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The Link: Special Issue

February 2020

8 Questions and Answers on SARS-CoV-2 and COVID-19

 

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Mary Anne Jackson, MD | Interim Dean and Professor of Pediatrics - UMKC School of Medicine | Medical Editor, The Link Newsletter

1. Why the name change for the virus and the disease?
The new naming of the coronavirus originating from Wuhan, China, identifies that the newest bat-derived strain is genetically linked to two other notable associated strains: Middle East respiratory syndrome coronavirus (MERS-CoV; 50% genetic link; case fatality rate 30%) and serious acute respiratory syndrome coronavirus (SARS-CoV-1; 79% genetic link; case fatality rate 10%, ≥40% in those >60 years). While the SARS-CoV-2 strain is closely related to the other bat SARS-like coronaviruses, it has a differentiating surface spike, ORF8 and ORF3B proteins. Investigators propose that these could result in different features in terms of pathogenesis and transmissibility. COVID-19 then refers to the name of the disease caused by SARS-CoV-2.

2. What are the newest updated numbers as of February 11, 2020?
The total number of confirmed cases on mainland China, is 38,800 with 1,113 deaths (2.9% case fatality rate). So far, adults, particularly older adults and those with co-morbidities, appear to be most at risk for severe complications. There have been few reports of pediatric COVID-19 and this is similar to SARS-CoV-1 and MERS, where a more benign course in children was reported.1

3. Are there any new clinical or laboratory features identified for COVID-19 cases?
Early reports of disease in patients in Wuhan showed severe pneumonia in a cohort of mainly men (median age 49 years; range 41-58 years), 33% of whom had co-morbidities.2 Fever was present in 40/41, cough in 76%, myalgia or fatigue in 44%. Pneumonia developed in 50% of the patients a median of eight days into illness. A more recent report of 13 patients treated outside the epicenter, in Beijing, China, showed mild disease in a mainly healthy cohort (median age 34 years; 77% male) that included two children (2 and 15 years of age). Clinical features included fever in 12, cough and URI symptoms in roughly 50% and myalgia and headache in 23%. Six had the typical ground glass opacities on CT.3

4. What is known about COVID-19 in pregnant women?
Respiratory viral infections consistently have an increased risk for severe complications in pregnant women. Emerging data demonstrate that SARS-CoV-2 has a similar receptor binding domain structure to that of SARS-CoV-1 and that suggested the pathogenesis may be similar for the two diseases. SARS-CoV-1 caused severe pneumonia in 50% of pregnant women with 33% requiring mechanical ventilation and a case fatality rate of 25%. A recent report in The Lancet4 detailed clinical characteristics of nine women (ages 26-40 years) with confirmed COVID-19 pneumonia who underwent caesarean section who delivered at 36 weeks (4 women) up to 39 plus 4 weeks gestation. Two of the patients had pregnancy related complications (gestational diabetes, severe preeclampsia). Most had fever, but none with temperatures >39°, and URI symptoms, and one had gastrointestinal symptoms. Elevated transaminases were documented in three women; one had ALT and AST of 2,093 and 1,263 U/L respectively. Bilateral ground glass opacities were noted on 8/9 CT scan images, but none of the women had severe pneumonia based on clinical findings and none required mechanical ventilation.

5. What are the clinical features of neonatal disease in infants of mothers with SARS-CoV-2?
SARS-CoV-1 has been associated with complications in pregnant women, fetal loss in the first trimester, maternal infection and preterm delivery, but there was no disease in the infants born to infected mothers.5

With SARS-CoV-2, there are two reports of neonatal pneumonia. In one infant, a throat swab was positive at 36 hours of life, but details of the infant’s course were not described. In a news report, the infant was said to have respiratory distress, abnormal chest x-ray and elevated transaminases. A second infant developed vomiting and respiratory symptoms at 17 days of age and was found to have pneumonia with a positive rectal swab for SARS-CoV-2; it is possible that this infant acquired disease after birth.

In the case of the nine infants described in The Lancet article, preterm labor occurred in all four infants whose mothers presented at 36 weeks’ gestation. The infant of the mother with pre-eclampsia was small for gestational age, weighing 1,880 gm. All infants had normal APGAR scores at delivery and none had clinical symptoms that required specific treatment. SARS-CoV-2 was not detected in neonatal throat, amniotic fluid, breast milk or cord blood collected at time of delivery in five term and four late-preterm infants.

6. What is the recommended treatment for COVID-19?
Supportive care is recommended and intensive care is required for the most severely affected. Because secondary bacterial infection has occurred in ~10%, empirical antibiotics are considered. While there is no recommendation for a specific antiviral treatment, two agents, one a broad spectrum, adenosine analogue antiviral that has been evaluated as a treatment for Ebola virus infection, remdesivir, and one, an antimalarial and autoimmune modulator, namely, chloroquine have shown the ability to inhibit SARS-CoV-2.6 What is intriguing about chloroquine is that it has been safely used for more than seven decades, is an inexpensive oral drug and is known to be widely distributed including the lungs.

7. When is a vaccine likely to be available?
The most likely vaccine will capitalize on the spike protein that SARS-CoV-2 uses to invade human cells. Identifying the specific genes that code for the spike protein is the key step to vaccine development, and that has been accomplished by Jason McLellan at University of Texas at Austin7; animal studies are in progress. The estimate is that a vaccine may be available in 18-24 months, which is quite amazing given that the normal estimate is that vaccine development may require up to 10 years.

8. How likely is it that SARS-CoV-2 will result in a pandemic?
SARS-CoV-2 is a new virus, there is a large susceptible population and the virus has spread globally. We currently do not have exact information regarding how many infected individuals have subclinical or only mild disease. In terms of transmissibility, a predictor for potential growth of an epidemic is the basic reproduction number which indicates how many new cases will occur from one infected individual. If that number is greater than 1, sustained transmission is likely. For SARS-CoV-2, the R0 value is 2, meaning for every case, two other people will become ill. Given what we know about the incubation period, the virus has the potential to double in size every four to seven days. While the virus seems to have lower pathogenicity than MERS or SARS-CoV-2, it may have a higher impact on the population level and be harder to contain, since identification of cases with mild symptoms, and therefore contact tracing, may not be feasible.

References:

1. Li AM, Ng PC. Severe acute respiratory syndrome (SARS) in neonates and children. Archives of Disease in Childhood - Fetal and Neonatal Edition 2005;90:F461-F465.

2. Chaolin Huang, Yeming Wang, Xingwang Li, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506. Published online January 24, 2020. https://doi.org/10.1016/S0140-6736(20)30183-5.

3. Chang D, Lin M, Wei L, et al. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA. Published online February 07, 2020. doi:10.1001/jama.2020.1623.

4. Huijun Chen, Juanjuan Guo, Chen Wang, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The Lancet. Published Online February 12, 2020. https://doi.org/10.1016/S0140-6736(20)30360-3.

5. Shell F. Wong, Kam M. Chow, Tse N. Leung, et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. American Journal of Obstetrics and Gynecology. 2004:191(1):292-297. Published online August 2, 2004. https://doi.org/10.1016/j.ajog.2003.11.019.

6. Wang, M., Cao, R., Zhang, L. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020. Published online February 4, 2020. https://doi.org/10.1038/s41422-020-0282-0.

7. Wrapp, Daniel., Wang, Nianshuang., Corbett, Kizzmekia S., et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. Published online February 19, 2020. DOI: 10.1126/science.abb2507.