With input from Dr Monica Vasudev

1164:  DG Alerts excerpts:  A whole genome study in children with COVID-19, published in Open Forum Infectious Diseases, noted a greater than expected genetic diversity across the SARS-CoV-2 genome, increased mutation, and a high prevalence of the D614G mutation, which is tied to increased disease transmission.

An analysis of serum from 141 pediatric patients who tested positive for SARS-CoV-2 from March 19 through June 16, 2020, revealed that all but 1 of the 141 isolates (99.3%) had the D614G mutation in the spike protein. The prevalence of the mutation in February was around 10%, while it was about 65% in March, when the first peak was occurring in California.

D614G mutation has been linked with lower cycle threshold values and heightened transmissibility, but appears not to be associated with disease severity. This study revealed that the mutation was present in almost all patients, irrespective of whether they were asymptomatic or had severe infection.

Besides D614G, investigators found 2 other common mutations -- F924F and P4715L. The latter is important for viral replication and has been associated with higher fatality rates.

An unexpectedly higher mutation rate of 22.5 substitutions/year was noted in this pediatric cohort when compared with other SARS-CoV-2 cases from California without the D614G mutation during the same period (13.5 substitutions per year).

All patients below the age of 5 years were symptomatic and had higher viral loads compared to older children, with detection of viral RNA as early as one day after symptom onset and highest viral loads in the first 2 days of symptoms onset. There was no difference in viral load in association with chronic underlying conditions, gender, or disease severity.

[Reference: https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa551/5981353]

1165:  Medpage Today Excerpts: A systematic review and meta-analysis has revealed that SARS-CoV-2 viral load in the upper respiratory tract reached a maximum during the first week of illness based on cycle threshold values, while people continued to shed viral matter for over 2 weeks. 

None of the 79 studies in the review could detect live virus beyond 9 days, (maximum 83), reported Müge Çevik, MD, of the University of St. Andrews in Scotland, and colleagues. Pooled mean viral shedding was found to be associated with age, but not sex, noted researchers online in The Lancet Microbe.

Majority of viral transmission events occur early, particularly within the first 5 days following the onset of symptoms. Investigators assessed the literature, including pre-print sites, for studies published between January 1 and June 6. Overall, 79 studies, with 5,340 patients, with 58 studies in China, and 73 studies including hospitalized patients only were identified. Sixty one studies reported median or maximum viral RNA shedding in at least one body fluid.

Forty three studies looking into shedding in the upper respiratory tract reported the duration of shedding as 17 days. Seven studies assessed shedding in the lower respiratory tract, which was a mean duration of 14.6 days. Thirteen studies assessed shedding in stool samples, which was a mean duration of 17.2 days. Two studies assessed shedding in serum samples, which was found to be a median of 16.6 days.

Viable virus was isolated during up to 4 weeks of illness in stool. The maximum duration of viral shedding was noted as 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stool samples, and 60 days in serum samples.

Eight of the 13 studies looking at the viral load in upper respiratory tract samples exhibited peak viral load within the first week of symptom onset. The highest viral loads were reported soon or after symptom onset, or day 3 to 5 of illness.

Twenty studies assessed duration of viral RNA shedding based on disease severity, and 13 of these found longer duration of viral shedding in patients with severe illnesses compared to non-severe illnesses.

Twelve studies reported on load dynamics or duration in individuals with asymptomatic infection. Two of these found lower viral loads among asymptomatic patients, while four noted similar initial viral loads. Among 11 studies that attempted to isolate live virus, eight that attempted virus isolation in respiratory samples successfully cultured viable virus within the first week of illness. No live virus was isolated from respiratory samples following day 8 in three studies or post day 9 in two studies.

1166: Older adults admitted and diagnosed with COVID-19 often presented with delirium and no other COVID-19 symptoms. Nearly 28% of COVID-19 patients aged 65 years and older presented with delirium, with delirium being a primary symptom in 16% of these patients, reported researchers. Over one-third (37%) of patients with delirium did not present with typical COVID-19 signs such as fever or shortness of breath, wrote researchers in JAMA Network Open. [Medpage Today]

1167: The US FDA authorized the use of baricitinib, an oral Janus kinase (JAK) inhibitor, in combination with intravenous remdesivir for the treatment of hospitalized patients with severe COVID-19. The combination treatment was granted emergency use authorization (EUA) for patients 2 years of age and older who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation. Both the drugs are already approved by the FDA for other indications. Baricitinib was approved in 2018 for moderate to severe rheumatoid arthritis, while remdesivir was recently approved to treat hospitalized COVID-19 patients. Remdesivir is also authorized to treat pediatric patients weighing about 7 pounds to about 88 pounds with suspected or laboratory-confirmed COVID-19. [Medpage Today]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA