Coronavirus

First Phase 3 COVID-19 vaccine trial in US is expected to begin next week

An employee works at the Stabilitech laboratory in Burgess Hill south east England, on May 15, 2020 where scientists are trying to develop an oral vaccine for the COVID-19 illness. - The scientists at Stabilitech are one of the teams attempting to develop a vaccine for COVID-19. Ingested in a capsule into the gut, Stabilitech's potential oral vaccine aims to prompt an immune response in mucosal cells in the respiratory system and elsewhere in the body. The firm believes that will be more effective in tackling respiratory illnesses like coronavirus. The British government is touting the country as a global leader in the big-money investment race to find a vaccine for COVID-19. (Photo by BEN STANSALL / AFP) / TO GO WITH AFP STORY BY JOE JACKSON (Photo by BEN STANSALL/AFP via Getty Images)

(CNN) — Much of the world has pinned its hopes on a vaccine as a way out of the COVID-19 pandemic that has infected more than 15 million and killed more than 630,000 people globally.

The World Health Organization says there are 25 potential coronavirus vaccines in clinical trials internationally.

Here in the United States, the government has put its money behind several different vaccine candidates through Operation Warp Speed.

One of those vaccines is being developed by the Vaccine Research Center at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, in partnership with the biotechnology company Moderna. The vaccine is expected to enter Phase 3 testing next week. This phase of the trial is expected to involve 30,000 volunteers and will test whether the vaccine protects people against the coronavirus.

The vaccine uses messenger RNA (mRNA), a molecule used by cells to build proteins — in this case, the proteins that are needed to build the coronavirus’ spike protein, which the virus uses to attach itself to and infect human cells. Once the immune system learns to recognize this target — thanks to the vaccine — it can mount a response faster than if it encountered the virus for the first time due to an infection.

Early results from the Phase 1 study were published in the New England Journal of Medicine in mid-July. The study showed that the vaccine, given at three different doses, triggered an immune response in the people who received it (the higher the dose, the higher the immune response). More than half of the participants experienced side effects including fatigue, chills, headache, muscle pain and pain at the injection site. The Phase 3 trial will involve the middle dose –100 micrograms (µg).

Dr. Barney Graham is the deputy director of the Vaccine Research Center. He spoke to Dr. Sanjay Gupta to explain a little bit about the technology behind the Moderna vaccine. What follows is a portion of their conversation, edited for length and clarity, to explain what is happening inside the body.

Dr. Sanjay Gupta: How does the vaccine work — you’re giving a little portion of messenger RNA [mRNA] to somebody. What is the mRNA and how does the body respond and create these antibodies?

Dr. Barney Graham: Our human genome is made of DNA; this is a double-stranded molecule. Most people have heard of DNA. The way our body makes proteins is that, from the DNA template that is made of nucleotides [basic building blocks], it does something called transcription: It uses its DNA template to make an RNA template. So, the RNA is the template we use in our own body normally to make proteins that are necessary for cell function … and that part is called translation …

And so when you put RNA directly into the muscle cell, by injecting it in as a vaccine, that RNA goes right into the cytoplasm [the body, not the nucleus] of the cell, is translated by the ribosomes to make a protein. And in our case, the mRNA that we use to make this protein is our vaccine. And when that RNA goes into the muscle cell, it creates and produces a protein, and when that protein is sitting on the muscle cell, it looks just like the protein that would be sitting on a virus, except we don’t have to give it the whole virus, we just give it the protein. And this is the main point of attack; the immune system recognizes this, it starts making antibodies to different surfaces on this protein. And then we count on those antibodies to be present if the virus ever shows up with this same exact protein on its surface. That’s the way this mRNA vaccine is working.

Some of the groundwork for the development of this vaccine was laid during another coronavirus outbreak, MERS in 2012, and from work on one of the endemic coronaviruses that circulates every winter. A key discovery came when Graham and his colleagues realized that the spike protein changes shape as part of the process it uses to fuse to the cell it is infecting. And to develop an effective vaccine for any of the coronaviruses, they would have to target the pre-fusion spike protein — the version of the spike protein before it fuses with a human cell receptor and changes shape — not the post-fusion one, which is what they did for this new coronavirus.

Graham: These kinds of proteins are important for the virus to enter cells. Those proteins sit on top of the virus, they interact with the cell and then undergo a rearrangement analogous to a Transformer toy, where robots can turn into cars. These proteins are interesting because they start in one shape and they end in a different shape and depending on which shape you use, you get a good response to a vaccine or not-so-good response to a vaccine. And for the last 30 or 40 years, people have been using the post-fusion, rearranged, non-functional form in their vaccines, and had not done very well. None of them really had worked … So in the Transformer analogy, if the cars are the important part, you need to make antibodies to the car and not to the robot … And that’s why for 30 or 40 years, people’s vaccines weren’t working. Before this, the concept of the pre-fusion conformation wasn’t really there.

Gupta: Obviously, you want to create a protein that represents the pre-fusion form of the spike protein, not the post-fusion form. But other than that, you’re basically having the body recognize the virus as if it had been infected, right? What I’m asking is, can people get sick, actually get the infection, from this vaccine?

Graham: No. The virus itself, its genome is 30,000 nucleotides. We’re only giving about 4,000 nucleotides, or maybe closer to 3,700 nucleotides, to make this protein. So, we’re only giving a 10th of the genome — and even those nucleotides are modified. There we use what’s called codon optimization; we’ve changed the sequence of the nucleotides but make exactly the same sequence of amino acids. So what we’re giving is not really like the virus, but it makes this viral protein.

Gupta: In this [New England Journal of Medicine] paper that just came out, they did talk about people having these side effects. In fact, everyone in the mid-dose group (100µg; two shots separated by a month) and the highest dose (250µg; two shots separated by a month) got some sort of side effect. It was not enough to stop the trial, but there were side effects. They were things like headache and fever and malaise and muscle pain. You’re not getting infected, obviously — it’s not the virus itself — so why do people develop these side effects, then?

Graham: I’m an infectious disease physician who’s done a lot of clinical trials and since the mid-1980s, over 100 clinical trials of different experimental vaccines. And these kinds of side effects, which we call reactogenicity, are very common to almost all vaccines, even the commonly used and licensed vaccines. What you saw in in this setting is that at the 25µg and 100µg dose, you saw very little reaction after the first shot, but then some reaction after the second shot. But virtually all those reactions were either mild or moderate. And so mild means you can notice it; moderate means it’s bothers you a little bit.

Now, it’s when you get to the higher dose of 250µg, that some of those people had more severe reactions. Three out of 14 [who received the 250µg dose] had grade-three reactions for fever and muscle aches and things like that — similar to what sometimes you experience after some of our licensed vaccines. But, you know, the reason for doing these Phase 1 trials is to find what dose level is acceptable and tolerable. And in this case, it was pretty clear that the 250µg is not something we want to give people, especially a large number of people, because it wasn’t tolerated. The 100µg dose was well tolerated. It’s a small number of people still, but there’s been another 300 people immunized in a Phase 2 that also have shown a similar reactogenicity profile. So we think that the 100µg dose should be acceptable going forward. And that’s what’s planned for the Phase 3 trial.

Gupta: Let me ask you about the study that just came out. We got the data, it showed that there was neutralizing antibody activity. Were you surprised or was that was that pretty much a given?

Graham: We had done a lot of studies with a similar vaccine that we made for the MERS spike and had done a lot of those studies in mice and knew that this protein was immunogenic — meaning that it was very effective at eliciting antibody responses that could neutralize the virus. So, we knew that this was working in mice before we ever injected the first person. So it wasn’t a big surprise that we could do that in humans.

I was pleasantly surprised, I think, about the level of neutralizing antibody — it exceeded my expectation. It almost achieved what I was hoping for. And, so we were happy with the level of neutralizing activity that was elicited by this vaccine in humans.

The other reason you do Phase 1 trials is to not just find the dose that’s tolerable but find the dose that has optimal immunogenicity. In this case, the 100µg dose was virtually the same as the 250µg dose in terms of the antibodies made. And those antibodies reached levels that were in that upper range of what convalescent people make who have been infected with the SARS-CoV-2 coronavirus. So, we felt like this was a good outcome.

Gupta: Let me just ask you one other thing. You’ve got about a third of the country that is already demonstrating some vaccine hesitancy — they’re already sort of showing some trepidation about this new vaccine that is not even out yet. How do you how do you handle vaccine hesitancy?

Graham: I think if people really understood the biological basis of vaccines and how they work — to see that it’s not magical or mysterious, that there’s actually a rationale and very specific understanding right down to the angstrom level of the structure of what we’re trying to do to make an immune response that could help protect you — I really hope that by trying to explain some of this and for people to start understanding the biology of vaccines, that it will make them less hesitant and more likely to join us in trying to establish this community of immunity that we’re looking for, what people called herd immunity.

The reason this is important is that I’m hoping that this vaccine could be as much as 70 or 80% effective — I think that would be a success. We need 60 or 70% of immunity [in the population] to really establish what’s called herd immunity. That means almost 100% of people would have to be vaccinated to establish that level of immunity in the population. So, if a third of people don’t take it, we’ll only be able to reach around 40 or 50% immunity in the population with that type of a vaccine. I think it’s really important for that third of people to come along and try to help us and understand how these vaccines work so they won’t be so hesitant.

Coronavirus links

Indiana coronavirus timeline

With information from the Indiana Department of Health through March 4, 2021, this timeline reflects updated tallies of deaths and positive tests prior to that date.

  • March 6, 2020: Indiana State Department of Health (ISDH) confirms the first case in Indiana. Officials say the Marion County resident had recently traveled to Boston to attend a BioGen conference as a contractor.
  • March 8: ISDH confirms a second case. A Hendricks County adult who had also traveled to the BioGen conference was placed in isolation. Noblesville Schools says a parent and that parent’s children will self-quarantine after attending an out-of-state event where someone tested positive.
  • March 9: Avon Community School Corp. says a student on March 8 tested positive.
  • March 10: ISDH launches an online tracker. Ball State University basketball fans learn the Mid-American Conference tourney will have no fans in the stands. Three businesses operating nursing homes in Indiana announce they will no longer allow visitors.
  • March 11: The Indianapolis-based NCAA announces the Final Four basketball tournaments will happen with essential staff and limited family attendance. The Big Ten announces all sports events, including the men’s basketball tournament at Bankers Life Fieldhouse, will have no fans starting March 12. Ball State University suspends in-person classes the rest of the spring semester. NBA suspends all games, including the Indiana Pacers, until further notice. Butler University and the University of Indianapolis extend spring break, after which they will have virtual classes.
  • March 12: Gov. Eric Holcomb announces new protections that led to extended public school closings and the cancellation of large events across the state. The NCAA cancels its basketball tournaments. The Big Ten suspends all sporting events through the winter and spring seasons. The league including the Indy Fuel hockey team suspends its season. Indy Eleven says it will reschedule four matches. Indianapolis’ annual St. Patrick’s Day Parade is canceled. 
  • March 13: The Indiana High School Athletic Association postpones the boys basketball tournament. Wayzata Home Products, a Connersville cabinet maker, shuts down and lays off its entire workforce due to market uncertainty. Holcomb announces actions including the elimination of Medicaid co-pays for COVID-19 testing and the lifting of limits on the number of work hours per day for drivers of commercial vehicles. Franklin College says it will begin online classes March 18 and empty residence halls of students in two days. The Children’s Museum of Indianapolis closes indefinitely. The Indianapolis Public Library joins other libraries across Indiana and closes all facilities indefinitely.
  • March 14: The Indiana Gaming Commission says all licensed gaming and racing operations will close in two days for an indefinite period.
  • March 15: Indiana had its first death. St. Vincent Hospital in Indianapolis announces it will suspend all elective, non-urgent surgeries.
  • March 16: Indiana had its second death. Gov. Holcomb announced the first Hoosier death. He closes bars, restaurants and nightclubs to in-person patrons, but maintains carryout and delivery services.
  • March 17: Indiana had its third and fourth deaths. ISDH announces Indiana’s second death. Gov. Holcomb activates the National Guard. Purdue, Butler and Indiana State universities cancel May commencement ceremonies.
  • March 18: Indiana had its fifth death. Eli Lilly and Co. says it will use its labs to speed up testing in Indiana. The 500 Festival suspends all events. Simon Property Group closes all malls and retail properties.
  • March 19: Holcomb extends Indiana’s state of emergency into May. Holcomb says he’ll close all K-12 public and nonpublic schools; standardized testing was canceled. The state’s income-tax and corporate-tax payment deadline was extended to July 15. Holcomb says the state will waive job search requirements for people applying for Temporary Assistance to Needy Families. Indiana’s high school boys basketball tournament was canceled.
  • March 20: Indiana’s death toll rose to 9. ISDH announces Indiana’s third death. Holcomb moves the state’s primary election to June 2. Indiana University says it is postponing May commencement ceremonies on all campuses.
  • March 21: Indiana’s death toll rises to 14. ISDH announces Indiana’s fourth death. Indiana National Guard says it and the state Department of Transportation are distributing medical supplies to hospitals.
  • March 22: Indiana’s death toll rises to 18. ISDH announces seven deaths.
  • March 23: Indiana’s death toll rises to 23. Holcomb orders nonessential Hoosiers to “stay at home” from March 24-April 7. Eli Lilly & Co. begins drive-thru testing for the coronavirus for health care workers with a doctor’s order. Ball State University cancels the May commencement.
  • March 24: Indiana’s death toll rises to 28. Fred Payne of Indiana Workforce Development says any Hoosiers out of work, including temporary layoffs, are eligible to apply for unemployment benefits.
  • March 25: Indiana’s death toll rises to 33. Indianapolis Motor Speedway announces the Indianapolis 500 is moved to Aug. 23.
  • March 26: Indiana’s death toll rises to 42.
  • March 27: Indiana’s death toll rises to 45.
  • March 28: Indiana’s death toll rises to 58.
  • March 29: Indiana’s death toll rises to 77.
  • March 30: Indiana’s death toll rises to 91.
  • March 31: Indiana’s death toll rises above 100, to 113. Holcomb extends the limits of bars and restaurants to offer only “to go” and “carryout” through April 6.
  • April 1: Officials extend Marion County’s “stay at home” order through May 1. Marion County health officials say they will start COVID-19 testing services for front-line employees.
  • April 2: The state announces K-12 schools will be closed for the rest of the school year. Indiana High School Athletic Association cancels spring sports seasons.
  • April 3: Holcomb extends the “stay at home” order through April 20. The Indiana National Guard says it, the Army Corps of Engineers and state health officials will begin to assess sites for alternate health care facilities.
  • April 6: The state reports a Madison County nursing home has had 11 deaths. Holcomb extends the “stay at home” order through April 20. He also limits additional businesses to carry-out only.
  • April 7: Indiana health commissioner Box says four long-term care facilities have 22 deaths that appear to be related to COVID-19.
  • April 10: ISDH said 24 residents of a long-term care facility in Madison County have died from COVID-related illness.
  • April 14: Indiana’s death toll rises above 500.
  • April 16: Indiana records more than 10,000 positive coronavirus tests. The governor says he expects Indiana to experience a reopening in early May.
  • April 20: Holcomb extends the “stay at home” order to May 1. The governor also says if the medical supply chain is in good shape, other elective medical procedures can resume April 27.
  • April 22: The Tyson facility in Logansport voluntarily closes so 2,200 employees can be tested for COVID-19.
  • April 24: The Indianapolis City-County Council approves $25 million to help small businesses. Fishers City Council creates a city health department.
  • April 25: ISDH says it will launch an antibody testing study for Hoosiers; thousands of residents were randomly selected to participate in the study.
  • April 27: Indiana’s death toll rises above 1,000.
  • April 28: Indiana officials say they will open COVID-19 testing to more Hoosiers, with expanded criteria and new testing services at 20 sites around the state.
  • April 29: The state says it will spent $43 million on contact tracing.
  • April 30: Indianapolis extends its stay-at-home order through May 15.
  • May 1: Gov. Holcomb announces a phased reopening plan for the state of Indiana. He also extends the “stay at home” order to May 4.
  • May 3: Indiana records more than 20,000 positive coronavirus tests.
  • May 4: Indiana enters Stage 2 of its Back on Track plan, which excludes Cass County until May 18, and Lake and Marion counties until May 11.
  • May 6:The state begins testing for all Hoosiers at 20 sites, with plans to expand the number of sites to 50 in a week. Ivy Tech Community College says it will continue virtual classes when summer courses begin in June. 
  • May 8: Cris Johnston, director of the Office of Budget and Management, says the state missed out on nearly $1 billion in anticipated April revenues; all state agencies will be given budget-cutting goals. Purdue University OKs plans to reopen for the fall semester with social distancing and other safety measures.
  • May 13: The first phase of a state-sponsored study of the coronavirus estimated about 186,000 Hoosiers had COVID-19 or the antibodies for the novel virus by May 1. Indianapolis Mayor Joe Hogsett announced plans for limited reopenings of worship services, retail establishments, libraries and restaurants.
  • May 15: Simon Property Group reopens Castleton Square Mall, Circle Centre Mall, and Fashion Mall at Keystone
  • May 18: Indiana reports its first case of multisystem inflammatory syndrome in a child. The Farbest Foods turkey-processing plant in Huntingburg is closed for three days; 91 people had tested positive there.
  • May 21: Indiana records more than 30,000 positive coronavirus tests.
  • May 22: Indiana advances to Stage 3 of the Back on Track reopening plan. Indianapolis closes portions of five streets to allow restaurants to reopen with outdoor dining only.
  • May 26: Indiana’s death toll rises above 2,000.
  • May 27: Indiana University says the fall semester will have in-person and online courses, plus an adjusted calendar through May 2021. Ball State University says the fall semester will be 13 straight weeks of in-person classes with no day off on Labor Day and no fall break.
  • May 29: Places of worship in Marion County can begin holding indoor services at 50% capacity with proper social distancing. Jim Schellinger, Indiana secretary of commerce, said the federal Paycheck Protection Program has made 73,430 loans in Indiana totaling $9,379,164,461, the federal Economic Injury Disaster Loan program has made 5,070 loans in Indiana totaling $445,428,500, and the federal Economic Injury Disaster Loans Advance program has made 38,365 grants in Indiana totaling $136,554,000.
  • June 1: Marion County restaurants begins serving customers indoors and outdoors with 50% capacity. Marion County salons, tattoo parlors reopen by appointment only. Marion County gyms, fitness centers and pools reopen with 50% capacity and no contact sports. However, a Marion County curfew that began the night of May 31 and continued into the morning of June 3 after rioting impacted the reopening of some businesses.
  • June 3: Phase 2 of statewide testing of random Hoosiers by the Indiana University Richard M. Fairbanks School of Public Health at IUPUI and the Indiana State Department of Health begins.
  • June 5: Indiana reports May tax revenues were 20% short of projections made before the coronavirus closings started.
  • June 8: Indianapolis leaders agree to spend $79 million in coronavirus relief funding on contact tracing, rent relief, personal protective equipment and support for small businesses.
  • June 12: Indiana, excluding Marion County, advances to Stage 4 of reopening plan.
  • June 15: Casinos and parimutuel racing reopen in the state. Marion County’s public libraries begin a phased reopening. Indiana records more than 40,000 positive coronavirus tests.
  • June 19: Marion County advances to Stage 4 of state’s reopening plan.
  • June 24: Holcomb says the state’s moratorium on the eviction on renters will be extended through July. Indiana announces it will create a rental assistance program July 13. Indiana Pacers guard Malcolm Brogdon says he has tested positive for COVID-19.
  • June 27: Indiana hospitalizations for COVID-19 begin to increase, with about 33 new patients a day through July 1.
  • July 1: The governor pauses Stage 5 final reopening plan, announces Stage 4.5 from July 4-17.
  • July 4: Indiana’s Stage 4.5 reopening plan begins.
  • July 9: Indiana records more than 50,000 positive coronavirus tests. Marion County mandates mask-wearing.
  • July 10: Indianapolis Public Schools announces its reopening plans.
  • July 11: Indy Eleven resumes 2020 season with victory at Lucas Oil Stadium. The Children’s Museum of Indianapolis reopens.
  • July 13: Indiana begins rental assistance program for all counties but Marion County. Marion County begins its own rental assistance program.
  • July 15: Indiana announces the Stage 4.5 reopening plan will continue another two weeks. The WNBA season begins.
  • July 16: Indianapolis suspends applications for its rental assistance program due to overwhelming demand.
  • July 24: Bars, taverns and nightclubs in Indianapolis are shut down again. City officials also return to other previous restrictions.
  • July 25: Indiana Fever begins WNBA season after delays.
  • July 27: Indiana governor’s order to wear face coverings begins. Great Lakes Valley Conference, which including University of Indianapolis, postpones most fall sports, including football, men’s and women’s soccer, and volleyball, until spring.
  • July 30: NBA season resumes.
  • Aug. 4: Indianapolis Motor Speedway announces the Aug. 23 Indianapolis 500 will be run without fans.
  • Aug. 9: Indiana records more than 75,000 positive coronavirus tests.
  • Aug. 11: Indiana’s death toll rises above 3,000.
  • Aug. 17: Indianapolis Public Schools restarts with online-only classes. News 8 learns the 2021 NBA All-Star Game will not happen on Presidents Day weekend in 2021.
  • Aug. 20: Purdue University suspends 36 students after a party at a cooperative house.
  • Aug. 21: Indiana high school football season begins with some teams not playing due to COVID-19 concerns.
  • Aug. 23: Butler University tells undergraduates that instruction will occur remotely for the first two weeks of the semester, starting Aug. 24, instead of in classrooms.
  • Aug. 24: Purdue, Indiana, IUPUI and Ball State universities resume in-person classes.
  • Aug. 25: Reports say a fraternity, a sorority and a cooperative house at Purdue University are under quarantines.
  • Aug. 26: Gov. Holcomb extends the mask mandate through Sept. 25. Indiana’s rental assistance program will take applications for one last day.
  • Aug. 27: Indiana University says eight Greek houses are under 14-day quarantines.
  • Sept. 2: Indiana University tells 30 Greek houses in Bloomington to quarantine.
  • Sept. 6: Indiana records more than 100,000 positive coronavirus tests.
  • Sept. 8: Marion County allows bars and nightclubs to reopen with 25% capacity indoors and 50% capacity outdoors.
  • Sept. 12: The Indianapolis Colts open their season with a loss in a Jacksonville stadium with a limited number of fans.
  • Sept. 21: The Indianapolis Colts home opener is limited to 2,500 fans.
  • Sept. 23: Gov. Eric Holcomb extends the mask mandate through Oct. 17.
  • Sept. 24: The state’s mask mandate is extended through Oct. 17.
  • Sept. 25: The Mid-American Conference announces it will start a six-game football season Nov. 4, with the championship game Dec. 18 or 19.
  • Sept. 26: Indiana advances to a revised Stage 5 of Indiana Back on Track plan with relaxed limits on gatherings, restaurants, bars, nightclubs and more. Marion, Monroe and Tippecanoe counties decided to have more restrictive limits, however.
  • Sept. 27: The Indianapolis Colts second home game is limited to 7,500 fans.
  • Sept. 28: Purdue University says it’s suspended 14 students, including 13 student-athletes, for violations of a pledge designed to curb the coronavirus pandemic on campus.
  • Sept. 30: The Indiana State Department of Health’s online coronavirus dashboard began showing data on positive coronavirus cases in Indiana schools.
  • Oct. 1: IU’s website shows two additional fraternities and a sorority at the Bloomington campus have been issued “cease and desist” orders.
  • Oct. 2: Franklin College suspends classes and moves to virtual education and activities through Oct. 9 after a “concerning and unusual” increase in the positivity rate for COVID-19.
  • Oct. 12: Franklin College returns to in-person classes.
  • Oct. 13: Indianapolis-based drugmaker Lilly pauses its trial of a combination antibody treatment for coronavirus for safety reasons.
  • Oct. 14: Indiana health commissioner Dr. Kristina Box announces she has tested positive for COVID-19.
  • Oct. 15: Gov. Holcomb issues executive order to extend mask mandate and Stage 5 reopening plan.
  • Oct. 16: Indiana’s death toll rises above 4,000.
  • Oct. 18: The Indianapolis Colts third home game was limited to 12,500 fans.
  • Oct. 23: The Big Ten begins its football season.
  • Oct. 30: Gov. Holcomb extends the public health emergency through Dec. 1.
  • Nov. 1: Indiana National Guard to begin deploying to long-term care facilities to provide coronavirus assistance. The Mid-American Conference football teams begins its six-game regular season.
  • Nov. 5: Indiana records more than 200,000 positive coronavirus tests.
  • Nov. 8: The Indianapolis Colts fourth home game was limited to 12,500 fans. .
  • Nov. 10: Indiana’s death toll rises to 5,000.
  • Nov. 12: Indianapolis calls for schools to go to virtual learning by Nov. 30.
  • Nov. 15: Indiana adds coronavirus-control restrictions for all businesses and gatherings in counties with the highest number of new cases as part of an update to the statewide COVID-19 pandemic response.
  • Nov. 16: Indianapolis limits capacity inside bars, private clubs, fraternal organizations and gyms to 25%; inside restaurants, libraries, funeral homes, swimming pools and shopping malls’ food courts to 50%; and inside religious services to 75%. Marion County Health Department requires preregistration for COVID-19 testing after increased demand at three drive-thru locations.
  • Nov. 22: Indiana records more than 300,000 positive coronavirus tests.
  • Nov. 23: Indianapolis Public Schools returns to virtual learning through Jan. 18.
  • Nov. 24: The NCAA men’s and women’s basketball seasons begin; some games had no fans in the stands.
  • Nov. 25: Indiana’s death toll rises above 6,000.
  • Nov. 26: Butler University men’s basketball cancels Nov. 29 game against Eastern Illinois after a positive COVID-19 test.
  • Nov. 28: Butler University men’s basketball team postponed two more games because of a positive COVID-19 test.
  • Dec. 1: Bankers Life Fieldhouse hosts its first NCAA men’s basketball game, Kansas vs. Kentucky, since the start of the pandemic.
  • Dec. 2: Indianapolis ends its rental assistance program.
  • Dec. 5: The men’s basketball game of No. 1 Gonzaga and No. 2, Baylor at Bankers Life Fieldhouse is postponed 90 minutes before tipoff after two Bulldogs test positive.
  • Dec. 6: Indiana’s death toll rises above 7,000.
  • Dec. 9: Indiana records more than 404,000 positive coronavirus tests. Holcomb says virus restrictions will now by county based on ratings that show the local virus spread. Indiana and Purdue universities cancel the Old Oaken Bucket football game set for Dec. 12.
  • Dec. 10: Indiana House Speaker Todd Huston says he tested positive for COVID-19.
  • Dec. 11: The Pacers lose to the Cavaliers as the NBA preseason begins. The Carmel Walmart in Westfield closes for nearly two days to sanitize the store.
  • Dec. 12: Ball State University President Geoffrey Mearns tests positive for the coronavirus.
  • Dec. 14: Health care workers receive the first coronavirus vaccinations in Indiana.
  • Dec. 15: Vice President Mike Pence holds a roundtable in Bloomington at pharmaceutical maker Catalent on the distribution of COVID-19 vaccines. Indiana and Purdue again cancel the Old Oaken Bucket football game that’d been reset for Dec. 18.
  • Dec. 16: Indiana’s death toll rises above 8,000.
  • Dec. 20: The Indianapolis Colts allows up to 10,000 attendees at Lucas Oil Stadium for the team’s game against the Houston Texans.
  • Dec. 22: NBA starts league’s 75th season, delayed and shortened to a 72-game schedule because of the pandemic.
  • Dec. 23: In response to the high volume of unemployment claims, Holcomb extends the suspension of certain requirements to expedite the hiring and training of temporary workers to more quickly resolve unemployment issues. Indiana Pacers to host first home game against New York Knicks with no fans present.
  • Dec. 27: Indiana’s death toll rises above 9,000.
  • Dec. 29: Indiana records more than 500,000 positive coronavirus tests.
  • Dec. 31: Indiana’s death toll for 2020 is 9,459 (as recorded through March 4, 2021).
  • Jan. 1, 2021: Indiana’s death toll rises above 9,500.
  • Jan. 3: The Indianapolis Colts allow 10,000 attendees at Lucas Oil Stadium for the team’s game against the Jacksonville Jaguars.
  • Jan. 4: Grades 1-12 schools in Marion County are allowed reopen to in-person learning. Perry Township Schools is the only district to reopen to in-person learning.
  • Jan. 5: Purdue and Nebraska postpone a men’s basketball game over health and safety concerns.
  • Jan. 7: Indiana’s death toll rises above 10,000.
  • Jan. 8: Hoosiers 80 and older start receiving the coronavirus vaccine.
  • Jan. 13: Hoosiers 70 and older can get the coronavirus vaccine.
  • Jan. 18: NFL announces the scouting combine will not happen in Indianapolis in February.
  • Jan. 20: Indiana records more than 601,000 positive coronavirus tests. Indiana Pacers host up to 1,000 at a game at Bankers Life Fieldhouse, the first fans since the pandemic began.
  • Jan. 21: Indiana’s death toll rises above 11,000.
  • Feb. 1: Hoosiers 65 and older can get the coronavirus vaccine. The Indianapolis St. Patrick’s Day parade is canceled for the second year in a row.
  • Feb. 4: More than 1,500 coronavirus deaths were added to the Indiana State Department of Health’s dashboard after an audit found they were not recorded. News 8 learns all games for the Big Ten men’s basketball tourney will move from Chicago to Indianapolis’ Lucas Oil Stadium.
  • Feb. 7: Indiana to change school protocols for classroom quarantine and contact tracing.
  • Feb. 14: Indiana’s death toll rises above 12,000. Indiana records more than 650,000 positive coronavirus tests.
  • Feb. 17: Indiana officials announced plans for a $448 million program to give housing assistance to Hoosiers.
  • Feb. 19: The NCAA says up to 25% capacity will be allowed for all rounds of the men’s basketball tourney including the Final Four. The Indianapolis Motor Speedway announces the May 30 Indianapolis 500 will have fans.
  • Feb. 19: Indiana’s death toll rises above 12,100.
  • Feb. 23: Hoosiers 60 and older can get the coronavirus vaccine.
  • Feb. 25: Indiana records more than 660,000 positive coronavirus tests. Capacity limits at bars, restaurants, gyms, and music venues in Marion County were adjusted after a consistent trend in the community’s COVID-19 positivity rate.
  • Feb. 25: Indiana’s death toll rises to 12,200.
  • Feb. 28: Indiana National Guardsmen to end assistance to long-term care facilities.
  • March 1: The 500 Festival Mini-Marathon says it will be virtual for the second year in a row.
  • March 2: Hoosiers 55 and older start receiving the coronavirus vaccine.
  • March 3: Hoosiers 50 and older start receiving the coronavirus vaccine.
  • March 4: News 8 learns up 8,000 fans will be allowed in Lucas Oil Stadium for Big Ten men’s basketball tournament games. Indiana records more than 665,000 positive coronavirus tests.
  • March 5: A three-day, drive-thru, mass-vaccination clinic opens at Indianapolis Motor Speedway for 16,800 Hoosiers.
  • March 12: A two-day, drive-thru, mass-vaccination clinic was set for Ivy Tech Community College in Sellersburg.
  • March 18: NCAA men’s March Madness games, all of them at venues in Indiana, to start with First Four games in Bloomington and West Lafayette.
  • March 26: A two-day, drive-thru, mass-vaccination clinic was set for Compton Family Ice Arena at the University of Notre Dame.
  • March 31: Holcomb’s emergency declaration with county-based restrictions and a mask mandate set to end at 11:59 p.m.
  • May 4: Indianapolis Indians set to begin delayed season with away game against Iowa Cubs.

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