MMSA SCOME's Covid-19 Information Booklet by Malta Medical Students' Association

MMSA SCOME'S

COVID-19

INFORMATION BOOKLET

WRITTEN BY

GABRIELLA DEBONO, DANIEL FORMOSA,Â MIGUEL VELLA, PETER SCIBERRAS

OWEN CACHIA

TABLE OF CONTENTS FORWARD MESSAGE FROM MMSA

MEDICAL EDUCATION OFFICER VIROLOGY

MODES OF TRANSMISSION

SIGNS AND SYMPTOMS

INVESTIGATIONS

PREVENTION AND TREATMENT

OUTCOMES AND COMPLICATIONS

REFERENCES

FORWARD MESSAGE FROM MMSA MEDICAL EDUCATION OFFICER Dear MMSA members and friends, COVID-19 has not only taken over our healthcare system but it has also taken over our friendships, discussions, plans and education! In this time of a world pandemic, the MMSA Medical Education Team has been working hard in order to stay in touch with students, faculty and international teams so that we keep track of our academical course in light of these unprecedented circumstances. As Medical students, we carry a lot of responsibility on our shoulders. People look up to us in order to provide healthrelated answers and insights regarding COVID-19. Additionally, through MMSA SCOPH's volunteering opportunities to help at the 111 helpline, we were getting asked a wide variety of

questions and all had to be answered with responsibility and knowledge. Hence, you are invited to go through this information booklet that consists of researched information from reputable sources in order to get equipped, informed and involved. As a disclaimer, this booklet has been written in late March 2020 and contains data published till now. The publication has been reviewed by Professor Victor Grech. This professional help was of great value. I would like to thank my great team for being so passionate in MMSA, Medical Education and health care in general. I would like to thank Gabriella Debono who led the team consisting of Daniel Formosa, Miguel Vella and Peter Sciberras. Also, great thanks to Katya Zerafa, SCOME

FORWARD MESSAGE FROM MMSA MEDICAL EDUCATION OFFICER Assistant for Internal Affairs and Owen Cachia from the PRO Team. As COVID-19 stories and posts continue to fill our feeds and pages, let us be selective and cautious of what we learn and and then what we say. We are young ambassadors for health and although we are not in our lecture theatres, let COVID-19 be a lesson to us all – both academically and socially. We’ll soon be back in nALR, at MDH canteen and at SCOME workshops – till then, take care! Kind regards, Gloria Montebello MMSA Medical Education Officer 2019-2020 Board of Studies Representative 2019-2020

VIROLOGY Coronavirus Disease 2019 (COVID-19) is a respiratory disease caused by the novel virus strain Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). The coronavirus family includes less pathogenic strains responsible for the common cold, as well as the viruses responsible for SARS and MERS. The disease was first identified in December 2019 in Wuhan, China among people linked to a local seafood market. The source is yet unclear, but bats and pangolins have been implicated through spillover infection. SARS-CoV-2 is a member of the coronavirus family, a group of enveloped positive-sense, single-stranded RNA zoonotic viruses that cause symptoms ranging from those similar to the common cold to more severe respiratory, enteric, hepatic, and neurological symptoms.

SARS-CoV-2 is the only member of the subgenus Sarbecovirus to contain a polybasic cleavage site, a characteristic known to increase pathogenicity and transmissibility (Walls et al., 2020). Each SARS-CoV-2 virion is approximately 50 to 200nm in diameter and its RNA sequence is approximately 30kbp in length. The spike (S) proteins coating the surface of the virus facilitate binding to angiotensin Converting Enzyme 2 (ACE2) receptors on type 2 pneumocytes and membrane fusion (Xu et al., 2020). Concerns were raised about the possibility of increased susceptibility to the virus in patients on ACE inhibitor or ARB therapy; clinicians have nevertheless been advised not to discontinue these medications as no data is yet available.

VIROLOGY Basic Reproduction Number (R0)[1]: SARS-CoV-2 has been found to have higher levels of transmissibility and pandemic risk than the SARS-CoV, with an effective reproductive number (R0) of circa 3. [1] an indicator of contagiousness of an infectious disease, used to estimate the average number of individuals who will catch a disease from one contagious subject. Case Fatality Rate (CFR): The median incubation period was estimated to be 5.1 days, and most of those who develop symptoms will do so within 11.5 days of infection (Sauer et al, 2020).

cases and contain spread include contact tracing, screening, and social distancing. The aim is to modify growth parameters in order to flatten the epidemic curve: the area under the graph (the number of cases) remains the same, but is distributed over a longer time period, ensuring that hospitals do not exceed capacity, and reducing the demand on the healthcare system, whilst buying time for to test and optimize new treatment strategies against the virus.

The World Health Organization (WHO) recommends a combination of measures, including rapid diagnosis and immediate isolation of cases, rigorous tracking, and precautionary self-isolation of close contacts. Strategies employed to detect [1] an indicator of contagiousness of an infectious disease, used to estimate the average number of individuals who will catch a disease from one contagious subject

MODES OF TRANSMISSION The main transmission routes for the SARS-CoV-2 are through droplets, indirect contact, and aerosols. One study also indicated the digestive system as a potential transmission route for SARSCoV-2 infection (Zhang et al., 2020). Further studies are required to determine whether the virus is infectious during the incubation period. The population most at risk appears to be people with poor immune function such as older people and those with renal and hepatic dysfunction (Li et al., 2020).

This is particularly true when it comes to individuals experiencing lack of paid sick leave, inability to take time off work, and financial instability among others. Social distancing may contribute towards increased social isolation and loneliness, particularly among the elderly population. The call for social distancing and recent volatility of the global financial market in light of the pandemic are also expected to heavily impact the economy.

COVID-19 has now been declared as a Public Health Emergency of International Concern by the WHO. The pandemic clearly has far reaching implications on society, not only with regards to its physical but also its social and financial wellbeing.

SIGNS AND SYMPTOMS The majority of COVID-19 patients present with pyrexia, cough (with or without sputum production) and myalgia or fatigue. Symptoms related to the upper respiratory tract, such as rhinorrhoea, sneezing and sore throat are less common. It is of utmost importance that suspected patients are immediately isolated. The median time from onset of illness to dyspnoea is 8 days. All patients have abnormal findings on chest CT scans that are characteristic of pneumonia. This indicates that most probably, the target cells of SARS-CoV-2 are located in lower airway (Huang et al., 2020).

Comparing SARS-CoV-2, SARS-CoV and MERS-CoV The features of SARS-CoV-2 infection closely resemble those of the SARS-CoV and MERS-CoV infections. The following table consists of some differences between the two. Table 1: Differences between SARS-CoV-2, SARS-CoV and MERS-CoV (Huang et al., 2020)

Only a few patients develop intestinal symptoms (e.g., diarrhoea). It is advised that faecal and urine samples are tested to exclude unknown routes of transmission.

INVESTIGATIONS Bloods: CBC: leukopenia, lymphopenia U&E: ↑ urea, ↑ Cr ratio Coagulation Profile: ↓ platelets Deranged LFTs RFTs ↑ CRP, ↑ LDH The above result may vary between individual patients.The neutrophil and lymphocyte count are reduced in most COVID-19 patients. The decrease in lymphocyte count could be due to the consumption of T lymphocytes by the virus (Huang et al., 2020). Respiratory Specimens: Once COVID-19 is suspected, respiratory specimens should be tested immediately. Upper Respiratory Tract: nasopharyngeal and oropharyngeal swabs

collected from the lower respiratory tract. Lower Respiratory Tract: - expectorated sputum (if produced), endotracheal aspirate - bronchoalveolar lavage fluid in ventilated patients. The specimens obtained from the lower respiratory tract are of higher diagnostic value (WHO, 2020a). The collection of blood cultures is indicated if pneumonia or sepsis is suspected (WHO, 2020b). Packaging of Specimens The specimens are delivered to the laboratory immediately at a temperature between 2 and 8°C. The use of viral transport medium is recommended if delivery is delayed (WHO, 2020c).

When COVID-19 is still clinically suspected and swabs are negative, specimens are

INVESTIGATIONS RT-PCR Assay The first positive RT-PCR test should be confirmed by a second RT-PCR assay which targets a different SARS-CoV-2 gene. This is particularly relevant in countries where the epidemic is not yet widespread. One gene target is enough in countries with an already widespread epidemic (ECDC, n.d.) The viral genes that are targeted include the N, E, S and RdRP genes (WHO, 2020c). The RT-PCR result in Malta is obtained within hours. Once a case is confirmed, the Superintendent of Public Health must be notified.

Imaging (Chen et al., 2020) Chest X-Rays: hazy, bilateral peripheral opacities

Chest CT Scans: bilateral ground-glass opacities and consolidation

COVID-19 is not excluded if: ·a test comes out negative, particularly if obtained from the upper respiratory tract, or a positive result is obtained for another respiratory pathogen (WHO, 2020d)

PREVENTION AND TREATMENT All those working with suspected COVID-19 patients must follow certain precautions- including wearing fit-tested N95 masks, eye protection and PPE. Proper hand hygiene is essential. Patients with mild clinical presentation may not initially require hospitalisation. However, symptoms may worsen within the second week of illness so all patients must be monitored closely. At present, the WHO only recommends supportive care. Patients with severe symptoms may benefit from oxygen support, fluid-sparing resuscitation and ventilator support (Fisher and Heymann.,2020). Most patients on respiratory support respond well to Positive End-Expiratory Pressure (PEEP). Non-invasive ventilation is useful to buy

time until an ICU bed becomes available. Extracorporeal Membrane Oxygenation (ECMO) may also be useful for those who are critically ill (Giwa and Desai., 2020). Antibiotic therapy is sometimes required to combat associated bacterial pneumonias. Ibuprofen should not be used to treat symptoms; the WHO recommends paracetamol instead. (Zafri., 2020) Investigational Therapies: There are currently no antiviral drugs licensed to treat patients with COVID-19. However, various drugs are currently being investigated and the first clinical trials for candidate vaccines for COVID-19 have now begun. However, at this point, there is no available

PREVENTION AND TREATMENT data from randomised controlled trials in humans to support recommending any investigational therapy (CDC., 2020). Examples of investigational therapies include antiviral drugs (remdesivir, lopinavir/ritonavir), antimalarial drugs (chloroquine/hydroxychloroqui ne), immunosuppressive medications (tocilizumab) as well as transfusion of antibodies against SARS-CoV2 analogues/ SARS-CoV. Corticosteroids like methylprednisolone are not recommended unless indicated for other reasons (Russell et al., 2020).

OUTCOMES AND COMPLICATIONS It is estimated that around 81% of all cases of SARS-CoV-2 infection will be mild i.e. without pneumonia or only mild pneumonia. 14% will be severe, requiring hospitalisation and 5% will be critical experiencing respiratory failure, septic shock and/ or multiple organ dysfunction/ failure. Mortality rate is estimated to be around 4% but many cases likely remain undiagnosed. CFR increases among the elderly and in people with preexisting conditions like cardiovascular disease or diabetes. (Roser et al., 2020)

The complications that may arise from COVID-19 include: Medium Likelihood: pneumonia, Acute Respiratory Distress Syndrome (ARDS), septic shock, Low Likelihood: acute cardiac injury, acute liver injury, secondary infection, acute respiratory failure, acute kidney injury, disseminated intravascular coagulation, pregnancyrelated complications. (BMJ Based Practice., 2020)

The Sequential Organ Failure Assessment (SOFA) score on admission to ICU also predicts mortality (based on the degree of dysfunction of six organ systems). Certain laboratory findings can also predict mortality, especially a raised Ddimer, ferritin, troponin and cardiac myoglobin.

OUTCOMES AND COMPLICATIONS

REFERENCES Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., ... & Xing, X. (2020). Early transmission dynamics in Wuhan, China, of novel coronavirus– infected pneumonia. New England Journal of Medicine Liu, T., Hu, J., Xiao, J., He, G., Kang, M., Rong, Z., ... & Zeng, W. (2020). Timevarying transmission dynamics of Novel Coronavirus Pneumonia in China. bioRxiv. Lauer, S. A., Grantz, K. H., Bi, Q., Jones, F. K., Zheng, Q., Meredith, H. R., ... & Lessler, J. (2020). The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Annals of Internal Medicine. Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., ... & Hao, P. (2020). Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China Life Sciences, 63(3), 457-460. Zhang, H., Kang, Z., Gong, H., Xu, D., Wang, J., Li, Z., ... & Liu, J. (2020). The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. BioRxiv.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X & Zhang L (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395, 507–513. ECDC (n.d.). Novel Coronavirus SARS-CoV-2. Huang C et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506. WHO (2020b). Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. Who12. WHO (2020a). Global Surveillance for human infection with coronavirus disease (COVID-19). 27– 29. WHO (2020c). Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human cases. WHO (2020d). Considerations in the investigation of cases and clusters of COVID-19. 1–4. –4. -Fisher, D. and Heymann, D., 2020. Q&A: The novel coronavirus outbreak causing COVID-19. BMC Medicine, 18-Giwa,A. and Desai, A., 2020. -Giwa,A. and Desai, A., 2020. Novel Coronavirus COVID-19: An Overview for Emergency Clinicians - EXTRA Supplement. EB Medicine.

REFERENCES Zafri N. Updated: WHO Now Doesn't Recommend Avoiding Ibuprofen For COVID-19 Symptoms [Internet]. ScienceAlert. 2020 [cited 19 March 2020]. Available from: https://www.sciencealert.com/whorecommends-to-avoid-takingibuprofen-for-covid-19-symptoms Coronavirus Disease 2019 (COVID19) [Internet]. Centers for Disease Control and Prevention. 2020 [cited 19 March 2020]. Available from: https://www.cdc.gov/coronavirus/20 19-ncov/hcp/clinical-guidancemanagement-patients.html Russell C, Millar J, Baillie J. Clinical evidence does not support corticosteroid treatment for 2019nCoV lung injury. The Lancet. 2020;395(10223):473-475. Coronavirus disease 2019 (COVID-19) - Complications | BMJ Best Practice [Internet]. Bestpractice.bmj.com. 2020 [cited 19 March 2020]. Available from: https://bestpractice.bmj.com/t opics/en-us/3000168/complications Roser M, Ritchie H, Ortiz-Ospina E. Coronavirus Disease (COVID-19) – Statistics and Research [Internet]. Our World in Data. 2020 [cited 19 March 2020]. Available from: https://ourworldindata.org/cor onavirus? fbclid=IwAR1WhBbrlZw7yO3lXFK34 X7nm2aeMqRjg7X8q9Kb3MxFVM9T pHTYmZfcp94#the-severity-of-thesymptoms-of-covid-19