The Virus

Airborne and contact spread is common in this virus as we now understand it. Thus, health care workers performing aerosol-generating procedures on patients with COVID-19 in the intensive care unit should wear fitted respirator masks (N95, FFP2, or equivalent) as opposed to standard surgical or medical masks, in addition to other personal protective equipment such as gowns, gloves, and eye protection. If possible, aerosol-generating procedures should be performed in a negative-pressure room. If a patient is not ventilated, medical/surgical masks, in addition to other personal protective equipment, should be worn. Similarly, if non–aerosol-generating procedures are performed, medical/surgical masks as opposed to respirator masks are recommended. Endotracheal intubation should be performed with video-guided laryngoscopy as opposed to direct laryngoscopy if this video technology is available. This group makes a weak recommendation with regard to sampling the lower respiratory tract favoring the collection of endotracheal aspirates as opposed to bronchial wash or bronchoalveolar lavage specimens.

Fluid support recommendations include conservative strategies and using crystalloids that are buffered over unbalanced crystalloids. “Conservative” fluid administration targets little or no net fluid accumulation on a daily basis. Gelatins and starches are not recommended as part of resuscitation protocols. Similarly, albumin should not be used for initial resuscitation, and dextrans should be avoided. Norepinephrine is considered the first-line vasoactive drug. Vasopressin and epinephrine may be used in patients with shock if norepinephrine is not available. This group recommends against the use of dopamine and supports using vasopressin as a second-line agent in combination with norepinephrine if a second drug is necessary. The mean arterial pressure goal recommended is 60 to 65 mm Hg. Dobutamine should be considered in patients with evidence of cardiac dysfunction and persistent hypoperfusion. In patients with COVID-19 and refractory shock, low-dose corticosteroid therapy should be considered typically at a dose of intravenous hydrocortisone 200 mg/d given as an infusion or intermittent doses.

The group made a number of recommendations with respect to pulmonary and oxygenation support. Supplemental oxygen was recommended if finger oximetry (peripheral capillary oxygen saturation) results are less than 90%. In patients with hypoxemic respiratory insufficiency on oxygen, peripheral capillary oxygen saturation should be maintained no higher than 96%. A high-flow nasal cannula is the next step up in treatment over conventional oxygen therapy. A high-flow nasal cannula is also recommended over other forms of noninvasive positive-pressure ventilation. If high-flow nasal cannula technology is not available, other forms of noninvasive ventilation may be tried. When patients fail noninvasive ventilation, intubation with low tidal volume ventilation (4-8 mL/kg/predicted body weight) is recommended with plateau pressures on the ventilator less than 30 cm/H₂O. A higher positive end-expiratory pressure (PEEP) strategy is recommended over a lower PEEP strategy in patients with refractory hypoxemia on mechanical ventilation. “Higher PEEP” consists of PEEP greater than 10 cm/H₂O. As in hemodynamic recommendations, conservative fluid administration is recommended over a liberal fluid administration strategy. Prone ventilation may be considered in patients with moderate to severe ARDS with intermittent doses of neuromuscular blockade to facilitate lung-protective ventilation. If ventilator dyssynchrony is a significant concern, continuous neuromuscular blockade for up to 48 hours is recommended. Inhaled nitric oxide is not recommended. Inhaled pulmonary vasodilators may be considered in patients with severe hypoxemia with recruitment maneuvers to reopen gas exchange units. Extracorporeal membrane oxygenation is a final therapy that should be considered in carefully selected patients with COVID-19 associated with severe ARDS.

Finally, the group makes a number of general therapeutic recommendations including avoidance of routine use of systemic corticosteroids, except possibly in the severely ill patient with COVID-19 and ARDS. Empiric antimicrobials should be considered over avoidance of antimicrobials. De-escalation of antimicrobial therapy should be considered daily, and the spectrum of coverage changed based on microbiology results and the clinical state of the patient.

Tylenol (Johnson & Johnson [McNeil Laboratories, Fort Washington, PA], New Brunswick, NJ) is recommended for a fever. Immunoglobulin administration is not recommended at this time. There is no clear evidence to support the use of specific antiviral agents in COVID-19 patients at this time. Similarly, recombinant interferons are not recommended. The group offered no recommendation regarding the use of chloroquine or hydroxychloroquine in critically ill patients with COVID-19.

Osterholm M. What's “Normal” Now? What's Next? Opinion Exchange. Minneapolis Star Tribune. March 22, 2020.

Morens DM, Daszak P, Taubenberger JK. Escaping Pandora's box–another novel coronavirus. N Engl J Med. 2020;382:1293-1295.

Professor Michael Osterholm, based in the Twin Cities, has been one of the nation's leading epidemiologists and has recently joined the faculty at the University of Minnesota. In previous publications, Osterholm, now a public health professor and director for the Center of Infectious Disease Research and Policy, reviewed older infections (MERS and SARS) caused by a coronavirus, the same viral family now driving the COVID-19 pandemic.

Osterholm makes two initial observations. First is that we, as a nation, had a sense of invincibility that we had a border that would not allow infectious disease agents to penetrate. We are now seeing that this is foolish. A microbe anywhere in the world today can be anywhere in the world tomorrow. A second fallacy was the lack of creative imagination “unless related to a video game or movie.” None of the COVID-19 presentation was exotic. People who knew health care and epidemiology knew that our health care system had been carved down to the bone for which there was no resiliency of any substantial nature, no excess capacity, and no money to stockpile large volumes of protective equipment. There has been no real understanding of the vulnerability of this country caused by outsourcing all of its drug manufacturing to places like China. COVID-19 showed that events in one country make many countries vulnerable. Even when COVID-19 was sitting on our doorstep, people did not take it seriously.

Osterholm offers no pretenses about what will ultimately happen. He says directly that we may never go back to normal. We will have a new normal just as the airlines did after 9/11. We want to do what we can to help people psychologically work through the implications of COVID-19. The bottom line is people need direct answers, straight talk, and the truth including what we know and what we don't know.

Ironically, companies that could be making protective equipment and ventilators had been working nonstop for weeks before the government showed interest. However, even if everyone recognized the need to increase manufacturing capability, this is impossible to do overnight. For example, after Pearl Harbor, it took over 3 years to restore the Pacific Fleet.

Osterholm had an interesting closing observation regarding keeping children out of school. He noted that Singapore and Hong Kong each broached the question of keeping children out of school. The bottom line was that Singapore did not close schools, whereas Hong Kong did. There was no difference in outcome. It appears that behavioral goals are more complex than simple school attendance. A more important factor in saving lives in a hospital is when you consider that 20% of nurses, doctors, and respiratory therapists are unable to work because they must stay home to watch their kids.

Another view comes from the Greek myth of Pandora's box; the gods gave Pandora a locked jar that she was never to open. Driven by human weakness, she nevertheless opened it and released the world's misfortunes and plagues.

In our crowded world of 7.8 billion people, a combination of altered human behaviors, environmental changes, and inadequate global public health mechanisms can easily turn obscure animal viruses into existential human threats. We have created a global human-dominated ecosystem that serves as a playground for the emergence and host switching of animal viruses, particularly the genetically error-prone RNA viruses whose high mutation rates provide opportunity for changing hosts in new ecosystems. For example, it took the genome of man millions of years to evolve by 1%. Many animal RNA viruses can evolve by more than 1% in a matter of days. It is not surprising that we see the emergence of more viral pathogens.

Preventing and controlling future pandemic episodes is a global priority. The present COVID-19 epidemic can be compared with the flu epidemic of 1918, which took millions of lives. Wherever the 1918 pandemic began, it spread silently around the world causing only mild cases but also mortality of 0.5% to 1% or higher, a rate that was initially too low to be detected against a high background of death from unrelated respiratory illnesses. Then, suddenly, the flu epidemic exploded in urban centers almost everywhere at once, making a dramatic entrance after a long stealthy approach. We now see the early stages of COVID-19 emergence in the form of growing and geographically expanding case totals, and there are concerning similarities between the two respiratory disease pathogens. Like the pandemic influenza of 1918, COVID-19 is associated with respiratory spread and an undetermined percentage of infected people with presymptomatic or asymptomatic cases transmitting infection to others with a high ultimate fatality rate.

The problem is that most influenza cases are either asymptomatic or subsymptomatic, undiagnosed, or transmitted to others before the onset of symptoms. Can we do better with the present viral pandemic, facing a pathogen with longer incubation and serial generation time but with an as-yet-undetermined ratio of silent cases to apparent cases and an unknown rate of asymptomatic spread? The answer to this question is vital. In the end, the only comfort for Pandora was hope.