Medical Bits – Vol. 4.1: Your Health and Medical News

Medical News: The End of the Pandemic?

The first Pandemic of the XXI century may be dwindling and becoming a more “endemic” condition. Pandemics usually do not just “puff”-dissolve into thin air and end. They tend to fade away and become more endemic in places that have low vaccination rates with seasonal flare-ups. Furthermore, the presence of large animal reservoir will lead to occasional infections into the distant future and an additional reason to be fully immunized. Regardless, barring new more “sneaky” strains, we can all “sense” the end of this long acute phase may be near. “Pandemic Finale” parties are contemplated and many already planned! Mask mandates are coming to an end and normal life and travel plans resuming with common-sense precautions.

This past week, the Centers for Disease Control and Prevention released new guidelines indicating that more than 70% of counties can stop wearing masks indoors. The recommendations direct counties to rely on three measures to assess risk: New Covid-related hospital admissions, proportion of beds occupied and new Coronavirus cases over the prior week.

The official Covid-19 world-wide deaths have almost reached 6 million, but the excess-mortality data may be closer to 20 million according to The Economist.

The discrepancy between “official” and “real” mortality data is due to lack of testing and accurate tallies. Review of excess mortality since the pandemic and counting all deaths, may provide a more accurate “toll”.

We can all breathe a big sigh of relief. Although Coronavirus is not done with humanity, over the course of 2022 the Pandemic is likely to slowly become an occasional nuisance. Despite the big initial failures at containment, the developed world and science have delivered effective and safe vaccines and several treatments to mitigate progressive disease and lethal outcomes for many. The infirm, the frail and the unvaccinated (stubborn in the developed world, and unfortunate in the poorer nations without access to effective immunizations) will remain at risk of poor outcomes.

But we have learned that SARS-CoV2 will continue to lurk in numerous species from where it could “spillover” and infect humans for many years to come, helping to fuel an “endemic” situation. Over the past two years, several reports have warned of this new reality and a recent study has dug deeper into this issue. Early on, we learned that Coronaviruses utilize the ACE2 receptor to gain access into mammalian cells of the upper and lower respiratory tracts.

This molecule is a cell surface receptor highly conserved across vertebrate species (probably due to its role in important physiologic pathways regulating blood pressure, cellular salt and water flows).

The vast majority of the odd 6000 mammal species journeying around the Sun along with humanity are anticipated to have them.

Dr. Han and her collaborators used computational analysis to predict the affinity of SARS-CoV2 to bind to more than 5400 mammal species, expanding our knowledge of “zoonotic capacity” and animals spillover infections.

As we ponder how the Pandemic has affected our lives, not all has been negative. We have all learned a lesson of humility and have become more accepting of uncertainties. I would dare say that our perception of space-time has changed and slowed down. We have grown more contemplative, accepting that our daily plans may be contingent to the hurdles and obstacles that the realities of life may offer us. Many of us have shared more time with our immediate families or have learned to spend more quality time with friends and neighbors and most have learned to treasure the simple pleasures of everyday life. More reading, more introspection, more kindness, more meditation, more exercise and possibly all at a slower speed.

In the midst of this improved spiritual harmony, it is difficult to observe and accept the challenges of the new geopolitical realities manufactured by vicious political “leaders”, spreading calamity, infamy, deception and human strife.

COVID-19 UPDATE

• The average new cases, hospitalizations and deaths, continues to drastically decline. As of February 26, 2022:
  • As indicated above, the CDC released a new system this past week to offer mitigation guidance county-by-county and adjusted weekly based on the number of new total cases, new hospital admissions and percentage of hospital beds occupied by Covid patients in each county weekly.
  • CDC will designate each county’s “Covid Level” as green (low), yellow (medium) and orange (high) with different recommendations for each category. The good news is that at present, only 30% of counties nationally and none in our region are in this category. We are all in the “GREEN” suggesting that school systems and offices will discontinue masking requirements.
  • The total new cases reported in Mgy County, MD, were 69 per 100,000 people and 88/100,000 in DC with a decline of 37.7% in the 7-day moving average of daily new cases in the US.
  • 64.8% of Americans have been fully vaccinated and 76.3% have received at least one dose.
  • The National 7-day moving average of hospitalizations stands at 6060, representing a 30% decline from the prior week.
  • The National 7-day moving average of deaths (1674) decreased by 19% compared to the prior week.
  • The National 7-day Covid-19 PCR positivity rate declined from 8.3% to 5.4%.
  • Case numbers continue to fall throughout the nation. Top states: KY, AL, IH, MN, NH, TN, NM, NC
• CDC study: Transmissibility of Omicron variant
  • Omicron transmission occurred in 8% of households.
  • The attack rate among contacts of index patients varied:
    • Vaccinated with booster within 5 months: 42.7%
    • Vaccinated without booster: 43.6%
    • Unvaccinated index patients: 63.9%
• Maternal Vaccination during pregnancy protects infants against hospitalization for several months after birth.
  • Of 176 infants admitted with COVID, 148 (84%) were born to unvaccinated mothers.
  • Almost 90% of the infants requiring ICU care had unvaccinated mothers.
  • Protection of vaccination greater if administered in the 3^rd trimester.
• Compounds from Propolis and Honey improve symptoms
  • Compounds from propolis and honey appear to interact with target proteins of SARS-CoV-2, interfering with viral entry and RNA replication improving symptoms and decreasing viral clearance time. 15 studies with small sample sizes.

• In Covid-19 pneumonitis, IV vitamin C administration does not improve disease severity or outcomes

  • Analysis of 7 studies did not demonstrate benefit.

• Vaccination reduces transmission

  • Among almost 150,000 tested contacts of 110,000 index patients in Britain, two doses of the Pfizer or A-Z vaccines reduced PCR positivity in contacts as compared with no vaccination.
  • Smaller reduction in transmission of Delta variant.
  • Efficacy decreased over time.

• Does infection with Omicron protect against other strains?
  • This study published by the researchers that identified Omicron from South Africa, suggests that the degree of protection may be related to the vaccination status prior to infection.
  • Vaccinated patients generated much higher levels of anti-Omicron neutralizing antibodies, with a mean titer of 12,197 vs. 4,288 for unvaccinated patients.
  • Priming the immune system with the original Spike protein antigen augments the immune response to a new variant, even one sufficiently diverse such as Omicron.
  • Vaccinated patients generated a volume of neutralizing antibodies against other variants 15 to 150-fold higher than the unvaccinated.
  • Lends additional support to why the vaccinated patients fare much better than the unvaccinated.

• Paxlovid (Nirmatrelvir+Ritonavir) is  effective against COVID-19 hospitalization or death.

  • Paxlovid is an oral antiviral agent that inhibits the Mpro enzyme essential for viral replication.
  • Symptomatic, unvaccinated and high-risk Covid + adults were given Paxlovid or placebo twice daily x 5 days within 3 days of symptom onset.
  • Paxlovid: 5/697 required hospitalization (0.72%) and 0 died.
  • Placebo: 44/682 required hospitalization (6.45%) and 9 died (1.32%).
  • Similar results among those who started therapy within 5 days.
  • 10-fold decrease in viral load at day 5 relative to placebo.
  • Most common side-effect: transient change in taste perception 5%.

COVID-19 Variants and Mutants

Since the first SARS-CoV2 was sequenced in Wuhan on January 10th, 2020, more than 6.6 million SARS-CoV2 genomes have been added to the GISAID database and arranged into “clades” – groupings with a distinct common ancestor.

As Dr. Anthony Fauci and his colleagues from NIH-NIAID explain, over the past two decades humanity encountered four coronavirus epidemics (as discussed in prior “BITS” – SARS 2002-2003 – MERS and now Covid-19). Due to loss of habitat and closer proximity to other mammals and bats in particular, additional coronaviruses are likely to emerge. The scientific community is working on characterizing the global coronavirus universe to use this information in the design of “universal” coronavirus vaccines.

There are several open-source databases tracking SARS-CoV-2 genomic sequences, but the largest and most popular is GISAID.

It was originally conceived in 2006 as a “bank” of genomic data from flu viruses, but the Pandemic has expanded its mission to promote the rapid sharing of data from all influenza and coronaviruses to help researchers understand how viruses evolve and spread during epidemics and pandemics. Scientists are able to upload the genomic sequence of the viral strain present in their communities. Their hard work has led to the sharing of more than 6.6 million coronavirus genome sequences from 172 nations, allowing researchers to track the development and movement of new variants across the planet.

Nextstrain, is another open-source consortium that follows numerous infectious diseases and updated several times weekly, tracking the global spread and flow of variants. You can read and explore more here.

The frequently updated Coronavirus Vaccine Tracker from the NYT is an excellent resource. Another excellent Covid-19 Research update from Nature. Also: National and International Vaccine information.

COVID-19 Q & A: Please, refer to prior Bits.

COVID-19 TREATMENTS

New oral treatments

PAXLOVID – RINOTAVIR

• In a study published this past week (preliminary information released in December 2021) this antiviral reduced the risk of hospitalization or death by almost 90% (within 3-5 days of symptom onset) compared to placebo in non- hospitalized, high-risk adults with COVID-19
• An ongoing second study in standard-risk adults showed a 70% reduction in hospitalization and no deaths in the treated population, compared to placebo.
• In vitro data confirmed that Paxlovid-Ritonavir is a potent inhibitor of the Omicron 3CL protease, retaining robust antiviral activity against Omicron and all variants to date.

Molnupiravir

• Antiviral developed by the Emory Institute for Drug Development, made by Merck and active against influenza and many other RNA viruses. In a trial published in December, 800 mg administered twice daily for 5 days and initiated within 5 days of symptoms onset, decreased the risk of hospitalization or death from 14 to 7% on interim analysis but from a more modest 9.7% to a 6.8% with an absolute difference of 3% on final analysis.

COVID-19 Monoclonal Antibodies

Monoclonal antibodies are expensive engineered human monoclonal antibodies specific against the Spike protein of SARS-CoV2 and have been investigated to prevent progression of mild-moderate Covid-19 infection in ambulatory, UNVACCINATED patients. Since the approval of Paxlovid, the use of these agents is anticipated to disappear.

There are many formulations and some trials have shown lower viral loads, and modestly lower rates of progression of disease. The FDA granted Emergency Use Authorization for some of them.

At present, the only that retains efficacy is Sotrovimab. Bamlanivimab is ineffective against the Delta or Omicron variants. Banlanivimab – Etesevimab are no longer effective against new variants. Casirivimab-Imdevimab combination retained efficacy against Delta but less effective against Omicron.

Sotrovimab, which neutralizes most sarbecoviruses is effective against Omicron and the 500 mg may be administered as an infusion or intramuscular.

COVID-19 – PROVEN THERAPY

It is important to emphasize what is effective and what is not.

While working in ICU, I have witnessed expensive and potentially deleterious and invasive treatments sometimes imposed by physicians and frequently demanded by family members, despite the lack of evidence for benefit or possible harm. The Hippocratic oath reminds us: “Primum non Nocere”.

The National Institutes of Health has a wonderful resource available to all which summarizes the evidence in their NIH Covid-Treatment Guidelines, which grows steadily and now stands at over 350 pages. Another excellent review is provided by Open Critical Care (also in Spanish).

In summary:

• Use Dexamethasone at 6 mg daily for 10 days after diagnosis of COVID- related pneumonitis.
• Remdesivir may help patients requiring oxygen, but benefit is marginal.
• A new Remdesivir oral formulation may be more effective if used earlier and before hospitalization.
• In hospitalized patients, use IV Tocilizumab.
• If Tocilizumab not available use Sarilumab IV
• Use Sotrovimab in similar Likely more effective w Omicron.
• Azithromycin and Ceftriaxone have no benefit
• Convalescent plasma – Ab from previously infected patients: No benefit
• Plasma exchange – No benefit, costly and invasive.
• Insufficient evidence. Do not use
• Interleukin 1 – 6 Insufficient evidence. Do not use.
• Ivermectin. NO evidence. Do not use. Now we know that it may be beneficial in lower- and middle-income nations where intestinal parasites are more prevalent, since the regular use of dexamethasone as part of the treatment may promote parasitic hyper-infection and infestation with bad pulmonary consequences.
• Janus Kinase Inhibitor Possibly beneficial in the right setting.
• Anticoagulants. Only in prophylactic doses.

YOUR HEALTH: Congestive Heart Failure

Heart Failure is a very common disorder whereby the heart cannot pump blood to the body to meet its demands, or can do so at the cost of high intracardiac filling pressures, which leads to progressive problems such as fatigue, malaise, breathlessness with exertion and decreased exercise capacity.

Symptoms:

The normal heart has an ejection fraction (EF) of 65-70% of the total diastolic volume (it is able to eject or pump this proportion of the total blood returning to the left ventricular chamber through a cardiac cycle.

Among patients with Heart Failure:

• >50% of patients have preserved pump function (heart failure with preserved ejection fraction – HFpEF) and the prevalence of this group is rising.
• 30-40% have reduced pump function with an “ejection fraction” (EF) < 40%
• 10-20% have an Ejection Fraction (EF) of 40-50%.

The proportion of patients with Heart Failure and preserved Ejection Fraction or Diastolic Dysfunction Heart Failure has been steadily increasing over the past few decades, and it is the dominant form among older adults.

Risk factors include hypertension, obesity, diabetes, sleep apnea, anemia, kidney disease and aging, but coronary artery disease and valvular heart dysfunction should also be considered. The prevalence is higher in women (as their longevity is greater) and the best test to determine diastolic ventricular features is Echocardiography.

The most common presenting complaint is breathlessness with activity, and one of the reasons we see this condition at least daily in our clinical practice. Physical activity demands an increase in cardiac output to the tissues of our body. As exercise increases, the rising blood return and heart rate, leads to elevation in filling pressures within the left ventricle and those pressures get transmitted along to the left atrium and consequently to the pulmonary veins which causes pulmonary capillary engorgement and increased vascular stiffness, precipitating breathlessness and leading to cessation of exercise or activity.

Echocardiography helps determine if we are dealing with Diastolic Dysfunction heart failure (Heart Failure with preserved Ejection Fraction – HFpEF) or Systolic Dysfunction heart failure or other conditions such as hypertrophic, restrictive or dilated cardiomyopathies, valvular diseases or other conditions.

Treatments:

Left-sided heart failure (Heart Failure with low Ejection Fraction)

 The following medicines are commonly used to treat heart failure with reduced ejection fraction.

• Medicines to remove extra sodium and fluid from your body, including diuretics and aldosterone antagonists (such as spironolactone). These medicines lower the amount of blood that the heart must pump. Very high doses of diuretics may cause low blood pressure, kidney disease, and worsening heart failure symptoms.
• Medicine to relax your blood vessels to make it easier for your heart to pump blood. Examples include angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Possible side effects include cough, low blood pressure, and short-term reduced kidney function.
• Medicines to slow your heart rate, such as beta blockers and ivabradine. These medicines make it easier for your heart to pump blood and can help prevent long-term heart failure from getting worse.
• Newer medications. Two new groups of medicines approved to lower blood sugar in patients with diabetes, sodium-glucose cotransporter-2 (SGLT-2) inhibitors such as dapagliflozin and empagliflozin and glucagon-like peptide (GLP) agonists such as semaglutide or dulaglutide, may also reduce heart failure hospitalizations.
• Digoxin to make your heart beat stronger and pump more blood. This medicine is mostly used to treat serious heart failure when other medicines do not help improve your symptoms. Side effects may include digestive problems, confusion, and vision problems.

Currently, the main treatment for heart failure with preserved ejection fraction are diuretics. SGLT-2 inhibitors Dapagliflozin and Empagliflozin appear very promising and effective on recent studies. Blood pressure medicines may help relieve your symptoms as well.

Right-sided heart failure

If you have right-sided heart failure, you me need medicines to remove extra sodium and fluid from your body, and medicines to relax the blood vessels.

Procedures and surgeries

If your heart failure with reduced ejection fraction worsens, you may need one of the following medical devices:

• A biventricular pacemaker (also called cardiac resynchronization therapy). This can help both sides of your heart contract at the same time to relieve your symptoms.
• A mechanical heart pump, such as a ventricular assist device or a total artificial heart. You may use a heart pump until you have surgery or as a long-term treatment.
• An implantable cardioverter defibrillator (ICD). An ICD checks your heart rate and uses electrical pulses to correct irregular heart rhythms that can cause sudden cardiac arrest.

You may also need heart surgery to repair a congenital heart defect or damage to your heart. If your heart failure is life-threatening and other treatments have not worked, you may need a heart transplant.

For people with heart failure and preserved ejection fraction, there are no currently approved devices or procedures to improve symptoms. Researchers are continuing to study possible treatments.

The best way to delay or avoid progression of diastolic dysfunction is to exercise, keep your ideal body weight, treat sleep apnea if present, correct arrythmias and keep your blood pressure as low as possible.

Diastolic Dysfunction is part of aging, and we will all eventually encounter the condition. The best way to delay its consequences are enumerated above. I cannot emphasize enough the importance of those simple recommendations!

If you have 7 minutes daily, you can start to improve your fitness right now with the Scientific 7- Minute Workout.

Get the app on your phone!

11 more minutes will get you in shape!

For core strength, try this 9-minute routine!

AND START EXPLORING AND PRACTICING MINDFULNESS! It will also

help you lower your blood pressure and levels of stress. It will raise pain threshold and your overall sense of well-being.

THERE ARE MULTIPLE RESOURCES ON THE WEB.

 Let’s all remember that the only certainty in life, is death and the only fountains of youth proven by science and experience are love, exercise, laughter, humor and a positive attitude!

OFFICE UPDATES

• Simran Singh, Samantha Morales, Sarah Molinari and Fiona MacNair are our capable and affable Medical Assistants and will continue to assist all of you with your healthcare need (before all move on to Medical School).
• Simran Singh at simrans@chevychasepulmonary.com is my personal assistant.
• I will be away for Spring-break from April 10th-17th, but never far from email and phone. My partners will cover emergencies in my absence as usual.

Wishing you a Happy Spring and a nice Pandemic Finale Celebration!

Carlos E. Picone, MD

5215 Loughboro Rd NW, Suite 400

Washington, DC 20016

301-656-7374

cpicone@chevychasepulmonary.com