COVID news & more 12/23/23

We are in a new COVID surge caused by the JN.1 variant with 1.1 million new COVID cases each day in the U.S. now. The World Health Organization (WHO) put out a special advisory on December 19th warning that due to its rapid spread, JN.1 was upgraded to a variant of interest. On a global level, the WHO said that JN.1 is low risk for causing a new pandemic, but combined with other winter respiratory viruses (the Flu, RSV, and “common childhood pneumonia”), JN.1 may push some hospitals and emergency rooms to their limits. The WHO now recommends that everyone wear masks in clinics and hospitals and that healthcare workers taking care of possible COVID patients should wear N95 masks (respirators) and personal protective equipment (PPE) like gowns and gloves.

The WHO also advised that the updated XBB.1.5 COVID vaccine protects people against severe disease and death from JN.1 and other circulating variants of SARS-CoV-2. Only 18% of American adults have gotten the new COVID vaccine, but there is plenty available and appointments can be found at vaccines.gov.

JN.1 now represents 57% of variants in the Northeast and 41% of circulating variants in the West.  Nationally, wastewater levels of SARS-CoV-2 are at the “VERY HIGH” level according to the CDC.

New York, which tends to be the bellwether for what will soon happen in the rest of the U.S., shows that hospitalizations have been increasing since JN.1 arrived. What happens in New York tends to happen in the rest of the country about a week or two later. As of today December 23rd, Jay Weiland calculated that there were 1.1 million new COVID infections each day in the United States and that every 1 in 29 people is currently infected. As he put so clearly, “hospitalizations and deaths are clearly not the only major risks from COVID. Long COVID and other new health problems are a roll of the dice with each infection.”

From JP Weiland

So what does this mean for Christmas and New Years? Based on wastewater levels of SARS-CoV-2, Michael Hoeger predicted that the risk of an infectious person coming to a Christmas Day gathering is high. 

So what can you do? Have everyone test for COVID right before coming over, crack open windows to improve ventilation, get out your HEPA air filters or Corsi-Rosenthal box, and stay home if you are sick. There is still time to get the updated XBB.1.5 COVID vaccine now which can (partially) protect you against COVID for New Years and which can reduce the need to go to the emergency room or be hospitalized for a more severe COVID infection.

If you do happen to get COVID, remember Paxlovid reduces the risk of both severe acute infections and Long COVID. Amazon Clinic has online appointments for $35 to get a Paxlovid prescription. A new study shows that starting Paxlovid (nirmatrelvir/ritonavir) as soon as possible on day 0 or day 1 of symptoms reduced deaths and hospitalizations by half as compared to starting Paxlovid on day 2 or after. 

I was surprised to find out that some healthcare providers do not prescribe Paxlovid because they are worried about viral rebound. Well, there is no need to worry about that. Two new reviews from the CDC (here and here) looking at both randomized clinical trials and observational studies show that COVID rebound happens equally in people treated with Paxlovid and those who were not. It turns out that it is the person’s immune response to the infection that determines whether or not they will get rebound. In general, SARS-CoV-2 rebound starts about 3 to 7 days after a person’s COVID infection first resolves and causes mild illness. There were no hospitalizations or deaths reported from rebound COVID infections. 

The NHS in the UK studied SARS-CoV-2 transmission risk from 7 million exposures using a smartphone app and found that "the cumulative duration of exposure to infected individuals is a key predictor of transmission". If you are farther away from an infected person for a longer time, you have a similar chance of catching a COVID infection as someone who sat close to an infected person for a short amount of time. Household spread was responsible for 40% of transmissions. 

A smartphone app used for contact tracing during the COVID-19 pandemic predicts the probability of SARS-CoV-2 transmission. 

A retrospective cohort study of more than 811,000 pregnancies shows that COVID infection during pregnancy through 6 weeks postpartum significantly increases the risk of venous thromboembolism (blood clots). The authors recommended that blood thinners should be considered in the pregnant or postpartum individuals who have a COVID infection.

In many countries, people believe that COVID infection in children is not a problem. This week, I came across this quote: “In the lab, COVID is a Level 3 biohazard. In schools, it's no big deal. I don't think you can reconcile those two statements,” said Colin Furness, infection control epidemiologist. More than 70% of US household COVID spread starts with a child, especially when school is in session. Reducing childhood COVID infections can benefit the whole family and it can also help the child. A new study in Nature shows that COVID vaccines reduce the risk of Long COVID in children. I am concerned about the long term effects of SARS-CoV-2 infections on children, including the risk of Long COVID. Anything that we can do to reduce the risk could be beneficial.

A review article in Nature looked at three recent studies in non-human primates using inhaled mucosal vaccines. Dr. Akiko Iwasaki of Yale was quoted, “These studies are showing you can get near sterilizing immunity [with mucosal vaccines]. It’s not complete science fiction to think about developing vaccines that would stop transmission and infection.˝ An article in the MIT Technology Review looked at needle-free COVID vaccines. SARS-CoV-2 mucosal vaccines (given through the nose or mouth) are being used in China, India, Iran, Indonesia, Morocco, and Russia, but not in the United States or Europe. The only mucosal vaccine approved in the U.S. is the FluMist nasal spray vaccine for influenza. Unless we have an “Operation Warp Speed”-like program to rapidly advance human studies, it may take another 2 to 3 years before some of these vaccines will be available here. 

Long COVID

Paxlovid is a combination therapy of Nirmatrelvir given with Ritonavir. Ritonavir gives Paxlovid the bad taste that many people complain of, but it is necessary to give it in order to increase nirmatrelvir concentrations to the target therapeutic range. The RECOVER-VITAL clinical trial plans to recruit 900 people with Long COVID from around the country and will compare Paxlovid (Nirmatrelvir with Ritonavir) given for 25 days vs. Paxlovid for 15 days and then Ritonavir with placebo for 10 days vs. Ritonavir with placebo for 25 days. One of the main theories about Long COVID is that it may be caused by SARS-CoV-2 viral persistence in the body after the acute infection has resolved. Giving antiviral Paxlovid for differing amounts of time will allow researchers to decipher what may be the best treatment. 

A new report in Nature shows that "Long COVID reduced Heart Rate Variability (HRV) at rest and during deep breathing. These findings may imply impairment of cardiac autonomic control.”  In Long COVID, dysautonomia (also known as autonomic dysfunction) causes an imbalance in HRV and this may explain some Long COVID symptoms. The autonomic nervous system controls heart rate, digestion, temperature control, sweat glands, as well as urinary and sexual function, so it affects many different systems in the body. 

Dr. Al-Aly is a Clinical Epidemiologist and Nephrologist who uses the power of big data from V.A. electronic medical records to understand gaps in medical knowledge. This week, Betsy Ladyzhets interviewed Dr. Al-Aly and spoke to him about his latest study which compared post-acute sequelae of the Flu versus COVID infection, the recent Canadian data which also showed that COVID reinfections increase the risk of Long COVID and the need for long term funding for Long COVID research and clinical trials. 

Salvatore Mattera tweeted about his loss of smell from a COVID infection and his visit to expert Dr. Zara Patel. She prescribed 2000 mg of fish oil per day, twice a day nasal rinse with budesonide, and 6 months of smell retraining. Salvatore also will try plasma rich platelet injections into his nasal cavity.

Have a great holiday weekend,

Ruth Ann Crystal MD

COVID news:

US Variant tracker: https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Well hello, JN.1.

JN.1 is 57% in northeast and 41% in the west:

CDC COVID data tracker: https://covid.cdc.gov/covid-data-tracker/index.html#datatracker-home

CDC COVID Hospitalizations (blue) and Emergency Room (orange) visits tracker: https://covid.cdc.gov/covid-data-tracker/index.html#trends_weeklyhospitaladmissions_7dayeddiagnosed_00

Weekly ED visits for respiratory illnesses, by age and disease: https://www.cdc.gov/ncird/surveillance/respiratory-illnesses/index.html

US Wastewater Monitoring:

NEW CDC wastewater reporting: https://www.cdc.gov/nwss/rv/COVID19-nationaltrend.html

CDC wastewater map: https://www.cdc.gov/nwss/rv/COVID19-currentlevels.html

Biobot: https://biobot.io/data/

From Dec 23, 2023

Wastewater SCAN: https://data.wastewaterscan.org/

Bay Area

Santa Clara County wastewater: https://covid19.sccgov.org/dashboard-wastewater

CDC Respiratory vaccination trends: https://www.cdc.gov/respiratory-viruses/data-research/dashboard/vaccination-trends-adults.html

12/19/23 WHO Advisory: COVID19 variant of interest JN.1 with update for health workers https://buff.ly/3NEQRvp

• Due to its rapidly increasing spread, WHO is classifying the variant JN.1 as a separate variant of interest (VOI) from the parent lineage BA.2.86.

• Universal masking in health facilities and respirators and PPE for health care workers taking care of possible COVID patients.

  

JP Weiland: https://twitter.com/JPWeiland/status/1737165762320638111

12/19/23 JN.1 is at 34% of lineages today per Raj Rajnarayanan. Starting to see a spike in hospitalizations. 

JP Weiland December 23rd Update:

Early update from Biobot due to holidays. Wastewater levels are approaching last year's peak. JN.1 dominance will exert increasing pressure.  Estimates:

• 1,120,000 new infections/day

• 1 in every 290 became infected today

• 1 in every 29 people currently infected

https://twitter.com/JPWeiland/status/1736954622164488357

Michael Hoerger modeling:  http://pmc19.com/data/

Twitter: https://twitter.com/michael_hoerger

• Risk of infectious person to gathering on Christmas Day given wastewater virus levels on December 18:

https://twitter.com/michael_hoerger/status/1736860057302905206

Real world COVID risk from Biobot wastewater data from @Michael_Hoerger 

Note: This chart only works with data from Biobot. 

https://twitter.com/luckytran/status/1738657257502487038

12/21/23 Michael Mina recommends the Flowflex rapid COVID test.

Variants 

12/17/23 Lancet (Yunlong Cao): Fast evolution of SARS-CoV-2 BA.2·86 to JN.1 under heavy immune pressure https://buff.ly/4atxvDk

• BA.2.86 had 44 new mutations total + 1(L455S) = JN.1

• "With just one additional receptor binding domain mutation (L455S) compared to its predecessor BA.2.86, the JN.1 variant rapidly became predominant in France, surpassing both BA.2.86 and the so-called FLip (L455F+F456L) strains." 

Acute COVID infections

12/20/23 Nature: Digital measurement of SARS-CoV-2 transmission risk from 7 million contacts https://www.nature.com/articles/s41586-023-06952-2

• NHS COVID-19 app

• Longer exposures at greater distances had similar risk to shorter exposures at closer distances.

• While most exposures were short (median 0.7 hours), transmissions typically resulted from exposures lasting one hour to several days (median 6 hours).

• Households accounted for about 6% of contacts but 40% of transmissions.

• "the cumulative duration of exposure to infected individuals is a key predictor of transmission" 

12/21/23 Nature: Contact-tracing app predicts risk of SARS-CoV-2 transmission https://buff.ly/3ti12PO

• Review of above article

• NHS COVID-19 smartphone app used for contact tracing calculated a risk score for getting a COVID infection using these 3 variables: 

  • 1) the amount of time spent with the infected person 

  • 2) proximity to an infected person, and 

  • 3)how infectious that person is.

Figure 1 | A smartphone app used for contact tracing during the COVID-19 pandemic can predict the probability of SARS-CoV-2 transmission. 

Pregnancy

1/2024 Obstetrics & Gynecology (Green Journal): Coronavirus Disease 2019 (COVID-19) and Venous Thromboembolism During Pregnancy and Postpartum https://buff.ly/3GME864

• Retrospective cohort study of 811,000 pregnancies 

• COVID infection during pregnancy through 6 weeks postpartum increased risk of venous thromboembolism (blood clots) compared to no COVID infection (1.0% vs 0.5%, adjusted hazard ratio 2.62). 

• Thromboprophylaxis should be considered in the obstetric population with SARS-CoV-2 infection.

Pediatrics

4/2023 CBC Canada “In the lab, COVID is a Level 3 biohazard. In schools, it's no big deal. I don't think you can reconcile those two statements.” - Colin Furness, infection control epidemiologist https://buff.ly/4aofJRZ

12/20/23 Nature: Vaccines reduce the risk of Long COVID in children https://buff.ly/4879S1L

• "vaccination reduced the likelihood of developing at least one long COVID symptom by 34% and of developing two or more symptoms by 48%. 

  • Yousaf says that this is likely to be an underestimate, because the study only looked at children who had an infection; it did not consider that the vaccine can reduce the chances of developing the infection, which also decreases the likelihood of long COVID." 

Masks

Vaccines

12/19/23 Nature: Inhaled (mucosal) COVID vaccines stop infection in its tracks in monkey trials https://buff.ly/3tivPfk

• 3 studies in monkeys with mucosal vaccines (through the nose or the throat) were discussed.

• “These studies are showing you can get near sterilizing immunity,” says Dr. Akiko Iwasaki of Yale. "It’s not complete science fiction to think about developing vaccines that would stop transmission and infection.˝

• Clinical studies in humans will take another 2 to 3 years.

12/15/23 MIT Technology Review: Needle-free covid vaccines are (still) in the works https://buff.ly/47d0MPD

• SARS-CoV-2 mucosal vaccines (given through the nose or mouth) are being used in China, India, Iran, Indonesia, Morocco, and Russia, but not the United States or Europe.

• However, the Flu Mist nasal vaccine is approved in the U.S.

• The new inhaled powder mucosal vaccine being tested in animals in China was discussed.

• Article reviews the latest studies.

12/13/23 BioRxiV (Veesler lab): A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines https://buff.ly/486oApL

Antiviral treatments

12/19/23 CIDRAP: Early Paxlovid for COVID-19 halved death, hospitalization in new study https://buff.ly/3TzK9KQ

• Starting Paxlovid on day 0 or day 1 of symptoms reduced deaths and hospitalizations by half as compared to starting Paxlovid on day 2 or after.

• “The observed benefit from administering nirmatrelvir/ritonavir as soon as possible after diagnosis or symptom onset may be attributable to an early suppression of viral replication, which in turn reduced the risk of subsequent deterioration to severe disease and death.”

Original study:

12/16/23 Nature (U of Hong Kong): Optimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation https://buff.ly/3Nz9EbB

12/21/23 CIDRAP: 2 Reviews uncover no consistent link between antiviral drugs like Paxlovid and COVID rebound https://buff.ly/48oO3un

• "Current evidence, including randomized controlled trial and observational data, suggests that SARS-CoV-2 rebound occurs initially as a mild illness 3–7 days after resolution of the initial acute illness, occurs in both treated and untreated patients, and is not associated specifically with receiving nirmatrelvir/ritonavir," 

12/22/23 CDC MMWR: SARS-CoV-2 Rebound With and Without Use of COVID-19 Oral Antivirals https://buff.ly/4asZbIv

• The CDC reviewed 7 studies looking at viral rebound with and without Paxlovid and they found that viral rebound:

• Was similar in people who got Paxlovid and those who didn’t

• Rebound happened more if the person did not mount a good immune response to COVID infection.  

• SARS-CoV-2 rebound started about 3 to 7 days after a person’s COVID infection resolved, causing mild illness. COVID rebound happened similarly in both people treated with Paxlovid and those who were not. There were no hospitalizations or deaths reported from rebound COVID infections. It appears that COVID rebound depending on the host’s immune response to the infection.

  

12/22/23 CDC MMWR: Evaluation of SARS-CoV-2 RNA Rebound After Nirmatrelvir/Ritonavir Treatment in Randomized, Double-Blind, Placebo-Controlled Trials — United States and International Sites, 2021–2022 https://buff.ly/3GPTmY6

• “Similar SARS-CoV-2 RNA rebound rates were observed in nirmatrelvir/ritonavir and placebo recipients in two randomized, double-blind, clinical trials. 

• Virologic rebound after nirmatrelvir/ritonavir treatment was not associated with COVID-19–related hospitalization or death.” 

To get a Paxlovid prescription with Amazon Clinic- Online visit $35

https://clinic.amazon.com/COVID-19-treatment/dp/B0BL1Z6VXB

Long COVID

12/21/23 RECOVER-VITAL clinical trial for Long COVID https://trials.recovercovid.org/vital

ClinicalTrials.gov ID NCT05965726

• Planning 900 participants from around the nation.

• Paxlovid 25 days vs. Paxlovid 15 days vs. Ritonavir with placebo (1:1:1)

12/20/23 Nature Scientific Reports: Impact of Long COVID on the heart rate variability at rest and during deep breathing maneuver - https://buff.ly/3GQYOtE

• 21 patients with long COVID and 20 controls

• "Long COVID reduced Heart Rate Variability (HRV) at rest and during deep breathing. These findings may imply impairment of cardiac autonomic control when symptoms of COVID-19 persist following initial recovery."

12/19/23 The Sick Times: Q&A with Ziyad Al-Aly on why Long Covid has a higher burden than “Long Flu,” his future research plans, the dangers of COVID reinfection and more https://buff.ly/4ar0ffX

• “The Sick Times is a non-profit news site chronicling the Long Covid crisis. Founded by  @betsyladyzhets and @mileswgriffis.”

12/19/23 Long COVID Moonshot: A way to easily write to your senators and representatives regarding the need for funding for Long COVID research.

https://www.postable.com/card/totally-your-design-a7h

Loss of Smell after COVID:

12/21/23 Salvatore Mattera

https://twitter.com/SalvMattera/status/1737911652262252832

After an 11 month wait, I finally had a consultation with Zara Patel, an expert in long COVID smell loss. None of this should be taken as medical advice. But here's what she told me: 

• She scoped me and found that the part of my nasal passage leading to my olfactory bulb was swollen almost completely shut 

• She prescribed 2000 mg of fish oil per day, twice a day nasal rinse with budesonide, and 6 months of smell retraining, holding the scent bottles far enough away from my face that it was very difficult to tell what they were 

• I'm also going to start plasma rich platelet injections into my nasal cavity. She doesn't know how many to do. She recommends 3 rounds of it, but is just trying to observe and figure out the right amount 

• She thinks stellate ganglion block can help people with a distorted sense of smell, but not people with smell loss 

• She's open to the viral persistence theory for some patients but thinks the jury is still out 

• She does think that if you lose your sense of smell and don't get it back, then you may be at risk for neurodegenerative diseases later in life 

• She thinks younger people and people who start treatment earlier may have a better chance of getting their sense of smell back 

• Finally, she hopes that improvement in the smell will also lead to an improvement in taste, but nothing specifically there in terms of intervention 

• I should add that each round of injections costs about $1800. My employer provides the best insurance coverage in the world (multiple rounds of IVF, etc.) and not even they will cover it. So I have to pay out of pocket. Good luck to everyone else. 

• And this is all from a delta infection I, a fully vaccinated person, contracted from my mom, also a fully vaccinated person in the late summer of 2021 when the government was still telling people that if you were vaccinated you couldn't catch or spread covid.