COVID-19 Intelligence Report: Diagnostics/pathology

Title: Extra-respiratory manifestations of COVID-19 Publisher: International Journal of Antimicrobial Agents Publication Date: May 25, 2020

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243791/pdf/main.pdf

Key Takeaway: SARS-CoV-2 infection often involves other organs/systems beyond the respiratory system.

 

Title: Viral Load Dynamics in Patients Infected with SARS-CoV-2

Publisher: NEJM Journal Watch (summarizing articles in BMJ and Eur J Clin Micro Infect Dis)

Publication Date: May 27, 2020

URL: https://www.jwatch.org/na51648/2020/05/27/viral-load-dynamics-patients-infected- with-sars-cov-2

Key Takeaway: This is a report of two recent publications on viral load dynamics in patients recovering from Covid-19 infection. Conclusions:

1. Patients with severe COVID-19 shed virus longer and in higher copy numbers.
2. Viral shedding appears to last longer in patients with severe disease, in those with corticosteroid treatment, in older individuals, and in men.
3. Quantitative RT-PCR and viral infectivity seem to be closely linked.

This information is of value when considering discontinuation of isolation in patients recovering from COVID-19. Unfortunately, the authors did not investigate the association between infectivity and time from symptom onset. Such data are urgently awaited.

 

Title: COVID-19 and Liver Dysfunction: a systematic review and meta analysis of retrospective studies

Publisher: Journal of Medical Virology Publication Date: May 23, 2020

URL: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26055

Key Takeaway: Meta‐analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID‐19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID‐19. Liver dysfunction was associated with a severe outcome of COVID-19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes.

Title: Findings from Investigation and analysis of re-positive cases

Publisher: Korean CDC

Publication Date: May 19, 2020

URL: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030

Key Takeaway:  Based on active monitoring, epidemiological investigation, and laboratory testing of re-positive cases and their contacts, no evidence was found that indicated infectivity of re-positive cases:

• Of the 447 re-positive cases as of 15 May, epidemiological investigation was conducted on 285 cases and laboratory analysis on 108 cases. (*473 as of 18 May)
• From monitoring of 790 contacts of the 285 re-positive cases, no case was found that was newly infected solely from contact with re-positive cases during re-positive period.
• Virus isolation in cell culture of respiratory samples of 108 re-positive cases, all result was negative (i.e. virus not isolated).
• Of the 23 re-positive cases from which the first and the second serum samples were obtained, 96% were positive for neutralizing antibodies.

Based on these data, the Korean CDC has updated their protocols to conduct no additional tests for cases that have been discharged from isolation.

Title: Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure 

Publisher: Annals of Internal Medicine

Publication Date: May 13, 2020

URL: https://www.acpjournals.org/doi/10.7326/M20-1495

Key Takeaway: This retrospective modeling study demonstrates the potentially high rate of false negativity of RT-PCR in the pre-symptomatic period of SARS-CoV-2 infection. If confirmed, this would reduce the predictive value of asymptomatic testing as a public health strategy (such as in a population health screening program).

Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to 65%). This decreased to 20% (CI, 12% to 30%) on day 8 (3 days after symptom onset) then began to increase again, from 21% (CI, 13% to 31%) on day 9 to 66% (CI, 54% to 77%) on day 21.

Title: Viral and host factors related to the clinical outcome of COVID-19

Publisher: Nature

Publication Date: May 20, 2020

URL: https://www.nature.com/articles/s41586-020-2355-0_reference.pdf

Key Takeaway: Genomic sequences of SARS-CoV-2 assembled from 112 quality samples together with sequences in the GISAID showed a stable evolution and suggested two major lineages during the early phase of the outbreak in Wuhan although they exhibited similar virulence and clinical outcomes. The determinants of disease severity seemed to stem mostly from host factors such as age, lymphocytopenia, and its associated cytokine storm, whereas viral genetic variation did not significantly affect the outcomes. Of note, this study only examined samples collected from China January-February. Other studies have shown more genetic diversity in the virus, as would be expected.

Title: Assessment of Specimen Pooling to Conserve SARS CoV-2 Testing Resources.

Publisher: American Journal of Clinical Pathology

Publication Date: April 18, 2020

URL: https://doi.org/10.1093/ajcp/aqaa064

Key Takeaway:  Proof-of-concept study evaluating pooled specimen group RT-PCR testing to detect SARS-Cov-2, to expand testing capacity in the future. Sample pooling has been used in other applications for years. When incidence of SARS-CoV-2 infection is 10% or less, group testing saves reagents and personnel time, increasing testing capability at least 69%.

Title: SARS-CoV-2 Shedding From Asymptomatic Patients: Contribution of Potential Extrapulmonary Tissue Reservoirs

Publisher: American Journal of Tropical Medicine and Hygiene

Publication Date: April 13, 2020

URL: http://www.ajtmh.org/content/journals/10.4269/ajtmh.20-0279

Key Takeaway:  Perspective paper, analyzing human and animal studies - prolonged COVID positivity even after symptoms resolved, likely explained by extrapulmonary reservoirs.

Title: Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19.

Publisher: IDSA

Publication Date: May 6, 2020

URL: https://www.idsociety.org/practice-guideline/covid-19-guideline-diagnostics

Key Takeaway:  This is the third of 3 IDSA guidelines on COVID, this one deals with diagnosis providing 15 practical recommendations and an associated algorithm for testing, the other two deal with treatment, and infection control.

Title: Society of Cardiovascular Computed Tomography guidance for use of cardiac computed tomography amidst the COVID-19 pandemic

Author affiliated with GW

Publisher: Journal of Cardiovascular Computed Tomography

Publication Date: 21 March 2020

URL: https://www.journalofcardiovascularct.com/article/S1934-5925(20)30125-8/fulltext

DOI: https://doi.org/10.1016/j.jcct.2020.03.002

Key Takeaways: The Society of Cardiovascular Computed Tomography offers recommendations for cardiac imaging amidst the COVID-19 pandemic and information on determining the optimal timing of outpatient and inpatient heart imaging exams.

Serologic testing has the potential to provide valuable information for public health decision-making when conducted as a complement to molecular testing, and is also in demand from individuals and employers to determine perceived immunity. 

• It is imperative to validate the tests as well as provide information about the uncertainties of the results. In addition to the potential for false positive and negative results, important areas of uncertainty that must be addressed through research include how long immunity lasts after infection, and whether that immune response is protective.

Title:  Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series

Publication: April 10, 2020 (not peer-reviewed)

URL: https://www.medrxiv.org/content/10.1101/2020.04.06.20050575v1.full.pdf?fbclid=IwAR0CO3WkFwsmfL5GQ85yj4e7qPdWJI8jPH7QfhRlicrW-AvNpzbgNderyCo

Key Takeaway: 

• The dominant histopathology was diffuse alveolar damage, with CD4 cells aggregating around blood vessels, resulting in thrombotic microangiopathy, usually restricted to the lungs. There was no indication of lymphocytic infiltrate of the heart, typically seen in viral myocarditis. There were no secondary infections.
• Effective therapy for these patients should not only target the viral pathogen, but also the thrombotic and microangiopathic effects of the virus, and possibly a maladaptive immune response to viral infection. 

Antibodies in Infants Born to Mothers With COVID-19 Pneumonia

• https://jamanetwork.com/journals/jama/fullarticle/2763854

• “Antibodies in Infants Born to Mothers With COVID-19 Pneumonia” Hui Zeng, Chen Xu, Junli Fan. JAMA. Published online March 26, 2020.
• Note from submitter: JAMA Research Letter outlining laboratory markers of serological characteristics of infants whose mothers are infected with SARS-CoV-2.