Here is a quick summary of this week’s COVID news.
XBB.1.5
The XBB.1.5 variant doubled its reach across the U.S. this week and is now responsible for 75% of cases in the Northeastern U.S. The only other variant to have such a rapid rise in cases was the original Omicron (BA.1) last year. Virus levels in wastewater across the states are high and we are seeing an increase in hospitalizations especially in people over age 70. Monoclonal antibody drugs do not work against XBB.1.5, but it appears that convalescent plasma from people who were vaccinated and then had a breakthrough infection with Omicron can fight XBB.1.5.
China
China went from a zero-COVID policy to an anything goes policy and it is a humanitarian crisis. Katelyn Jetelina’s post this week explains the situation well. China is not reporting cases or variants, but it appears that BF.7 is the main variant infecting people there. Starting January 5th, travelers from China, Hong Kong and Macau will need a negative COVID test within 48 hours of travel. Japan is having another BA.5 wave and Hong Kong has a very high case rate probably related to China’s high cases.
Medications:
Convalescent plasma from breakthrough Omicron infections can help fight XBB.1.5, BQ.1(1), and other variants with immune escape. This week, a study in people with a high BMI who were at high risk for severe disease, showed that if they took Metformin for two weeks during their acute COVID infection, their risk of Long COVID decreased by 42%.
A study from Shanghai shows that an oral analogue of the antiviral Remdesivir called VV116 worked as well as Paxlovid to reduce the length of acute COVID infection. No participants in either group (VV116 vs. Paxlovid) died or had had progression to severe Covid-19 by day 28. This could be very helpful as Paxlovid has many more drug interactions than Remdesivir.
Molnupiravir was found not to decrease severe disease or death, and Molnupiravir (Lageviro) leads to the rapid accrual of hundreds of SARS-CoV-2 mutations in immunocompromised patients via its mechanism of action. Molnupiravir should be recalled.
Long COVID:
As mentioned above, Metformin taken during acute infection reduced the risk of Long COVID in high risk people by 42%. Dr. Tom Frieden, former CDC director, wrote a helpful review of Long COVID (PASC) symptoms, prevalence, and ways to avoid getting it. There was also a literature review with recommendations for Postural Orthostatic Tachycardia Syndrome (POTS) and pregnancy from Dr. Svetlana Blitshteyn et al.
Long COVID that has ME/CFS symptoms are thought to possibly be from a reactivation of latent viruses like EBV. Blood tests for reactivated viruses did not show them present. But, saliva tests do show reactivation of EBV, HHV-6 and HERV-K in people with ME/CFS and Long COVID.
“SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples).”
Finally, a Twitter thread from Bob Wachter MD shows how he calculates if he should go to an indoor event. A case rate of 5 to 10 cases per 100,000 people in a community is Bob Wachter’s cut off for indoor dining or small gatherings without masks. If the community level is higher than that, he layers in protections that each cut risks by about 50% by 1) testing the group before meeting and 2) by increasing the ventilation if the event cannot be moved outdoors. A bivalent booster within 2 months also will reduce the risk by 50% per Dr. Wachter. If the case rate is still too high with these measures, he simply won’t go to the indoor event.
12/30/22 Older people in the Emergency Dept. after being visited by a sick family member.
12/29/22 With waning immunity, 25% of the population over age 65, and not enough boosters, Japan is seeing the highest death rate during a second COVID wave with BA.5 per Eric Topol.
Among adults aged ≥65 years, many of whom have multiple comorbid conditions and who are at highest risk of severe COVID-19, recent bivalent booster vaccination offers >80% protection against COVID-19 hospitalization.
In the US, only 16% of adults age 18+ and only 36% of adults age 65+ have received a bivalent booster.
12/29/22 Katelyn Jetelina: COVID in China, the U.S., and everything in-between https://buff.ly/3G1KZb0
12/29/22 NEJM: VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19 https://buff.ly/3jG3p9T
VV116 is an oral analogue of Remdesivir.
Phase 3 trial of VV116 during an Omicron outbreak in Shanghai and 75.7% of the participants had been vaccinated against SARS-CoV-2.
Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir–ritonavir (Paxlovid) with respect to the time to sustained clinical recovery, with fewer safety concerns.
VV116 was better than or similar to nirmatrelvir–ritonavir with respect to the time to sustained symptom resolution and to a first negative SARS-CoV-2 test.
12/19/22 Dr. Tom Frieden (Former CDC director): Understanding Long Covidhttps://buff.ly/3WVTLOF
Review of Long COVID (PASC) symptoms, prevalence, and ways to avoid getting it.
Physical exhaustion, “brain fog,” and shortness of breath are the three most common symptoms of long Covid, and how they tend to cluster based on sequence of onset and by age.
Because so many people have gotten a COVID infection, even a low rate of long Covid following infection translates into a large number of people suffering.
12/28/22 NPR: U.S. will require travelers from China, Hong Kong and Macau to show negative COVID test before flight https://buff.ly/3YYf7N5
Starting January 5th, passengers from China will need a negative COVID test (PCR or monitored antigen test) within 48 hours of departure.
12/23/22 MedRxiV: On the role of different age groups in propagating Omicron epidemics in France https://buff.ly/3Q5m2Ae
Children aged 10-19y played the greatest relative role in propagating the Omicron variant in France, particularly when schools were open, followed by children aged 0-9y and adults aged 20-29y, as well as adults aged 30-49y.
Persons aged over 50y played a more limited role in propagating Omicron infection in the community.
Additional efforts are needed to increase vaccination coverage in children aged 10-19y, as well as younger children and young adults to mitigate Omicron epidemics in the community.
XBB.1.5
12/27/22 XBB.1.5 is taking over very quickly. It is dominant in the northeastern U.S. as of last Friday.
In New York State, XBB evolved further to XBB.1.5, with 3 new mutations. A steep rise of hospitalizations in New York coincides with the arrival and growth of XBB.1.5.
12/16/22 BioRxiV: Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ.1.1 and XBB.1https://buff.ly/3Z0k5Jp
Recent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies.
Boosted VaxCCP (polyclonal antibodies from individuals who are both vaccinated and recently recovered from an Omicron infection within 6 months) represents a robust, variant-resilient, passive immunotherapy against the new Omicron BQ.1.1, XBB.1 and BF.7 variants.
Monoclonal antibody drugs no longer work against the newest COVID variants.
But, plasma from vaccinated people who got an Omicron breakthrough infection contains polyclonal antibodies that potently neutralize BQ.1.1, XBB.1 and BF.7 variants.
12/27/22
3/1/22 Neurology (Avindra Nath): Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVIDhttps://buff.ly/3YTb056
Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset.
Various evidence suggested infection-triggered immune dysregulation as a common mechanism.
12/26/22 Forbes: COVID isn't just infecting you—it could be reactivating viruses that have been dormant in your body for years https://buff.ly/3WFh92A
Herpes viruses like EBV (Epstein-Barr virus which causes mononucleosis) can reactivate and cause myalgic encephalomyelitis/Chronic Fatigue Syndrome (MECFS) symptoms. The nebulous condition with no definitive cause can lead to symptoms like fatigue, brain fog, dizziness when moving, and unrefreshing sleep.
There are no antiviral treatments for EBV reactivation.
“If a patient doesn’t respond to treatment, maybe we’ll test for other things,” he said.
There is a strong possibility that COVID is weakening the immune systems of “a good deal of people,” Galiasatos added. “I do think the immunodeficiency—when it’s there, it’s transient—allows those viruses to reemerge,” he said.
10/20/22 Frontiers in Immunology: Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome (MECFS) https://buff.ly/3I10umf
SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of EBV, HHV6, and HERV-K, as detected by antibody fingerprints locally in saliva but not seen in blood or plasma.
Long COVID, PASC, ME/CFS
12/26/22 BioRxiV (Yale- Moriyama, Iwasaki): SARS-CoV-2 Omicron subvariants evolved to promote further escape from MHC-I recognition https://buff.ly/3vjxA9k
In addition to escape from neutralizing antibodies, the success of Omicron subvariants to cause breakthrough infection and reinfection may in part be due to its optimized evasion from T cell recognition by suppressing MHC I expression.
Why do we get more breakthrough infections from Omicron?
Omicron subvariants escape neutralizing antibodies more, but they also escape MHC-I recognition by cytotoxic T cells better. https://buff.ly/3vjxA9k
12/24/22 MedRxiV (U Minnesota): Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up. https://buff.ly/3Vt5Mtz
Results from a blinded randomized clinical trial of 1,125 adults age 30 to 85 with overweight or obesity, fewer than 7 days of symptoms, and enrolled within three days of a documented SARS-CoV-2 infection.
42% relative decrease in the incidence of Long Covid when patients were treated with metformin during the acute Covid infection.
Immediate release metformin titrated over 6 days to 1,500mg per day given for 14 days total.
To aid tolerability, the metformin dose was titrated up, starting at 500 mg on day 1, then 500 mg twice daily for 4 days; then 500 mg mornings and 1000 mg evening through 14 days.
Long COVID in controls: 10.6%, Long COVID in metformin treated: 6.3%
Ivermectin and Fluvoxamine did not help.
Metformin has a low risk of hypoglycemia but does exert significant gastrointestinal side effects, especially diarrhea, nausea, and vomiting.
12/24/22 Int J of Women's Health: Postural orthostatic tachycardia syndrome (POTS) and pregnancy: literature review, recommendations https://buff.ly/3hTJkMK
POTS, a common autonomic disorder, is not a contraindication to pregnancy, but may necessitate special considerations, monitoring and management via a multi-disciplinary team, including an obstetrician, a maternal-fetal medicine specialist and a clinician with knowledge of POTS and its various comorbidities
each case carries a ~5% chance of symptomatic Long Covid
Increased risk of long-term odds of death, heart attack, stroke, & dementia.
Not to infect others.
In general, Dr. Wachter:
Doesn’t mask outdoors.
Always wears masks in crowded spaces like an airplane.
He checks:
Case rates (knowing that they are an underestimation)
Wastewater levels of virus
Asymptomatic positive rates
Case rate of <5-10 cases/100K/day in a community is Bob Wachter’s cut off for indoor dining or small gatherings without masks.
If the community level is higher than that, he layers in protections that each cut risks by about 50%:
Test the group before meeting.
Increase ventilation if you can’t move event outdoors.
Bivalent booster within 2 months.
Cases at <5-10/100K/day tends to correlate w/ asymptomatic test positivity rates of <1%, meaning <1 in 100 chance that my food server or fellow poker player has Covid, & thus a <10% chance that in a group of 10 any one person is positive.
Layering protection (Swiss cheese model)
Thread includes examples using 10 cases/100K/day as a threshold using his 50% Rule:
Dr Koralnik, professor of Neurology and chief of Neuro-infectious Disease and Global Neurology at the Feinberg School of Medicine at Northwestern Medicine discusses Long COVID and neurologic symptoms.
“Unfortunately, a lot of people who come to our clinic tell us that they're not being taken seriously by the medical establishment. Nonspecific symptoms have been chalked up to stress (especially during a pandemic) or are just considered psychosomatic issues, which is not the case.
“We give patients a validated questionnaire — the Patient-Reported Outcome Measure Information System (PROMIS), asking about quality of life, self-perceived cognitive ability, fatigue, anxiety, depression, and sleep disturbances. Quality of life among long-COVID patients is worse than it is among the US normative population.”
Debilitating brain fog and cognitive dysfunction that impedes their daily activities. Long COVID is real, unfortunately, and it can lead to severely impaired quality of life as well as economic hardship because these patients are not able to function the way they were able to before COVID.
Many Long COVID patients who have Long COVID after a mild infection are women in their 40s.
MRIs are usually normal. They don't do lumbar puncture because they are usually normal as well.
Molnupiravir should be recalled. It doesn’t decrease hospitalizations or deaths and causes mutations in the virus which can cause new variants.
12/24/22 Lancet: Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomized controlled trial https://buff.ly/3WIEpgb
Molnupiravir does not decrease COVID hospitalizations or death in a large randomized trial (N>25,000 participants, mean age 57, 99% vaccinated).
Although the time to recovery was shortened, Molnupiravir works by making viral mutations which could be dangerous.
12/22/22 MedRxiV: Antiviral treatment Molnupiravir (Lageviro) leads to the rapid accrual of hundreds of SARS-CoV-2 mutations in immunocompromised patients https://buff.ly/3VrpJ4g
"Our study demonstrates that this commonly used antiviral can supercharge viral evolution in immunocompromised patients, potentially generating new variants and prolonging the pandemic."
China:
12/25/22 CNN: China's top health body stops publishing daily Covid case figures as infections soar https://buff.ly/3Gjungn
China no longer officially tallies its total number of infections, after authorities shut down their nationwide network of PCR testing booths and said they would stop gathering data on asymptomatic cases.
Rapid antigen tests do not need to be reported if positive.
Almost 250 million people in China may have caught Covid-19 in the first 20 days of December, according to an internal estimate from the nation’s top health officials
12/26/22 CTV news, Canada: Long COVID: Could mono virus (EBV) or fat cells be playing roles? https://buff.ly/3jtMKpO
"Stanford University researchers are among those who have found evidence that the coronavirus can infect fat cells. In a recent study, they found the virus and signs of inflammation in fat tissue taken from people who had died from COVID.
Lab tests showed that the virus can reproduce in fat tissue. That raises the possibility that fat tissue could serve as a "reservoir," potentially fueling long COVID."
The research is preliminary, said Dr. Catherine Blish, a Stanford infectious diseases professor and a senior author of the study."
11/1/22 Obesity Surgery: Lingering SARS-CoV-2 in Gastric and Gallbladder Tissues of Patients with Previous COVID-19 Infection Undergoing Bariatric Surgeryhttps://buff.ly/3vqCD7W
n = 80 patients undergoing bariatric surgery
Gastric specimens from 26 (32.5%) patients and 4 (100%) cholecystectomy specimens showed positive cytoplasmic staining for the anti-SARS-CoV-2 nucleocapsid protein in surface mucosal epithelial cells.
The median time between initial COVID-19 infection and surgery was 274 and 380 days in the positive and negative staining groups, respectively.
Someone in Lakewood dons a unicorn costume while snow blowing after the big storm. (photo: u/cosmicdicer)
Thank you for your newsletter and all of the info you share. I've learned so much from you! (Sometimes there are terms that are over my head, but I google them and get A-Ha moments.) Wishing you all the best for a happy, successful, and healthy 2023. Thank you again!
Thank you for your newsletter and all of the info you share. I've learned so much from you! (Sometimes there are terms that are over my head, but I google them and get A-Ha moments.) Wishing you all the best for a happy, successful, and healthy 2023. Thank you again!