COVID-19 updates: A 2020-2021 Global Pandemic


COVID Pandemic data

COVID-19 has been a clear and present danger to global public health. Vaccinations have had a positive impact on the number of COVID-19 infections in the US. The number of infected individuals appears to be declining as of mid-April 2021. However, the actual figures may be underestimated due to underreporting of cases, varying testing capabilities and other factors. These figures are critical to the evaluation of containment and mitigation strategies going forward and for targeting follow-up diagnostic testing. Globally, more than 144 million cases have been reported, with over 5 million new cases reported in the third week of April 2021 with the death toll increasing for the fifth week since March 2021. As pointed out by the WHO Director-General Tedros Adhanom Ghebreyesus “It took nine months to reach 1 million deaths, four months to reach 2 million and three months to reach 3 million deaths.


US Scenario

The US was headed for a nation-wide public health disaster following the first reported case in Washington State on January 20, 2020. The US soon surpassed Italy in the number of reported deaths twelve weeks later [1]. As of April 25, 2021 more than 32 million COVID-19 cases have been reported in the US with more than 500,000 deaths [2]. In January 2021, the US reported an average death rate of more than 3,100 individuals per day; however, the number of new cases fell dramatically in January, with the death rate falling in February as well. New cases began to increase in March 2021 due to the relaxation of restrictions in some states. In the past seven days (as of April 25, 2021), the number of daily reported cases (per 100,000 people) as declined nationwide by 17% [2].


Pandemic Data in other parts of the world

The SARS-CoV-2 outbreak occurred in Wuhan, China in the October – December 2019 timeframe. The virus was sequenced from isolates of three Wuhan patients using next generation sequencing on samples of bronchoalveolar lavage fluids [3]. By March – April 2021, there have been more than 100 million confirmed reports of COVID-19 cases with new cases arising from the Asian and South American continents. The current epicenters are Brazil and India with more than 200,000 newly confirmed cases [4]. Particularly India, the world’s largest democracy with more than 1.3 billion population, the current situation is devastating. India’s healthcare system is near collapse as facilities are inundated with new patients at an alarming rate. It is second only to the US in terms of global case totals. India reported nearly 1.5 million cases in the third week of April 2021 alone. Other Asian countries like Thailand also are reporting a surge in cases. However, the number of cases in the European Union seems to be plateauing.


Circulating variants

The first genomic sequence of the COVID-19 virus, isolated from a patient in Wuhan, China, was posted online on January 10, 2020. Currently 468,000 sequences of the virus from around the world have been uploaded into publicly available databases, including more than 93,000 from individuals in the United States. Like other RNA viruses, the COVID-19 virus is constantly changing through mutation, with new variants occurring over time. A very small number of these variants have been detected. These variants concern public health officials as they, in some cases, appear more virulent and more transmissible than the original virus. Additionally, those individuals who have been vaccinated may not be afforded the same protection as with the original virus. Three specific variants have emerged that require close monitoring: B.1.1.7, B.1.351, and P.1. [10]. The B.1.1.7 strain (also known as 20I/501Y.V1 or variant of concern [VOC] 202012/01) was first detected in the UK in December 2020 and has now been identified in at least 80 countries. In the US, the B.1.1.7 variant was first detected in Colorado in late December 2020 and since that time, has been detected in 33 US states. The B.1.351 variant (known as 20H/501Y.V2) was first identified in the Republic of South Africa in December 2020 and since then has spread to at least 41 countries including the United States, where it was first detected in South Carolina and Maryland in late January 2021. The SARS-CoV-2 P.1 strain (known as 20J/501Y.V3) was first detected in Brazil in December 2020 with the first case in the US reported in Minnesota in January 2021. Preliminary data suggest that these three variants are more transmissible than previous variants of the COVID-19 virus and may also result in a more severe illness after infection.


Current Challenges

The challenges of combating this highly transmissible disease lies in the tracing and diagnosis of cases, especially asymptomatic cases which appear to be the majority of cases in the general population. Adherence to protocols is highly variable among states in the US and elsewhere around the world. While US Federal government figures may not track all infected people as well as associated deaths, Johns Hopkins University (JHU) Coronavirus Resource Center routinely tracks and updates COVID-19 cases several times daily. Although the daily number of vaccinations has increased, with approximately 3 million US citizens are vaccinated daily, statistically there were periods in March where the virus was spreading faster. This increase is likely due to the outbreak of new, more transmissible and more virulent variants. Potentially exacerbating the problem is that many states and communities are opposing addition of restrictions. Noteworthy, this pandemic has affected the Black, Hispanic and Native American communities particularly harshly. Moreover, according to an analysis by the CDC, as reported by The Washington Post, people in very rural areas may be more vulnerable to the COVID-19 outbreak than urban communities.


Many Americans who have been vaccinated believe that the side effects from the vaccination suggest that your immune response was strong, and the vaccine was working. This is a misconception. An adaptive immune response generally takes approximately two weeks after the vaccination in order to produce specific antibodies against the virus. Generally, sides effects are due to non-specific innate immune responses and inflammation which is encountered after injection.


Current risk factors

Individuals over the age of 65 and those with obesity and underlying health problems are the mostly likely to die of COVID-19 infection. Notwithstanding the foregoing, a large percentage of infections have also occurred in younger, more active people. People under the age of 40 tend to be less sick, or asymptomatic when infected, but as a consequence are more likely to transmit the disease to others because they are unaware of being infected. Moreover, recent trends suggest the virus transmission is shifting towards younger adults (25-59 years age). This may be due to the emergence of new variants of the virus found in Brazil and India as well as relaxation of restrictions. A global analysis has also found a worrisome connection between COVID-19 and diabetes in people who had no previous history of blood-sugar problems [2].


Administered Vaccines

Various methods are used for vaccine discovery and manufacturing. As of April 2021, The New York Times Coronavirus Vaccine Tracker lists 3 vaccines in emergency use in the United States. Several other vaccines are approved for full use (outside the United States) and 22 vaccines are in phase 3 clinical trials globally. A number of antiviral medications and immunotherapies are also under investigation for coronavirus disease 2019 (COVID-19). The FDA has granted EUAs for three SARS-CoV-2 vaccines since December 2020. Two are mRNA vaccines – BNT-162b2 (Pfizer) and mRNA-1273 (Moderna), whereas the third is a viral vector vaccine – Ad26, the Johnson and Johnson vaccine.


About one-fourth of the population in the United States has been vaccinated against Covid-19, according to the latest data provided by the US Centers for Disease Control and Prevention (CDC). The data further revealed that 39 per cent of the US population has received at least one dose of a COVID vaccine whereas 24.8% of the US population has been totally vaccinated.


Vaccines in Late-Stage Development

  • NVX-CoV2373 (Novavax) is engineered using recombinant nanoparticle technology from a SARS-CoV-2 genetic sequence to generate full-length, prefusion spike (S) protein. This is combined with an adjuvant (Matrix-M). Results of preclinical studies showed that it binds efficiently with human receptors targeted by the virus. The phase III trial in the United Kingdom has shown 86.3% efficacy against the UK variant and 96.4% efficacy against the original strain. In addition, the phase 2b trial in South Africa has reported results with 55.4% efficacy for the prevention of mild, moderate, and severe COVID-19 disease and 100% efficacy against severe disease.

  • AZD-1222 (ChAdOx1 nCoV-19; AstraZeneca) is a replication-deficient chimpanzee adenoviral vector vaccine containing the surface glycoprotein antigen (spike protein) gene. This vaccine primes the immune system by producing antibodies to attack the SARS-CoV-2 virus if it later infects the body. Owing to the testing of a different coronavirus vaccine in 2019, development for AZD-1222 was faster than that of other viral vector vaccines.


A group of European nations including Denmark, Norway, Iceland, Thailand, and Bulgaria suspended the use of the AstraZeneca vaccine (AZD-1222) on March 10–11, 2021. These suspensions arose from allegations that the vaccine caused blood clots in some recipients of the vaccine. However, on March 12, 2021, AstraZeneca defended its vaccine, saying there was “no evidence of an increased risk” of blood clots, and European and UK medicines regulators have each said the link between the vaccine and blood clots has not been confirmed. Eventually, the European Medicines Agency (EMA) did not recommend suspending the vaccine. On or about March 22, 2021, AstraZeneca stated Phase III clinical trial results of 79% and 100% efficacy was achieved at preventing symptomatic COVID-19 and preventing severe hospitalization cases, respectively [5]. If after a few days subsequent to vaccination, symptoms of headache, shortness of breath or breathlessness, chest or stomach pain, swelling in arm or leg, persistent bleeding, multiple small bruises and/ or blood blisters under the skin continue, a patient should seek medical attention immediately [6]. As of April 25, 2021, the FDA has not approved the AstraZeneca vaccine for use in the United States. The Johnson & Johnson (JNJ) vaccine received emergency use authorization on February 26, 2021 from the FDA. By March 2021, reports stated that one dose was attaining 66% effectivity and 100% effectivity in preventing moderate to severe COVID-19 and in preventing hospitalization related severity and death, respectively [7]. However, the JNJ vaccine was also linked to blood clot formation during the first week of April 2021. The FDA and the CDC reported on April 12, 2021, that out of more than 6.8 million doses given in US, six individuals reported a rare and severe type of blood clot in combination with thrombocytopenia after receiving the vaccine. Use of the JNJ vaccine was halted on or about April 13, 2021 in the USA [8]. However, on April 23, 2021, the FDA and CDC said the US would resume use of the JNJ vaccine [9].

Written by: Lawrence D. Jones, Ph.D. and Souvik Datta, Ph.D.


Keywords: COVID-19, thrombocytopenia, Johnson and Johnson, AZD-1222, vaccine


References:

1. Bergquist S, Otten T, Sarich N. COVID-19 pandemic in the United States. Health Policy Technol. 2020;9(4):623-638. doi:10.1016/j.hlpt.2020.08.007.

2. https://www.washingtonpost.com/graphics/2020/national/coronavirus-us-cases-deaths/?itid=sf_coronavirus_sn_coronavirus-us-cases-deaths_1

3. To KK, Sridhar S, Chiu KH, et al. Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic. Emerg Microbes Infect. 2021;10(1):507-535. doi:10.1080/22221751.2021.1898291.

4. Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/

5. https://www.astrazeneca.com/media-centre/press-releases/2021/astrazeneca-us-vaccine-trial-met-primary-endpoint.html

6. Merchant, H.A. CoViD vaccines and thrombotic events: EMA issued warning to patients and healthcare professionals. J of Pharm Policy and Pract 14, 32 (2021). https://doi.org/10.1186/s40545-021-00315-w

7. Livingston EH, Malani PN, Creech CB. The Johnson & Johnson Vaccine for COVID-19. JAMA. 2021 Mar 1

8. https://www.cdc.gov/media/releases/2021/s0413-JJ-vaccine.html

9. https://www.nbcnews.com/health/health-news/u-s-should-resume-j-j-vaccinations-warning-notice-cdc-n1265073