by a founding variant and its descendants. Names are assigned to SARS-CoV-2 lineages using manual and automated methods. Lineage designations are based on phylogenetic grouping followed by the identification of shared, common mutations.

The above chart illustrates how - since the first week of January - 3 variants (B.1.1.7, B.1.526, B.1.429)  have emerged and now make up the bulk of cases in the United States. The B.1.1.7 variant, which barely registered on January 1st, appears on track to become the dominant COVID variant in the U.S. in the next few weeks.  

Testing for variants remains limited, and the data generally lags behind by several weeks, so the picture today could be markedly different from what is depicted above for mid-March.  From the above chart, however, it is apparent that B.1.429 and B.1.526 are also gaining ground. 

The prevalence of each variant varies by state, with the `California variants' not surprising leading the pack in California, while the B.1.1.7 variants are surging in places like Florida, Minnesota and Michigan.  

The data below is only current as of February 27, 2021, and so big swings have undoubtedly occurred over the past 30 days. 

Variant proportions are based on representative CDC sequence data (NS3 + CDC-funded contract sequencing) collected over a four-week period ending February 27, 2021. Proportions  are only shown for states for which CDC has 300 sequences from specimens collected during this timeframe.

Last fall, none of these VOCs were on our radar, and since the these viruses continue to evolve,  it is fair to say that six months from now we may be looking at an entirely different set of COVID concerns.

Some of these variants are more likely to be controlled by our current crop of vaccines than others, and as more people are immunized, that could alter their individual trajectories.  Not all of these VOCs are destined to be contenders. 

While we are making substantial progress against COVID-19, and the continued roll out of vaccines will undoubtedly save many lives, the pandemic we face today is in many ways far more complex than what  emerged a little over a year ago. 

As tired as we all are of lockdowns, social distancing, and other restrictions  . . . we should not expect this virus to give up without throwing a few more surprises our way. 

Tuesday, March 30, 2021

Canada: NACI Statement Recommending Halt Of AstraZeneca Vaccine For Those Under 55


Credit ACIP/CDC 

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The rollout of Pfizer and Moderna mRNA COVID vaccines has been exceedingly smooth, and serious side effects have been thankfully rare (see CDC: Updated Guidance On COVID-19 Vaccines and Allergic Reactions), but the same cannot be said for the much beleaguered AstraZeneca vaccine from the U.K.

Three weeks ago the Denmark's Health Authority ordered a Temporary Suspension of AstraZeneca Vaccine following rare reports of blood clots in a small number of recipients.  Within days, more than a dozen other countries - mostly in Europe - announced similar suspensions. 

Despite investigations and statements of support for the AstraZeneca vaccine by the WHO (see WHO statement on AstraZeneca COVID-19 vaccine safety signals) and the European Medicines Agency (see EMA Statement On AstraZeneca Vaccine), Demark's suspension remains in place.  

While a number of other countries, reassured by the WHO and EMA statements that the benefits of the AZ vaccine outweigh the risks, have resumed using the AstraZeneca vaccine, late yesterday Canada's NACI (National Advisory Committee on Immunization) issued the following recommendation pending a new risk analysis. 

NACI rapid response: Recommended use of AstraZeneca COVID-19 vaccine in younger adults
 
Recommendation

NACI recommends that AstraZeneca COVID-19 vaccine should not be used in adults under 55 years of age at this time while the safety signal of Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT) following vaccination with AstraZeneca COVID-19 vaccine is investigated further.

Summary of rationale

Rare cases of serious blood clots, including cerebral venous sinus thrombosis, associated with thrombocytopenia have been recently reported in Europe following post-licensure use of AstraZeneca COVID-19 vaccineFootnote1Footnote2. Cases identified so far have been primarily in women under the age of 55 years; although cases in men have also been reported and have mostly occurred between 4 and 16 days after receipt of vaccine. 

This adverse event is being referred to as Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT)Footnote3.
 
This entity is associated with the development of antibodies that "activate" platelets, which stimulate the formation of clots and result in thrombocytopenia. The mechanism of action is similar to heparin-induced thrombocytopenia (HIT). The exact mechanism by which the AstraZeneca vaccine triggers VIPIT is still under investigation. At this time, no other risk factors have consistently been identified in patients who develop VIPIT. This adverse event has not been identified following receipt of mRNA COVID-19 vaccines to date.

The rate of this adverse event is still to be confirmed. Based on information from the European Medicines Agency on March 18, 2021 it was originally estimated at approximately 1 per 1,000,000 people vaccinated with the AstraZeneca vaccine, however a higher rate of 1 per 100,000 was reported by the Paul-Ehrlich Institut in GermanyFootnote4. Additional information is currently being gathered to characterize more accurately the rate of VIPIT. Based on available information, the case fatality of VIPIT is approximately 40%, however, the case fatality may decrease with increased awareness of the adverse event and appropriate early treatment.

Following population-based analyses of VIPIT assessing risk of COVID-19 disease by age, and considering that alternate products are available (i.e., mRNA vaccines), from what is known at this time, there is substantial uncertainty about the benefit of providing AstraZeneca COVID-19 vaccine to adults under 55 years of age given that the potential risks associated with VIPIT, particularly at the lower estimated rates. As a precautionary measure, while Health Canada carries out an updated benefit/risk analysis based on emerging data, NACI recommends that the vaccine not be offered to adults under the age of 55. Adults 55 years of age and older may still be offered the AstraZeneca vaccine with informed consent, given the increased risk of hospitalization and death due to COVID-19 disease in this populationFootnote5 and since VIPIT appears to be a rarer event in that age groupFootnote6.
 
Since the current cases have occurred primarily in women, men may be less at risk of this adverse event and could potentially have a different benefit/risk assessment, however investigations are ongoing as it is possible that the reported female predominance of VIPIT is because more women received the AstraZeneca vaccine, making it difficult to assess risk based on sex. Young healthcare workers, one of the early priority groups receiving this vaccine globally, include a higher proportion of females.

Anyone receiving the AstraZeneca COVID-19 vaccine should be informed of this potential adverse event and advised to seek immediate medical attention if they develop symptoms of thromboembolism and/or thrombocytopenia between days 4 and 20 following receipt of the AstraZeneca vaccineFootnote3. Symptoms to be vigilant for include: shortness of breath, chest pain, leg swelling, persistent abdominal pain, neurological symptoms including sudden onset of severe or persistent worsening headaches or blurred vision, skin bruising (other than at the site of vaccination) or petechiaeFootnote3Footnote6. In addition, healthcare professionals should be aware of VIPIT including how to diagnose and treat the condition (see Ontario Science Table guidelinesFootnote3).

Canada is expected to receive sufficient mRNA COVID-19 vaccines to fully vaccinate the population with two doses of mRNA vaccine before fall 2021. AstraZeneca COVID-19 vaccine was expected to make up a small proportion of the COVID-19 vaccines available for use in Canada; therefore, COVID-19 vaccinations will not be significantly delayed without using AstraZeneca COVID-19 vaccine in younger adults.

Based on the international data that continues to emerge regarding VIPIT following receipt of AstraZeneca COVID-19 vaccine, the precautionary principle, and Canada's expected supply of mRNA COVID-19 vaccines, NACI has made a recommendation that will continue to be reassessed based on the rapidly evolving evidence.

Given the rare but severe VIPIT events reported in Europe, mainly in women under 55 years of age, and a plausible causal mechanistic explanation, NACI has evaluated the benefit/risk ratio comparing this adverse event to the risk of COVID-19 deaths for individuals in Canada in various age strata and considering the supply of alternate COVID-19 vaccines available in Canada (mRNA vaccines). While awaiting the results from Health Canada inquiries and the overall risk assessment, NACI recommends immediately pausing the use of the AstraZeneca vaccine in all individuals less than 55 years of age in Canada.

Decisions on the type of second dose that will be offered to those individuals under 55 years of age who have been vaccinated with AstraZeneca COVID-19 vaccine will be determined based on the latest evidence and research. NACI will continue to review evidence as it emerges, including evidence on mixed COVID-19 vaccine schedules, to provide advice to public health programs on the potential for completing the series with other vaccine products.

Further information on signs and symptoms of this adverse event and treatment can be found on Health Canada's website.

          (Continue . . . )
 

I checked the AstraZeneca website for a press release addressing this development, but as of this writing (4am EDT) nothing appears on their press release page.

While these blood clot events appear to be exceedingly rare, and causality has not been established, there is little appetite for any elevated risk given the amount of vaccine hesitancy by the public. 

We'll be watching today, and the rest of this week, to see if any other countries follow suit. 

Stay tuned. 

MMWR: Interim Estimates of Vaccine Effectiveness of mRNA COVID-19 Vaccines in Preventing SARS-CoV-2 Infection


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Although there are unanswered questions over how long its protective effect will last, and how well it will fare against some of the emerging SARS-CoV-2 variants (e.g. B.1.351, P.1, etc.), interim results suggest the two mRNA vaccines authorized for emergency use in the United States (Pfizer & Moderna) are nearly as effective in the real world as early estimates suggested. 

Two weeks after the 1st dose, recipients are about 80% protected against infection, and 2 weeks after the 2nd dose, that protection rises to roughly 90%.

A remarkable and reassuring outcome, particularly when you consider how many vaccines have been administered over the past 3 months in the United States.  

The introduction and spread of new variants many impact the effectiveness of these vaccines over time, but even so, they are expected to provide some protection against developing severe disease.   While a decided victory, the war against COVID is far from over. 

Despite this excellent showing - even though I'm scheduled to receive my 2nd dose this Friday. and will be considered `fully vaccinated' by mid-April - I still intend to take the recommended precautions when in public (see CDC guidelines When You’ve Been Fully Vaccinated).

Two stops this morning.  First, excerpts the press release from the CDC on this study, followed by a link and excerpts from the MMWR report. 



Study involved health care personnel, first responders, and essential workers in six states

Press Release
Embargoed until: 11 a.m. ET, Monday, March 29, 2021
 

A new CDC study provides strong evidence that mRNA COVID-19 vaccines are highly effective in preventing SARS-CoV-2 infections in real-world conditions among health care personnel, first responders, and other essential workers. These groups are more likely than the general population to be exposed to the virus because of their occupations.

The study looked at the effectiveness of Pfizer-BioNTech and Moderna mRNA vaccines in preventing SARS-CoV-2 infections among 3,950 study participants in six states over a 13-week period from December 14, 2020 to March 13, 2021.

Results showed that following the second dose of vaccine (the recommended number of doses), risk of infection was reduced by 90 percent two or more weeks after vaccination. Following a single dose of either vaccine, the participants’ risk of infection with SARS-CoV-2 was reduced by 80 percent two or more weeks after vaccination.

It takes about two weeks following each dose of vaccine for the body to produce antibodies that protect against infection. As a result, people are considered “partially vaccinated” two weeks after their first dose of mRNA vaccine and “fully vaccinated” two weeks after their second dose. These new vaccine effectiveness findings are consistent with those from Phase 3 clinical trials conducted with the vaccines before they received Emergency Use Authorizations from the Food and Drug Administration. Those clinical trials evaluated vaccine efficacy against COVID-19 disease, while this study evaluated vaccine effectiveness against infection, including infections that did not result in symptoms.

          (Continue . . . ) 

The MMWR report link along with some excerpts.  Follow the link to read the report in its entirety.        


Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021

Early Release / March 29, 2021 / 70
Mark G. Thompson, PhD1; Jefferey L. Burgess, MD2; Allison L. Naleway, PhD3; Harmony L. Tyner, MD4; Sarang K. Yoon, DO5; Jennifer Meece, PhD6; Lauren E.W. Olsho, PhD7; Alberto J. Caban-Martinez, DO8; Ashley Fowlkes, ScD1; Karen Lutrick, PhD2; Jennifer L. Kuntz, PhD3; Kayan Dunnigan, MPH9; Marilyn J. Odean, MS10; Kurt T. Hegmann, MD5; Elisha Stefanski6; Laura J. Edwards, MPH7; Natasha Schaefer-Solle, PhD8; Lauren Grant, MS1; Katherine Ellingson, PhD2; Holly C. Groom, MPH3; Tnelda Zunie9; Matthew S. Thiese, PhD5; Lynn Ivacic6; Meredith G. Wesley, MPH7; Julie Mayo Lamberte, MSPH1; Xiaoxiao Sun, PhD2; Michael E. Smith9; Andrew L. Phillips, MD5; Kimberly D. Groover, PhD7; Young M. Yoo, MSPH1; Joe Gerald, MD2; Rachel T. Brown, PhD5; Meghan K. Herring, MPH7; Gregory Joseph, MPH1; Shawn Beitel, MSc2; Tyler C. Morrill, MS7; Josephine Mak, MPH1; Patrick Rivers, MPP2; Katherine M. Harris, PhD7; Danielle R. Hunt, PhD7; Melissa L. Arvay, PhD1; Preeta Kutty, MD1; Alicia M. Fry, MD1; Manjusha Gaglani, MBBS9,11 (View author affiliations)View suggested citation

Summary

What is already known about this topic?

Messenger RNA (mRNA) COVID-19 vaccines have been shown to be effective in preventing symptomatic SARS-CoV-2 infection in randomized placebo-controlled Phase III trials.

What is added by this report?

Prospective cohorts of 3,950 health care personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing for 13 consecutive weeks. Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%.

What are the implications for public health practice?

Authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

(SNIP)

Discussion

Prospective cohorts of health care personnel, first responders, and other essential and frontline workers over 13 weeks in eight U.S. locations confirmed that authorized mRNA COVID-19 vaccines (Pfizer-BioNTech’s BNT162b2 and Moderna’s mRNA-1273) are highly effective in real-world conditions. Vaccine effectiveness of full immunization with two doses of mRNA vaccines was 90% (95% CI = 68%–97%) against RT-PCR–confirmed SARS-CoV-2 infection. These findings are consistent with those from the mRNA vaccines’ Phase III trials (1,2) and recent observational studies of the mRNA vaccine effectiveness against severe COVID-19 (3). The findings complement and expand upon these preceding reports by demonstrating that the vaccines can also reduce the risk for infection regardless of COVID-19–associated illness symptom status (4,5). Reducing the risk for transmissible infection, which can occur among persons with asymptomatic infection or among persons several days before symptoms onset (6), is especially important among health care personnel, first responders, and other essential and frontline workers given their potential to transmit the virus through frequent close contact with patients and the public.

Partial immunization (≥14 days after first dose but before second dose) provided preventive benefits with vaccine effectiveness of 80%. This finding is similar to an analysis of Phase III trial results (1,2,7) and two other recent estimates of vaccine effectiveness for partial immunization with Pfizer-BioNTech vaccine among health care personnel, including a vaccine effectiveness (≥21 days after first dose) of 72% (95% CI = 58%–86%) against PCR-confirmed infection identified by routine testing in the United Kingdom (4) and a vaccine effectiveness (>14 days after first dose) of 60% (95% CI = 38%–74%) against PCR-confirmed infection identified by records review in Israel (5). This finding is also consistent with early descriptive findings of SARS-CoV-2 employee and clinical testing results by mRNA vaccination status in the United States (8,9).

The findings in this report are subject to at least three limitations. First, vaccine effectiveness point estimates should be interpreted with caution given the moderately wide CIs attributable in part to the limited number of postimmunization PCR-confirmed infections observed. Second, this also precluded making product-specific vaccine effectiveness estimates and limited the ability to adjust for potential confounders; however, effects were largely unchanged when study site was included in an adjusted vaccine effectiveness model and when adjusted for sex, age, ethnicity, and occupation separately in sensitivity analyses. Finally, self-collection of specimens and delays in shipments could reduce sensitivity of virus detection by PCR (10); if this disproportionately affected those who received the vaccine (e.g., because of possible vaccine attenuation of virus shedding), vaccine effectiveness would be overestimated.

The scientific rigor of these findings is enhanced by its prospective design and the participants’ very high adherence to weekly specimen collection. As the study progresses, viruses will be genetically characterized to examine the viral features of breakthrough infections. Given that there is uncertainty related to the number of days required to develop immunity postvaccination (3–5,7), future research examining vaccine effectiveness at different intervals is warranted.

These interim vaccine effectiveness findings for both Pfizer-BioNTech’s and Moderna’s mRNA vaccines in real-world conditions complement and expand upon the vaccine effectiveness estimates from other recent studies (3–5) and demonstrate that current vaccination efforts are resulting in substantial preventive benefits among working-age adults. They reinforce CDC’s recommendation of full 2-dose immunization with mRNA vaccines. COVID-19 vaccination is recommended for all eligible persons, which currently varies by location in the United States.

While these vaccines should help to substantially reduce the impact of the next pandemic wave in the United States, most of the world's population remains unvaccinated, and that provides the virus ample opportunities to spread, evolve, and potentially learn to evade our current generation of vaccines. 

Meaning that while the news on these vaccines is exceedingly good, it is too soon to start popping the champagne corks and declaring victory over the pandemic. 

Monday, March 29, 2021

CMAJ: Burden of Noninfluenza Respiratory Viral Infections in Adults Admitted to Hospital

 image

Even during the Height of the 2009 Pandemic (Oct) - ILI’s Aren’t Always The Flu


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When it comes to epidemics, pandemics, and infectious diseases, the past 20 years has shown that conventional wisdom isn't what it used to be. Many of the widely held assumptions from early in the 21st century have been shown to be shortsighted, or even naive. 

Twenty years ago, coronaviruses were thought to be relatively benign producers of mild, flu-like illnesses in humans, and incapable of producing a pandemic.  

That perception began to change in 2003 - with the SARS epidemic (and the emergence of MERS-CoV in 2012) - but novel influenza remained at the top of most expert's pandemic threats list until COVID-19 emerged roared to life in early 2020.

Another widely held belief has been that non-influenza respiratory infections are inherently less serious than influenza A, even though we've seen anecdotal evidence to the contrary.  A few examples:



DOH: 2nd NJ Facility Reporting Adenovirus Outbreak & 10th Fatality At Wanaque Center
 


Non-influenza  Respiratory Viral Infections (NRIVs) are less well studied (and tested for) than influenza, and therefore don't tend to get the same level of respect, yet they produce a high burden of illness, hospitalization, and death each year. 

While we have vaccines and antivirals for the `flu', for NRIVs care is mostly supportive while the virus runs its course (note: There is an adenovirus vaccine, but it is only approved for the military).  

All of which brings us to a new study, published today in the Canadian Medical Association Journal (CMAJ), which looks at the burden of NRIVs among hospitalized adults across 3 seasons (2015-2018) in Edmonton, Alberta and Toronto, Ontario.

Not only were NRIVs responsible for more than half of all admissions (54.6%), they produced similar rates of illness and deaths to Influenza A.

First a brief press release, followed by a link and the Abstract from the study.  Follow the link to read it in its entirety.  I'll have a brief postscript when you return. 

Noninfluenza viruses have rates of illness, death similar to flu

CANADIAN MEDICAL ASSOCIATION JOURNAL

Noninfluenza respiratory viral infections (NIRV) are associated with illness and death rates similar to influenza in hospitalized adults, according to new research in CMAJ (Canadian Medical Association Journal).

In a study of 2119 adults admitted to two hospitals over three seasons (2015-2018) in Edmonton, Alberta, and Toronto, Ontario, with confirmed viral acute respiratory infections, more than half (54.6%) were NIRV infections compared with influenza viruses (45.4%). Among patients with NIRV infections, 21.1% needed respiratory support, 18.2% required lengthy hospital stays and 8.4% died within 30 days of diagnosis. About 15% of NIRV infections were acquired in hospital.

"These findings show that clinical status changes for patients with NIRV infections were comparable to patients with influenza," writes Dr. Nelson Lee, Division of Infectious Disease, Department of Medicine, University of Alberta, Edmonton, with coauthors. "The associated costs of hospital admission were substantial."

Patients with NIRV infections were generally younger than those with influenza, although many had underlying conditions, such as compromised immune systems.

"Our findings highlight unmet needs and research gaps in therapeutics and vaccines for people at high risk of NIRV infection," the authors conclude.


Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres
Nelson Lee, Stephanie Smith, Nathan Zelyas, Scott Klarenbach, Lori Zapernick, Christian Bekking, Helen So, Lily Yip, Graham Tipples, Geoff Taylor and Samira Mubareka
CMAJ March 29, 2021 193 (13) E439-E446; DOI: https://doi.org/10.1503/cmaj.201748

Abstract

BACKGROUND:
Data on the outcomes of noninfluenza respiratory virus (NIRV) infections among hospitalized adults are lacking. We aimed to study the burden, severity and outcomes of NIRV infections in this population.


METHODS: We analyzed pooled patient data from 2 hospital-based respiratory virus surveillance cohorts in 2 regions of Canada during 3 consecutive seasons (2015/16, 2016/17, 2017/18; n = 2119). We included patients aged ≥ 18 years who developed influenza-like illness or pneumonia and were hospitalized for management. We included patients confirmed positive for ≥ 1 virus by multiplex polymerase chain reaction assays (respiratory syncytial virus [RSV], human rhinovirus/enterovirus (hRV), human coronavirus (hCoV), metapneumovirus, parainfluenza virus, adenovirus, influenza viruses). We compared patient characteristics, clinical severity conventional outcomes (e.g., hospital length-of stay, 30-day mortality) and ordinal outcomes (5 levels: discharged, receiving convalescent care, acute ward or intensive care unit [ICU] care and death) for patients with NIRV infections and those with influenza.


RESULTS:
Among 2119 adults who were admitted to hospital, 1156 patients (54.6%) had NIRV infections (hRV 14.9%, RSV 12.9%, hCoV 8.2%) and 963 patients (45.4%) had influenza (n = 963). Patients with NIRVs were younger (mean 66.4 [standard deviation 20.4] yr), and more commonly had immunocompromising conditions (30.3%) and delay in diagnosis (median 4.0 [interquartile range (IQR) 2.0–7.0] days). Overall, 14.6% (12.4%–19.5%) of NIRV infections were acquired in hospital. Admission to ICU (18.2%, median 6.0 [IQR 3.0–13.0] d), hospital length-of-stay (median 5.0 [IQR 2.0–10.0] d) and 30-day mortality (8.4%; RSV 9.5%, hRV 6.6%, hCoV 9.2%) and the ordinal outcomes were similar for patients with NIRV infection and those with influenza. Age > 60 years, immunocompromised state and hospital-acquired viral infection were associated with worse outcomes. The estimated median cost per acute care admission was $6000 (IQR $2000–$16 000).


INTERPRETATION: The burden of NIRV infection is substantial in adults admitted to hospital and associated outcomes may be as severe as for influenza, suggesting a need to prioritize therapeutics and vaccines for at-risk people.

The global burden of lower respiratory tract infections is substantial, leading to many hospital admissions and deaths, especially among young children and older adults.1 Respiratory viruses are responsible for almost half of such infections in adults that require in-hospital management; previous studies estimate that 28%–62% are caused by noninfluenza respiratory viruses (NIRVs).24 With some geographical and seasonal variations, respiratory syncytial virus (RSV), human rhinovirus (hRV) and human coronavirus (hCoV) are among the most frequently identified NIRV infections.17
Most infected adults develop mild, self-limiting illnesses, but increasing evidence suggest that NIRVs, either alone or with coinfecting bacteria, can result in severe pneumonia and death.8,9 For instance, RSV has been shown to cause severe respiratory failure, with fatality rates comparable to or exceeding those observed among adults admitted to hospital with influenza.1012
Data on hRV, hCoV and other NIRVs are more limited, owing to the lack of accurate diagnostics and systematic case-finding approaches.79 However, with the increasing availability of multiplex polymerase chain reaction (PCR) assays that can simultaneously detect influenza and NIRVs, these infections are now readily diagnosed as part of a syndromic approach in patients who present with acute respiratory illnesses.25,13,14 The burden, clinical significance and impacts of NIRVs on the health care system remain inadequately characterized.

To address this gap, we analyzed the relative frequencies, patient characteristics, location of acquisition (community or hospital), severity and clinical outcomes of patients with NIRV and influenza infections diagnosed by multiplex PCR in a cohort of adults admitted to hospital in 2 large Canadian health care centres during a 3-year surveillance period. The associated health care resource use was also estimated.
(Continue . . . )


One of the big unknowns is what happens after COVID-19 runs its course.  

Does influenza A quickly regain its prior position as king of the respiratory virus hill, or does something else - at least temporarily -  fill the vacuum?  If it is influenza A, will it be a return of H1N1 or H3N2, or will some other subtype seize the day?

We've essentially gone a year without influenza A or B, or any other (non-COVID) NRIV - and community immunity presumably wanes across the board with every passing month.  Whether this situation changes this summer, next fall, or potentially sometime in 2022 or 2023, we will find ourselves in uncharted territory. 

In the fall of 2017, in PLoS Comp. Bio.: Spring & Early Summer Most Likely Time For A Pandemicwe looked at a study that found that pandemics are most apt to emerge in the `off season', when novel viruses have less competition from other seasonal viruses, and community immunity is low.

While the big concern would be the emergence of a novel avian or swine flu virus, epidemics of `lesser' respiratory viruses - whether it be seasonal flu viruses, adenoviruses, enteroviruses,  parainfluenza viruses, etc.  - could prove daunting as well. 

Today's study suggests that such an event - even with a noninfluenza respiratory virus - could produce substantial morbidity and mortality.   

Saturday, March 27, 2021

Preprint: Sudden Rise In COVID-19 Case Fatality Among Young & Middle Aged Adults - Paraná, Brazil


(COVID Deaths In Brazil)
Credit FIOCRUZ

#15,888


We've been watching the devastating second COVID wave in Brazil - and the concurrent rise of a new, more aggressive SARS-CoV-2 variant B.1.1.28.1 (P.1) - since early January. 

A January technical report from FIOCRUZ (Fundação Oswaldo Cruz) found that the P.1 variant had rapidly overtaken all other variants in the region, jumping from 51% of all sequenced samples in December to 91% by the first half of January.

Early reports (see The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence) also suggested a higher reinfection rate, and anecdotal reports (see Amazonas Transfers 235 COVID Cases To Other States Amid Critical Oxygen Shortage) hinted at an  increased severity. 

Over the past month, we've watched as the reports from Brazil have grown increasingly dire. 

Brazil: FIOCRUZ Calls For Stricter Measures To Combat COVID-19

FIOCRUZ Special Bulletin: The biggest Sanitary and Hospital Collapse in the History of Brazil

FIOCRUZ Weekly Bulletin: Worst COVID Scenario Since The Beginning Of The Pandemic

While its impact outside of Brazil has been limited, we've also seen evidence that the P.1 variant continues to spread around the world, sparking concerns that what is happening in Brazil today may begin to happen elsewhere in the months ahead (see UK PHE Now Tracking 9th Variant (VUI 202103/01) & Update On P.1 Variants).

And over the past few days, Brazil's neighbors have reported surges in COVID as well (see Reuters report 'Alarm bells': Brazil's COVID-19 chaos sparks fear, countermeasures from neighbors').

While the evidence suggests the P.1 variant is more transmissible than the `wild type' COVID, and it has been linked to reduced antibody recognition - which may increase reinfection risks and potentially lower the effectiveness of current vaccines - less is known about its severity. 

Today we have a pre-print, published yesterday on MedRxiv, that reports a dramatic increase in case fatality rates during the month of February in Paraná, Brazil, particularly among young and middle aged adults. 


The table above shows a more than 3-fold increase in deaths among COVID cases aged 20 to 29, compared to January.  Deaths among those aged 30 to 49 roughly doubled.

Of particular note, these increases `coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases', lessening the the likelihood that overcrowded or stressed hospitals played a significant role in these deaths. 

This is a yet-to-be peer reviewed article, and is based on data collected from just one Brazilian state, and so these findings should be interpreted with a certain amount of caution.  But these results appear consistent with what we have seen from media reports out of Brazil, and the alarms being raised by FIOCRUZ.

Sudden rise in COVID-19 case fatality among young and middle-aged adults in the south of Brazil after identification of the novel B.1.1.28.1 (P.1) SARS-CoV-2 strain: analysis of data from the state of Parana

Maria Helena Santos de Oliveira, Giuseppe Lippi, Brandon Michael Henry
doi: https://doi.org/10.1101/2021.03.24.21254046

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Abstract

Brazil is currently suffering a deadly surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, which has been attributed to the spread of a new strain known as P.1 (B.1.1.28.1). In this investigation, we analyzed coronavirus disease 2019 (COVID-19) public health data from Parana, the largest state in southern half of Brazil, between September 1, 2020 and March 17, 2021, to evaluate recent trends in case fatality rates in different age groups. 

A total of 553,518 cases of SARS-CoV-2, 8,853 currently registered as fatal, were finally included in our analysis. All age groups showed either decline or stabilization of the case fatality rates (CFRs) between September 2020 and January 2021. 

In February 2021, an increase in CFR for almost all age groups could be instead observed. All groups above 20 years of age showed statistically significant increases in CFR when diagnosed in February 2021 as opposed to January 2021.
Patients aged 20-29 years experienced a tripling of their CFR, from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling. Individuals between 20 and 29 years of age whose diagnosis was made in February 2021 had an over 3-fold higher risk of death compared to those diagnosed in January 2021 (Risk Ratio (RR): 3.15 [95%CI: 1.52-6.53], p<0.01), while those aged 30-39, 40-49, 50-59 years experienced 93% (1.93 [95%CI:1.31-2.85], p<0.01), 110% (RR: 2.10 [95%CI:1.62-2.72], p<0.01), and 80% (RR: 1.80 [95%CI:1.50-2.16], p<0.01) increases in risk of death, respectively. 

Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil, and this should raise public health alarms, including the need for more aggressive local and regional public health interventions and faster vaccination.

          (Continue . . . )

 
Vaccination, even with deduced antibody recognition by the P.1 variant - is believed to help lower the severity of infection with this virus, even if it doesn't always prevent reinfection.

 But for countries yet to deploy vaccines in quantity - or those with low uptake due to vaccine hesitancy - P.1 could prove a real threat should this variant continue its world tour. 
 

Friday, March 26, 2021

CDC FluView Week 11: Novel Influenza Variant A/H1N1v virus (2020)


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While seasonal influenza remains at historic lows, in late January in CDC FluView Week 3: 1st Novel Flu (H3N2v) of 2021 - Wisconsin, we looked at the first novel flu report in the United States for 2021.

Since 2005, over 465 human `swine variant' infections (H1N1v, H1N2v or H3N2v) have been documented in the United States, with over 300 of those reported in 2012. H3N2v viruses have been, by far, the most common - followed by H1N2v and then H1N1v.

This past year we've seen a big drop in novel flu reports in the United States, almost certainly due to the shuttering of county and state fairs which have previously been linked to large outbreaks.  Today however, this week's FluView carries a report of an A/H1N1v infection in an  adult > 18 years of age in North Carolina.

The illness onset, however, occurred in 2020, and has only recently been reported to the CDC. 

Novel Influenza A Virus

One human infection with a novel influenza A virus was reported by North Carolina. This person was infected with an influenza A(H1N1) variant (A(H1N1)v) virus in 2020. The patient is an adult > 18 years of age, was not hospitalized, and has recovered from their illness. An investigation into the source of the infection revealed that the patient worked with and had daily contact with swine.
No human-to-human transmission has been identified in association with this patient. While this variant virus infection was not identified until 2021, it represents the first influenza A(H1N1)v virus identified from a specimen collected in the United States in 2020 (during the 2020-21 season). No influenza A(H1N1)v virus infections have been identified in specimens collected in 2021 thus far.

Early identification and investigation of human infections with novel influenza A viruses are critical so that the risk of infection can be more fully understood and appropriate public health measures can be taken. Additional information on influenza in swine, variant influenza infection in humans, and strategies to interact safely with swine can be found at http://www.cdc.gov/flu/swineflu/index.htm.

Additional information regarding human infections with novel influenza A viruses can be found at http://gis.cdc.gov/grasp/fluview/Novel_Influenza.html.
While most swine variant infections don't appear to transmit well in humans, the CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).
 
H1N2 variant [A/California/62/2018]  Jul   2019   5.8  5.7 Moderate
H3N2 variant [A/Ohio/13/2017]          Jul   2019   6.6  5.8 Moderate
H3N2 variant [A/Indiana/08/2011]      Dec 2012   6.0  4.5 Moderate 

The CDC's Risk Assessment for these viruses reads:

Sporadic infections and even localized outbreaks among people with variant influenza viruses may occur. All influenza viruses have the capacity to change and it’s possible that variant viruses may change such that they infect people easily and spread easily from person-to-person. The Centers for Disease Control and Prevention (CDC) continues to monitor closely for variant influenza virus infections and will report cases of H3N2v and other variant influenza viruses weekly in FluView and on the case count tables on this website 

Recently China's EA H1N1 `G4' swine flu virus has garnered a lot of attention (see ECDC Risk Assessment: Eurasian avian-like A(H1N1) swine influenza viruses), as have other swine variant viruses round the globe (Brazil: Paraná Health Reports Novel H1N2 Flu Case).

Six weeks ago the CDC added this EA H1N1 `G4' virus to their IRAT list (see CDC Selects New Swine-Variant EA H1N1 Virus For The Top Of Their IRAT List), giving it the highest risk assessment of any of the 20 novel viruses on their list.

Summary: A risk assessment of Eurasian avian-like swine influenza A(H1N1) [A/swine/Shandong/1207/2016] virus, clade 1C.2.3 and genotype 4, was conducted in July 2020. With point scores ranging from 1 to 10, the overall IRAT risk assessment score for this virus falls into the moderate risk category, which ranges from 4.0 to 7.9.

The average risk score for potential emergence of the virus to achieve sustained human-to-human transmission was 7.5, within the upper moderate range. The average risk score for the virus to impact public health if it were to achieve sustained human-to-human transmission was 6.9, also in the upper moderate range. Full report here pdf icon[PDF – 272 KB].

Although it only happens rarely, swine influenza viruses can sometimes adapt well enough to humans to spark a pandemic, and so we monitor these viruses carefully. 

CDC: Investigating Possible Mink-To-Human Transmission Of SARS-CoV-2 In The United States



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Although humans are the primary carrier of SARS-CoV-2, we are pretty certain it originated in bats, and we've seen it jump from humans to companion animals (dogs & cats) and to farmed mink, and laboratory experiments have demonstrated other species are susceptible to infection as well. 

Four months ago - weeks before news of the B.1.1.7 `UK' variant emerged - our attentions were focused on a mink variant that had successfully jumped back into Denmark's human population (see Denmark SSI: Increased Mink Variant COVID In Human Population - COVID Risk Assessment).

Between having a high susceptibility to the virus, and being housed in high density mink farms, mink-to-mink transmission of SARS-COV-2 has repeatedly resulted in the creation of mink variant viruses (see Preprint: Recurrent Mutations in SARS-CoV-2 Genomes Isolated from Mink Point to Rapid Host-Adaptation) as illustrated in the serial passage graphic below.

    

While most of the mink farm outbreaks have been reported from Europe, the United States has reported a handful, including last August (see USDA APHIS Confirms SARS-CoV-2 in Farmed Mink in Utah). The USDA maintains an interactive map (below) showing where SARS-CoV-2 has been detected in animals in the United States.


As of their last report, 16 mink farms in the United States have reported COVID-19. 

Last month, in EID Journal: SARS-CoV-2 Exposure in Escaped Mink, Utah, USA, we looked at a seroprevalence study done on wildlife captured in and around two infected mink farms, looking for signs of spillover. 

While 11 mink escapees tested positive for SARS-CoV-2 antibodies, somewhat reassuringly none of the other tested animals had a detectable antibody response.

Although Denmark's mink-variant problem has receded, due primarily to the introduction a more aggressive B.1.1.7 variant in December, concerns over the creation and emergence of additional variants from non-human mammals remain.  

Yesterday the CDC updated their COVID-19 and Animals webpage for the first time since February 10th. In their previous update, they stated:

Currently in the United States, there is no evidence of SARS-CoV-2 spreading from mink to people, but investigations are ongoing. More information will be shared when it becomes available. 

While most of the information remains unchanged, they substantially increased their section on Mink and SARS-CoV-2, including new data suggesting mink-to-human transmission might have occurred in the United States.

I've reproduced the revised section (including links to new guidance for mink farms) below.  

Mink and SARS-CoV-2

SARS-CoV-2 has been reported in mink on farms in multiple countries, including the United States.
  • In the United States, respiratory disease and increases in mink deaths have been seen on most affected mink farms. However, some infected mink might also appear healthy.
  • Infected workers likely introduced SARS-CoV-2 to mink on the farms, and the virus then began to spread among the mink. Once the virus is introduced on a farm, spread can occur between mink, as well as from mink to other animals on the farm (dogs, cats).
    • One wild mink found near an affected Utah farm was found to be infected with SARS-CoV-2. However, there is no evidence that the virus is currently circulating in free-living wildlife in the United States. 
  • Currently, there is no evidence that mink are playing a significant role in the spread of SARS-CoV-2 to people. However, there is a possibility of mink spreading SARS-CoV-2 to people on mink farms. Mink to human spread of SARS-CoV-2 has been reported in the Netherlands, Denmark, and Poland, and new data suggest it might have occurred in the United States. 
    • Investigations found that mink from a Michigan farm and a small number of people were infected with SARS-CoV-2 that contained unique mink-related mutations (changes in the virus’s genetic material). This suggests mink to human spread might have occurred.
    • The animals on the farm have since tested negative for SARS-CoV-2 twice, and the infected people have since recovered.
    • Finding these mutations in mink on the Michigan farm is not unexpected because they have been seen before in mink from farms in the Netherlands and Denmark and also in people linked to mink farms worldwide.
    • Currently there is limited information available about the genetics of the SARS-CoV-2 virus that has infected people living in the communities near the mink farm. Thus, it is difficult to know with certainty whether the mink-related virus mutations originated in people or in mink on the farm.
    • To confirm the spread of SARS-CoV-2 from mink to people, public health officials would need more information on the epidemiology and genetics of the virus in mink, mink farm workers, and the community around mink farms.
    • These results highlight the importance of routinely studying the genetic material of SARS-CoV-2 in susceptible animal populations like mink, as well as in people.
  • For most people in the United States, the risk of getting COVID-19 from animals is low, but there is a higher risk for people working on mink farms. 
    • Worker safety is critical to protect people and animals on mink farms. Mink farm workers with suspected or confirmed COVID-19 should avoid contact with animals, including mink, and should follow available guidance for farmed mink and other mustelids (animals such as weasels, ferrets, badgers, wolverines, and otters) to avoid introducing SARS-CoV-2 to mink on farms. 
  • CDC is aware of reports of a strain of SARS-CoV-2 virus in mink in Denmark that was also present in the local human population. 
    • This strain, called “Cluster 5,” had not been seen before and was made up of five mutations. The World Health Organization (WHO) reported that as of November 2020, the Cluster 5 variant was no longer circulating in Denmark.
    • Of mink and human samples tested so far in the United States, none have contained all the mutations that make up the Cluster 5 strain.

Mink Guidance

Guidance is available to protect worker and animal health, developed collaboratively by the US Department of Agriculture (USDA), CDC, and state animal and public health partners using a One Health approach:

With several highly competitive COVID variants already spreading across the United States (B.1.1.7, B.1.351 & P.1),the risks from any COVID spillover from mink to humans are likely low.  But it is important that we monitor, and analyse new variants, since we can never know from where the `next contender' will emerge. 

For now, the advice from the CDC on SARS-CoV-2 and animals remains pretty much unchanged. 

What you need to know
  • We do not know the exact source of the current outbreak of coronavirus disease 2019 (COVID-19), but we know that it originally came from an animal, likely a bat.
  • At this time, there is no evidence that animals play a significant role in spreading SARS-CoV-2, the virus that causes COVID-19, to people.
  • Based on the available information to date, the risk of animals spreading COVID-19 to people is considered to be low.
  • More studies are needed to understand if and how different animals could be affected by COVID-19.
  • We are still learning about this virus, but it appears that it can spread from people to animals in some situations, especially during close contact.
  • People with suspected or confirmed COVID-19 should avoid contact with animals, including pets, livestock, and wildlife.

Thursday, March 25, 2021

Brazil: FIOCRUZ Calls For Stricter Measures To Combat COVID-19

 

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The worsening COVID epidemic in Brazil - once centered primarily in Amazonas state (see Brazil: Amazonas Transfers 235 COVID Cases To Other States Amid Critical Oxygen Shortage) - has expanded to include virtually the entire nation, leading FIOCRUZ (Fundação Oswaldo Cruz) to declare The biggest Sanitary and Hospital Collapse in the History of Brazil last week. 

Driven in large part by the P.1 COVID variant - which has demonstrated a high re-infection rate (see The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence) - the number of cases and deaths reported in March far exceed anything Brazil has seen during this pandemic. 

(COVID Deaths In Brazil)

 

In their latest special Bulletin Colapso do Sistema de Saúde (Collapse of the Health System), FIOCRUZ calls once again for strict measures to slow or prevent the spread of COVID-19. 


"Since the beginning of March, the country has witnessed a framework that denotes the collapse of the health system in the Brazil for the care of patients who require complex care for Covid-19. Researchers from the Fiocruz Covid-19 Observatory, responsible for the Bulletin, point out that this collapse was not produced in March 2021, but over several months, reflecting the ways of organization to face the pandemic in the country, in the states and municipalities. Below we highlight 6 factors that characterize this collapse."
Although the P.1 variant remains a relatively minor player outside of Brazil, the events of the past two months in South America should give us pause, as P.1 continues to show up in increasing numbers around the world.
 
Below you'll find the (translated) press release on this week's Boletim Extraordinário. .
Bulletin indicates adoption of strict measures to block Covid-19

03/23/2021

Renata Moehlecke (Fiocruz News Agency)
 

Released on Tuesday (23/3), the new Covid-19 Fiocruz Observatory Extraordinary Bulletin calls attention to the need for the adoption of strict measures to block the transmission of the disease in all states, capitals and municipalities that are in the critical alert zone. The main recommendations pointed out are the restriction of non-essential activities for about 14 days, to reduce approximately 40% of transmission, and the mandatory use of masks by at least 80% of the population. 

The document produced by Fiocruz Covid-19 Observatory also highlights the worsening of the national scenario, which has extremely high values ​​of cases and daily deaths by Covid-19, the worrying permanence of the trend of accelerating the transmission of Sars-CoV-2 and the very critical situation of bed occupancy rates. ICU Covid-19 for adults in the Unified Health System (SUS) throughout Brazil.

"Since the beginning of March, the country has seen a picture that shows the collapse of the health system in Brazil for the care of patients who require complex care for Covid-19", say the Observatory researchers. "This collapse was not produced in March 2021, but over several months, reflecting the ways of organizing to face the pandemic in the country, in the states and in the municipalities".

According to the data, there were, on average, 73 thousand daily cases and 2 thousand deaths per day in the last analyzed epidemiological week (period from 14 to 20 March 2021). In addition, the number of cases grows at a rate of 0.3% per day and the number of deaths by Covid-19 increased to 3.2% per day, an even greater rate than in previous weeks. There has also been a disproportionate increase in mortality in the country, from around 2% in late 2020 to 3.1% now in March. "The scenario is worrying, as it indicates that there may be a situation of lack of assistance and failures in the quality of care provided to patients with severe conditions in Covid-19", comment the experts. "The inability to diagnose serious cases correctly and in a timely manner, added to the overload of hospitals,

Regarding the occupancy rates of beds in the ICU Covid-19 for adults in the SUS, the data obtained on March 22 continue to indicate an extremely critical situation in Brazil. The Bulletin highlights, in the North region, the departure of Amazonas from the critical zone to the intermediate alert zone, now with a rate of 79%. On the other hand, he warns of the worsening of the situation in the Southeast: in the last week, in Minas Gerais, the rate increased from 85% to 93%; in Espírito Santo, from 89% to 94%; in Rio de Janeiro, from 79% to 85%; and in São Paulo, from 89% to 92%. The South and Midwest regions maintained rates above 96%. Piauí (96%), Ceará (97%), Rio Grande do Norte (96%) and Pernambuco (97%) stood out with the worst rates in the Northeast region.

The researchers warn that, in this moment of crisis, it is urgent to rigorously adopt measures to block transmission in almost all states and capitals that are in the critical alert zone, as well as in the municipalities that are part of health regions where there are high rates of occupancy of ICU beds Covid-19. "The coordination and integration of these measures, articulated between the different levels of government and with broad participation by society, is vital at this moment. Thus, even if several municipalities and states have already adopted these measures, it is essential that municipal, state and federal governments all move in the same direction to expand and strengthen them, since partial and isolated adoption will lead us to the prolongation of the health crisis ", they affirm.

The document presents a list of urgent measures aimed at containing the health crisis and the collapse of the health system. "For these blocking measures to be successful, they must be adopted together, requiring about 14 days to produce results in reducing transmission rates by approximately 40%, requiring daily monitoring to track their impacts on reduction of cases, occupancy rates of hospital beds and deaths ", highlights the Bulletin , which also takes as a basis for the recommendation the Letter of the National Council of Health Secretaries (Conass) and studies carried out in other countries.

"Increase the availability and use of masks, with the goal that at least 80% or more of the population uses them properly; campaigns for the free distribution of multi-layered cloth masks, in areas and points of greater population concentration and a low percentage of use, combined with governmental and non-governmental campaigns on its importance and the correct way of use should be part of this strategy ", complement the researchers in the document.

"The continuity of the scenarios in which we have the growth of all indicators for Covid-19, such as transmission, cases, deaths and occupancy rates of ICU beds, results in a collapse that affects the entire health system in the country and an increase in deaths for lack of assistance ", highlight the scientists in the Bulletin. "This is a scenario that is not only a health crisis, but also a humanitarian one, if we consider all its impacts".