New research looks at drug safety in COVID-19, quarantine length in asymptomatic contacts

Use of immunosuppressive drugs and renin-angiotensin system inhibitors does not appear to adversely affect outcomes in patients with COVID-19, and a seven-day quarantine may be sufficient in asymptomatic contacts with confirmed COVID-19 exposure.

Chronic use of immunosuppressive drugs does not appear to be associated with severity of COVID-19 in hospitalized patients, according to a recent retrospective cohort study. Researchers examined 2,121 consecutive adults with acute inpatient admission between March 4 and Aug. 29, 2020, for confirmed or suspected COVID-19. The goal of the study was to determine whether chronic immunosuppression, defined as a current prescription for immunosuppressive drugs at the time of admission, was linked to worse outcomes in patients with COVID-19. The study outcomes included mechanical ventilation, in-hospital mortality, and length of stay. Results were published Jan. 7 by Clinical Infectious Diseases.

Of the 2,121 patients, 1,967 (93%) had laboratory-confirmed COVID-19 and 154 (7%) had suspected disease. Median age was 55 years. One hundred eight patients were classified as being immunosuppressed before COVID-19, mostly due to prednisone, tacrolimus, or mycophenolate mofetil therapy. Three hundred eleven patients (15%) received mechanical ventilation, the median length of stay was 5.2 days, and 1,927 patients (91%) survived to discharge. No significant difference was seen after adjustment in risk for mechanical ventilation (hazard ratio [HR], 0.79; 95% CI, 0.46 to 1.35), in-hospital mortality (HR, 0.66; 95% CI, 0.28 to 1.55), or length of stay (HR, 1.16; 95% CI, 0.92 to 1.47) in patients with immunosuppression versus those without.

“In this analysis of a large, diverse cohort of adults hospitalized with COVID-19 in the United States, we did not find differences in risk of mechanical ventilation, in-hospital mortality, or length of stay among individuals with and without chronic use of immunosuppressive medications,” the authors wrote. “Our results contribute to a growing body of evidence that should provide reassurance to clinicians and patients using chronic immunosuppressive medicines.”

Similarly, a study published Jan. 7 by The Lancet Respiratory Medicine found no link between renin-angiotensin system inhibitors and COVID-19 disease severity in hospitalized patients. Researchers in the multisite, multicountry REPLACE COVID trial evaluated adult patients admitted to the hospital with COVID-19 who were receiving a renin-angiotensin system inhibitor before admission and were randomly assigned to continue or discontinue therapy.

The study's primary outcome was a global rank score that incorporated time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during hospitalization. Seventy-five patients were assigned to continue renin-angiotensin system inhibitors, and 77 were assigned to discontinue them. Compared with discontinuation, continuation did not affect the global rank score. ICU care or invasive mechanical ventilation was required in 16 participants (21%) in the continuation group and 14 (18%) in the discontinuation group. Mortality rates in each group were 15% versus 13%, respectively, while 39% and 36% had at least one adverse event. Blood pressure, serum potassium level, and creatinine level did not differ during follow-up between the two groups. The researchers noted that their study was small and had other limitations but concluded that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can be safely continued in hospitalized patients with COVID-19 unless there is a clear contraindication.

Finally, recent data from Vermont indicate that a seven-day rather than a 10-day quarantine period may be sufficient for asymptomatic persons exposed to a patient with confirmed COVID-19. A report published Jan. 8 by MMWR looked at the effectiveness of a policy instituted by the Vermont Department of Health in May 2020 allowing persons with confirmed exposure to COVID-19 to end quarantine if they had remained asymptomatic and received a negative result on a polymerase chain reaction test for SARS-CoV-2 on or after day 7.

From May 8 to Nov. 16, 2020, the health department identified 8,798 exposed contacts of COVID-19 patients. Of these, 3,983 (45%) had sought testing within 14 days of exposure. In this group, 2,200 (55%) received testing on days 7 to 10, and of these, 977 (44.9%) had a specimen collected on day 7. In the latter group, 34 (3%) had positive results, 940 (96%) had negative results, and three (<1%) had indeterminate results. Twenty-two of the 34 contacts with positive results were symptomatic at testing, and 12 were not. One hundred fifty-four of the 940 contacts who received negative results on specimens collected on day 7 had another test within the next seven days, and of these, 152 (99%) received negative results and two (1%) received indeterminate results. Among all of the 2,200 contacts who were tested on days 7 to 10 after exposure, 87 (4%) had a positive result, and of these, 24 (28%) were asymptomatic.

The researchers concluded that no quarantined contacts who tested negative at day 7 after exposure and were retested between days 8 and 14 tested positive, indicating that shortening quarantine in asymptomatic persons with a negative test result on day 7 or later has not been shown to result in SARS-CoV-2 transmission. “In addition to reducing the duration of quarantine for exposed contacts, Vermont's policy might have provided additional benefits to the state's pandemic response by identifying some asymptomatic patients earlier in the course of their illness through enhancing statewide surveillance testing of an exposed group,” they wrote. “This assessment supports Vermont's policy as being effective and offers data to support recommendations to shorten quarantine with testing such as those provided in CDC's updated quarantine guidance.”