1217: New Variant of SARS-CoV-2

1. The new variant carries a set of mutations (3) including an N501Y mutation in the receptor binding motif of the spike protein.
2.   Prof Chris Whitty has stated that this one appears to have quite a few more mutations than some of the other variants.
3.   The strain was identified by Public Health England monitoring, after an increase in cases seen in Kent and London.
4.   The variant was named VUI – 202012/01, identifying it as the first variant under investigation in December 2020.
5.   Initial analysis has shown that this variant is growing faster than the existing variants.
6.   Cases had been identified in nearly 60 different local authority areas and the numbers are increasing rapidly. As of 13 December, 1108 cases with this variant have been detected, especially in the South and East of England.
7.   Changes in part of the spike protein may cause the SARS-CoV-2 virus become more infectious.
8.   High numbers of cases of the variant virus have been observed in some areas where there is also a high incidence of COVID-19.
9.   However, there is nothing to suggest that this variant is more likely to cause serious disease.
10. In the case of SARS-CoV-2, these mutations are accumulating at a rate of nearly one to two mutations per month worldwide, according to the COG-UK genetics specialists. As a result, several thousands of mutations have already been observed in the SARS-CoV-2 genome since the virus emerged in 2019.

The change is called N501Y, and the deleted parts are named His69 and Val70. The mutations represent the changing of one amino acid to another and the deletion of two other amino acids. (Source: Medscape)

 1218: The USFDA has granted EUA for an innovative COVID-19 viral antigen test developed with support from the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) Initiative.

The test has been designed for use at home without a prescription. This is the first EUA granted for an over the counter at-home COVID test.  Ellume USA LLC developed the test with a $30 million contract and technical support from the RADx Tech program, which is managed by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of NIH.

The test is performed with a mid-turbinate nasal swab.  The sample is inserted into a single-use cartridge that gives results within 15 minutes. The test analyzer connects to the user’s smartphone through Bluetooth and pairs with a downloadable app that provides step-by-step instructions and displays results. Users are able to share real-time results from the test with healthcare professionals, employers, and schools for efficient COVID-19 tracking. The company plans to scale-up manufacturing to deliver millions of home tests per month in 2021. (Source: NIH)

1219:  Brazils Health Ministry is evaluating 58 suspected cases of COVID-19 re-infection after confirming the first case of re-infection caused by the coronavirus. The first case was that of a health worker in the northern city of Natal. The 37-year-old woman tested positive in June and again 116 days later in October. Thus far, 58 suspected cases of re-infection have been reported.

It appears that the woman did not develop enough antibodies to avoid getting infected again more than 90 days later. The woman was infected by a different strain of coronavirus the second time. The pathogen of the sample collected in June belonged to the B.1.1.33 strain while the October sample was from the B.1.1.28 strain. Both had already been detected in Brazil. (Source: Reuters)

1220: SARS-CoV-2 sometimes damages childrens blood vessels

SARS-CoV-2 may damages childrens blood vessels with consequences that might be seen decades after the infection subsides, suggested a study. A large number of the children in the study met the clinical criteria for thrombotic microangiopathy (TMA). Even children with mild or asymptomatic COVID-19 might develop TMA, with potential risk to their long-term health.

 In adults with COVID-19, endothelial cell damage to small blood vessels can lead to TMA, resulting in hemolytic anemia, thrombocytopenia, and sometimes organ damage. TMA may occur when complement dysregulation causes unregulated formation of the C5b9 membrane attack complex. Soluble C5b9 (sC5b9) may also act as a biomarker of the condition.

 Most children with COVID-19 have no symptoms or have only mild symptoms. Some of them, most often teenagers with other underlying health problems, develop severe respiratory symptoms that require hospitalization. A few may develop multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory syndrome which is marked by fever, inflammation, and organ dysfunction in the setting of recent SARS-CoV-2 infection. The condition is rarely seen in adults. Severe MIS-C involves shock and cardiovascular collapse, with about 80% of those afflicted needing care in a pediatric intensive care unit. It appears to be a postinfectious immune-mediated condition distinct from other manifestations of SARS-CoV-2. It can occur weeks or months after a SARS-CoV-2 infection, and is considered a separate entity from COVID-19.

In the study, sC5b9 levels were found to be higher in those infected than those who werent. Those with infection also had higher sC5b9 levels than normal (257 ng/mL or less). (Source: Medscape)

1221: Bell Palsy Cases

There have been reports of cases of Bell palsy in testing of both the Pfizer-BioNTech and Moderna vaccines. However, neither of them has been definitively linked to the risk. The handout prepared for clinicians for the Pfizer-BioNTech vaccine mentions four cases of Bell palsy in people who received the active drug in testing, but none in the placebo group.

There appeared to be no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic or neuroinflammatory, and thrombotic events) that would point to a causal relationship to Pfizer-BioNTech COVID-19 vaccine.

In the review of the Moderna vaccine, the FDA staff noted that there was a small imbalance in the number of participants reporting Bells palsy - 3 vaccine recipients and 1 placebo recipient reported this adverse event.

One case of Bell palsy in the vaccine group was a serious adverse event (SAE). A 67-year-old woman with diabetes was hospitalized for stroke due to new facial paralysis 32 days following vaccination. The FDA staff said the case has been reported as resolved.

Another Bell palsy case in the Moderna vaccine group was observed 28 days after vaccination in a 30-year-old woman who reported an upper respiratory infection 27 days prior to the onset of facial paralysis. This case was also reported as resolved.

Another Bell palsy case in the vaccine group was that of a 72-year-old woman and was still ongoing at the time of a report included in Modernas EUA application.

The Bell palsy case in the placebo group occurred 17 days after injection in a 52-year-old-man and has resolved.

FDA intends to recommend surveillance for cases of Bells palsy with deployment of the vaccine into larger populations.

The Moderna vaccine vials can be stored refrigerated between 2° and 8 °C for up to 30 days prior to first use. Unopened vials may be stored between 8° and 25 °C for up to 12 hours.

After the first dose has been withdrawn, the vial should be kept between 2° and 25°C and discarded after 6 hours.

The Pfizer COVID-19 vaccine has to be shipped and stored at -70 °C. (Source: Medscape)

1222: COVID-19 Pathology

1.   Extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, and infected cell syncytia are the hallmarks of advanced COVID-19, suggests a study published in EBioMedicine.
2.   Virus-infected cells that persist weeks after the initial diagnosis may have a key role in symptoms and severity of COVID-19.
3.   A post-mortem analysis was conducted on the lungs, brains, hearts, livers, and kidneys of 41 consecutive patients who died of COVID-19 at the University Hospital in Trieste, Italy. Six of these required intensive care (IC).
4.   At baseline, the most common comorbidities included hypertension (n=17), chronic cardiac disease (n=13), dementia (n=13), diabetes (n=12), and cancer (n=12).
5.   Eleven samples were subjected to in situ hybridization. Ten of these showed numerous SARS-CoV-2-infected cells expressing viral spike protein in lung tissue. There was extensive lung vessel thrombosis in the micro- and macro-vasculature in 5 IC patients (83%) and 16 non-IC patients (46%). These thrombi exhibited different stages of organization, pointing to an endogenous ongoing thrombotic process in the lung.
6.   Overall, 29 patients (71%) had a sporadic lung thrombosis and 10 patients (24%) had ongoing vasculitis in the lung micro- and macro-vasculature. Dysmorphic cells, often showing syncytia, were seen in pneumocytes of 20 patients (50%), including all 6 IC patients.
7.   The presence of SARS-CoV-2 RNA in lung cells weeks after initial diagnosis challenges the theory that COVID-19 follows a biphasic course - an initial phase of viral replication and a second phase of hyperinflammation with less relevant viral replication.
8.   Presence of abundant cytoplasmic RNA signals and expression of the spike protein in the lungs after 30-40 days from diagnosis indicates ongoing replication and postulates a continuous pathogenic role of viral infection.
9.   Other hallmarks of COVID-19 were massive lung thrombosis and endothelial dysfunction, and both were directly linked to the persistence of these virus-infected cells.

(Reference: EBioMedicine. 2020;61(103104). doi: 10.1016/j.ebiom.2020.103104. Source: https://www.infectiousdiseaseadvisor.com/)

1223: Treatment of COVID-19 with remdesivir in the absence of humoral immunity

Remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA).

Despite evidence of complement activation and strong T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease.  [Source: Nature Communications volume 11, Article number: 6385 (2020)]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA