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By Christian Hoffmann &
Bernd S. Kamps
2 June
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Summary
Summer is coming! The next edition of COVID Reference (around 350 pages) will be published within days! Today we have some more good news. Please read here why.
First, discuss with your colleagues that famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients; plan pharmacokinetic studies that will help to optimize dosage and formulation of favipiravir; and determine if positive PCR means infectivity.
Afterwards, discover the influence of COVID-19 on seasonal influenza activity; reduce the titer of SARS-CoV-2 in human plasma using riboflavin and UV light; describe why a decrease in B cells was independently associated with prolonged viral RNA shedding; and describe the characteristics associated with hospitalization for COVID-19 in people with rheumatic disease.
Finally, find out that of 509 medical staff working to treat COVID-19 patients at the Hyogo Prefectural Kakogawa Medical Center, none had IgG antibodies for SARS-CoV-2 in early May; write a systematic review of chest CT findings in 4410 adult patients with COVID-19; and evaluate a recently released assay which uses isothermal nucleic acid amplification of the RdRp viral target and is capable of producing positive results in as little as 5 minutes.
Epidemiology
Lee H, Lee H, Song KH, et al. Impact of Public Health Interventions on Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Korea. Clin Infect Dis. 2020. PubMed: https://pubmed.gov/32472687 . Full-text: https://doi.org/10.1093/cid/ciaa672
Efforts to activate high level national response not only led to a decrease in COVID-19, but also a substantial decrease in seasonal influenza activity. During the period of enforced social distancing from week 9 to 17 of 2020 in Korea, influenza hospitalization cases were 11.9-26.9-fold lower compared with previous seasons. This is good news, because nobody needs influenza.
Transmission
Ragan I, Hartson L, Pidcoke H, Bowen R, Goodrich R. Pathogen reduction of SARS-CoV-2 virus in plasma and whole blood using riboflavin and UV light. PLoS One. 2020 May 29;15(5. PubMed: https://pubmed.gov/32470046 . Full-text: https://doi.org/10.1371/journal.pone.0233947. eCollection 2020
Plasma and whole blood units infected with SARS-CoV-2 underwent treatment with riboflavin and UV light. Riboflavin and UV light effectively reduced the titer of SARS-CoV-2 to the limit of detection in human plasma and by 3.30 ± 0.26 on average in whole blood. This is good news, because these treatments may reduce blood-borne pathogens in high-risk settings while maintaining blood product quality.
Nagano T, Arii J, Nishimura M, et al. Diligent medical activities of a publicly designated medical institution for infectious diseases pave the way for overcoming COVID-19: A positive message to people working at the cutting edge. Clin Infect Dis. 2020 May 31. PubMed: https://pubmed.gov/32474577 . Full-text: https://doi.org/10.1093/cid/ciaa694
Of 509 medical staff members working to treat COVID-19 patients at the Hyogo Prefectural Kakogawa Medical Center, a large medical institution for infectious diseases in Japan (mean number of hospitalized COVID-19 patients was 20), none had IgG antibodies for SARS-CoV-2 on May 1-8. This is good news, because results show that standard preventive measures against infectious diseases can prevent SARS-CoV-2 exposure in medical staff.
Diagnostics
Bullard J, Dust K, Funk D, et al. Predicting infectious SARS-CoV-2 from diagnostic samples. Clinical Infectious Diseases 2020, May 22 2020. Full-text: https://doi.org/10.1093/cid/ciaa638
This retrospective cross-sectional study determined PCR positive samples for their ability to infect cell lines. Of 90 samples, only 29% demonstrated viral growth. There was no growth in samples with a Ct > 24 (the lower the cycle threshold, the higher the viral load) or duration of symptoms > 8 days. This is very good news, because positive PCR does not mean infectivity. And infectivity duration is short.
Hao S, Lian J, Lu Y, et al. Decreased B cells on admission was associated with prolonged viral RNA shedding from respiratory tract in Coronavirus Disease 2019: a case control study. J Infect Dis. 2020 May 31. PubMed: https://pubmed.gov/32474608 . Full-text: https://doi.org/10.1093/infdis/jiaa311
In 104 patients, a decrease in B cells was independently associated with prolonged viral RNA shedding. The viral RNA shedding from respiratory tract in patients with normal B cell count was significantly shorter than patients with decreased B cell on admission (median 11 vs 16 days). This is good news, because these observations may help to individualize monitoring of COVID-19 patients.
Ojha V, Mani A, Pandey NN, Sharma S, Kumar S. CT in coronavirus disease 2019 (COVID-19): a systematic review of chest CT findings in 4410 adult patients. Eur Radiol. 2020 May 30. PubMed: https://pubmed.gov/32474632 . Full-text: https://doi.org/10.1007/s00330-020-06975-7
A total of 45 studies comprising 4,410 (!) patients were included in this review. Ground glass opacities (GGOs), whether isolated (50%) or coexisting with consolidations (44%) in bilateral and subpleural distribution, were the most prevalent chest CT findings in adult COVID-19 patients. Follow-up CT shows a progression of GGOs into a mixed pattern, reaching a peak at 10-11 days, before gradually resolving or persisting as patchy fibrosis. Younger people tend to have more GGOs. Older or sicker people tend to have more extensive involvement with consolidations. This is good news, because it’s good to see that there are nerds out there (like us) who have nothing better to do than look through 4,410 CT scans.
Basu A, Zinger T, Inglima K, et al. Performance of Abbott ID NOW COVID-19 rapid nucleic acid amplification test in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution. J Clin Microbiol. 2020 May 29. PubMed: https://pubmed.gov/32471894 . Full-text: https://doi.org/10.1128/JCM.01136-20
The authors evaluated the recently released Abbott ID NOW COVID-19 assay (uses isothermal nucleic acid amplification of the RdRp viral target) which is capable of producing positive results in as little as 5 minutes. Results were compared with RT-PCR Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs. Regardless of method of collection and sample type, the rapid test had negative results in a third of the samples that tested positive by PCR when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs. This is good news, well, because this is the-good-news-day. However, these rapid tests (if further improved) may find their role in clinical settings such as emergency departments where rapid diagnosis is crucial.
Comorbidties
Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020 May 29. PubMed: https://pubmed.gov/32471903. Full-text: https://doi.org/10.1136/annrheumdis-2020-217871
Case series of 600 COVID-19 patients with rheumatic diseases from 40 countries. Nearly half of the cases were hospitalized (277 or 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalization but not the use of conventional disease-modifying anti-rheumatic drug (DMARD) alone or in combination with biologics, the Janus Kinase inhibitors. This is good news because only high glucocorticoid exposure (which has well-known side effects anyway) is associated with a higher odds of hospitalization but not either DMARDs or NSAIDs.
Treatment
Irie K, Nakagawa A, Fujita H, et al. Pharmacokinetics of Favipiravir in Critically Ill Patients with COVID-19. Clin Transl Sci. 2020 May 31. PubMed: https://pubmed.gov/32475019 . Full-text: https://doi.org/10.1111/cts.12827
In 7 patients with severe COVID‐19 who were admitted to the intensive care unit and placed on mechanical ventilation, the favipiravir trough concentration was much lower than that of healthy subjects in a previous clinical trial. This is, however, good news, because this will lead to further PK studies that will help to optimize dosage and formulation – and improve efficacy of this drug.
Freedberg DE, Conigliaro J, Wang TC, et al. Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study. Gastroenterology. 2020 May 21. PubMed: https://pubmed.gov/32446698 . Full-text: https://doi.org/10.1053/j.gastro.2020.05.053
Famotidine is a histamine-2 receptor antagonist that suppresses gastric acid production. It is thought to inhibit the 3-chymotrypsin-like protease (3CLpro) and/or to act via its antagonism or inverse-agonism of histamine signalling. This retrospective study looked at 1,620 patients, including 84 patients (5.1%) who received different doses of famotidine within 24 hours of hospital admission. After adjusting for baseline patient characteristics, use of famotidine remained independently associated with a reduced risk for death or intubation (adjusted hazard ratio 0.42, 95% CI 0.21-0.85) and this remained unchanged after careful propensity score matching to further balance the co-variables. Of note, there was no protective effect associated with use of PPIs. The maximum plasma ferritin value during hospitalization was lower with famotidine, indicating that the drug blocks viral replication and reduces the cytokine storm. RCTs are underway, keep an eye on this! This is damned good news!