Preprint: Mapping the Antigenic Diversification of SARS-CoV-2

#16,479

We seem to be in a bit of an informational limbo on COVID - at least from official sources - these past few days with relatively few updates coming from public health agencies.  Hopefully that will change later today, as we expect updates from the CDC Nowcast and the WHO's mid-week update on COVID either today or tomorrow. 

There are plenty of media reports, mainly containing speculation about where the pandemic will go  after Omicron has run its course.  No one really knows, but that isn't stopping the presses. 

Journal articles, and preprints, are beginning to pick up again, following the holidays, including the follow pre-print - published yesterday on MedRxiv - that illustrates how antigenically different Omicron is to all of the other COVID variants we've seen to date. 

I've included the abstract below, but you'll want to follow the link to read the report in its entirety - followed be a Twitter thread started by one of the authors; Professor of Applied Evolutionary Biology at Amsterdam University Medical Center, Colin Russell @colinrussell.

I'll have a postscript after the break. 

Mapping the antigenic diversification of SARS-CoV-2

Karlijn van der Straten, Denise Guerra, Marit van Gils, Ilja Bontjer, Tom G Caniels, Hugo D van Willigen, E Wynberg, Meliawati Poniman, Judith A Burger, Joey H Bouhuijs, Ayesha Lavell, Brent Appelman, Jonne J Sikkens, Marije Bomers, Alvin X Han, Brooke E Nichols, Maria Prins, Harry Vennema, Chantal Reusken, Dirk Eggink, Menno de Jong, Godelieve J de Bree, Colin A Russell, Rogier Willem Sanders

doi: https://doi.org/10.1101/2022.01.03.21268582

Abstract

Large-scale vaccination campaigns have prevented countless SARS-CoV-2 infections, hospitalizations and deaths. However, the emergence of variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similar to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. 

Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants-of-concern (VOCs) of a unique set of sera from patients infected with a range of VOCs. Infections with ancestral or Alpha strains induced the broadest immunity, while individuals infected with other VOCs had more strain-specific responses. Omicron was substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that all VOCs preceding Omicron belong to one antigenic cluster, while Omicron forms a new antigenic cluster associated with immune escape and likely requiring vaccine updates to ensure vaccine effectiveness.

While there are  hopes that Omicron might be the `last major wave' of the COVID pandemic, this report illustrates how radically COVID can reinvent itself, practically overnight - and while Omicron has thankfully been `milder' - its rate of transmission is nothing less than phenomenal. 

As much as I'd like to pop the champagne corks, and declare the pandemic to be near its end, SARS-CoV-2 continues to surprise us with both its tenacity, and its mutability.  

While the COVID pandemic will eventually run its course, and Omicron might be its last hurrah, it is too soon to declare victory.  No matter how badly we may want to. 

CDC FluView Week 51: Flu Activity Increasing Sharply In Some Parts Of The Country

#16,478  

Today's FluView Report - delayed 3 days due to the Holidays - shows a sharp increase in flu activity, particularly across the southern tier of states.  While some parts of the country are still reporting minimal ILI activity, 19 jurisdictions are reporting either High or Very High Activity. 

ILI rates are above the National baseline (see chart above) for the 3rd week in a row, and have chalked up their biggest weekly increase of this 2021-2022 flu season to date.  

In Week 51 influenza A makes up more than 99% of the flu cases detected, and H3N2 makes up > 99% of the influenza A viruses identified. 

While early concerns have been raised over this year's vaccine match to the H3N2 virus in circulation (see Preprint: Antigenic & Virological properties of an H3N2 Variant That Will Likely Dominate the 2021-2022 Influenza season) - it is still expected to lower the risks of severe illness - and is very much worth getting. 

The Summary from today's FluView report:

Key Points

• Influenza activity is increasing, with the eastern and central parts of the country seeing the majority of viruses reported and the western part of the country reporting lower levels of influenza virus circulation.
• The majority of influenza viruses detected are A(H3N2). Most influenza A(H3N2) infections have occurred among children and young adults ages 5-24 years; however, the proportion of infections occurring among adults age 25 years and older has been increasing.
• While there are little data to date, most of the H3N2 viruses so far are genetically closely related to the vaccine virus, but there are some antigenic differences that have developed as H3N2 viruses have continued to evolve.
• The percentage of outpatient visits due to respiratory illness is trending upwards and is above the national baseline. Influenza is contributing to levels of respiratory illness, but other respiratory viruses are also circulating. The relative contribution of influenza varies by location.
• Hospitalizations for influenza are starting to increase.
• The flu season is just getting started. There’s still time to get vaccinated. An annual flu vaccine is the best way to protect against flu and its potentially serious complications. CDC recommends everyone 6 months and older get a flu vaccine.
• There are early signs that flu vaccination uptake is down this season compared to last.
• Flu vaccines are available at many different locations, including pharmacies and health departments. With flu activity just getting started, there is still time to benefit from flu vaccination this season. Visit www.vaccines.gov to find a flu vaccine near you.
• There are also flu antiviral drugs that can be used to treat flu illness.

Increasing influenza around the nation also coincides with a rapid rise in the Omicron COVID variant, and that can make diagnosis of either infection more difficult. Additionally, there are concerns over the potential for seeing dual infections, which have been linked to more severe illness.

Clinical and virological impact of single and dual infections with influenza A (H1N1) and SARS-CoV-2 in adult inpatients

While the COVID vaccine (and booster), the flu vaccine, the wearing of face masks, and social distancing may individually provide less-than-perfect protection against infection or illness - when combined - they can substantially reduce your risk of serious illness. 

Given that hospitals and emergency services are likely to overwhelmed in the months ahead (see More U.S. Hospitals Inch Towards Invoking Crisis Standards of Care), anything you can do to reduce your risk of either COVID or Flu infection would be of considerable advantage. 

Denmark SSI: Unvaccinated 5 Times More Likely To Be Hospitalized With COVID

#16,477

Public health agencies around the world have been slow to update their websites following the long  New Year's Holiday weekend, with some reporting delays due to data issues. 

Given the almost universal interruption in data we've seen due to two long holiday weekends in a row, I expect it will be several days before we begin to see semi-reliable data. 

Denmark, however, has broken the ice with a new report (that once again) confirms that those who are fully vaccinated (and/or boosted) are less likely to be hospitalized with COVID. 

          (translated)

Larger proportion of covid-19-related admissions among unvaccinated individuals

The number of covid-19 related admissions in week 51 was 59.1 per. 100,000 unvaccinated persons aged 12 years and over. For persons with full effect of the primary vaccination course and persons with full effect of revaccination, the numbers were 10.8 and 12.7, respectively. So far less.

Last edited January 3, 2022

There are relatively more unvaccinated among the covid-19-related admissions.

This is stated in the latest report on breakthrough infections and vaccine efficacy from the Statens Serum Institut (SSI).

The report shows a clearly higher incidence of covid-19-related admissions among unvaccinated individuals. Weekly counts for week 51 for persons aged 12 years and over thus show 59.1 covid-19-related admissions per 100,000 unvaccinated persons. At the same time, the number is only 10.8 per 100,000 people with full effect of the primary vaccination course and 12.7 per 100.00 people with full effect of revaccination. So far less.

"It is clear that it is the unvaccinated who get so sick from the corona infection that they have to be hospitalized. There are not that many unvaccinated adults in all in Denmark, but they fill a relatively large amount in the numbers for admissions, ”says department head Palle Valentiner-Branth from SSI.

The slightly higher incidence among people with full effect of revaccination compared to people with full effect of primary course can possibly be explained by the fact that people with an increased risk of a serious covid-19 course were vaccinated first and thus were also the first to be revaccinated.

The 5-11-year-olds are not yet included

There are only very few children between the ages of 5 and 11 who have currently achieved the full effect of the primary vaccination course. Therefore, they are not yet included in the inventories.

Increase in the number of covid-19-related admissions

The number of covid-19-related admissions has generally been slowly increasing from week 41, and the number of admissions among vaccinated with full effect of primary vaccination course is now at the highest level since the beginning of the vaccination roll-out.

High vaccine efficacy against covid-19-related admissions

Vaccine efficacy (VE) against covid-19-related admissions after the delta variant remains high for individuals with full efficacy of primary vaccination course.

The latest inventory in the Breakthrough Infections and Vaccine Efficiency Report shows for the Comirnaty vaccine (Pfizer-BioNTech) a protection against covid-19-related admissions of 92.9% (95% SI: 65.2; 98.5), 90, respectively, 9% (95% SI: 89.1; 92.4) and 64.5% (95% SI: 56.0; 71.4) for the age groups 12-15 years, 16-64 years and ≥65 years compared to unvaccinated in the same age groups.

Vaccine efficacy is even higher for the Spikevax vaccine (Moderna).

Covid-19-related deaths

The weekly inventories overall show a very low incidence of covid-19-related deaths. The highest incidences are seen among persons ≥80 years and especially among unvaccinated.

In week 51 for the age group ≥80 years, the incidence of covid-19-related deaths is 88.5 per 100,000 for unvaccinated persons and 42.7 and 5.8 per 100,000 for persons with full effect of primary course and with full effect of revaccination, respectively.

The latest report on breakthrough infections and vaccine efficacy shows that the number of covid-19-related deaths among those vaccinated with full effect of primary vaccination course has increased in the period from week 42 to week 47, and since week 47 there has been a slight decrease to a stable and slightly higher level than earlier in the year.

The small decrease in the number of covid-19-related deaths in this group despite the high infection pressure may be due to the fact that the people at highest risk have been revaccinated.

Saudi Arabia Announces 4 Additional MERS-CoV Cases To End 2021

Credit CDC

#16,476

On Dec 30th, in Three Blind Spots Going Into 2022, I listed MER-CoV as one of 3 credible viral threats that are frequently under reported around the globe. 

While the COVID pandemic has no doubt hampered infectious disease reporting around the world, we've had difficulties getting good MERS-CoV data from the Middle East since the virus first emerged in 2012. 

Saudi Arabia has reported the vast majority of known cases with WHO EMRO Reporting in early November. 

At the end of October 2021, a total of 2578 laboratory-confirmed cases of Middle East respiratory syndrome (MERS), including 888 associated deaths were reported globally for a case-fatality ratio (CFR) of 34.4%. The majority of these cases were reported from Saudi Arabia, which had 2178 cases including 810 related deaths (CFR 37.2%).

Despite reporting roughly 85% of the world's cases, there are strong suspicions that the virus is chronically underreported in KSA, and likely many other Middle Eastern countries. 

• In 2015, when Saudi Arabia had recorded fewer than 1200 MERS cases, a seroprevalence study (see Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study by Drosten & Memish et al.,) suggested nearly 45,000 might have been infected.

• A 2018 study, written by former Deputy Health Minister Ziad A. Memish et al. (see Evaluation of a Visual Triage for the Screening of MERS-CoV Patients), concluded that Saudi Arabia's screening process for MERS testing was `. . .  not predictive of  MERS  infection.'

• And we've seen repeated `lapses' in MERS reporting over the years - sometimes lasting months - by KSA (see Saudi MOH: 5 Months Without A MERS-COV Update) and other countries, making the relatively few cases being reported less than reassuring. 

Up until a few days ago, Saudi Arabia's MERS Surveillance website only showed 13 cases in 2021, with the last one reported in late September. This is roughly a 20-fold drop over the average number of cases reported in the 5 years before COVID (2014-2019). 

The last WHO EMRO update - released in early November - stated: No new cases of MERS were reported to WHO during the month of October 2021.  The WHO did not report any new cases in their September report, either.  

Going back to their August report, 4 cases were noted, with one going back as far as March 2021. 

During the month of August 2021, four laboratory-confirmed cases of MERS and 2 deaths were reported to WHO from Saudi Arabia. One of the deaths was of a case reported in March 2021. The four reported cases are all male, non-healthcare workers and with co-morbidities. All cases were primary cases with history of contact with dromedaries and  consumption of their raw milk in the 14 days prior to the onset of symptoms. 

Which brings us to a very recently updated list for 2021 from the Saudi MOH that adds 4 more cases (1 in October, 1 in November, and 2 in December) to their list. 

While the addition of 4 new cases is notable, so too are the facts that 2 of these cases are deceased, and 3 of the 4 appear to have had no contact with camels in the 2 weeks prior to infection, suggesting community acquired infections. 

 

While many human MERS cases have been linked to recent camel (or camel product) exposure, or had contact with a confirmed case, hundreds of others are listed as `primary' (community acquired) cases with no known risk exposure. 

The assumption is that some of these cases may be due to unidentified, mildly symptomatic (or asymptomatic) cases, who occasionally transmit the virus on to others in the community.

In 2018, the WHO listed some of the `milder' symptoms that may be associated with MERS-CoV infection, including:

Low-grade fever, cough, malaise, rhinorrhoea, sore throat without any warning signs, such as shortness of breath or difficulty in breathing, increased respiratory (i.e. sputum or haemoptysis), gastro-intestinal symptoms such as nausea, vomiting, and/or diarrhoea and without changes in mental status (i.e. confusion, lethargy).

Essentially, the same symptoms one would expect to see with mild-to-moderate COVID infection.  It is plausible that many mild MERS cases have gone undetected, due to the pandemic and other lapses in surveillance and reporting. 

Prior to the emergence of COVID-19, MERS-CoV was viewed as the coronavirus with the most pandemic potential (see 2017's Study: A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia). 

While it may not be ready for prime time, MERS-CoV continues to evolve - mostly outside of our view - making it very much worth our attention. 

Update: More Reports of HPAI H5N1 in Eastern Canada

 

Credit City of St. John's

#16,475

Nine days ago, in Canada: N.L. Reports HPAI H5N1 in Captive Birds, we looked at the first reports avian flu on the remote Avalon Peninsula on the island portion of Newfoundland and Labrador. Early analysis found the virus belong to clade 2.3.4.4B, which is the same Eurasian lineage that is currently sparking a major epizootic in Europe. 

While North America has been spared any large avian epizootics since the spring of 2015, we've seen numerous studies on how migratory birds - from either Asia or Europe - could cross oceans bringing the virus with them, including PLoS One: North Atlantic Flyways Provide Opportunities For Spread Of Avian Influenza Viruses). 

Yesterday the City of St. John's - which is the capital of Newfoundland and Labrador - issued the following statement on their Facebook page.

City of St. John's

In response to recent testing, Environment and Natural Resources in Canada has confirmed the presence of the highly pathogenic avian flu in wild birds in the St. John's area, including Bowring Park, Quidi Vidi Lake and other areas frequented by flocks of birds.

The public are asked to refrain from feeding, touching or handling wild birds including ducks, pigeons and gulls. http://www.stjohns.ca/media.../refrain-feeding-wild-birds

A report from CBC.ca (see Avian flu discovered in birds around St. John's, Environment Canada says) confirms this to be the same HPAI H5N1 reported before Christmas.  

As I mentioned in my first report, this has the potential to spread, as pointed out in the follow notice posted on the AASV website. 

OFFLU Statement on Outbreak of H5N1 High Pathogenicity Avian Influenza in Newfoundland, Canada

December 29, 2021 —

The recent detection of an H5N1 high pathogenicity avian influenza (HPAI) virus in Newfoundland, Canada represents the first identification of goose/Guangdong/1/96-lineage (Gs/GD/96) H5 HPAI virus in the Americas since June 2015. This is cause for concern for wild birds, zoological collections, and poultry in the Americas.

Some east coast states of the United States of America (USA) are home to very large poultry populations that could be at risk of exposure and outbreaks in the next few months. This finding raises concerns about the potential of this virus becoming established in the Americas within migratory and resident birds. [Source: OFFLU 23 December 2021]

Read the full statement at https://www.offlu.org/wp-content/uploads/2021/12/OFFLU-statement_Newfoundland__H5N1.pdf.

On Wednesday, Dec 29th, the USGS published a 3-page report on this outbreak. 

While we may get luckier than we did in 2015 - when we saw North America's worst avian epizootic on record - these reports should remind poultry producers that we are not immune to HPAI - that migratory birds can cross oceans - and that now is a good time to review their biosecurity.

The USDA has some advice on how to Defend The Flock at the website below.

CDC HAN #00461: Using Therapeutics to Prevent and Treat COVID-19

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The rapid emergence of the Omicron variant of COVID, which some see as `good news' - in that it is appears to be less pathogenic than Delta - is not without its downsides.  

• Omicron is spreading at several times the rate of all previous COVID variants and threatens to overwhelm hospitals and impact the global workforce due to high absenteeism
• Omicron partially evades prior immunity (acquired either via vaccination or previous infection)
• And Omicron has taken a number of therapeutic options (monoclonal antibodies & antivirals) off the table, leaving limited options for treatment

All of these are potential issues that we were warned about six months ago - long before Omicron emerged - in UK SAGE: Can We Predict the Limits of SARS-CoV-2 Variants and their Phenotypic Consequences?, and which may affect future variants as well.  

While milder illness is certainly a good thing, not everyone will emerge unscathed, and treatments are needed. Two of the most frequently prescribed monoclonal antibody treatments (bamlanivimab and etesevimab  and casirivimab and imdevimab) are no longer effective against Omicron.

The one remaining monoclonal antibody sotrovimab expected to be effective against Omicron is in very short supply, and its use must be strictly prioritized. 

The news regarding antivirals isn't much better.  IV Remdesivir which is FDA approved for hospitalized COVID patients appears to still be effective (based on limited in vitro data), but is difficult to administer, and more clinical data on effectiveness is needed.  

There are two oral antivirals (Paxlovid and molnupiravir) still available, but Paxlovid is in very short supply while molnupiravir provides significantly less effectiveness (30% vs 88%), and has several use restrictions (including in pregnant women, women who are breastfeeding, pediatric patients, etc.).

Pharmacologically, the cupboard for Omicron has grown relatively bare (at least compared to Delta). 

In order to help clinicians wend their way through this rapidly changing situation, late on New Year's Eve the CDC issued the following HAN Health Advisory on those therapeutics currently available for Omicron. 

Follow the link to read it in its entirety. 

Using Therapeutics to Prevent and Treat COVID-19

Distributed via the CDC Health Alert Network

Friday, December 31, 2021, 5:00 PM ET
CDCHAN-00461

Summary

The SARS-CoV-2 Omicron variant has quickly become the dominant variant of concern in the United States and is present in all 50 states. The Centers for Disease Control and Prevention (CDC) recommends that eligible individuals should get all vaccines and booster shots as the best preventive measure available against severe disease, hospitalizations, and death due to COVID-19.

Therapeutics are also available for preventing and treating COVID-19 in specific at-risk populations. These therapeutics differ in efficacy, route of administration, risk profile, and whether they are authorized by the U.S Food and Drug Administration (FDA) for adults only or adults and certain pediatric populations. 

Some therapeutics are in short supply, but availability is expected to increase in the coming months. This Health Alert Network (HAN) Health Advisory serves to familiarize healthcare providers with available therapeutics, understand how and when to prescribe and prioritize  them, and recognize contraindications.

Background

On November 24, 2021, a new variant of SARS-CoV-2, B.1.1.529 (Omicron), was reported to the World Health Organization external icon (WHO). On December 1, 2021, the first case of COVID-19 attributed to Omicron was reported in the United States. CDC has been working with state, tribal, local, and territorial public health officials to monitor the spread of the Omicron variant in the United States and has identified a rapid increase in infections consistent with what has been observed in other countries.

Current CDC recommendations for vaccines and booster shots are expected to protect against severe illness, hospitalizations, and deaths from infection with the Omicron variant. Some studies have found lower effectiveness of the primary series of vaccines against infection and demonstrated the importance of booster doses (1-3). The United States Government is continuously working with private and public partners to bring new therapeutic options for use against SARS-CoV-2 variants of concern, including the Omicron variant.

Monoclonal Antibodies

The Omicron variant, with its numerous mutations in the spike protein, is not neutralized by bamlanivimab and etesevimab or casirivimab and imdevimab the most frequently prescribed monoclonal antibody-based COVID-19 treatments (4-5).

Despite some reduction in neutralization concentrations, sotrovimab remains effective against all variants of concern, including Omicron (6). However, sotrovimab is currently in limited supply, and its use should be prioritized for nonhospitalized patients with risk factors for progression to severe COVID-19, including individuals who are unvaccinated, have not received all vaccines and booster shots as recommended by CDC, individuals with clinical risk factors, older age (for example >65 years of age), and individuals not expected to mount an adequate immune response.  Sotrovimab can be used in these high-risk individuals when Paxlovid (described below) is not indicated due to potential severe drug-drug interactions or if Paxlovid is not available.

Antivirals

• Remdesivir is a nucleoside analog approved by FDA for the treatment of hospitalized patients with COVID-19. A recent randomized placebo-controlled outpatient study evaluated three daily intravenous (IV) infusion of remdesivir given within seven days of symptom onset. This study found that the reduction in hospitalization rates was similar to that achieved by using anti-SARS-CoV-2 monoclonal antibody-based therapy (7). Remdesivir is expected to be effective against the Omicron variant based on in vitro data; however, in vivo data are currently limited (8). Outpatient use of remdesivir requires support of IV infusion centers with appropriate skilled staffing.
• Two oral antivirals, Paxlovid (ritonavir-boosted nirmatrelvir) and molnupiravir, are now available under Emergency Use Authorization by FDA for treating COVID-19 in outpatients with mild to moderate disease. Each drug is administered twice daily for five days. There are considerable differences in efficacy, risk profiles, and use restrictions between the two oral antivirals. From their individual clinical trials, compared to placebo, severe outcomes (hospitalization or death) were reduced by 88% for Paxlovid  compared to 30% for molnupiravir (9). Healthcare providers need to be familiar with these distinctions to make clinical decisions and inform patients. In addition, initiating treatment with these oral antivirals must begin within five days of symptom onset to maintain product efficacy. Paxlovid is currently in very limited supply and use should be prioritized for higher risk populations. Due to the potential for severe drug-drug interactions with ritonavir, a medication used for HIV treatment, CDC strongly suggests that healthcare providers not experienced in prescribing Paxlovid refer to the NIH Statement on Paxlovid Drug-Drug Interactions | COVID-19 Treatment Guidelines.

• Healthcare providers could also contact a local clinical pharmacist or an infectious disease specialist for advice. Like Paxlovid, molnupiravir is expected to be active against all circulating variants of concern, including Omicron (8). Molnupiravir should only be used when other options are not available, due to its lower efficacy. Molnupiravir use is not recommended  in pregnancy because of potential mutagenicity. Molnupiravir is also not recommended  in patients who are breastfeeding or pediatric patients due to limited data within these populations and concerns for potential bone growth toxicity in the young.

Pre-exposure therapeutics for high-risk groups

AstraZeneca’s EVUSHELD, which includes two long-acting anti-SARS-CoV-2 monoclonal antibodies, is the only Emergency Use Authorization pre-exposure prophylaxis product available. EVUSHELD is expected to be effective against the Omicron variant; however, treatment effectiveness should be monitored. EVUSHELD is intended for the highest risk immunocompromised patients who are not expected to have an effective response to vaccination. EVUSHELD is indicated for pre-exposure prophylaxis only and not for treatment of patients with COVID-19.

Recommendations for Healthcare Providers

• As with all therapeutics, the best use of therapeutics includes an appropriate clinical assessment and an up-to-date and informed risk-benefit discussion to address any questions or concerns from patients.
• Obtain further information on clinical use of products through NIH’s COVID-19 Treatment Guidelines, the Assistant Secretary for Preparedness and Response Public Health Emergency COVID-19 Therapeutics site, and through professional societies such as IDSA’s Guidelines on the Management of Patients with COVID-19.
• Check with state and local health departments on key sites that have been identified for distribution of therapeutics, including cancer treatment centers and oncology providers.
• If the Delta variant still represents a significant proportion of infections in a region and other options are not available or are contraindicated, eligible patients can be offered bamlanivimab and etesevimab or casirivimab and imdevimab, with the understanding that these treatments would be ineffective against the Omicron variant. This concern can be mitigated if virus-specific diagnostic testing  a given patient indicates infection with the Omicron variant is unlikely.
• Prioritize high risk patients, particularly if therapeutics are in short supply, using NIH COVID-19 Treatment Guidelines when supply constraints exist. This document presents a tiered approach to prioritization.
• Continue to encourage COVID-19 vaccination, including booster vaccination.  

Recommendations for Public Health Departments and Public Health Jurisdictions

• State and local health departments should be aware of locations of available therapeutics within their jurisdictions.
• Health departments should communicate ongoing and up-to-date information on therapeutics for COVID-19 and their availability to healthcare providers within their jurisdiction until product locators become readily available.

For More Information

• Omicron Variant: What You Need to Know | CDC
• Interim Clinical Considerations for Use of COVID-19 Vaccines | CDC
• CDC COVID Data Tracker
• COVID-19 Treatment Guidelines: What’s Newexternal icon
• COVID-19 Treatment Guidelines: Antiviral Therapyexternal icon
• NIH Statement on Therapies for High-Risk, Nonhospitalized Patients | COVID-19 Treatment Guidelinesexternal icon
• NIH Statement on Paxlovid Drug-Drug Interactions | COVID-19 Treatment Guidelines external icon
• The COVID-19 Treatment Guidelines Panel’s Interim Statement on Patient Prioritization for Outpatient Anti-SARS-CoV-2 Therapies or Preventive Strategies When There Are Logistical or Supply Constraintsexternal icon
• Side by Side Overview of Outpatient Therapies Authorized for Treatment of Mild-Moderate COVID-19 

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