COVID-19: What We Know and Next Steps

Daniel R. Kuritzkes, MD

Chief, Division of Infectious Diseases
Brigham and Women's Hospital
Harriet Ryan Albee Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Daniel R. Kuritzkes, MD, has disclosed that he has received funds for research support from Gilead Sciences, Merck, and ViiV Healthcare and consulting fees from Gilead Sciences, GlaxoSmithKline, Merck, and ViiV Healthcare.

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Released: March 19, 2020

Today, the world faces a viral respiratory disease outbreak whose scope has not been seen in more than a century. As of March 19, 2020, more than 225,000 cases of COVID-19 have been confirmed worldwide, and more than 9000 have died. By the time you read these words, the numbers will surely have increased. The COVID-19 pandemic is caused by a novel coronavirus now named SARS-CoV-2 (a note on terminology: SARS-CoV-2 is the official name for the coronavirus that causes the disease COVID-19). This coronavirus is closely related to, but distinct from, the coronavirus that caused an epidemic of severe acute respiratory syndrome (SARS) in 2002-2003. Coronaviruses are widespread in nature and account for up to 25% of “common colds.” Certain coronaviruses, such as those responsible for SARS and Middle East Respiratory Syndrome (MERS), lead to far more serious disease. Various species of bats serve as the natural host for coronaviruses, which periodically break out into human populations as zoonotic epidemics.

Brief Overview: What We Know
The current COVID-19 epidemic began in Wuhan, China, in December 2019. Within a few weeks, physicians and health authorities in China recognized that a novel virus was causing severe respiratory disease, resulting in pneumonia and respiratory failure in the most severe cases. Although symptoms of COVID-19 often resemble those of influenza, including fever and cough, COVID-19 appears to be far more contagious than the flu and has a case fatality rate that may be up to 10 times higher than that of influenza. While the crude case fatality rate, based solely on reported numbers of cases and deaths, appears to be 3.96%, the actual risk of death from COVID-19 is unclear because testing for SARS-CoV-2 infection and supportive care for COVID-19 vary widely across the world. Actual death rates vary enormously, from 7.3% in Italy to 0.9% in South Korea. Although the reasons for these wide disparities in case fatality rates are unclear, what is clear is that older age (particularly patients older than 70 years of age) and underlying medical conditions, such as hypertension and cardiovascular and pulmonary diseases, substantially increase the risk of death. Conversely, in contrast to the H1N1 swine flu epidemic of 2009, rates of symptomatic infection and serious illness among children and adolescents are significantly lower with COVID-19 than for older adults.

Preventing Transmission
Absent of an effective vaccine, what measures can be taken to prevent COVID-19? Traditional measures for epidemic control of respiratory illness such as influenza are effective, including social distancing, frequent hand washing, and avoiding touching your eyes, nose, and mouth. Those who have had close contact with a person with confirmed COVID-19 should self-quarantine for 14 days (the average incubation period is 5-7 days, but some cases have occurred as long as 12-14 days after exposure).

Antiviral Therapies
In contrast to influenza infection, there are no proven effective antiviral therapies for COVID-19. In vitro data and animal models (based on MERS) suggest that the investigational RNA polymerase inhibitor remdesivir may have activity against SARS-CoV-2 and prevent serious pulmonary complications; several clinical trials are currently underway. Likewise, in vitro data suggest that chloroquine or hydroxychloroquine may have antiviral activity by blocking egress of SARS-CoV-2 from endocytic vesicles, similar to the mechanism by which amantadine blocks infection by influenza. Trials of this agent for treatment and prevention are underway. More controversial is the role of HIV-1 protease inhibitors such as lopinavir. Although in vitro data suggest some antiviral activity, the concentrations required to inhibit viral replication in that setting are at the margins of what may be achievable with in vivo dosing. A randomized clinical trial of lopinavir/ritonavir conducted in China found no difference in time to clinical improvement, viral shedding, or 28-day mortality. There is also controversy on the role of angiotensin II receptor inhibitors, since SARS-CoV-2 uses this receptor for cell entry. Tocilizumab and other IL-6 receptor antagonists may have a role in modulating the inflammatory state engendered by COVID-19 but remain investigational.

The medical, social, and economic consequences of COVID-19 are unprecedented in contemporary society. Severely restrictive measures may still be necessary to bring the current pandemic under control. Each of us has a responsibility through our own actions, professionally and personally, to contribute to control of this pandemic.

Your Thoughts?
What measures are you recommending, and which are you personally taking, to protect against COVID-19? Answer the polling question and leave a comment in the discussion section.

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