Coronavirus Disease 2019 / COVID-19 Symptoms

Coronavirus disease 2019 (COVID-19) is an infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1]. An outbreak of a pneumonia of unknown cause was identified in Wuhun City, Hubei Province, China at the end of December 2019 [2]. China shared the genetic sequence of COVID-19 in January 2020 and the World Health Organization (WHO) also reported a limited number of cases of human-to-human transmission [3]. Over the next 7 weeks, cases of COVID-19 were found in other countries showing widespread human to human transmission and many deaths resulted from respiratory failure. On 11 March 2020 WHO declared COVID-19 a pandemic.

As this was a new infection which hadn’t been seen before and due to how easily it spreads it was imperative to understand associated symptoms, transmission and how the disease could be tested for and find possible treatments.

Epidemiology:  Current cases of COVID-19 by country can be seen at John Hopkins University COVID-19 information: https://coronavirus.jhu.edu/map.html Currently over 13.3 million cases of COVID-19 have been reported globally, with over 7.5 million recovered and over 577,000 deaths. The United States (U.S.) has the highest number of reported infections accounting for 26% of all global cases and the greatest number of deaths. After the U.S, countries with the greatest number of cases are Brazil, India and Russia. Europe was badly affected at the beginning of the pandemic but has now successfully navigated the first wave and cases are currently low.

Adults are more affected by COVID-19 than children are, although there have been pediatric cases and deaths plus rare reports of a inflammatory syndrome in children which has an association with COVID-19 called Multisystem Inflammatory Syndrome in Children (MIS-C).  For the COVID-19 illness there is a difference in symptoms between children and adults where children seem to get a milder disease or do not show obvious symptoms. Hospitalizations in pediatric populations are low. In pediatric cases, the symptoms are fever, cough or shortness of breath. In adults, 93% will have a symptom complex where multiple symptoms are present, and it is not linked to one chief symptom complaint, so presentation is wide. Adults of all ages are affected but many of the deaths have been seen in adults over 65 years with one or more pre-existing conditions. Within the U.S. population racial disparities are being seen where African Americans account for 70% of the deaths but only makeup 30% of the population as in Chicago and Louisiana. Work is ongoing to understand why the elderly and these racial groups are affected so disproportionately.

Etiology and Pathophysiology:  SARS-CoV-2 caused the disease COVID-19 and is related to bat coronaviruses and other Severe Acute Respiratory Syndrome (SARS) coronaviruses. SARS-CoV-2 is a betacoronavirus belonging to the same sub-genus as the virus responsible for SARS and the Middle East Respiratory Syndrome (MERS). SARS-CoV-2 enters cells using the angiotensin-converting enzyme 2 (ACE-2) receptor. It is believed initial spreading of COVID-19 was from animal to human via exposure at a seafood and animal market in China as the first cases were linked to there. Virus shedding has been found to be prolonged with a median of 20 days making it highly infectious.

History and Symptoms:  80% of people with COVID-19 have a mild illness or show no COVID-19 symptoms. Initial symptoms are very similar to other viral respiratory illness including Influenza. Initial common symptoms of COVID-19 include fever, cough, shortness of breath and tiredness. Other symptoms which have been seen in COVID-19 are myalgias, nasal congestion, runny nose, sore throat[4], loss of smell and taste, neurological symptoms [5] and also gastrointestinal symptoms [6] including diarrhea, abdominal pain and vomiting. Chest x-ray findings have included bilateral pneumonia, ground-glass opacities and pneumothorax. Lab testing has revealed increased lactate dehydrogenase, decreased hemoglobin, neutrophilia, lymphopenia, leucocytosis, thrombocytopenia and thrombocytosis. The 20% who have had a severe form of COVID-19 have developed complications including Acute Respiratory Distress Syndrome (ARDS), acute respiratory injury, septic shock, pulmonary embolism, stroke and acute kidney injury. More information on the extrapulmonary complications of COVID-19 and how they have manifested is available.  When these patients have developed complications which have required extra ventilatory and intensive care support it has been seen that there is a high mortality rate especially in patients over 65 years of age and those with associated risk factors including diabetes, chronic lung disease or heart conditions.

As the number of cases have grown throughout the world more has been discovered about the vast array of symptoms which COVID-19 patients are displaying. It is important to take cognizance of all the various presentations as this is a new disease and if we do not take cognizance of these symptoms then the disease will be missed.   Initial history taking in a COVID-19 suspected patient centered around a patient’s travel history or being in contact with a COVID-19 confirmed patient. The problem with this was it was spreading easily among people by human to human transmission and sometimes without any symptoms appearing so the disease took a foothold in many countries at an alarming rate. Tests for COVID-19 also had to be developed and it has been difficult for testing to be carried out in many countries at an effective level and as the disease has spread so rapidly the required number of tests to identify cases and isolate contacts cannot be carried out. There is also no effective treatment for COVID-19 or vaccine to prevent the disease and so people with suspected COVID-19 with mild symptoms have been told to isolate until their symptoms are better so health services around the world concentrate on the cases which are seriously unwell and need supportive nursing and medical care.

From the various studies which have been released over the past five months the symptoms, lab results and risk factors for COVID-19 amounts to over a hundred clinical features or findings. Therefore, in order to ensure COVID-19 appears on a health professional’s differential list a tool such as Isabel is essential to make sense of these vast array of symptoms. Rules based symptom checkers have been unable to have their algorithms tailored to adapt to showing COVID-19 on their differential lists mainly as they work off a chief symptom. COVID-19 has been found to present in a lot of different ways making it impossible to link it to one chief symptom. Isabel has taken cognizance of these symptoms and presentations and uses them within its algorithm to ensure COVID-19 presents appropriately on Isabel’s differential list as a possible disease.

Management and Treatment: The severity of the COVID-19 symptoms dictates where and how patients should be treated. Patients with mild illness will not require hospitalization and are encouraged to self-isolate at home until their symptoms have resolved. Those who develop complications including pneumonia, worsening shortness of breath, low oxygen saturation's, confusion, sepsis and shock will need hospitalization to help track their symptoms and provide nursing and medical interventions as necessary.

In severe COVID-19 hospitalized patient’s various trials are underway to monitor effects of medication. Hydroxychloroquine, Lopinavir, Ritonavir have been discontinued from trials as they showed little or no reduction in the mortality of hospitalized COVID-19 patients compared to standard of care. Trials are still underway with these medications to evaluate if they are effective in non-hospitalized patients or as pre or post-exposure prophylaxis for COVID-19. Other trials with Remdesivir and convalescent plasma are being conducted to see if they improve the trajectory of COVID-19 symptoms and ultimately reduce the mortality rate. Treatment is currently supportive but Dexamethasone was used in the RECOVERY trial in the United Kingdom and was found to have benefits for critically ill patients. For those patients on ventilators, Dexamethasone reduced mortality by one third and for patients requiring only oxygen therapy it cut mortality by one fifth.

There are around 200 groups around the world working on a COVID-19 vaccine and currently 23 of those groups are now testing a vaccine on people in clinical trials. Research and vaccine development is being accelerated for COVID-19 and its hoped that a vaccine will become widely available by mid-2021. More information from the World Health Organization on the COVID-19 candidate vaccines is available: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

The greatest weapon we have currently with COVID-19 is patient education and ways to limit the spread of this infection. Many countries have introduced stay at home orders or lockdowns to restrict people from passing the infection from one to another and overwhelming the health systems intensive care beds. Other ways to limit spread of COVID-19 include:

• Washing hands frequently with soap and water
• Do not touch your case
• When coughing or sneezing cover your mouth and nose with a flexed elbow. Throw tissues away immediately and wash your hands
• Avoid close contact with anyone who is displaying fever and cough symptoms
• Consider using a face mask when shopping or out in public
• Social distance from people who you do not live with keeping 6 feet apart
• Limit large groups of people meeting
• If you display mild COVID-19 symptoms which do not require hospitalization, then you should self-isolate or quarantine until symptoms have resolved for at least 48 hours. If you live with your family then all family members should also quarantine at home for 14 days after your symptoms develop.
  
  COVID-19 is a new disease which we are still learning much about in terms of how it presents, how it infects people and why in some people severe complications are seen. We do not currently have effective treatment or a vaccine for COVID-19. Due to people having to isolate to prevent the spread in communities around the world the economic and financial impacts of this pandemic are wide and repercussions will be felt for some time. The curve has been negotiated in some regions including China and Europe but in other regions of North America and South America infections are continuing to rise and we are still negotiating the first wave. Other regions which are reopening may have second and third waves of the disease to contend with. Early detection of COVID-19 symptoms is essential to recognize the disease and ensure people quarantine to prevent further community spread or if their symptoms are worsening to seek appropriate medical care. Health systems are overwhelmed and having to be innovative to reduce patient contact in person and focus on using online tools. Isabel for health professionals aids in helping you work through your clinical reasoning and generating a differential  to ensure you consider all possible diseases including the new COVID-19 and MISC-C disorders searching via the multitude of symptoms they present with. The Isabel Symptom Checker for patients also contains these new disorders and can also help patients know where to seek care and healthcare professionals prioritize those which need care.  The Isabel Symptom Checker and triage system is also available as a triage chat bot through our partners MedChat. The Triage bot integrates with most telehealth, EHR and CRM platforms to provide a seamless experience. These are front line weapons we can use to manage the effects of this pandemic and coordinate care effectively as well as ensure we are not missing other important diagnoses that the patient could have when presenting with symptoms.

References:

1. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020 Apr;5(4):536-44.  
2. Ren LL, Wang YM, Wu ZQ, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J (Engl). 2020 Jan 30 [Epub ahead of print].  
3. WHO Timeline – COVID-19 
4. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). 28 February 2020. 
5. Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhun, China. JAMA Neurol. 2020 April 10 [Epub ahead of print] 
6. Gu Jinyang, Han Bing and Wang Jian. COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission. Gastroenterology. 2020 Mar 3 [Epub ahead of print].