What We Know and Still Don’t Know About COVID-19

Researchers and physicians from the Mailman School of Public Health and Columbia University Irving Medical Center weigh in on what we have learned so far about the novel coronavirus.

Carla Cantor and Caroline Harting
July 22, 2020

The world has been living through the COVID-19 pandemic for nearly eight months. 

Much is still unknown about the illness that has stricken 14.8 million people and killed more than 610,000 worldwide, but every day brings new insights and developments.

Columbia experts have been at the forefront of the international response to this crisis. We asked them to review what we’ve learned, so far, and to discuss the most significant challenges ahead.

The Second Wave

Q: We have had some success in flattening the curve, but there are worrying signs that infections are surging. Do you see a second wave coming?

A: While some states h​a​​ve made progress on flattening the curve​ of the infection​, many have recently reported record numbers of new cases. The daily coronavirus death toll in the United States increased in mid-July after months of decline as hospitals in hot-spot states, such as Florida and Texas, fill up with new patients. I’m hopeful that enough people will wear masks and practice social distancing most of the time and flatten these additional waves. 

On the other hand, the Spanish flu started in the winter of 1918, quieted down in the summer and came back with a vengeance in the fall of 1918, in part because of mutations in circulating virus strains. We don’t know if mutations in the SARS-CoV-2 virus will lead to a similar scenario with COVID-19 this fall. Although we have learned a great deal about this virus in the first half of 2020, there are still many unknowns. We have to hope for the best and be prepared for the worst. 

Jessica Justman, Associate Professor of Medicine in Epidemiology and the International Center for AIDS Care and Treatment Programs at the Columbia University Irving Medical Center

Signage on Columbia's campus near Butler Library stating that people need to wear face masks.

A Surge in Infections Among Young Adults

Q: Why is the uptick in young adult cases happening now, and what could this mean for the direction of the outbreak overall? What are the risk factors for this otherwise healthy population? 

A: The number of coronavirus hospitalizations among 18- to 29-year-olds is four times what it was a few months ago; the major thrust is in the South and West where the virus is still surging. We know that behavior has a lot to do with the spike in younger people. The elderly, well known to be at greater risk for more severe disease or death, are more likely to stay home or be cautious when they go out. 

Young adults, on the other hand, have heard that they are at far lower risk for severe disease and are more inclined to take greater risks. Everyone is tired of lockdowns. We’ve all seen photographs of beach parties with people in close quarters and congregating in crowded bars; these are invitations to disasters. When we’re bored and eager to get back to normal life, this is when we have to be especially careful and to take seriously all those precautions: masks, social distancing, good ventilation and hand hygiene. Proportionately, young adults have a much lower risk (per capita) of severe illness or death, but they can still get infected and spread the virus to others, often unknowingly.

It’s a numbers game. If you have enough infected people, numbers of severe illnesses will go up. There are also a variety of factors that can increase severity of disease even in the young, including obesity, smoking, weakened immunity, diabetes and heart, lung or kidney disease; and deaths occur, even in young adults. Unfortunately, these horror stories will increase as more young adults get infected. This is not the time to let down our guard. 

Stephen S. Morse, Professor of Epidemiology and Director, Infectious Disease Epidemiology Certificate, Mailman School of Public Health

Treatments and Vaccines

Q: What is the timeline for a coronavirus vaccine and treatments? What are the stages of development for the vaccine?

A: Operation Warp Speed, a public-private partnership to facilitate vaccine and drug development within the United States, has set a goal of a safe and effective vaccine by January 2021. Vaccines go through various stages of development. In the preclinical stage, vaccines are tested within animal models of disease to ensure they provide robust protection without signs of adverse reactions. They then typically proceed through three additional phases of development within humans in which larger and larger numbers of volunteers are treated with the vaccine to test for safety and efficacy.

There are currently more than 100 vaccines in development, with several that have completed Phase I human trials (testing for safety and dosage); some that are in Phase II trials (expanded human trials to test for safety and dosage); and others are scheduled to begin large-scale Phase III trials this summer, where a vaccine is given to tens of thousands of people to test for its efficacy.  

What we don’t know is the level of protection that each vaccine will provide; whether certain age groups will show a difference in the efficacy of the vaccine; and if the disease enhancement will occur, which means that people who receive the vaccine develop a more severe form of disease if infected (as has been observed in some previous animal studies with vaccines against SARS-CoV-1).

Alejandro Chavez, Assistant Professor of Pathology and Cell Biology at Columbia University Irving Medical Center

Children and COVID-19

Q: Why do some children develop an inflammatory syndrome from coronavirus? 

A: What we do know about is that the demographics of MIS-C, or Multisystem Inflammatory Syndrome in Children. 

To date there have been 383 patients with MIS-C described in the literature. The average age is 8 years, with 49 percent of the patients male and 37 percent of African origin. There have been no significant co-morbidities reported apart from the fact that about 16 percent were overweight or obese. We also know there is a temporal association with the height of COVID-19 pandemic and the appearance three to five weeks later of MIS-C.

What we do not know is the etiology and why some children develop MIS-C. 

MIS-C appears to be caused by a delayed, dysregulated immune response to the coronavirus that somehow goes into overdrive, causing inflammation that has multisystemic effects via a cytokine storm. SARS-CoV-2 could act as a direct trigger or cause a post-infectious IgG antibody-mediated phenomenon. Coronaviruses are known to block interferons which help in viral clearance. This delayed interferon response and subsequent higher viral burden results in worsening inflammation via the uncontrolled release of cytokines. A genetic predisposition is suspected but a unified theory as to why some children in certain geographical areas develop MIS-C is yet to be elucidated.

Anne Ferris, Assistant Professor of Pediatrics at the Columbia University Irving Medical Center

Signage in a Columbia University bathroom asking people to wash their hands.

Public Health Measures

Q: What level of public health and social measures must be put in place to prevent high-risk exposure as we move forward?

A: As communities reopen we will need to maintain many of the public health and social measures we adopted over the past months. Without a vaccine or medical cure, suppressing the epidemic requires each of us to do our parts. Public health and social measures for COVID-19 have worked. We don’t know precisely how much of the impact is down to which tool.  Most of us didn’t really start physical distancing, avoiding gatherings and washing our hands frequently until the pandemic was upon us, just as lockdown orders were issued. And facemasks have only been recommended for the general public since April, and they are still contentious in many places. 

We know that none of these is sufficient alone and that they are more effective when used together. We know they can slow transmission, even when people don’t know they’re infected. But only when most of us practice them consistently. Together, they can keep infections within manageable numbers that we can contain through widespread testing, contact tracing and isolating affected people. 

Some critics have decried these measures as an infringement on individual freedom. Instead, we ought to celebrate them as the keys to lifting more imposing restrictions and liberating us to re-engage cautiously in renewed economic and interpersonal activity. Pushing aside effective public health and social measures before the epidemic is declining has almost certainly contributed to the rising numbers of cases currently being reported throughout large parts of the country.

S. Patrick Kachur, Professor at Columbia University Irving Medical Center and the Mailman School of Public Health

The Long-term Impact

Q: What do we know or suspect about the long-term impacts of COVID-19 on the body?

A: Scientists are still learning about the many ways the virus that causes COVID-19 affects the body, both during initial infection and as symptoms persist. Patients can suffer long-term effects, including lung damage, thromboembolic complications, heart damage, neurocognitive manifestations and uncontrolled inflammation. Not every patient with COVID-19 makes a full recovery. By the time the first lung transplant for a COVID patient was performed at Northwestern Memorial Hospital in Chicago, it was clear that some people’s lungs never recover from the disease. Similar to SARS, which left 30 percent of survivors with permanently scarred lungs, COVID-19 is leaving a number of survivors with irreversible lung damage.

Among the most devastating of COVID-19’s thromboembolic complications are strokes, which may occur in patients requiring hospitalization as well as in those with mild or moderate illness. Although mortality rates are lower in younger people who suffer strokes, about half of them become disabled and are unable to return to work. Also devastating is amputation of limbs because of arterial clotting complications. Clots in the legs and pulmonary emboli can result in long-term issues, such as chronic leg swelling, marked limitation in physical activity and challenges performing the simple activities of daily living.

COVID-19 patients with pre-existing chronic conditions, as well as previously healthy patients, can develop irreversible damage to heart tissue, and there is a high incidence of neurological complications in patients requiring hospitalization, including intensive care treatment. Acute respiratory distress syndrome, which can develop in COVID patients, is associated with long-term cognitive impairment in about one in five individuals. Patients also may develop a late inflammatory process resulting in disorders such as pediatric multisystem inflammatory syndrome, with an expected risk of myocardial and vascular complications in coming years; Guillain-Barré syndrome, with paralysis; autoimmune hemolytic anemia; and a growing number of other autoimmune symptoms.

Daniel Griffin, Instructor in Clinical Medicine and Associate Research Scientist at Columbia University Medical Center

COVID-19 and Psychiatric Disorders

Q: What do we know about COVID-19, depression and psychiatric disorders?

A: We know that the pandemic has had a profound effect on the mental health of infected individuals and on the community in general, and that the impact and psychological effects of the COVID-19 crisis differs for each generation. A study by the CDC in the spring of 2020 revealed that about one-third of Americans have clinically significant anxiety or depression, a three- to four-fold increase compared to the same time last year; the youngest age groups (18-29 years) and those from minority communities had the highest rates.

From prior studies of MERS and SARS, we know there is an increased incidence of cognitive impairment, depression, anxiety and insomnia in the acute phase of infection and of PTSD in the post-infection phase. While the acute mental health effects of COVID-19 are beginning to be clear, the long-term impacts on the central nervous system will take time to uncover; neuropsychiatric manifestations may emerge long after the virus has been contained.

There are several reasons why severe infections might have psychiatric consequences, including direct effects of the virus itself on the central nervous system; the impact of the human immune response to the infection (inflammatory cytokines, post-infectious autoimmunity); and the impact of interventions (prolonged intubation and use of sedatives). 

But there are other factors to consider. For example: How much of the increase in anxiety and depression are due to the effects of the virus itself versus the collateral effects of the pandemic—social isolation, personal loss, economic insecurity, fear of infection and death and uncertainty about the future?                                             

Columbia researchers are attempting to learn more from neuropsychiatric and immunologic studies that will track the health of COVID-19 survivors from childhood to old age. In the meantime, clinicians must be alert for both the acute and potential long-term mental health effects of the virus, such as depression, fatigue, cognitive problems and PTSD. Mental health systems throughout the country have set up rapid response and outreach teams. CopeColumbia, for example, provides mental health services and resilience training to all members of the Columbia University Irving Medical Center community.   

Brian A. Fallon, Professor of Clinical Psychiatry and Director of the Lyme and Tick-Borne Diseases Research Center at Columbia University Irving Medical Center