COVID cases are very high across the United States since the Thanksgiving holiday. Reported cases do not reflect the true number of people with COVID since many people are either testing at home or are no longer testing if they feel sick because of the optic that “the pandemic is over”. The problem is that the pandemic is far from over. This week, the CDC strongly recommended that people start wearing high quality N95 or KN95 masks again because of the high number of cases of respiratory illness including COVID, Influenza and RSV across the United States which are filling hospitals. COVID hospitalizations for seniors now exceed hospitalizations in the BA.5, BA.2 and Delta waves.
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The best way to understand the true number cases is to follow wastewater levels of SARS-CoV-2. Across the United States this week, virus levels in wastewater are very high and continue to rise. In all but four states, hospitalizations have also risen since Thanksgiving. New York City is a hotspot with a 60% increase in cases this week. Los Angeles county, the largest county in the US, is seeing a large rise (up 86%) in cases and in hospitalizations. Here in the Bay Area, the Palo Alto watershed, which includes sewer water from Palo Alto, Los Altos and Mountain View, has SARS-CoV-2 virus levels that are higher than they have been at any other time during the pandemic. This week, the CDC recommended wearing N95 or KN95 masks again because of full emergency rooms and filling hospitals. Trustworthy masks can be found on
https://www.projectn95.org/. Other mitigation measures such as using air filters, washing hands often, staying home when sick and getting both the flu vaccine and the bivalent booster against COVID are important.
Immunity wanes after 4 to 6 months so booster shots are important. A new study shows that the bivalent boosters may improve Long COVID in some people. The new bivalent boosters were also found to increase neutralizing antibodies against the newly dominant and immune evasive variant BQ.1.1 by a factor of 5x to 10x.
This week, the California Department of Public Health (CDPH) posted a letter to healthcare providers recommending prescribing Paxlovid (and Remdesivir if appropriate) to almost everyone. There is ample supply of Paxlovid now and Paxlovid rebound is actually fairly low. People who qualify include people with common conditions and behaviors such as physical inactivity, obesity, depression, smoking (former or present), and disabilities. There are many other qualifications including being over age 50. Paxlovid prevents severe acute infections and deaths from COVID, and newer studies show that it also can reduce the risk of future Long COVID. To quote the CDPH,
“The decision to not prescribe COVID-19 treatment should be reserved for situations in which the risk of prescribing clearly outweighs the benefits of treatment in preventing hospitalization, death, and the potential for reduced risk of long COVID.”
There may be another new drug in the arsenal to decrease risk of severe COVID disease- Ursodeoxycholic acid (UDCA). UDCA is a safe, generic medicine typically used for liver disease. UDCA reduces COVID infections and severity of infections by blocking the ACE2 receptor used by the SARS-CoV-2 virus. For the obstetricians in the crowd, we already use UDCA or Actigall to treat cholestasis of pregnancy.
Long COVID:
Regarding Long COVID, a meta-analysis showed that 45% of people infected worldwide have at least one Long COVID symptom, most commonly fatigue, 4 months after infection. The UK’s Office of National Statistics (ONS) reported this week that 60% of workforce inactivity (i.e. people not working) is now due to Long COVID. That is a huge amount of people with significant disability. The new bivalent booster has been found to help some people with Long COVID in a small study. There really are not a lot of great treatments at this point for Long COVID, but I hope that in 1 to 2 years we will have data back from all of the clinical trials being done around the world now. Still, that is a very long time to wait for people who are suffering from Long COVID now.
Kids:
A study entitled “Pulmonary Dysfunction after Pediatric COVID-19” from September 2022 shows that there are abnormalities in the lungs of children who have had a prior COVID infection. For those kids that now have Long COVID, pulmonary dysfunction is more pronounced over time as seen by ventilation, perfusion and combined defects noted on V/Q scans. The MRI films of the lungs are quite impressive and are pictured below.
People say that history repeats itself and it looks like it is. A historical essay entitled “Encephalitis Lethargica: Last century’s long haulers?” reviews post-infection symptoms after the Spanish Flu of 1918 and those of Long COVID post-infection symptoms today. The history of "encephalitis" (a.k.a. brain fog, etc) and Parkinson's symptoms after infection with the Spanish Flu in 1918 parallel symptoms that people with Long COVID have today.
So, keep your masks handy, get Paxlovid if you come down with even a mild case of COVID, and consider Tamiflu if you get Influenza A. Get your bivalent COVID booster and your flu shot to help protect yourself and your family members.
Have a good weekend,
Ruth Ann Crystal MD
P.S. See the article below on using urine and plasma free glycosaminoglycan profiles (GAGomes) to detect early Stage I cancers.
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Other stuff:
12/5/22 PNAS: Noninvasive detection of any-stage cancer using free glycosaminoglycans https://buff.ly/3Has7Zt
Urine and plasma free glycosaminoglycan profiles (GAGomes) are powerful multi-cancer early detection (MCED) metabolic biomarkers, potentially doubling the number of Stage I cancers detectable using genomic biomarkers such as serum circulating free DNA (cfDNA).
For these 14 cancer types:
Diffuse glioma (DG)
Head and neck cancer (HN)
Non-small cell lung cancer (NSCLC)
Breast cancer (BC)
Diffuse large B cell lymphoma (NHL)
Chronic lymphocytic leukemia (CLL)
Small intestinal neuroendocrine tumor (GNET)
Colorectal cancer (CRC)
Prostate cancer (PCa)
Gynecological cancers (Cervical, Endometrial and Ovarian cancers)
Bladder cancer (BCa), Renal cell cancer (RCC)
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COVID news:
The CDC Clinician Call Center is available to clinicians who have COVID-19 clinical management questions. Call 800-CDC-INFO (800-232-4636) to be routed to Infectious Diseases Society of America (IDSA) volunteer clinicians.
12/7/22 Palo Alto Online: COVID-19 levels in the Palo Alto sewershed — which includes the cities of Los Altos, Palo Alto and Mountain View — are higher than at any point in the pandemic.https://buff.ly/3FBD2tX
In Santa Clara county, "We not only have COVID, as we've had the last two winters, but we have flu and RSV and other viruses circulating as well," Cody said.
Dr. Cody recommends wearing masks indoors, getting the bivalent COVID booster and the flu vaccine.
Only 25% of eligible Santa Clara county residents have gotten the updated bivalent COVID booster vaccine.
12/8/22 Nature (Mount Sinai): Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae https://buff.ly/3iNVdE0
n =165 patients hospitalized for COVID that were followed for 1 year.
Two patterns of gene expression related to antibody production to the SARS-CoV-2 spike protein during acute severe COVID infection predicted subsequent PASC (Long COVID) at least 6 months later.
Additional studies are needed to see if these findings generalize to mild COVID-19 and asymptomatic infections.
12/8/22 The FDA approves the Moderna's updated bivalent vaccine for children 6 months to 5 years.https://buff.ly/3iRFQdu
12/6/22 Eric Topol MD's Op-Ed in LA Times:
Immunity's down. Infection rates are up. And what happened to everyone's masks? https://buff.ly/3hb6opF
Hospitalizations for people over 70 are up and are higher than the BA.5 wave and Delta waves.
Wastewater virus levels are high in many states.
Immunity against COVID wanes over 4 to 6 months. Booster shots increase antibodies and protect against hospitalizations.
We need to bring back mitigation measures which protect against COVID, but also influenza and RSV which are rampant now:
KN95 or N95 masks
Testing
Ventilation and air filtration
BQ.1.1 is bad (very immune evasive and is becoming dominant).
Bivalent booster shots work well, but only 1/3 of seniors and only 15% of those people eligible (age 5 and over) have received one despite its better protection against Omicron variants.
The bivalent booster increases antibodies to BQ.1.1 by 5x to 10x.
We need to protect ourselves against Long COVID too.
12/6/22 Los Angeles county has a new COVID surge where reported cases have doubled since Thanksgiving. Also there are concerns about hospitals filling up and stressing the healthcare system.
12/2/22 California Department of Public Health (CDPH): Reminder to Lower Barriers to Prescribing COVID-19 Therapeutics to Mitigate Impact of COVID-19 https://buff.ly/3Y2mMtp
Any patient with suspected COVID-19 should be tested for SARS-CoV-2 infection and all symptomatic patients with a positive COVID-19 test of any type should be evaluated for treatment with nirmatrelvir/ritonavir (Paxlovid) or remdesivir.
Providers should have a low threshold to prescribe COVID-19 therapeutics (Paxlovid or Remdesivir) given the broad range of individuals who are at higher risk for severe COVID-19 and can benefit from COVID-19 treatment given that:
People at higher risk for hospitalization include:
Racial and ethnic minority groups
People who are unvaccinated or not up to date with their vaccination series against SARS-CoV-2
People with common conditions and behaviors such as physical inactivity, obesity, depression, smoking (former or present), and disabilities. Please see the Comprehensive CDC discussion.
Older adults, especially those above the age of 50 years, regardless of the presence of a medical condition.
COVID-19 treatments may reduce the risk of long COVID.
There is ample supply of therapeutic agents now.
Rebound can happen but it is not that common and is usually mild.
Providers should prescribe COVID-19 therapeutics to the extent possible for eligible patients as noted above. The decision to not prescribe COVID-19 treatment should be reserved for situations in which the risk of prescribing clearly outweighs the benefits of treatment in preventing hospitalization, death, and the potential for reduced risk of long COVID.
The following factors should NOT be reasons to withhold COVID-19 treatment:
Being fully or partially vaccinated.
Prior SARS-CoV-2 infection.
Mild disease. Patients with mild symptoms are, in fact, included in criteria for outpatient treatment according to the FDA EUA and NIH recommendations.
A lack of recent renal or liver function tests. The FDA EUA does not require assessment of laboratory results.
High risk patients co-infected with influenza and SARS-CoV-2 should receive treatment for both viruses.
There are no clinically significant drug-drug interactions between the antiviral agents or immunomodulators that are used to prevent or treat COVID-19 and those for influenza.
12/7/22 How many people in the US have had COVID?
Anywhere from 42% to 94% depending on the study.
94% was calculated with mathematical modeling but the other studies showing 42% to 61% actually tested nucleocapsid antibodies.
Table by Eric Topol MD
Summary: 45% of people have at least 1 Long COVID symptom at 4 months worldwide
12/1/22 Lancet eClinical Medicine: The prevalence and long-term health effects of Long Covid among hospitalized and non-hospitalised populations: A systematic review and meta-analysis https://buff.ly/3VFQgM2
Worldwide, 45% of COVID-19 survivors, regardless of hospitalization status, went on to experience at least one unresolved symptom (mean follow-up 126 days).
Fatigue was frequently reported.
Amongst the hospitalized cohort, abnormal CT patterns/x-rays were frequently reported, alongside ground glass opacification, and impaired diffusion capacity for carbon monoxide.
Must read article about the unprecedented levels of respiratory illness including flu and COVID now.
Increasing hospitalizations are especially worrisome in children under age 4 and people over age 65. But, bivalent boosters and flu shots can prevent this.
photo from Washington Post
12/5/22 WebMD: Have Long COVID? Newest Booster Vaccines May Help You https://buff.ly/3VUn03Q
Each reinfection increases the risk of acute severe disease, but also increases your risk of Long COVID.
Boosters may get rid of persistent virus in the body.
Vaccination immunity wanes. Plus new variants arise that can evade at least some of the immunity provided by vaccination.
Only 12% of Americans 5 and older have received the updated booster.
Vaccine improved LC in 7 studies, remained the same in 4 studies, worsened in some people with LC in 1 study.
“The antibody response is appropriately boosted, and there is a decent chance this will help reduce the impact of long COVID as well,” he says. “Waiting will only increase the risk of getting infected and increase the chances of long COVID.”
12/5/22 Bloomberg: UK Says Long Covid May Explain Much of Spike in Workforce Inactivity (people not working)Rate https://buff.ly/3P4q3Ep
Long-term sickness accounts for over 60% of the 630,000 rise in workforce inactivity, which measures people who neither have a job nor are looking for one.
12/5/22 PopSci: What patients find at long COVID clinics: rejection, outdated therapies, and unanswered questions https://buff.ly/3P705A9
Excellent article
12/5/22 MIT Review: A new app called Visible aims to help the millions of people living with Long Covid https://buff.ly/3FrlEYU
Low-field MRI showed persistent pulmonary dysfunction in both children and adolescents recovered from COVID-19 and with long COVID.
V/Q match:
81% in controls
62% in recovered from COVID group
60% in Long COVID group
An increase in ventilation, perfusion, and combined defects was related to the time since infection:
81% healthy controls (81±6.1%)
63% for infection <180 days ago (p=.03)
63% for infection 180 to 360 days (p=.03)
41% for infection >360 days ago (P<.001)
12/5/22 Nature: FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2 https://buff.ly/3UxyUzA
Ursodeoxycholic acid (UDCA) , an FXR (farnesoid X receptor) blocker, is an off-patent drug used for liver disease. It downregulates ACE2.
(UDCA (aka Ursodiol or Actigall) has been used for cholestasis of pregnancy.)
This study repurposes UDCA in organoid models, mouse and hamster models and in people and shows that UDCA may block or reduce the severity of COVID infections.
In many US states, such as New York and California, the rate of Covid hospitalizations for seniors now exceeds the BA.5, BA.2 and Delta waves.
This new wave is not getting enough attention.
Importance of boosters and masks.
12/3/22 Nature Medicine: Effect of air pollution on the human immune systemhttps://buff.ly/3EX4eSF
Inhaled particulates from environmental pollutants accumulate in macrophages in lung-associated lymph nodes over years, compromising immune surveillance via direct effects on immune cell function and lymphoid architecture.
These findings reveal the importance of improved air quality to preserve immune health against current and emerging pathogens.
The history of "encephalitis" and Parkinson's symptoms after infection with the Spanish Flu in 1918 parallel symptoms that people with Long COVID have today.
11/22/22 MedRxiV: Susceptibility-Weighted Magnetic Resonance Imaging Highlights Brain Alterations in COVID Recovered Patients https://buff.ly/3uxOgJG
Study by Sapna S. Mishra et al was discussed in a press release from the RSNA meeting.
