People that had SARS-CoV-2 infections may think that they have “natural immunity” and are protected from getting re-infected from this COVID-19 virus. But there are 2 new studies showing evidence that vaccination generates a more vigorous B and T cell (immune memory cells) response than does natural infection. It shows that vaccination is particularly stronger in people with previous SARS-CoV-2 infections.

Researchers evaluated people who were vaccinated with the mRNA vaccine after natural infection and people who were vaccinated but had no prior infection. Memory B cells against SARS CoV-2 were 5-10-fold higher when vaccination followed natural infection than after natural infection or vaccination alone. The most surprising result was that in people who were vaccinated after natural infections, neutralizing antibodies against the beta variant were higher. They were 25 times higher than after vaccines alone and 100 times higher than after natural infection alone. This was amazing since natural infections were almost never with the beta variant and that vaccines don’t target the beta variant spike protein.

Other studies as well have shown similar results. A study in the CDC (Centers for Disease Control and Prevention) Morbidity and Mortality Weekly report shows 2.3 times the number of reinfections with natural immunity compared to breakthrough infections in those who are vaccinated. It is unclear how effective natural infection is against other variants, particularly the Delta variant. This new variant, as well as the lambda variant, may weaken the protection provided by having been previously infected by SARS-CoV-2.

People who have had COVID-19 are advised to be vaccinated. It will very likely offer better protection against symptomatic reinfections, even with the Delta and future variants.

References: Diamond, F. Kavanagh, K. Get vaccinated even if you’ve gotten COVID-19, study suggests. Infection Control Today 2021, Aug 8.

Stamatatos, L et al. mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection. Science 2021 Mar 25; 372: 1413.

Deepti Gurdasani is a British-Indian epidemiologist who is a public researcher at the Queen Mary University of London. This is a part of a thread in which she discusses Long COVID and the implications in the community.

Several studies have put the overall incidence of long COVID between 10-50% of those infected. Scientific consensus is that Long COVID is not just a respiratory disease but a “real” multi-system syndrome that occurs in those infected- predominantly impacting the young. The Office of National Statistics (ONS) data and REACT-1 data compares symptoms post infection among those infected with control groups of those confirmed not to have infection. These are some of the most robust data on Long COVID based on PCR tests through random nationally representative surveys of thousands of people (ONS data 313, 216, and REACT-1 data 508,707 samples).

Here are some highlights:

Most people present with a combination of symptoms and of the 1 million people affected, 2/3rds said it impacted their day-to-day activity. About 400,000 have had persistent symptoms for over 1 year. Sadly this included 9000 children who have been affected for more than a year. Those with the highest risk factors were women, increasing age, smoking, and low income.  There is strong evidence that even those with mild symptoms can have long-term structural brain changes including thinning of grey matter in brain areas related to smell, taste, memory and emotion. The risk of organ dysfunction was 38.9% in those aged 19-49 years. This clearly impacts a large proportion of young people.

So to summarize, long COVID is common- even in young children with mild infection. It usually includes multiple symptoms, that in many, affects day-to-day lives. Remember that children under the age of 12 cannot get vaccinated. Let’s do our part and get fully vaccinated for ourselves, our families (and children) and our community.

Follow the full thread at @dgurdasani1. Other links are Post Acute COVID-19 Syndrome and Survivor Corps

Electronic health records were studied at multiple institutions in the U.K. Researchers estimated the incidence of neurological or psychiatric sequela in 236,000 people with COVID-19 infection. During the 6 month follow-up, 13% were diagnosed for the first time with either a neurological or psychiatric condition with no prior history of these conditions. Another 21% of patients who had prior conditions developed new conditions.

These rates were compared with rates in 342,000 people with influenza and other respiratory tract infections. The incidence of neurological and psychiatric diagnoses were significantly higher in COVID- 19 patients. The most common diagnoses were anxiety (17.4%), psychotic disorder (2.8%), ischemic stroke (2.1%), dementia (0.7%) and intracranial hemorrhage (0.6%).

The most concerning were those whose acute COVID-19 infection caused encephalopathy (defined as delirium or other altered mental states). In those with encephalopathy, the chances of developing mood disorder were 22%, anxiety disorder 22%, ischemic stroke 9%, psychosis 7% and dementia 5%.

This large study demonstrates that various psychiatric and neurological conditions develop with a relatively high incidence in 6 months following acute COVID-19 infection in people with or without previous disorders. We need to look for interventions to address these sequela for post COVID patients. It is not just about surviving this infection, but hoping that you don’t fall into the long-hauler conditions that are so debilitating. One site connecting people with these symptoms that provides support and resources is survivor corps.

It is unknown whether the post COVID mood and anxiety disorders are due to the psychological stress of the illness, or that they are triggered by neuro-inflammation caused by the infection. Regardless of whether it’s the “chicken or the egg”, these symptoms are real and thus far unpredictable as to how long they may last.

Reference: Taquet M et al. Six month neurological and psychiatric outcomes in 236379 survivors of COVID-19; A retrospective cohort study using electronic health records. Lancet Psychiatry 2021 April 8:416.

The question that remains on people’s minds is how effective and long lasting the immunity is from either having had the COVID-19 infection or the vaccine. Now we are starting to get some answers. According to a population-wide study in Australia using data from the SARS-CoV-2 national infection reporting system, the re-infection rate has been low.

Researchers compared the odds of SARS-CoV-2 re-infections of COVID-19 survivors of the first wave (February- April 30, 2020) versus the odds of first infections in the remainder general population (by tracking PCR confirmed infections of both groups) during the second wave (September 1st-November 30, 2020). Out of the almost 15,000 COVID-19 survivors of the first wave and 253,000 infections in the 8.9 million individuals of the remaining general population, only 40 tentative re-infections were recorded.

This shows a relatively low re-infection rate of SARS-CoV-2 in Australia. Assuming that convalescents were exposed to COVID-19 at the same rate as people in the general population during the second wave, reduction in risk for re-infection was >90% which lasted for at least 7 months. Protection against SARS-CoV-2 after natural infection is comparable with the highest estimates on vaccine efficacies. Based on this data, there appears to be considerable protective immunity for at least 7 months after COVID-19 infection and no urgent need for booster vaccinations in COVID-19 convalescents. More well-designed research is needed for improving evidence-based public health decisions and vaccination strategies.

Reference: Pilz S et al. SARS-CoV-2 re-infection risk in Australia. Eur J Clin Invest 2021 April; 51:e13520.

I’ve published many studies linking the gut microbiome to certain health conditions. One of the conditions that has shown significant interest is mood disorders, especially major depressive disorder (MDD). Studies that have linked the gut microbiome to major depressive disorder have been small and have been met with skepticism. A recent study from China may give us more insight into the mechanism by which bacteria in the gut might influence brain chemistry. Researchers collected 311 fecal samples from people with MDD (unmedicated) and from healthy controls. Microbiome researchers were looking for a more precise picture of the organisms present versus a genus level within a batch of microorganisms.

Results found 18 specific bacterial species that were more abundant in those with MDD. They also found 3 specific bacteriophages (viruses that infect bacteria), and 50 fecal metabolites that were significantly associated with MDD verses healthy controls.  The gut bacterial metabolites that correlated with MDD were molecules that are involved in amino acid metabolism. The most important pathways were related to gamma-aminobutyric acid (GABA), phenylalanine, and tryptophan metabolism. These molecules enter the blood from the gut, affect neurochemistry, and have been implicated in MDD.

Researchers point out that GABA, a neurotransmitter in the brain, is made by gut microbes. Fecal levels of GABA and some of its metabolites were decreased in the MDD patients. GABA related microbial genes were also altered in MDD patients suggesting that microbes modulate GABA levels. It is possible that this may dysregulate the function of GABA in the brain, and could lead to depressive symptoms.

Scientists also hypothesize that an increase in certain phyla called Bacteroides could increase inflammation which has been linked to MDD. Also decreased Blautia bacteria which has been shown to have anti-inflammatory effects could contribute to MDD. Other studies have found that when fecal transplanting the entire microbiota of a person with MDD into a germ-free rat, it causes “depressive-like” behaviors in the rat.

Epidemiological researchers have found that many people with irritable bowel syndrome are also depressed. Also those on the autism spectrum tend to have digestive problems, and people with Parkinson’s disease are prone to constipation. Researchers have also noticed people taking antibiotics are more prone to depression compared to those taking antiviral or antifungal medications that leave gut bacteria unharmed.

So what is the mechanism behind the actually pathway from the gut to the brain? Some substances secreted by the gut microbes may infiltrate blood vessels for a direct ride to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Indirect links might also exist. Gut bacteria is so important to proper immune function and studies show that having the wrong mix of microbes can promote inflammation. Microbial products can influence enteroendocrine cells which reside in the lining of the gut and release hormones and other peptides. Some of these cells regulate digestion and control insulin production. They also release the neurotransmitter serotonin which escapes the gut and travels throughout the body. This is where our gut flora might influence weight gain, sleep and how we respond to stress.

It’s crazy to think how much influence our gut has to our mood. Depressed symptoms can influence our diet behavior which can influence our gut characteristics and composition. On the other hand, our bacteria can produce some special metabolites and have a specific pathway that can influence our brain function. More research needs to be done to determine whether any of these pathways are actually causally related to depression. Nutritional psychiatry is a new emerging field that is so exciting. We may be able to target the microbiome through diet (and specific probiotics) which could alleviate some of the symptoms of depression.

This is one more piece of evidence that shows a strong association of microbiome function and mental wellbeing.

Reference: Yang J et al. Landscapes of bacteria and metabolic signatures and their interactions major depressive disorders. Sci Adv 2020 Dec 2; 6:eaba8555.

The Psychbiome

The start of 2021 is all about getting this COVID pandemic under control. Distributing vaccines as quickly as possible and continue to social distance, avoid large gatherings, wearing masks and washing our hands will be an essential part of  developing herd immunity and getting our lives back to what was once normal.

Another part of reducing the presence of SARS-CoV-2 (the virus that causes COVID-19) is to find ways to destroy the virus in the environment before there is an opportunity for it to infect us. Much research has looked at the benefits behind good filtration systems and higher humidity to reduce the virulence of the virus. We are now re-visiting the benefits of ultraviolet light and its ability to kill viruses, bacteria and mold. Scientists have known about the disinfectant capabilities of ultraviolet light for decades. More than a century after Niels Finsen in 1903 won the Nobel prize for discovering that ultraviolet (UV) light could kill germs, UV light started being used in hospital rooms and other public places.

There are 3 types of ultraviolet light based on wavelength. The longest wavelengths are UV-A (315-400nm) and UV-B (280-315nm) which are found in ordinary sunlight. These rays can cause sunburn if you are outside too long without protection. They have limited germ-killing ability. But UV-C light (200-280nm) is part of the ultraviolet spectrum that can inactivate pathogens like bacteria and viruses. Because of their effectiveness, they are incredibly useful for hospitals, senior living centers, fire and police stations, schools, airports, hotels, office buildings and pretty much everywhere. So what’s the problem?

Similar to UV-A and UV-B rays from the sun, UV-C can damage the skin and eyes. You need to follow strict safety guidelines when the products are being operated. Basically, UV lamps should not be run when anyone is nearby. Trained workers should use the right personal protective equipment (PPE) and make sure products are turned off before performing maintenance. So this is maybe not as simple as screwing in a lightbulb. Disinfection with far-UVC lamps remains largely experimental but it may be safer in that it does not cause temporary skin burns and eye damage.

The other main problem is that if a surface is in shadow, it will not be disinfected. In a recently published study, a standard UV-C lamp was placed in the center of a typical hospital room and some places were partly or completely in shadow and did not receive the full dose needed to assure 99.99% disinfection. To address this problem, UVD Robots, a company based in Odense Denmark, developed a UV system that moves around the room autonomously. These robots are now available in 2000 Chinese hospitals and they are being used in more than 50 countries.

A company called Healthe has made progress on far UV-C lighting. They have developed systems that will be affordable for bars, restaurants, and other small businesses while close to eliminating the potential for spreading viruses. An LED version of UV-C may eventually be in our homes and offices. This can stop all viruses and bacteria. Can this finally be the cure for the common cold?? We will have to wait and see, but I can’t imagine a better time to push the technology envelope to help eliminate this pandemic and any future infections.

References: Lindblad M., Tano E., Lindahl C., Huss F. Ultraviolet-C decontamination of a hospital room: amount of UV light needed. Burns. 2019;46(4):842–849. [PubMed] [Google Scholar] [Ref list]

Mauldin, John. The Grip tightens. Jan 15, 2021. Mauldin Economics. https://www.mauldineconomics.com/frontlinethoughts/the-grip-tightens/

Tornberg, B. Using UV Light to kill Viruses Like COVID-19. Dec. 16, 2020. https://insights.regencylighting.com/can-uv-light-kill-viruses-like-covid-19

Mackenzie, D. Ultraviolet Light Fights New Virus. June 27, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319933/

Many of us have had some minor injuries in our lives. Some of them may include sprains, strains, contusions (bruises), whiplash, nonsurgical fractures of ribs or toes. We typically reach for over-the-counter Tylenol (Acetaminophen) or Ibuprofen or other nonsteroidal anti-inflammatory’s (NSAID). But are there dangers to these drugs and which one is best to take?

Several sponsoring organizations reviewed 207 trials that included more than 30,000 participants, most younger than 40 with common musculoskeletal injuries that did not involve the lower back. The authors were evaluating best treatments for pain for these common injuries. The results were the following:

For immediate pain relief, best quality evidence supported the use of acetaminophen alone or combined with oral diclofenac (NSAID) or an opioid. Tramadol alone was not effective. The use of oral or topical NSAID’s alone also was supported by lesser quality evidence. For pain control during the first week after injury, acetaminophen plus opioids, topical or oral NSAID’s and acetaminophen alone were effective. Gastrointestinal side effects were associated primarily with opioids and NSAID’s. Neurological side effects were associated with opioids and the use of ibuprofen and cyclobenzaprine (muscle relaxant) together.

Among non-pharmacologic alternatives, massage and specific acupressure was supported by better evidence than was transcutaneous electrical stimulation (TENS).

What this meta-analysis did not tell you were the risks with using NSAID’s.  These drugs raise the risk for cardiovascular disease, GI bleeding and acute kidney injury (AKI).  This is why they need to be avoided or very closely monitored in people at high risk for heart disease (heart failure, congestive heart disease, hypertension, atrial fib, stroke), chronic kidney disease or gastrointestinal bleeding.

Now let’s look at more specific types of NSAID’s and their safety profile. A Danish study was done comparing diclofenac, ibuprofen, acetaminophen and naproxen and their risk for major cardiovascular (CV) events and gastrointestinal (GI) bleeding. Diclofenac was associated with excess short-term cardiovascular and GI bleeding risks compared with the other NSAID’s or acetaminophen (NEJM JW Gen Med Sep 15 2018 and Ann Rheum Dis 2018; 77: 1137). Also, in a U.K. study, diclofenac but not naproxen was associated with excess risk for myocardial infarction. Several studies have suggested that naproxen might pose the least CV risk, especially among patients with spondyloarthropathies (ankylosing spondylitis and psoriatic arthritis) and osteoarthritis. (NEJM JW Gen Med Aug 1 2006 and BMJ 2006; 332:1302; NEJM JW Gen Med Jul 15 2011 and Circulation 2011; 123:2226). So if an NSAID is going to be used, the best choice would be naproxen.

The best recommendations are the use of topical NSAID’s with or without menthol gel due to its effectiveness and lack of toxicity. Of course a combination of a topical anti-inflammatory and non-pharmacologic options (acupressure, massage, chiropractic, physical therapy, supplements) are the way to go. Avoid using NSAID’s long-term as well as opioids, including Tramadol because of substantial potential harms.

All medications have associated risks. Therapeutic doses for a limited time are considered safe and effective. But prolonged use of NSAID’s not only increases the risk of AKI and chronic kidney disease progression but puts those that are older who have diabetes or hypertension at a higher risk of developing these conditions. A clinical report showed that even young healthy adults with no risk factors of kidney disease had developed AKI due to NSAID use. With the opioid crisis still in the national news, nonnarcotic alternatives for pain control are more popular and effective for the most part. But we need to weigh the risks and benefits, and now we know that there are some NSAID’s (naproxen) and their delivery systems (topical) that are safer and should be the first choice in pain management. Make sure to discuss with your practitioner any over-the-counter medications, herbs, or supplements that you are taking. Not all over-the-counter products are safe or benign to adverse effects.

References: Qaseem A et al. Nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults: A clinical guideline from the American College of Physicians and American Academy of Family Physicians. Ann Intern Med 2020 Aug 18; [e-pub]. (https:/doi.org/10.7326/M19-3602)

Busse JW et al. Management of acute pain from non-low back musculoskeletal injuries: A systematic review and network meta-analysis of randomized trials. Ann Intern Med 2020 Aug 18; [e-pub]. (https:/doi.org/10.7326/M19-3601)

Riva JJ et al. Predictors of prolonged opioid use after initial prescription for acute musculoskeletal injuries in adults: A systematic review and meta-analysis of observational studies. Ann InternMed 2020 Aug 18; [e-pub]. (https:/doi.org/10.7326/M19-3600)

Schmidt M et al. Diclofenac use and cardiovascular risks: Series of nationwide cohort studies. BMJ 2018 Sep 4; 362:k3426. (http://dx.doi.org/10.1136/bmj.k3426)

Apple, A. The unsaid dangers of NSAIDs. Clinician Reviews. Sep/Oct 2018; ExpertQ&A p. 16.

Mariano F, Cogno, C, Giaretta F, et al. urinary protein profiles in ketorolac-associated acute kidney injury in patients undergoing orthopedic day surgery. Int J Nephrol Renovasc Dis. 2017;10:269-274.