As of March 26, 2020, the number of cases
of coronavirus disease 2019 (COVID-19) in the United States has surpassed that
of all other countries. According to data from Johns Hopkins University in
Baltimore, Maryland, there are currently over 245,000 cases of COVID-19 in the
United States compared with a seemingly plateaued number of82,000 cases in China
and over 117,000 and 115,000 each Spain and Italy, respectively.¹ These
numbers are almost continuously increasing.

Over the last 2 weeks, both the spread
and response to COVID-19 in the Unites States — especially in New York and
California — has been substantially more dramatic and severe than previously
observed. On March 20, 2020
— the day Governor Cuomo of New York signed the New York State on PAUSE
executive order — there were roughly 5000 cases of infection with severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) in New York City.^2,3
As of the last update from the New York City Department of Health and Mental
Hygiene on April 1, 2020, there are approximately 45,000 cases.² New
York City now accounts for roughly 5% of the global cases of COVID-19.

However, because SARS-CoV-2 is highly contagious, more uniform secondary prevention measures (ie, quarantine/isolation, adequate stores of personal protective equipment for healthcare workers) are highly needed. Currently, many of the decisions regarding isolation measures, as well as the burden of acquiring and purchasing equipment, fall on individual states. This has resulted in at least 23 states instituting clear mandates urging their citizens to stay at home.⁴ An additional 15 states have either had suggestions to isolate as much as possible from respective governors, or official orders to stay at home from municipalities throughout the individual states.⁴

The efficiency of this patchwork management for stalling the spread of SARS-CoV-2 is concerning. In a matter of roughly 3 weeks, much of what was established, known, and expected for the course of COVID-19 has been upended. This highlights the need to revisit and reassess some of the information we presented previously.  

1. Social Distancing: What is it? How does it help? And how important is it?

Much data has been presented on the
importance of social distancing and in the current state of the COVID-19
pandemic this cannot be overstated. At present, there are over 1 million cases
of infection with SARS-CoV-2 worldwide.¹ On March 5, 2020, there
were an estimated 100,000 cases.¹ This is a greater than 9-fold
increase over 30 days. Concerns about community-spread have become fact and
arguably the most important issue to address in order to change the direction
of the pandemic.

The most effective way to stall the spread of a pathogen that demonstrates such substantial transmissibility is to place physical distance between the vectors of transmission (in this case, people) for a significant period of time.⁵ Without finding new hosts to live in, the virus will eventually die out. In fact, without a curative medication or preventative vaccine this is the only effective way to eradicate SARS-CoV-2, as was the case with its 2002 precursor. To this end, countries have adopted a spectrum of isolation measures, ranging from mandated regional quarantines to municipal recommendations to avoid large gatherings.⁴

2. Are there concerns for getting infected with SARS-CoV-2 via packages?

Many people are doing their part and voluntarily self-isolating; many companies have taken the initiative and responsibility of creating work-from-home possibilities for employees; the government of several states have issued directives for nonessential workers to stay home. These measures are necessary, but have led to a number of people ordering necessities online and there remains a concern about the possible transmission of SARS-CoV-2 from packages. The data continues to report that while coronaviruses may survive on inanimate surfaces from 3 to roughly 72 hours, the risk for transmissibility is low.^6,7 The risk for person-to-person interaction between people delivering mail and those receiving it, however, does however remain; a preliminary study demonstrated that the virus can be aerosolized for up to 4 hours.^6,7 Therefore, social distancing and hand hygiene practices continue to be the mainstay for minimizing the risk for transmission. Where possible, it is suggested that packages be delivered in a contact-less fashion.

3. Is any symptom-level of a cough a sign of COVID-19?

A dry cough continues to be a staple symptom of infection with SARS-CoV-2; however, COVID-19 is a constellation of symptoms that includes fever, shortness of breath, cough, and in some patients, diarrhea.⁸ Further, some individuals do not exhibit any symptoms and proceed to clear the infection without developing COVID-19.⁸ So when are symptoms a cause for a concern? When there is a progressively worsening picture of symptoms over a period of 2 to 3 days, particularly when these include shortness of breath. The Centers for Disease Control and Prevention (CDC) advises that individuals refrain from seeking in-person care immediately because the majority of people have been shown to convalesce without the need for intervention. These measures also decrease the risks of transmitting the infection to other individuals.^8,9

This tactic also aids in controlling the burden placed on healthcare facilities and allows them to apply their resources to patients in critical need. However, this does not mean that patients who are feeling unwell will go unattended. The advent of telemedicine has allowed for the best of both worlds, giving patients an opportunity to receive an evaluation and counselling for any symptoms or illnesses they develop without the need to engage physically.¹⁰ Therefore, patients are encouraged to call their physician and discuss any onset of new symptoms and progression thereof.⁹ There is also a symptom self-checker available on the CDC website.

Of note, in order to aid clinicians in diagnosing patients there are several resources also available on the CDC website. These resources highlight the fact that roughly 80% of cases are mild to moderate, but among patients who are severe or critical, symptom progression can be rapid with some patients deteriorating within 1 week of symptom onset.⁸ While this has been managed largely via early, low-threshold procedures for intubation and mechanical ventilation, there is early evidence that supports the use of BiPAP and CPAP, with adjusted settings, in patients who are not in dire conditions.

4. Is there any benefit to wearing a mask?

Because there are
so many people who have a confirmed infection with SARS-CoV-2 and likely
significantly more who are or have been infected, but have not received testing
— in conjunction with the concern for the time the virus survives in an aerosolized
state — the use of masks remains a contentious subject.¹¹ Wearing a
surgical mask is certainly warranted for individuals who have symptoms of a
cough or sneezing because this mask is effective in preventing this person from
infecting other people. The ability to prevent a healthy person from being
infected is less effective, but still plausible. This is especially pertinent because
research has also suggested the presence of asymptomatic viral shedders.⁸

However, there is still a concern regarding the
shortage of personal protective equipment for healthcare workers, including
supplies of surgical masks, N-95 respirator masks, and gloves. Although many
private manufacturing companies have undertaken the task of remedying this
shortage, it is also the responsibility of the general public to not overuse or
overbuy these supplies. In terms of risk stratification, there is a
significantly lower risk in non-healthcare workers of reusing a mask compared
with a healthcare worker reusing a mask for several reasons, not the least
being a staggering difference in viral exposure. Of note, early research has
demonstrated that there may be effective ways to sanitize and reuse the vitally
important N95 masks.

There are similar concerns regarding the accessibility and availability of ventilators. This is a more difficult challenge to overcome, but here, too, the private sector and innovators are working to close the gap. Although the Society of Critical Care Medicine (SCCM), American Association for Respiratory Care (AARC), and American Society of Anesthesiologists have recommended against the use of a single ventilator for 2 patients,¹² previous research in emergency medicine has demonstrated the feasibility of this type of care. Further, the United States Food and Drug Administration has granted emergency use authorization to a novel device that attaches to a ventilator and allows it to be used by up to 4 patients.^13,14

5. Hydroxychloroquine? Chloroquine? Remdesivir? No Ibuprofen? No ACE-I/ARBs?

In an effort to
care for close to 1 million people, serious efforts have been undertaken to
find effective treatment and other ways to either prevent or ameliorate the
symptoms of COVID-19.

Due to the
mechanism of action the virus uses to infect cells, the use of medications such
as angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor
blockers (ARBs), as well as cyclooxygenase inhibitors such as ibuprofen have
been debated as potentially harmful or risk-increasing. However, there is currently
no clinical evidence or research to support this theory.

The rheumatologic
medication hydroxychloroquine and the antimalarial chloroquine are in preliminary
clinical trials, but limited current in
vitro evidence has shown that
both medications are effective in inhibiting viral entry of SARS-CoV.^15,16
Further, this data has also shown that between these 2 medications, the 50%
maximal effective concentration of hydroxychloroquine is higher than that of
chloroquine, to a statistically significant degree (17.31 μM vs 7.14 μM, at a multiplicity of infection of
0.2; P < .001).¹⁵
However, the adverse events, toxicity, and US availability associated with
chloroquine, in conjunction with the anti-inflammatory effects of
hydroxychloroquine, have highlighted a preference for the latter as a potential
treatment for COVID-19. However, the concerns for QT prolongation, especially
when used with azithromycin is paramount; there have been several deaths
associated with overdoses of these medications.¹⁷

Remdesivir has been also been recognized as a promising antiviral drug against a wide array of RNA viruses, including the family of beta-coronaviruses (which cause SARS, and the Middle Eastern Respiratory Syndrome). In vitro studies have demonstrated a solid response with remdesivir in its ability to inhibit the transcription of SARS-CoV-2 and demonstrated a substantially lower 50% maximal effective concentration compared with chloroquine (0.77 μM vs 1.13 μM), as well as a higher selectivity index (>129.87 vs >88.50).^17,18

References

1. Johns Hopkins University School of Medicine. Coronavirus COVID-19 global cases. Updated April 2, 2020. https://coronavirus.jhu.edu/map.html. Accessed April 2, 2020.
2. New York State. Governor Cuomo signs the ‘New York State on PAUSE’ executive order. https://www.governor.ny.gov/news/governor-cuomo-signs-new-york-state-pause-executive-order. Updated March 20, 2020. Accessed March 31, 2020.
3. New York City Department of Health and Mental Hygiene. COVID-19: Data. Updated April 1, 2020.  https://www1.nyc.gov/site/doh/covid/covid-19-data.page Accessed April 2, 2020.
4. Mervosh S, Lu D, Swales V. See which states and cities have told residents to stay at home. The New York Times. https://www.nytimes.com/interactive/2020/us/coronavirus-stay-at-home-order.html Updated April 2, 2020. Accessed April 2, 2020.
5. National Institutes of Health. New coronavirus stable for hours on surfaces: SARS-CoV-2 stability similar to original SARS virus. https://www.nih.gov/news-events/news-releases/new-coronavirus-stable-hours-surfaces. Updated March 17, 2020. Accessed April 2, 2020.
6. Hackensack Meridan Health. Can you get coronavirus from packages and mail? https://www.hackensackmeridianhealth.org/HealthU/2020/03/26/can-you-get-coronavirus-from-packages-and-mail/. Updated March 26, 2020. Accessed March 31, 2020.
7. Centers for Disease Control and Prevention. Frequently Asked Questions. https://www.cdc.gov/coronavirus/2019-ncov/faq.html. Updated April 1, 2020. Accessed April 2, 2020.
8. Centers for Disease Control and Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html. Updated April 1, 2020. Accessed April 2, 2020.
9. Harvard Health Publishing. Coronavirus resource center. https://www.health.harvard.edu/diseases-and-conditions/coronavirus-resource-center. Updated April 1, 2020. Accessed April 2, 2020
10. Rockwell KL, Gilroy AS. Incorporating telemedicine as part of COVID-19 outbreak response systems. Am J Manag Care. 2020;26(4).
11. van Doremalen N, Morris DH, Holbrook MG, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 [published online March 17, 2020]. N Engl J Med. doi:10.1056/NEJMc2004973
12. American Association for Respiratory Care [news release]. Irving, TX. Joint statement on multiple patients per ventilator. https://www.aarc.org/wp-content/uploads/2020/03/032620-COVID-19-press-release.pdf. March 26, 2020. Accessed March 31, 2020.
13. Neyman G, Irvin CB. A single ventilator for multiple simulated patients to meet disaster surge. Acad Emerg Med. 2006;13(11).
14. NS Medical Devices. FDA grants EUA status for Prisma Health’s VESper ventilator expansion device for COVID-19 patients. https://www.nsmedicaldevices.com/news/prisma-healths-vesper-covid/. March 26, 2020. Accessed April 2, 2020.
15. Liu J, Cao R,Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro [published online March 18, 2020]. Cell Discov. doi:10.1038/s41421-020-0156-0
16. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19 [published online March 4, 2020]. Int. J. Antimicrob. Agents. doi:10.1016/j.ijantimicag.2020.105932
17. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro [published online February 4, 2020]. Cell Res. doi:10.1038/s41422-020-0282-0
18. Kupferschmidt K, Cohen J. WHO launches global megatrial of the four most promising coronavirus treatments [published online March 22, 2020]. Science. doi:10.1126/science.abb8497

This article originally appeared on Infectious Disease Advisor