Categories
Innovative Solutions

Holiday Bubble

Christmas is 14 days away and Kwanzaa is 16 days away. (Happy Hannukah!)

If you plan to see family, today’s the day to start your holiday bubble. Here’s a calendar to follow.

The safest thing for you and your family is to skip the holidays in person. This is not an endorsement to get together. But we know, way too well, that abstinence is not an effective approach for the public either. So, epidemiologists need to arm people with tools to reduce risk. Here is one way to be smart.

Love, YLE

Categories
Antibodies Drug treatments Innovative Solutions

Plasma and COVID-19

What is plasma? When people get sick, immune systems generate antibodies to fight the disease. Those antibodies (especially among very sick patients) float in people’s blood plasma — the liquid component of blood. 

How can it be used? Plasma from a recovered person (who was very sick) can be injected into a currently sick person. The antibodies fight the virus early until the patient’s own immune system has enough to fight. Plasma has been used to fight epidemics, like the 1918 Spanish Flu, diphtheria epidemic in the 1920s, and the Ebola outbreak in 2014.

Plasma to fight COVID19? This has slowly come to the surface in the 2020. Here’s a timeline…

January 20-March 25: China treated 5 COVID19 patients with plasma. It worked.

March 24: FDA issued guidelines for using plasma in emergency investigations of new drug protocols (called eIND)

March 31: COVID19 plasma was used for the first time in the U.S. (Houston Methodist). It worked (for the most part).

May 14: A meta-analysis was published. Only 8 plasma studies had been conducted thus far and they were mainly “case studies” (basically a story with what happened with a few patients). There were no randomized control trials (RCT). The conclusion? We have no idea if plasma works because we don’t have enough evidence.

July 10: An updated meta-analysis was published pooling all studies on plasma. There were 20 published studies by now, but only 1 RCT. Their conclusion? We have no idea if plasma works because we don’t have enough evidence.

August 13: Mayo Clinic released a study with over 35,000 patients. They found that plasma helped with patient outcomes (like less death). BUT this was not peer-reviewed, which is important because this study has some serious limitations. Most importantly, there was no placebo group. The specific role of plasma is unclear because all patients received at least one additional medicine at the same time. This makes it difficult to know whether it was the plasma or the drug that helped the patients.

August 23: Nonetheless, the FDA allowed emergency authorization for doctors to treat Covid-19 using plasma

August 25: Three randomized control trials had concluded (one in China, Netherlands, and Iraq). The Chinese study was stopped early because they couldn’t get enough people to enroll. The Netherlands study was stopped early because most of the participants already had antibodies. The Iraq study was too small to see whether plasma helped.

Today: From my count, there are 98 ongoing studies evaluating plasma, of which 50 are randomized. We don’t have the results of these studies yet.

But… if it’s worked for other pandemics, why not just use plasma for everyone? Safety. 14 of the current 20 studies have reported serious adverse events with plasma. In one study, scientists reported that 4 deaths were directly linked to plasma infusion (out of 15 deaths total). It’s important we get this science right.

So, now what? We wait. We NEED rigorous studies to conclude. These are very difficult to conduct, though, because we need enough people to donate plasma AND we need enough people to agree to be infused. But, thanks to the perseverance of many scientists and brave community members, results should be coming out soon. TBD.

Love, YLE

First plasma treatment in China: https://jamanetwork.com/journals/jama/fullarticle/2763983

May study: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600/full

July study: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600.pub2/epdf/full

Mayo clinic study: https://www.medrxiv.org/content/10.1101/2020.08.12.20169359v1

FDA August announcement: https://www.fda.gov/media/141480/download

Categories
Antibodies Children GA Innovative Solutions National changes Social Distancing

Update

Buckle up. In true 2020 fashion, several scientific developments popped up while I was on vacation…

1. Teachers’ and parents’ risk for severe COVID19

• 2.95 million teachers (50.6%) have risk factors for severe COVID19. This is mostly driven by obesity or heart conditions

• 37.7 million adults living with school-aged children (54%) have risk factors for severe COVID19. This is mostly driven by age, heart problems, or diabetes

• Risk is the same for those living with younger children compared to older children.

• So… what? “Without adequate safeguards, reopening schools could put millions of vulnerable adults at risk for severe COVID-19 illness”.

2. First global case of COVID19 re-infection

• In March, a 33-year-old man in Hong Kong was infected with COVID19. He had mild symptoms.

• Last week, he was infected with a different COVID19 strain and tested positive upon his arrival to Hong Kong from Spain. He is asymptomatic.

So…what?

• After the first infection, he had no antibodies. But we already know that not everyone gets antibodies (especially mild symptoms; see my previous posts)

• After the second infection, he did produce antibodies. This is consistent with the immune system building stronger with each exposure to a pathogen, so second and third exposures may increase the chances to develop antibodies.

• In the words of immunologist Dr. Akiko Iwasaki, “This is no cause for alarm – this is a textbook example of how immunity should work.”

• Vaccination (and social distancing and masking) needs to be considered among people that have already been infected with COVID19

3. Wearing masks works (I feel like this is no duh, but in case you needed more ammunition)

• US states with high mask wearing compliance were more likely to have a R(t) less than 1 (control of community transmission)

• Mask wearing was higher among women, elderly, non-white or Hispanic, lower income people

• Mask wearing is highest along the coasts, southern border, and urban areas (see Figure)

• Mask wearing is even more important when (or if) social distancing is relaxed

4. Super-spreaders played a key role in MERS and Ebola. Their role in COVID19 was just revealed in Georgia:

• 2% of the population is responsible for 20% of infections• Super-spreaders likely explain major outbreaks in rural areas • Younger people are more likely to be super-spreaders

Love, YLE

Teacher: https://www.acpjournals.org/doi/10.7326/M20-5413?fbclid=IwAR0UWoRjCPDsrFEG1PDe5KqpmJu_qhADXOfPVQ_BYB0w2Y9NVYkT74DVl6U

Reinfection: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1275/5897019

Masks: https://www.medrxiv.org/content/10.1101/2020.08.23.20078964v1.full.pdf

Superspreaders: https://www.medrxiv.org/content/10.1101/2020.06.20.20130476v3.full.pdf

Categories
Deaths Hospitalizations Innovative Solutions

Meta-Analysis: COVID19 drug treatment

Alright, now we are talking! I knew this had to be coming out soon… A meta-analysis on COVID19 drug treatments (yes, including hydroxychloroquine).

What is a meta-analysis? One massive study that combines the results of ALL previous studies. This is a really powerful tool because it takes into account whether past studies were “strong” or “weak”. It also takes into account different populations (think different genes, different environments, different cultures, different confounders). Basically, this allows us to get an overarching idea of what is working and what is not working.

Why aren’t more meta-analyses done? It takes a LOT of time to do this. Typically years (sorry graduate students). We also need “enough” studies on one topic so we can combine them.

Fortunately, with the onslaught of COVID19 publications, we already have enough COVID19 drug treatment studies that we can do a meta-analysis.

This was published over the weekend. These scientists combined ALL randomized control studies (the gold standard) on COVID19 drug treatments. They looked at which drugs impact mortality, ventilation use, and symptoms by combining 23 studies. 

What did they find?

  1. Glucocorticoids was the ONLY intervention that reduced mortality and the need for mechanical ventilation
  2. The effects of hydroxychloroquine, remdesivir, and lopinavir-ritonavir is highly uncertain because studies were small, have serious imprecision, and have concerning limitations (like lack of double-blinding)

Considering this, though, authors concluded…

  • Hydroxychloroquine, remdesivir, and lopinavir-ritonavir MIGHT reduce symptom duration
  • Hydroxychloroquine might INCREASE the risk of adverse events when coupled with other interventions
  • Remdesivir might NOT increase the risk of adverse events

Translation? We need more studies. Specifically ones with more than 100 patients. Not very exciting, I know, but a stark reality of science. The science is not strong enough to say that, as a population, we can use anything but glucocorticoids to improve COVID19.

Next Steps? The even cooler thing about this publication is that the scientists created a “living” meta-analysis. I’ve never seen this before. As new studies come in, this analysis will be automatically adjusted each time. Giving us a better and better picture of COVID19 drug treatments in real-time. 9 studies are already in the queue to be included in the next update. Check out the study link for their visualization.

Love, your local epidemiologist

Data source: Table and meta-analysis conducted by the brilliant: Siemieniuk et al. (2020). Drug Treatments for Covid-19: Living Systematic Review and Network Meta-Analysis. BMJ.

Categories
Innovative Solutions National changes Social Distancing

Election Season

Election season is upon us! Milwaukee was the first to hold an in-person election during the COVID19 pandemic. Scientists just (July 31) published a case study on COVID19 spread at this Milwaukee election.

What happened?
March 3: CDC published health and safety guidelines for state elections
March 13: 1st ever COVID19 case popped up in Milwaukee
March 25: Stay-at-home statewide policy implemented in Wisconsin
April 7: Election day
April 9-21: Incubation period (that is, IF people were infected at the polls, this is when their symptoms would start). 
May 5: Marks 4 weeks after the elections (i.e. that is, IF people were infected at the polls, this is when we should see deaths by)

What did they find?
• Cases did not increase after the election. Of the COVID19 infections seen throughout Milwaukee, 28% occurred BEFORE the election and 21% occurred AFTER the election (within the incubation period). 
• Deaths did not increase after the election. Of the COVID19 deaths seen throughout Milwaukee, there were 36 deaths pre-election compared to 24 deaths post-election (within the lagged death timeline)
• Hospitalizations also did not increase post-election compared to pre-election

So….what?
Milwaukee made key changes to mitigate COVID19 spread during their election:
• Public messaging campaigns to limit in-person voting (people who voted by absentee mail-in ballots in Milwaukee increased from 4% in 2016 to 68% in 2020; Voting while remaining in vehicle increased in Milwaukee from 4.7% in 2016 to 12.2% in 2020)
• Polling site safety (employing PPE and environmental cleaning to lower transmission risk at in-person polls)
• CDC also recommends: longer voting periods, and other options such as increasing the number of polling locations to reduce the number of voters who congregate indoors in polling locations

All cities can learn from this case study. We can still have an election season while mitigating COVID19 spread and, thus, medically benefit the community. 

Love, your local epidemiologist

Data Source: Figure by me. 
Data from: Paradis H, Katrichis J, Stevenson M, et al. Notes from the Field: Public Health Efforts to Mitigate COVID-19 Transmission During the April 7, 2020, Election ― City of Milwaukee, Wisconsin, March 13–May 5, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1002–1003. 

Categories
Innovative Solutions

Social distancing

Yesterday’s post received a lot of debate regarding the efficacy (effectiveness) of social distancing. Well, guess what! There’s a study for that…

It actually just came out two days ago (July 30). And there’s a lot to unpack.

This study evaluated whether social distancing mitigates spread. Spoiler: It does. BUT, and this is a big but, it’s dependent on whether the response was coordinated or not. These scientists looked at 134 nations and compared the impact of their social distancing policies. Briefly:

-Countries with a national, coordinated social distancing response (i.e. not the US) reduced COVID-19 transmission by 65% in two weeks. Yes, only two weeks. This prevented an estimated 1.57 million COVID19 cases.


-Interestingly, and importantly for the US, COVID19 spread was NO different among countries with regional responses (i.e. the US) compared to countries that had NO social distancing response at all.

-In the US: There were/are 3 states without statewide social distancing policies: SD, WY, NE. SD and NE has seen the two smallest reductions in COVID19 spread.

So, like I said yesterday, a fragmented, whack-a-mole response is just not going to work. Cases were up in the Northeast, then went down. Then went up in the South (and are still up). Now the Midwest is seeing their second wave. We better buckle up until our response, as a nation, changes.

Love, your local epidemiologist

Data source: Figures and data are from the brilliant: McGrail et al. (July 30, 2020). Enacting National Social Distancing Policies Corresponds with Dramatic Reduction in COVID19 Infection Rates. PLOS ONE.

Categories
Innovative Solutions

Hydroxychloroquine

This keeps coming up again and again. I wanted to provide you all with a timeline of the scientific evidence. Because, honestly, I was curious too…

May 2005: Scientists found chloroquine was protective against SARS among PRIMATES (this is what prompted that viral doctor video). This is a good start but does not have ANY bearing on the impact of hydroxychloroquine on COVID19 among humans.

April 2020: There were two small studies conducted…

  • France: 20 patients were given hydroxychloroquine. This was NOT a randomized control trial, but they found a beneficial effect of hydroxychloroquine.
  • China: 62 patients were randomly placed in control and treatment groups. The treatment group (i.e. hydroxychloroquine) did better than the control group.

April 2020: FDA authorized emergency use of hydroxychloroquine. This drug started to became a household name.

May 2020: Two large randomized studies (1446 patients in NYC and 1438 patients in 25 hospitals in NY state) found no beneficial effect of hydroxychloroquine. The NIH to recommend that hydroxychloroquine NOT be used in routine care (only for research).

May 2020: A Lancet article was published (96,000 patients across the US) which found no beneficial effect of hydroxychloroquine. However, the veracity of the data and analyses was questioned. So, Lancet attempted to conduct a third-party review to replicate the findings. The data source (Surgisphere Corporation) would NOT share their data for this “double check”. Lancet retracted the paper.

June 2020: Four large studies were conducted…

  • Nashville: A randomized trial (470 patients) was told to STOP because there was no beneficial effect of hydroxychloroquine. Continuing the study would unethical to study participants.
  • UK: (11,000 patients in 175 hospitals) No beneficial effect of hydroxychloroquine. They also had to STOP the study.
  • US and Canada: A large randomized study (821 patients) tested whether this drug prevented COVID19 BEFORE infection compared to a placebo. No beneficial effect of hydroxychloroquine
  • China: 150 patients randomized to hydroxychloroquine. No beneficial effect of hydroxychloroquine.

June 15: FDA deauthorized emergency use of hydroxychloroquine

July 2020: In the US, a large randomized study (491 patients) found no beneficial effect of hydroxychloroquine.

There are some scientific principles that are certain. They are called scientific laws (think the law of thermodynamics). EVERYTHING ELSE IS FLUID. Science if ever-changing and extends itself. The virus doesn’t change, but our understanding of the virus changes. Because of this, scientific and medical recommendations adapt. ESPECIALLY when there is a novel disease like COVID19. If this WASN’T happening, then we wouldn’t be doing our job.

Everyone needs to have a more realistic expectations of what science can and can’t do.  

Love, your local epidemiologist

Data sources: Peer-review articles are linked throughout the post above.

Categories
Antibodies Herd immunity Innovative Solutions Long-term effects

T-cells

Never thought my physiology degree would be worth anything. But here we are!

Our immune system has special types of cells with different functions: 1) B-cells (antibodies) latch on to the virus so they can’t enter the cells; 2) T-cells find and destroy the virus (and then remember who they need to destroy). T-cells have been found effective in MERS and SARS, but their role in COVID19 has not been clear.

One study in Singapore was just published on COVID19 t-cells. Briefly, they found:
• T-cell response is high among mild COVID19 cases (unlike the antibody studies we have seen)
• Interestingly, healthy people have COVID19 t-cells. This be due to exposure to other related coronaviruses, such as the common cold and SARS. This MAY explain why some people control the infection (and recover much better) than others.
• T-cells lasted over 17 years among SARS survivors, and the SARS t-cells WORK against COVID19

So far, all vaccines being developed target B-cells (antibodies), but scientists are starting to explore the potential of leveraging T-cells for therapeutic options. The problem is t-cells are much more complicated to analyze compared to antibodies. If fact, they require a special laboratory. So, we can’t do large population-based studies like we saw in Spain (https://yourlocalepidemiologist.com/?p=214).

To my knowledge, there are only three other published studies on this topic (regarding COVID19). I’ve included them below.

Love, your local epidemiologist

• Diao et al, 2020. https://pubmed.ncbi.nlm.nih.gov/32425950/
• Grifoni et al, 2020. https://pubmed.ncbi.nlm.nih.gov/32473127/
• Weiskopf et al, 2020. https://pubmed.ncbi.nlm.nih.gov/32591408/
•Le Bert et al., 2020 (Singapore study): https://www.nature.com/arti…/s41586-020-2550-z_reference.pdf

Categories
Children Daycare Deaths Innovative Solutions Long-term effects

COVID19 and child abuse

Thought I would sprinkle some of my own research in this blog because…why not?

For those of you that don’t know, I am a violence and injury epidemiologist. My research lab focuses on how violence is contagious (just like infectious diseases) and predictable. Because if it’s predictable, then it’s preventable.

As we ALL know by now, COVID19 has not only caused major medical problems in our community but has caused social problems. The strains and stresses of the COVID-19 pandemic (like job loss, financial struggles, food insecurity, mental health, and lack of social support) have exacerbated the risk of violence at home.

My colleagues and I are continually working to understand how the stay-at-home orders/school cancelled impacts child abuse.

Figure 1 shows the impact of COVID19 on child abuse hospital visits in 2020 compared to 2019. Briefly, we found less kids are going to the hospital for child abuse after stay at home orders compared to last year. Unfortunately, though, we hypothesize that this isn’t because child abuse is getting better, but rather because kids are interacting less with mandatory reporters (i.e. teachers, daycare teachers) and the public.

Among kids that ARE going to the hospital for child abuse, physicians are reporting even MORE severe injuries (traumatic brain injuries, intentional burns) than before the pandemic. Typically, a hospital system has 5-10 child abuse deaths per year. It is not uncommon for a hospital to now report 2 child abuse deaths in one week.

The realities of this crisis are immediate. Researchers and clinicians are working hard to urgently address this public health crisis in real-time. 

Prevention can also start at home. The Prevent Child Abuse America posted some fantastic resources for parents, children, educators and everyone else. This includes tips for staying connected to the community, tips for staying engaged as a family, and tips to manage stress and anxiety. Check it out: https://preventchildabuse.org/coronavirus-resources/.

These efforts are especially relevant given that a lot of schools are delaying in-person school. While this delay is desperately needed medically, it will have an impact on kids’ health and safety. 

Love, your local (violence) epidemiologist

Source: Data comes from my lab in which we are working directly with pediatric hospitals. Data is not published; this is only a high-level preliminary report. We are working on it!

Categories
Children Innovative Solutions

Contact Tracing

The power of contact tracing.

Yesterday, the CDC published one of the first comprehensive contact tracing studies. It was conducted in South Korea.

I threw together a figure that depicts the study design. Briefly, South Korea identified 5,706 confirmed cases (i.e. index cases) and asked them to report their contacts (both in the household and out in public). The cases reported a total of 59,073 contacts. The cases and contacts were followed for at least 2 weeks. 

This is what they found:

  • You are more likely to get sick if you’re in the household with an index case than out in public (12% vs. 2%)
  • The age of the index case can INCREASE or DECREASE your chances of infection
    • Interestingly, an older kid (age 10-19) that gets COVID19 has the HIGHEST rate of infecting a contact compared to other ages (20%). This obviously has important implications for the school opening debate. 

Contact tracing (followed by quarantine) is one of the original and BY FAR the most effective ways to curb a pandemic. Other countries have been highly successful in achieving this. The United States has not. It’s a mess. Why?

  • Funding. We have a terrible history of not funding public health. So, when a pandemic hit, health departments were (and still are) scrambling for support (personnel, technology, infrastructure, etc). Even DURING the pandemic, I know of a couple health departments that have asked for funding for contact tracing and were denied. 
  • Spread. COVID19 has reached SO far, that this preventative measure is just not feasible. In Dallas, we are reporting ~7000 NEW cases per week. If each person had at least 2 contacts, this is 21,000 phone calls weeks PLUS follow-up phone calls. Contact tracing is best to use BEFORE uncontrollable spread. This has led to health departments prioritizing who they call; where they can make the most impact in terms of mortality.  
  • Lack of trust. Even if public health departments successfully reach an index case, the majority don’t answer their phone OR they report no contacts (which is most likely false). This chronic distrust in the US government is significantly impeding on public health efforts. 

Nonetheless, health departments are working incredibly hard with what they got. This has resulted in a few important case studies (see figures 2 and 3).

Contact tracing could answer SO MANY questions. This would better inform decision making and planning. For now, we will rely on small case studies in the US and comprehensive data from other countries. 

Love, your local epidemiologist

Data source: https://wwwnc.cdc.gov/eid/article/26/10/20-1315_article