Scientists search for ways to impede, treat COVID-19

March 31, 2020

Nursing homes must identify and bar staff and visitors who may be infected with COVID-19, monitor patients for infection, and take stringent infection-control measures to prevent outbreaks such as the deadly one in King County, Washington, experts said in an epidemiologic study published March 27 in The New England Journal of Medicine.

Meanwhile, preliminary research from China involving five patients suggests that transfusion with the plasma of recovered coronavirus patients that contains neutralizing antibody could benefit patients critically ill with the pandemic coronavirus and acute respiratory distress syndrome (ARDS).

In the nursing home study, public health officials in Seattle–King County and the US Centers for Disease Control and Prevention (CDC) performed a case investigation, contact tracing, quarantine of potentially infected people, isolation of confirmed and possible cases, and enhanced infection prevention and control.

In that outbreak, which involved the Life Care facility in the Seattle suburb of Kirkland, 167 people were sickened from Feb 28 to Mar 18, including 101 of 130 residents, 50 of 170 staff, and 16 visitors. The outbreak threatened the health of residents and strained the ability of hospitals to care for them.

As of Mar 18, 30 nursing homes in King County had reported at least one confirmed COVID-19 case. The spread was likely due to staff working at multiple facilities while ill, patient transfers among facilities, scarcity of and frequent changes in types of available personal protective equipment (PPE), and lack of a designated staff member to ensure proper staff use of PPE, the researchers said.

The hospitalization rate for residents was 54.5%, while 50.0% of visitors and 6.0% of employees were admitted. Thirty-four residents (33.7%) and 1 of the 16 visitors died. No healthcare worker deaths were reported.

The vast majority of residents (94.1%) had underlying health problems, the most common of which were high blood pressure (67.3%), heart disease (60.4%), kidney disease (40.6%), diabetes (31.7%), lung disease (31.7%), and obesity (30.7%). Seven residents had high blood pressure as their only coexisting condition.

Median resident age was 83 years (range, 51 to 100), while median visitor age was 62.5 years (range, 52 to 88), and median staff age was 43.5 years (range, 21 to 79).

The authors urged nursing homes to provide hands-on training, store adequate supplies, and ensure adherence to infection prevention and control protocols, with routine auditing and feedback from observing staff workflow.

"The impact of these policies in protecting long-term care facilities should continue to be evaluated, along with the role of serial testing strategies to identify infected staff or patients as testing reagents and supplies become more available," they wrote.

In a preliminary, uncontrolled case series in China published in JAMA, scientists reported that four of five patients undergoing mechanical ventilation due to COVID-19 infection had normal body temperatures and lower sequential organ failure assessment (SOFA) score (i.e., milder illness) within 3 days of receiving the plasma of a recovered patient, or convalescent plasma.

Convalescent plasma has been used for different diseases for at least a century on the premise that disease-fighting antibodies in the recovered patient's blood boost the immune response against the disease in the patient receiving the plasma.

The patients, who were 36 to 65 years old, had been given antiviral agents and the corticosteroid methylprednisolone. One patient was on extracorporeal membrane oxygenation life support, and two patients had pneumonia. Four patients had no underlying conditions and received convalescent plasma about 20 days after hospitalization, while a fifth with high blood pressure and mitral valve insufficiency received it at day 10.

In four patients, oxygenation increased and viral loads decreased and became negative within 12 days, and neutralizing antibody titers increased 1 to 12 days after transfusion (range, 40 to 60 before and 80 to 320 after 7 days of treatment).

ARDS resolved in four patients on day 12, and mechanical ventilation was stopped in three patients within 2 weeks of transfusion, the authors wrote. Three of the five patients were released from the hospital (length of stay was 51, 53, and 55 days), while the others were in stable condition 37 days after transfusion.

The investigators note, however, that their results are inconclusive because of the small sample size and study design and call for clinical trials of the treatment method. In a commentary in the same journal, John Roback, MD, PhD, and Jeannette Guarner, MD, of Emory University School of Medicine in Atlanta, agreed.

The two said that the lack of a control group makes it impossible to know whether the transfusion aided recovery or whether recovery might have occurred without transfusion. "In addition, patients received numerous other therapies (including antiviral agents and steroids), making it impossible to disentangle the specific contribution of convalescent plasma to the clinical course or outcomes," they wrote.

They added that, because convalescent plasma was administered for as long as 3 weeks after hospital admission, "it is unclear whether this timing is optimal or if earlier administration might have been associated with different clinical outcomes." 

However limited, the study does provide some evidence to support further study of the therapy in larger, randomized, controlled trials, noting that it has been used with some apparent success to treat patients with severe acute respiratory syndrome, H1N1 influenza, avian influenza, hemorrhagic fevers, and other infections, they said.

In hard-hit New York, Governor Andrew Cuomo announced on Mar 24 that a trial of convalescent plasma in seriously ill coronavirus patients would commence within the week.

A total of 1,218 fatalities have occurred in New York, the hardest-hit state, with 66,497 cases. New York City has 37,453 cases. NYC Health said that 42% of confirmed cases have been in adults ages 18 to 44, and only 17% have been in adults over the age of 65.

"We have been playing catch-up from day 1; you never win playing catch up," said Governor Andrew Cuomo today at a press conference. "If you wait to prepare for the storm to hit, it is too late, my friends." Cuomo warned that New York has not seen its apex off cases yet, and likely will not for another 2 weeks, at least.

Cuomo also asked medical personnel from other states to consider coming to New York to practice during the outbreak, and promised them that New Yorkers would return the favor when their communities were facing an influx.

Monday, the USS Comfort, a naval ship hospital, docked in Manhattan, and the Javits Convention Center opened as a field hospital. Both developments add 2,000 hospital beds to New York City.

Local media in the city warned that 900 city police officers would likely be infected with the virus by today, and 13% of the city's uniformed workforce was out sick.

Ford CEO Jim Hackett announced the automaker will produce 50,000 ventilators in 100 days in a partnership with GE Healthcare. After the first 100 days, Ford said it will be able to produce 30,000 ventilators per month for as long as is needed.

"The Ford and GE Healthcare teams, working creatively and tirelessly, have found a way to produce this vitally needed ventilator quickly and in meaningful numbers," said Hacket. The ventilators will be made at a plant in Ypsilanti, Michigan, which is expected to start production Apr 20.

Following an Emergency Use Authorization by the Food and Drug Administration (FDA), the Department of Health and Human Services (HHS) announced it accepted 30 million doses of hydroxychloroquine sulfate donated by Sandoz, the Novartis generics and biosimilars division, and 1 million doses of chloroquine phosphate donated by Bayer Pharmaceuticals, to use as treatments on hospitalized COVID-19 patients or in clinical trials

Chloroquine and hydroxychloroquine are antimalarials with some anti-inflammatory benefits that may be useful in treating COVID-19, but large trials have not been completed on COVID-19 patients.

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