Author: Yuezhe Li
SARS-COV-2 is a coronavirus, named so because its glycoprotein envelope resembles crowns. Like other coronaviruses, SARS-COV-2 is an RNA virus, its genetic material is not preserved in DNA molecules, like humans, but in RNA molecules. Once a virus enters a host cell, the virus will hijack host cell machinery to transcribe and translate its RNA to produce more viral particles.
In total, there are seven identified human coronaviruses. One of these viruses causes severe acute respiratory syndrome, more commonly known as SARS. The symptoms of SARS are influenza-like: fever, malaise, pain in muscles, headache, diarrhea, and shivering. The first SARS outbreak was in southern China in 2002. This SARS epidemic swept 26 countries, caused more than 8000 cases and 774 deaths. Middle East respiratory syndrome, known as MERs, is another disease caused by a coronavirus. Although it is not clear where the virus originated from, camels likely played an important role in passing the virus to humans. Since 2012, 2494 cases of MERS have been reported in 27 countries, with 858 patients reported dead.
Like COVID-19, the viruses that cause SARS and MERS can be transmitted between humans. Unlike COVID-19, they caused fewer cases and deaths, and SARS is only transmitted by patients showing symptoms. STAT news predicts the total US death toll will be between 60,000 and 240,000.
To put the Covid-19 death toll into perspective, Covid-19 deaths could rank similarly to cancer and heart disease (see table). What makes it scary is that COVID-19, unlike the other leading causes of death, is highly contagious.
COVID-19: Current treatment
There is no gold-standard treatment for COVID-19. But some treatments have been applied clinically — they are divided into three categories: antivirals, anti-inflammatories, and antibody-based therapy.
Many antiviral drugs hinder viral replication. For example, Lopinavir/ Ritonavir, a drug combination used to treat HIV infection, limits viral replication by inhibiting a protease that is essential for the virus to mature. Unfortunately, an investigation has shown that Lopinavir/ Ritonavir cannot treat COVID-19 effectively. Another antiviral drug, Remdesivir, developed by Gilead to fight Ebola, has been used to treat COVID-19 patients on a compassionate basis, meaning that some severe COVID-19 patients were treated with Remdesivir even though the drug has not received FDA approval. A recent retrospective study analyzed data from these patients, 40 of the 53 patients, 63%, receiving the proper dose of Remdesivir showed improvements. More recently, a leaked video of Phase 3 clinical trials suggests Remdesivir treatment is effective for Covid-19 patients, even though clinical trial data from China remains inconclusive thus far. More recently, a trial carried out by National Institute of Allergy and Infectious Disease seems to cast a positive light on Remdesivir Covid treatment. This trial is so far the most rigorously designed. However, we are still waiting for the data to be released.
Anti-inflammatory treatments focus on alleviating lungs from an overwhelmed immune system. When human bodies are exposed to pathogens, immune cells secrete cytokines, small signaling proteins, into the bloodstream to recruit additional components of the immune system to fight off infections. However, an overwhelmed immune system produces an excessive amount of cytokines, resulting in lung inflammation and fluid buildup. The excess of fluid causes respiratory distress, which may lead to bacterial pneumonia and an increased risk of mortality.
To reduce risk, doctors are focusing on developing methods to decrease cytokine concentrations. One way is to purify the blood. The FDA has granted an emergency authorization for a blood purification device that removes cytokines from the bloodstream. Another way is to target cytokines with antibodies to inactivate them. Some anti-cytokine drugs, such as Actemra, were initially designed to treat cytokine release syndrome and rheumatoid arthritis. Regeneron, Sanofi, and Roche are currently developing drugs in this category to treat COVID-19.
The antibody-based treatment focuses on using antibodies, either from laboratories or from recovered COVID-19 patients, to neutralize coronavirus. One study showed promise in using plasma from recovered patients to treat severely ill patients. Takeda and Regeneron are developing antibody-based therapy for COVID-19.
Developing vaccines against SARS-COV-2
A vaccine is a biological preparation that provides active acquired immunity to a specific infectious disease. Historically, scientists have used live-attenuated or inactivated viruses to make vaccines. Polio vaccines were generated using inactivated poliovirus. Newer methods, including RNA vaccines and using parts of viral particles or proteins as antigens, are implemented to develop vaccines.
So far, there are 115 vaccines in the R&D landscape for Covid-19. Some big pharma companies, such as Sanofi, GSK, J&J, have joined the race. Big pharmaceuticals developing vaccines is considered necessary by many, as these big firms are more likely to have the ability to mass-produce once they find an effective vaccine. Yet, two smaller companies, Moderna Therapeutics and CanSino Biologicals are quite successful in their vaccine development thus far.
Moderna develops RNA vaccines. Their RNA vaccines contain RNA molecules that encode SARS-COV-2’s spike proteins. These spike proteins are essential for the coronavirus to invade human cells. The RNA molecules are encapsulated in lipid nanoparticles. The vaccine is currently in Phase I clinical trial to test its safety. The results of this clinical trial are anticipated by the summer of 2021.
In contrast, CanSino chose to use adenovirus type 5 vector to deliver DNA that encodes spike proteins into cells. An adenovirus type 5 vector is derived from adenovirus, a DNA virus that causes minimal symptoms and does not incorporate their genomes into host cells. Some adenovirus type 5 vectors are excellent vaccine carriers because they are modified to improve immune response. CanSino has previously used similar techniques to develop Ebola vaccines. Currently, their COVID-19 vaccine is in Phase II clinical trial. Additionally, two other vaccines based on live-attenuated or inactivated viruses are approved for clinical trials in China.
Will vaccines be safe?
Phase I of the clinical trials will test for the safety of the newly developed vaccines. Vaccines might have side effects; for example, flu vaccines may cause fever, headache, nausea, etc. Rarely, vaccines might lead to outbreaks of the disease that it is supposed to prevent. The latest incident happened in 2018 in Pakistan, where polio vaccines triggered poliovirus outbreaks. However, it is irrational to avoid vaccination because of unlikely issues. People choke because of eating food. In 2015, 5051 people died because of choking, but so far, I have yet to see people giving up eating to avoid death by choking.
Pandemics do not happen all the time. But its occurrence causes great pain to society. However, pandemics may also produce positive outcomes. For example, the black death in Europe removed around half of the population, leading to a shortage of labor that resulted in wage increases and granting women more freedom to work outside their households. If countries can use the COVID-19 pandemic to push through necessary reforms (e.g., healthcare in the US and banning wild animal trade in China) and raise awareness of good hygiene, the whole society might gain a long-lasting positive impact.
For many scientists, the pandemic has given us time to write. From our home offices and kitchen tables, we are constructing grants, manuscripts, qualifying exams, science communication pieces, and theses. Personally, I love writing; it's my favorite part about being a scientist. But my enthusiasm isn't shared by all of my colleagues and friends. For many, writing is a necessary evil, and regardless if you enjoy or loathe the writing process, afterward comes the true nightmare, editing.
My Master of Science thesis was my first major editing experience. Previous to this writing venture, I was lauded for my writing ability. During my master's program, writing assignments usually landed me good grades and praise. Heck, I was a writing tutor; I knew my stuff. The first draft of my thesis manuscript was written carefully over the course of my final semester. I sent the draft to my PI, expecting to get an email back with minor edits and complements for my well-written work. (Oh, the naivety.)
My first draft was marked up in strikeouts and overflowed with comments. Surprised, I braced myself, read through her comments, and made draft #2. I figured I was done now that I had addressed her edits. Nope, more edits came. Draft #3 was written, and she sent along more edits. I edited five drafts in all and probably would've had more if we hadn't run out of time. The editing was hell, but undeniably, my thesis was astronomically improved due to the monotony of rereading and rewriting the fifty pages over and over.
Since my thesis, I've had numerous writing ventures, and rather than dread the editing phase, I have learned to embrace it, not as a chore I begrudgingly endure, but as an opportunity to sculpt my work as a piece of art. This change in mindset has decreased the anxiety and stress associated with editing. So, I am sharing my tips with you on how to improve your editing attitude.
Editing turns an isolating experience into a collaborative project. Embrace the edits and keep an open mind to colleagues' opinions — happy writing and editing to all those working on projects during this pandemic.
Author: Viola Kajendrakumar
Do other women go through their daily responsibilities and wish they could sit down and have an open conversation about more “taboo” science matters? That’s how I feel about women’s reproductive health. We, as a society, have come so far in encouraging the conversation, but there is still confusion and discomfort for women of all backgrounds. Away from my research laboratory technician duties, I am passionate about having that conversation based on solid scientific facts for those who are navigating and discovering their reproductive health. Women should pay as much attention to their reproductive health as they would for cardiovascular health. Please note that I am in no way a doctor of any sort. I only speak on my own research, observations, and experiences at my job. I have to surround myself with the clinical and research side of reproductive health for my job. Always remember to do your research and consult with medical professionals before taking any steps in your journey. My goal with this piece is to simply demystify and further encourage the fertility conversation.
Fertility and the modern woman
Historically speaking, in Canada, the average age of first pregnancy has changed over the years. Between the 1940s to 1960s, the average age for first pregnancy was between 24-26 years old. In our modern time, the average age of first pregnancy is about 30 years old. In planning for children, there is always a chance of experiencing infertility. Infertility occurs in 4 out of 10 women and 3 out of 10 men and can come from conditions like endometriosis and hormonal imbalances. But one significant consideration is age. Age affects fertility; it will decrease for women after the age of 35. 91% of women can get pregnant by the age of 30; the rate drops to 77% by age 35 and 53% by age 40.
There are medical options for women to consider. At fertility clinics, there are options of having a donor egg or sperm given to a potential parent, or parents can use their own eggs and sperm to produce a baby using technologies like in-vitro fertilization (IVF) or Intra-cytoplasmic sperm injection (ICSI).
At the Fertility Clinic
IVF is the process where the egg is fertilized outside the body with sperm in hopes of pregnancy, a 2-5-week process per cycle. ICSI is also a method of egg fertilization where sperm is injected into the egg with a thin needle (refer to the image above). This procedure is done when sperm quality or count is poor. Undergoing fertility treatment will include consultations, bloodwork, medication, ultrasounds, and more. The preparation continues until the big day, the Ovum Pick-Up (OPU). The OPU is where eggs and sperm are retrieved in hopes of creating a healthy developing embryo. It involves observing the embryo under specific dishes to watch for development every day for 5-7 days. After the OPU, there are additional optional procedures, like pre-genetic screening, to determine various traits of the embryo. For example, pre-genetic testing aneuploidy (PGT-A) checks if there are the correct number of chromosomes. An incorrect number of chromosomes can lead to implantation failure and miscarriage. Embryologists and andrologists work hard towards giving the patient the best embryo possible. From there, the embryo is transferred back into the female patient or surrogate, and a pregnancy test is needed about two weeks after the embryo transfer.
Financial and emotional support
Working in a fertility clinic, I see individuals from all walks of life, hoping to have a child. Going through with IVF, ICSI, or other treatment options can be stressful and expensive, but it doesn’t mean that fertility clinics don’t have resources available to help patients. Fertility clinics may have counselors to support and guide people through this process. Counselors may also set up support groups so patients and non-patients alike can meet and discuss their thoughts and feelings about their fertility journey.
Fertility clinics may also have financial aid options for those who need it, and some governments may have plans set out as well. In Ontario, Canada, there are financial guidelines for the coverage of treatment costs, depending on the treatment, age, and number of cycles. In the United States, the government does not help with the cost of IVF. Sixteen states like New York, Ohio, Texas, Delaware, and Hawaii have passed laws that would require insurers to have an offer for coverage or have coverage of infertility related diagnosis or treatment. California and Texas are the two states that will require insurance companies to offer infertility treatment coverage. Each country has different laws, insurance coverage, support groups, and additional services when it comes to infertility treatment.
Success stories do exist at fertility clinics. Every day, I see the pictures of doctors holding the babies of patients they treated, a constant reminder to prospective patients and staff that this really does work. It is easy to get caught up with figures and numbers when you do research, but when I see the pictures of those babies, it re-energizes my purpose and my passion for communicating about this topic. To bring things back to perspective, the first step is to do your research and consult with medical professionals to know your options. Doctors will do everything they can to help you accomplish your goals and dreams. Remember to be patient and understanding with yourself too. Sometimes, some things are out of your control, and you are doing the absolute best you can. With that, I say good luck to those who are beginning their fertility journey or in the middle of that journey, as you read this. Take care, and stay healthy.
Author: Kerry Silva McPherson
Chloroquine has acquired infamy in the past few weeks and is currently a highly debated pharmaceutical. Chloroquine and hydroxychloroquine are antimalaria drugs and are proposed as a treatment for Covid-19. Sifting through the media’s coverage on chloroquine is frustrating. Unfortunately, many news stories report little to no scientific information about the drug, choosing instead to report it as a political issue. CNN, with a reputation for its democratic bias, reports that Trump’s optimism of the drug is dangerous rhetoric. Fox News, notorious for its right-wing ideology, argues that Democrats are spreading misinformation about chloroquine to push their anti-Trump agenda. Mistrusting the media bias, I did my own investigating using solely reliable sources to sort out the information (and misinformation) of the drug.
Is chloroquine a relatively safe drug?
Yes and no. Patients often experience no side effects, but side effects are possible, including headache, stomach pain, and eye disease. Overdoses can be fatal. Chloroquine can also react with other drugs and should not be used by individuals with psoriasis.
Evidence for chloroquine as Covid-19 treatment
Viruses use our cells as factories to reproduce themselves. They invade our cells, hijack our cell’s machinery (proteins) to replicate itself, and then exit the cell to do it all over again. Antivirals try to stop one of these three steps to block the propagation of the virus.
Hydroxychloroquine and chloroquine have antiviral activity and are currently being investigated for HIV treatment. We aren’t entirely sure why this drug is antiviral, but two theories exist: 1) the drug affects the processing of proteins that the virus needs to invade cells, 2) the drug affects inner-cellular membrane fluidity which impedes the virus’s ability to burst out of the cell. Hydroxychloroquine has anti-Covid-19 efficacy in vitro — science talk for in a test tube. But, testing anti-viral activity in a human is much more complicated.
Anecdotal evidence for hydroxychloroquine is quite prevalent, mostly due to social media. Doctors are claiming they are curing Covid-19 patients with chloroquine. But anecdotal evidence is dangerous; it doesn’t take into account numerous factors that affect disease progression:
So how do we account for the variables that can affect the outcome of the disease? We perform clinical trials, of course.
Clinical trials are designed to discover if the outcome we observe is due to a drug or happenstance. In a nutshell, doctors and scientists assign patients to an experimental group that receives the drug and a group that gets a placebo (no drug). Clinical trials have four stages; three must be passed to earn FDA approval:
Fortunately, hydroxychloroquine and chloroquine clinical trials are repurposing clinical trials. The FDA already approved the use for one disease, and they are checking if hydroxychloroquine and chloroquine will work for Covid. These trials take less time and money since we already have data collected about toxicity. If they work, they will release to market quicker than a novel medicine.
Chloroquine clinical trials are underway!
Two clinical trials yielded promising, yet inconclusive, results. A Chinese study conducted a clinical trial with 62 Covid-19 positive patients; 31 patients were given hydroxychloroquine along with the standard Covid-19 treatment, and 31 patients were given standard treatment only. 25 of 31 patients in the hydroxychloroquine treated group and 17 of 31 patients in the untreated group had improved symptoms. This data suggests the treatment may be beneficial, but statistical analysis does not confirm so. A larger test group is necessary. Furthermore, the presence of the virus after treatment was not evaluated in this study.
A French study tested 36 patients, 20 treated with hydroxychloroquine, and 16 untreated. 70% of treated patients and 12% of untreated patients tested negative for Covid-19 after 6 days of treatment. Unlike the Chinese study, this study has statistically significant results, suggesting that this outcome is not by chance but due to drug efficacy. However, this study is half the size of the Chinese study. Another notable difference is the French patients received both hydroxychloroquine and azithromycin, a drug that showed promise against the Zika virus.
The scientific community is continuing to test chloroquine as a treatment for Covid-19. In biomedical science, reproducibility is imperative. If one science does a test, another scientist should be able to perform the same experiment and get the same answer. The University of Oxford is starting a 10,000 participant study to determine if chloroquine can prevent Covid-19. The US approved emergency use of chloroquine and hydroxychloroquine to hospitalized patients, an endeavor that may save lives and help collect more data. Chinese scientists are planning a stage 3 clinical trial for hydroxychloroquine to take place in June 2020.
Should we expect to see an FDA approval immediately? Probably not, we still have many questions to answer about chloroquine before it’s safe for widespread use. What is the effective dose? Does it prevent the virus, or only treat viral colonization? Since chloroquine is immunosuppressive, will it increase disease spread? If treated with chloroquine, are we still carriers?
Even with these unanswered questions, there is advocacy to bypass FDA regulations and approve chloroquine for Covid-19 treatment and prevention. With the current data, doing so is certainly taking a chance and could set a dangerous precedence. But, perhaps, it's worth the risk.
Author: Monica Mame Soma Nyansa
Have you ever wondered, or are you always wondering if your dietary pattern can affect your mental health? Have you ever heard the phrase "you eat how you wanna feel?"
The answer may be a big "yes," according to the growing body of research literature on nutritional psychiatry. The determining factor of mental health seems complex, but increasing evidence points to a strong association between low-quality diet patterns and worsening of mental health.
For over three decades, researchers have studied the relationship between nutrients and how it affects our mental health. Recently, more studies are being conducted to assess how dietary patterns associate with commonly existing mental disorders such as depression and anxiety.
The brain is one of the largest and most complex parts of the human body. Just as we need energy from food to do physical activities, such as walking and running, the brain requires energy to maintain its structure and function. It consumes 20% of the energy we get from the food we eat. The brain is responsible for our thought process, movement, breathing, and controlling our emotions.
The term mental health is often used on social media, and we all personally know someone who struggles with mental health, yet do we know what it means? Before we move on to talk about the do's and don'ts when it comes to food and your mental health, let's talk a bit about what mental health is and what it isn't.
The basics of metal heath
Mental health problems change the mental wellbeing of a person, specifically with regards to how a person thinks, feels, or behaves, and tends to cause the person distress or difficulty in functioning. A person suffering from mental illness may not look sick physically, especially in mild cases. Mental illness ranges from anxiety and depression to bipolar disorder and schizophrenia. Mental health is our emotional, psychological, and social wellbeing.
The brain runs on electrical signals and chemical messages to do its work. There are hundreds of thousands of chemical reactions that occur in the brain every second. Chemical compounds called neurotransmitters send messages across the brain from one part to the other. Predominant amongst neurotransmitters are serotonin, dopamine, glutamate, and norepinephrine, and some are implicated in mental illnesses.
Listening to your gut?
Mental illnesses such as depression are related to changes in brain chemicals. For example, scientists found that the levels of serotonin are lower in individuals suffering from depression and have developed medications that boost serotonin levels called selective serotonin reuptake inhibitors. Serotonin regulates mood, appetite, sleep, and prevents pain. Serotonin is synthesized from the essential amino acid tryptophan. Most of the body's serotonin is produced outside the brain, specifically in the gastrointestinal (GI) tract, and is believed to serve as a link in the brain-gut connection. This might explain why we feel 'butterflies in our stomach' when nervous because the signals are likely coming from the "second brain" in your gut.
This brain-gut connection is helping researchers understand more about the link between digestion and your mental health. The gut microbiome (microbes and their genetic materials residing in the GI tract) also affects the production of serotonin in the GI tract. The microbiome functions to establish and maintain the intestinal lining. Diet and nutrition change the makeup of our gut microbiota. Using fermented milk products containing probiotics have been reported to affect emotional behavior. Research studying the effect of probiotics and prebiotics on mental health show that they might improve mental health via several mechanisms.
Food-mental health connection
One of the ways we can take care of our mental health, as the literature suggests, is to be more mindful of our diet and nutrition. Healthy dietary patterns that include fruits, vegetables, whole grains, and legumes affect your brain health as well as your mood.
In a study to assess how habitual diet influences the development of commonly existing mental disorders such as depression and anxiety in women, 1046 Australian women between the ages of 20-93 were randomly selected. Using a food frequency questionnaire, a general health questionnaire, and a structured clinical interview, the researchers were able to identify habitual dietary patterns, measure psychological symptoms, and assess the current depressive and anxiety disorders of the women. The dietary pattern was grouped into 'traditional' and 'Western.' A 'traditional' diet consisted of vegetables, fruits, meat, whole grains, and fish, while a 'western' diet was mostly meat pies, processed meats, pizza, chips, hamburgers, white bread, sugar, flavored milk drinks, and beer. The study reports a lower likelihood of depressive and anxiety disorders of women who consumed a traditional diet, while women who consumed a western diet had increased psychological symptoms. The higher the quality of the diet, which was judged by the diet quality score, the lower the psychological symptoms after adjustment for differences in age, socioeconomic factors, education, and physical activity.
Also, on the benefit of fruits and vegetable consumption and its effects on psychological wellbeing, a study by researchers at the University of Otago reported the association of diet rich in fruit and vegetable with increased reported happiness and higher psychological wellbeing, even if it's for a short period of time. The researchers hypothesized that the increased wellbeing might be due to vitamin C and carotenoids, which act as cofactors for dopamine, which boosts motivational states. Or, this correlation could be due to the positive psychological expectancies, such as the perception that consuming fruits and vegetables will make you feel better.
Alcoholic consumption plays a huge part in your mental health
Another major part of our nutrition that could affect our mental health is alcohol. Alcohol is known to have a depressant effect on the brain. Heavy alcohol usage alters brain chemicals and affects its function. Mood disturbances are the commonest effect of alcohol on mental health wellbeing. Epidemiological studies looking at the effect of alcohol dependence on the brain have shown that it could lead to major depression, bipolar disorder, and less likely, anxiety.
The message in a nutshell