COVID-19 Alaska Clinical Update, June 25

Tocilizumab

An Italian retrospective cohort study including 544 patients with severe COVID-19 pneumonia compared 179 patients treated with tocilizumab, a monoclonal antibody that blocks one type of cytokine from binding to its receptor, to 365 patients treated with standard care. Cohorts required intubation at a comparable frequency, 18% and 16% respectively. Mortality was 20% in the standard care group and 7% in the tocilizumab group. After controlling for sex, age, center, duration of symptoms and SOFA score, tocilizumab seemed to produce a significantly reduced risk of mortality: adjusted hazard ratio 0.38, 95% confidence interval 0.17-0.83, p-0.015, with the largest difference seen in the subgroup with baseline PaO2/FiO2 <150mmHg. Patients given tocilizumab had a significantly higher rate of secondary bacterial infection (13% vs 4% in the standard care group). One patient in the treatment group also died of severe liver failure after herpes simplex virus 1 reactivation. Several smaller studies have also hinted that tocilizumab may decrease duration of vasopressors or need for oxygen, and a small prospective study found improved survival (hazard ratio 2.2, 95% confidence interval 1.3-6.7, p<0.05). 

Limitations of the Italian study include that standard of care included not just oxygen but treatment with hydroxychloroquine and lopinavir-ritonavir or darunavir-cobicistat. Azithromycin was sometimes added if respiratory bacterial superinfection was suspected. Patients who received tocilizumab received it in addition to these medications if they met certain criteria (SpO2<93% and a PaO2/FiO2 <300mmHg on room air), so the cohort receiving tocilizumab likely had a worse overall respiratory status than the standard care cohort. They also note that there was a national shortage of tocilizumab at one point during the study and an unspecified number of patients eligible for tocilizumab never received the drug, further confounding results. While these data are interesting and support the need for further research into tocilizumab, it may be too early to draw firm conclusions about its effect in severe COVID-19. IDSA recommends its use only in the context of a clinical trial. 

Risk to household contacts

A study looking at household contacts of 391 known cases of COVID-19 in Shenzen found that around 11% of household contacts and 7% of all close social contacts of known cases who were tested at regular intervals for SARS-CoV-2 had a positive result on RT-PCR. Children acquired COVID-19 atabout the same rate as adults.  

In contrast, a small Norwegian study used antibody tests to find a 31% positive rate among asymptomatic household members of known household cases. The antibody test they used was specific for the receptor binding domain of SARS-CoV-2. They also tested the known cases and 79% tested positive for antibodies. 

Possible limitations of antibody testing include specificity concerns, so the difference between these studies may be attributable to several factors: different behaviors influencing transmission between household contacts in China and Norway, lower sensitivity and increased underdetection using an intermittent RT-PCR testing strategy to identify household acquired cases, and/or lower specificity of antibody testing. Also, contacts included in the Norwegian study lived with the known case, while the Chinese study also included those who travelled, shared a meal, or socially interacted with the known case as well as people living in the same dwelling (which was split off as a subgroup analysis). Because of these differences, the Norwegian study may prove to be a better reflection of the real risk to household contacts, while the Chinese study may help emphasize that social interaction and sharing a meal are high-risk activities in terms of transmission among households. 

COVID-19 collections of clinical resources

Several vetted, searchable collections of current clinical research in COVID-19 are publicly available for clinicians to use to search for literature covering specific questions. The World Health Organization has compiled a comprehensive, multilingual database that is updated five times a week with current research from all over the globe. The CDC maintains a downloadable collection of recent articles intended for researchers, while the NIH has a similar collection. For topic suggestions or requests for literature reviews for these updates to address specific clinical questions relevant to Alaska, you may use this form. 

AK Clinical Reminders: COVID-19 testing guidelines and  testing site locator Report any positive test to the state Section of Epidemiology using the COVID Reporting Hotline at 1-877-469-8067 or by faxing in the Infectious Disease report form. If you suspect COVID-19 in an outpatient who cannot isolate in their own home (for example they are unsheltered or from out of town) or for another urgent situation call SOE at 907-269-8000 or 800-478-0084 (after-hours). Join us for the ECHO series for more information and discussion: Use the links below to register beforehand for the online meeting Large Gatherings and Community Events: Mondays, 2-3PM COVID-19 for Alaska Healthcare Providers: Tuesdays, 7-8:30PM Healthcare Specific COVID-19 Situational Awareness: Tuesdays and Thursdays, 12-1PM Alaska Perinatal ECHO: Every other Thursday beginning 5/7/20, 7-8PM Palliative Care in COVID-19 ECHO: Wednesdays, 12-1PM EMS ECHO: Thursdays, 10-11AM Dental ECHO: Every other Wednesday beginning 5/13/20, 3:30-4:30 PM AK COVID-19 clinical hotline for physicians: 833-751-4212. Staffed 24/7. 8PM-8AM is for urgent/emergent questions only.  AK Responders Relief Line: 24/7 behavioral health for everyone working in healthcare during the COVID-19 pandemic:  1-844-985-8275