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Revista médica del Hospital General de México

versão On-line ISSN 2524-177Xversão impressa ISSN 0185-1063

Rev. med. Hosp. Gen. Méx. vol.85 no.1 Ciudad de México Jan./Mar. 2022  Epub 02-Maio-2022

https://doi.org/10.24875/hgmx.21000048 

Original articles

Clinical identification and severity in patients with COVID-19

María L. Hernández1  2  4 

Raúl Romero-Cabello1  2  * 

Ulises Hernández-Dávalos3 

Samuel Sevilla-Fuentes1 

Manuelita Zavala-Pineda1  4 

Silvia N. Martínez-Jiménez1  4 

Margarito T. Santos-González1  2 

Miguel Á. Solís-Bravo1 

Mario Sierra-Garduño1 

Joaquín Moreno-Moreno1 

Juan J. Fonseca Mata1 

1Department of Infectious Diseases, Hospital General de México

2Faculty of Medicine, National Autonomous University of Mexico

3Department of Internal Medicine, Hospital General de México

4School of Medicine, National Polytechnic Institute. Mexico City, Mexico


Abstract

The clinical evaluation of the patient with COVID-19 allows better care, application of safety criteria and preventive measures. The disease progresses from mild to severe and critical. In this work, is evaluated in patients with COVID-19 clinical format to identify moderate to severe stages of the disease. Following a cohort of male and female patients over 18 years of age admitted to the Infectology Service of the General Hospital of Mexico. Each patient is studied using the “COVID-19 Infectology” clinical format and in the first 24 hours of admission, a real-time RT-PCR molecular test is performed for SARS-CoV-2 infection. 65 patients classified as severe COVID-19 were studied, the RT-PCR was positive in 60 patients and negative in 5, clinical data did not differ from the positive ones and the 5 negative were considered false negative cases of the molecular test. There were no differences between positives and negatives with Fisher’s test, and no difference in age, comorbidities, or prognostic evaluation with Student’s t test. The conclusion is that the clinical format “COVID-19 Infectology” allows to recognize the cases and identify those that are in a severe evolution.

Keywords Clinical identification Covid-19; Identification severe Covid-19; Clinical evaluation Covid-19

Introduction

When dealing with patients with COVID-19, diagnosing the disease in time and providing early management, even if it isn´t etiological due to the fact we don´t have it, enables us to improve patient care and, to the extent possible, prevent progression to severe disease. As such, doctors in clinical practice faced with this disease need to refine their evaluation, as clinical evolution is extremely variable.

The incubation period for SARS-CoV-2 ranges from 2 to 14 days from contact with the infecting person. The signs appear as an acute disease that evolves from mild to severe or critical as follows: 80% of patients have mild to moderate disease, 14% severe, and 5% critical. Many patients develop a mild, uncomplicated, flu-like upper respiratory infection with non-specific symptoms such as moderate fever, dry cough, nasal congestion, fatigue, anorexia, general malaise, myalgia, dysphagia, and headaches; 90% of patients have more than one of these symptoms. Some patients also have gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain1,2.

The evolution of COVID-19 may also give rise to arthralgia, dyspnea, anosmia or dysosmia, dysgeusia or ageusia, hyporexia, sputum production, conjunctivitis, sore throat, mental confusion, dizziness, rhinorrhea, chest pain, hemoptysis, and skin disorders. There is so much clinical data available that we have grouped it into General, Algological (Table 1), Respiratory, Neurological (Table 2), Gastrointestinal, Ocular and Cutaneous (Table 3) clinical manifestations. In general, patients that develop moderate disease have respiratory symptoms such as a cough, dyspnea and tachypnea; unlike the more severe disease, with mild pneumonia with no signs of severity, but with oxygen saturation in ambient air of less than 90% and/or a respiratory rate greater than 30 breaths a minute, or severe pneumonia with acute respiratory distress syndrome. 5% of the latter patients may develop critical illness with cardiac injury, septic shock, or multi-organ dysfunction3.

Table 1 General clinical manifestations in different series of patients 

General clinical manifestations Algological manifestations
Fever Myalgia
Shivering Arthralgia
General malaise Arthralgia in the fingers
Body pain Lack of strength in the hands
Dizziness Pain in:
Headache Face
Drowsiness Oral mucosa
Hemoptysis Molars
Fatigue - Weariness Neck
Lack of energy Shoulders
Weakness Arms
Hyporexia Wrists
Facial edema Hands
Tachycardia Hips
Sweating Knees
Head Legs
Neck Thighs
Forehead Ankles
Head and neck Feet
Feet Heels
Middle body Soles of the feet
Cold sweating Testicular pain
Edema in the fingers Renal fossa pain
Intense pain throughout the body

Table 2 Clinical respiratory and neurological manifestations 

Respiratory Neurological
Pharyngeal pain Anosmia - Hyposmia - Hyperosmia
Pharyngeal burning Ageusia - Dysgeusia
Dry throat Facial itching
Sore throat, sensation of something stuck (obstruction) Tinnitus
Pharynx sores Numbness
Tickly throat Hands
Mouth sores Legs
Pimply tongue Arms
Dysphonia Sensation of edema in the feet
Coughing Sometimes burning heat
Nasal congestion Face
Sputum Eyes
Dry nose Ears
Rhinorrhea Hands
Mucus with blood from the nose Feet
Epistaxis Knees
Sensation of fullness in the middle of the face Calves
Otic fullness Thighs
Ear pain Legs
Tinnititus Considerable heat with no fever
Sneezing Sensation of inner heat in the torso, throat and feet
Dyspnea Burning sensation in the back
Chest pain Cold
Retrosternal pain Chest
Burning sensation in the chest Feet
Burning sensation in the chest when breathing in air Soles of the feet
Chest congestion General
A sensation of obstruction in the chest Feeling cold when inhaling
Sensation of blocked phlegm Burning
Back pain Feet
Burning sensation in the back Toes
Rales Soles of the feet
Wheezing Fine trembling of the hands
Tachypnea Sweaty hands
Insomnia
Anguish
Tingling
Face
Nose
Hands
Chest
Abdomen
Legs
Pruritus
Face
Ears
Body
Feet
Heaviness
Head
Feet
Lack of strength
Legs
Wrists
Hands
Clumsy hands
Bewilderment
Confusion
Disorientation
Non-specific discomfort from the knees down
Mouth sensation of rough lips and cheeks
Cramp
Feet
Arms
Tired feet
Mild shaking
Limbs
Trembling voice, I feel shaky inside
Stabbing pain in the chest and left armpit
Numb fingers
Numb hands
Facial pain
Scalp pain
Numb tongue
Numb legs
Bewilderment
Ringing in the ears

Table 3 Clinical gastrointestinal, ocular and cutaneous manifestations 

Gastrointestinal Ocular Cutaneous
Dry mouth Photophobia Erythematous lesions on the fingers and soles of the feet
Scalded tongue Ocular erythema Intense peeling of the soles of the feet
Eye pain Ecchymosis
Abundant night sialorrhea Itchy eyes Legs
Discomfort when swallowing Burning eyes Buttocks
Belching Periorbital edema Hyperpigmentation of the genitals
Nausea Tearing Urticaria
Vomiting Eye secretion Gallbladder
Hiccups Eyelid edema Petechiae
Abdominal pain Acroischemia
Epigastralgia Rash
Transprandial fullness Erythematous
Abdominal distension Macular
Rumbling Maculopapular
Flatulence Perifollicular
Diarrhea Purpuric
Constipation Morbilliform
Rectal tenesmus Erythema
Fetid stool Multi-form
Palmar
Facial
Enanthem
Pityriasis rosea
Necrotic lesions
Rash on the face, back and chest
Red spots in the mouth
Pale skin
Red and sweaty hands and feet
Itchy penis with burning sensation, appearance of ulcers and significant dryness
Dry calves
Hand edema
Dry lips

The evolution of patients is variable, and in some cases deterioration can occur in as little as 2 to 3 days, characterised by the presence of signs of pneumonia and ventilatory insufficiency, the patient has a grim appearance, worsens quickly and suffers from tachypnea. Signs of inspiratory crackles, rales, bronchial respiration, tachycardia, tachypnea and cyanosis should be looked out for and oxygen saturation is reduced. It should be pointed out that patients with COVID-19 can develop what has been called “silent hypoxia”; in these cases oxygen saturation drops to low levels and precipitates acute respiratory failure without the previous presence of data on ventilatory difficulties3,4.

The measurement of oxygen saturation is essential and is interpreted as follows: between 95% and 99% normal; 91% to 94% mild hypoxia; 86% to 90% moderate hypoxia; and less than 86% severe hypoxia. This may vary slightly due to differences in the altitude above sea level where the person is.

The purpose of this work is to evaluate and identify patients with probable COVID-19 in need of in-hospital management using a clinical format.

Material and Method

The study is conducted on a cohort of patients of 18 years of age or older diagnosed with COVID-19, admitted to the Infectious Diseases Department of the “Eduardo Liceaga” General Hospital of Mexico. Each patient was evaluated as follows:

Anyone with suspected COVID-19 requesting an appointment was granted one in the external appointments area of the Infectious Diseases department. A detailed clinical evaluation was carried out using the Clinical Format known as “COVID-19 Infectology” for the evaluation of suspected cases of COVID-19 classified as moderate and severe. This format is based on the assessment of the following clinical data grouped into three sections: A.- Fever, cough, and headache. B.- Arthralgia, myalgia, odynophagia, rhinorrhea, conjunctivitis and chest pain. C.- Dyspnea and oxygen saturation less than 90%. The following severity criterion was then applied to identify the patients in need of hospitalization: at least two positive items from section A, at least one positive item from section B, and all positive items from section C.

Once the evaluation had been carried out and the clinical diagnosis and scores had been established, the patients identified with a moderate to severe probability of COVID-19 were offered a hospital bed in the Department; those who accepted were then required to complete the acceptance and informed consent forms. A sample of nasopharyngeal and oropharyngeal exudate was taken within the first 24 hours of the patient being admitted to perform a real-time RT-PCR molecular test for SARS-CoV-2 infection; the sample was submitted to the Molecular Biology laboratory for the respective tests.

The descriptive statistical analysis consisted of determining the measures of central tendency and dispersion for the quantitative variables and percentages for the qualitative variables. For the inferential statistical analysis, a Fisher exact test was conducted for qualitative variables and a Student t test for quantitative variables.

Results

65 patients were analysed, 39 (60.0%) of were male and 26 (40.0%) female. Table 4 illustrates the age breakdown of the 65 patients: less than 30 years of age: 3 (4.6%); 31 to 40 years of age: 7 (10.8%); 41 to 50 years of age: 16 (24.6%); 51 to 60 years of age: 20 (30.8%); 61 to 70 years of age: 16 (24.6%); and more than 70 years of age: 3 (4.6%). The highest number of cases (52 (80%) occurred in people in the fourth, fifth and sixth decades of life, with an average age of 52.6 ± 12.5 years and a range of 24 to 83 years of age (Table 4).

Table 4 Breakdown of age of patients with COVID-19 

Age PCR+ PCR- Total
(years) No. % No. % No. %
< 30 3 5.0 3 4.6
31-40 6 10.0 1 20.0 7 10.8
41-50 13 21.7 3 60.0 16 24.6
51-60 20 33.3 20 30.8
61-70 15 25.0 1 20.0 16 24.6
> 70 3 5.0 3 4.6
Total 60 100.0 5 100.0 65 100.0

The clinical manifestations observed in patients upon admission were classified in 4 groups: systemic, respiratory system, digestive system and others (Table 5). With regard to general symptoms, fever was registered in 87.7% (57); headache in 66.2% (43); general deterioration 55.4% (36); shivering in 41.5% (27); and irritability in 30.8% (twenty). As can be seen, the three symptoms with a percentage of over 50% were: fever, headache and general deterioration. The respiratory system registered cough in 92.3% (60); dyspnea in 86.2% (56); rhinorrhea and odynophagia in 30.8% (20); chest pain in 27.7% (18); polypnea in 15.4% (10); and cyanosis in 6.2% (4). The main manifestations in relation to the respiratory system were undoubtedly coughing and dyspnea. The digestive system featured diarrhea in 16.9% (11); abdominal pain in 15.4% (10); and vomiting in 9.2% (6). Other symptoms were: arthralgia in 56.9% (37); myalgia in 55.4% (36); and conjunctivitis in 4.6% (3); (Table 5).

Table 5 Clinical data on patients with COVID-19 

Patients with PCR + PCR - Total P
General symptoms No. % No. % No. %
Fever 53 88.3 4 80.0 57 87.7 0.493
Headache 40 66.7 3 60 43 66.2 0.555
General deterioration 34 56.7 2 40.0 36 55.4 0.397
Shivering 26 43.3 1 20.0 27 41.5 0.302
Irritability 19 31.7 1 20.0 20 30.8 0.509
Gastrointestinal symptoms No. % No. % No. %
Diarrhea 10 16.7 1 20.0 11 16.9 0.617
Abdominal pain 10 16.7 0 0 10 15.4 0.421
Vomiting 6 10.0 0 0 6 9.2 0.606
Other symptoms No. % No. % No. %
Arthralgia 36 60 1 20 37 56.9 0.104
Myalgia 34 56.7 2 40 36 55.4 0.397
Conjunctivitis 3 5 0 0 3 4.6 0.783
Respiratory symptoms No. % No. % No. %
Coughing 56 93.3 4 80.0 60 92.3 0.339
Dyspnea 52 86.7 4 80.0 56 86.2 0.538
Odynophagia 20 33.3 0 0 20 30.8 0.148
Rhinorrhea 18 30 2 40 20 30.8 0.491
Chest pain 16 26.7 2 40.0 18 27.7 0.426
Polypnea 10 16.7 0 0 10 15.4 0.421
Cyanosis 4 6.7 0 0 4 6.2 0.72

All the patients were evaluated using the Call Scale to predict risk progression, and it was found that 13 were low risk, 24 medium risk and 28 high risk (Table 6).

Table 6 CALL Score for patients with COVID-19 

Call Total PCR+ PCR- Total
No. % No. % No. %
4 2 3.3 2 3.1
5 4 6.7 4 6.2
6 7 11.7 7 10.8
7 8 13.3 2 40.0 10 15.4
8 8 13.3 8 12.3
9 5 8.3 1 20.0 6 9.2
10 10 16.7 1 20.0 11 16.9
11 10 16.7 10 15.4
12 4 6.7 1 20.0 5 7.7
13 2 3.3 2 3.1
Total 60 100 5 100 65 100

The results of the real-time polymerase chain molecular test for SARS-CoV-2 were positive in 60 patients (92.3%) and negative in 5 patients (7.7%); 4 of the latter being female and and 1 male.

43 (66.2%) of the 65 patients registered an improvement while they were in hospital and 22 (33.8%) died.

Discussion

Despite the fact that COVID-19 is a new disease, it is clear that clinical studies are essential to identifying it in the patient. The “COVID-19 Infectology” clinical format was used in this study to identify severe cases in the 65 patients admitted to the Department of Infectious Diseases, who were already hospitalised, and a detailed clinical study confirmed the presence of fever, coughing and headache, arthralgia, myalgia, odynophagia, rhinorrhea, conjunctivitis and chest pain, along with dyspnea and hypoxemia. Oxygen saturation of less than 90%, fever, headache, general deterioration, coughing, dyspnea, arthralgia and myalgia stood out as the most frequent data; Other authors have already used evaluation models, also known as triage systems5.

All the patients were evaluated using the Call Scale to predict risk progression, and it was found that 24 (36.9%) were medium risk and 28 (43.1%) high risk (Table 6). It should be pointed out that the patients´ outcomes were as follows: Discharge due to improvement 43 (66.2%) and death 22 (33.8%). When correlating the CALL scale results with evolution to death, it was found that most of the deaths involved patients from the high-risk group, illustrating that the CALL scale did predict the risk of progression in our patients and, as such, that this scale is quite useful, as other researchers have published6 (Fig. 1).

Figure 1 Call score and evolution of patients. Number of patients, improvement and death. 

As we have pointed out, the clinical manifestations of this disease are very varied and when reviewing the literature on the subject we found that other authors have published series of cases with reports on different clinical characteristics. We have compiled comparison tables to illustrate the consistency with the findings registered in our patients, whereby we suggest that special attention needs to be paid to researching and acknowledging all this clinical data when caring for patients with COVID-192,4,7-11 (Tables 7 and 8).

Table 7 Clinical respiratory manifestations in different series of patients 

Symptoms Lei P Wang D Guan W Chen N Huang Ch Lechein JR Chiesa-Estomba CM Romero-Cabello R
No. of patients 204 138 1099 99 41 2579 542 65
Fever 92.23 98.6 43.8 83 98 42.1 35.4 87.7
Myalgia 14.56 34.8 14.9 11 53.5 62.7 55.4
Dyspnea 31.2 18.7 31 55 45.2 5.8 86.2
Expectoration 26.8 33.7 28 13 18.6
Coughing 67.8 82 76 55.2 43.6 92.3
Headache 6.5 13.6 8 8 59.8 72.5 66.2
Rhinorrhea 4.8 4 7.4 30.8
Arthralgia 39.5 47 56.9
Chest pain 2 17.9 27.7

Table 8 Clinical gastrointestinal manifestations in different series of patients 

Symptoms Lei P Wang D Lechein JR Chiesa Estomba CM Romero-Cabello R
No of patients 204 138 2579 542 65
Loss of appetite 78.64 39.9 40.6 46.7
Diarrhea 33.98 10.1 31
Vomiting 3.88 3.6 17.5 19.9 16.9
Abdominal pain 1.94 2.2 15.4
Nausea 10.1 9.2

The real-time polymerase chain reaction test registered SARCoV2 infection in 60 of the 65 patients. It should be pointed out that the 5 negative cases involved four females and one male, and the main clinical manifestations were fever, headache, coughing and dyspnea; these being no different to the symptoms registered in the 60 positive cases to RT-PCR, which were fever and headache in systemic data and coughing and dyspnea in respiratory data (Table 5).

The definitive test for SARS-CoV-2 is the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test. It is regarded as highly specific, however the sensitivity of the test ranges from 60% to 97%, compared to specificity of 89%. The sensitivity varies in relation to the time elapsed since exposure to SARS-CoV-2, in such a way that there are 100% false negatives on the first day after exposure and 67% on the fourth day. The false negative rate remains at 38% and reaches its lowest point of 20% three days after the onset of symptoms. The false negative rate begins to rise again from this time on, reaching 66% on the 21st day after exposure. Hence, false negatives are a real clinical problem, and multiple negative tests may be required in a single case to be sure disease can be ruled out. We need to bear in mind that negative results in the SARS-CoV-2 RT-PCR test do not rule out the possibility of infection, particularly if the patient has highly suspicious clinical manifestations of COVID-19.

This test involves the use of biological products from the nasopharynx, oropharynx or saliva, and targets the following RNA genes: envelope (ENV), nucleocapsid (N), spike (S), RNA polymerase, RNA-dependent (RdRp) and ORF1. The identification of viral RNA is achieved at the threshold of the cycle (Ct is the number of replication cycles required to produce a fluorescent signal), which varies in the days of evolution and reaches its maximum point in the first week of the onset of symptoms; positivity decreases at week 3 and then becomes undetectable. It also varies in accordance with differences in Ct for the different genes in question. The biological product to be studied causes variations in the results of the test; positivity in bronchoalveolar lavage (93%), followed by sputum (72%), nasal swab (63%) and pharyngeal swab (32%)5. Moreover, false negative results occur due to unreliable sampling techniques, in particular nasopharyngeal swabs, and due to technical errors and the contamination of reagents6,12-15. Despite the fact that this technique features high sensitivity and specificity, its effectiveness depends on proper processing, as there are many factors that can affect the results of the test, including the effective collection of samples using a swab in the nasopharyngeal area, as this region in which the virus undergoes a higher rate of replication, in addition to transporting samples to the laboratory in the appropriate manner with no contamination16). Another factor we need to bear in mind is the RT-PCR technique, which needs to be carried out in the proper manner in order to guarantee the maximum performance of the test, which involves obtaining a good quality RNA, as this material is susceptible to degradation due to the action of ribonucleases (RNAs). To this end, this material needs to be kept in cold conditions during handling. Another relevant factor is the concentration of the PCR components, as the improper amount of reagents used to amplify samples inhibits the amplification of genes17.

The main clinical symptoms included in the evaluation carried out in our study with the use of the “COVID-19 Infectology” Clinical Format are fever, coughing and dyspnea, in addition to the other symptoms of headache, arthralgia, myalgia, chest pain, odynophagia, rhinorrhea and conjunctivitis, in addition to oxygen saturation of less than 90%. When analysing the negative PCR cases, we see that the 5 negative patients registered the same clinical data as the 60 positive cases, reason for which they were regarded as being in the false negative range for the molecular test. A statistical analysis was conducted of the two groups using the Fisher test and the results show that the negative cases are no different clinically to the positive cases. Moreover, the student t test shows that there is no difference in age, comorbidities or the Call scores6,18.

In relation to the development of variants of the virus, the United States government´s Inter-Agency Group on SARS-CoV-2 has classified the genetic variants of the virus in 3 groups: Variants of interest, Variants of concern and Variants of high consequence. The first group includes the ETA variant, identified in the United Kingdom, the IOTA variant, identified in New York and the KAPPA variant, identified in India. The characteristics of these three variants are a possible reduction in neutralisation with monoclonal antibodies and in neutralisation with convalescent sera and post-vaccination sera. This group also includes the LAMDA variant, identified in Peru, the EPSILON variant, identified in the United States, the THETA variant, identified in the Philippines and the ZETA variant, identified in Brazil. The characteristics of the latter variants have still not been clarified, and the MU variant, identified in Colombia, could pose the risk of immune evasion or resistance to vaccines.

The Variants of Concern group includes the ALPHA Variant, identified in the United Kingdom, with increased levels of transmission and potential greater severity in hospitalisations and deaths. The BETA Variant, identified in South Africa, with increased levels of transmission, less susceptibility to monoclonal antibody treatment and less neutralisation with convalescent and post-vaccination sera, and the DELTA Variant, identified in India, with increased levels of transmission, potential reduction in neutralisation in some monoclonal antibody treatments and a reduction in neutralisation using post-vaccination sera, can cause symptoms two to three days faster, in addition to more severe disease and a reduction in the efficacy of vaccines and treatment. Finally, the GAMMA variant, identified in Japan and Brazil, with a considerable reduction in susceptibility to monoclonal antibody treatment and less neutralisation of convalescent and post-vaccination sera.

The variants of high consequence that have not yet been identified would cause problems in diagnostic tests, less efficacy with regard to vaccines, less response to treatment and generate more serious cases19-21.

Conclusion

The clinical evaluation of patients with COVID-19 and the use of evaluation models such as the “COVID-19 Infectology” Clinical Format enable us to recognise cases and to identify those that are progressing to severity. Given that this pathology features a large number of manifestations, the clinical physician requires a comprehensive evaluation in professional practice. The pulse oximeter is now an instrument that every clinical physician should use in the evaluation of patients on a daily basis.

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FundingWe do not receive any type of financing.

Ethical disclosures

Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study.

Confidentiality of data. The authors declare that they have followed the protocols of their work center on the publication of patient data.

Right to privacy and informed consent. The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.

Received: June 22, 2021; Accepted: November 18, 2021

* Correspondence: Raúl Romero-Cabello E-mail: romerocabello@idisalud.com

Conflict of interests

The authors declare that they have no conflict of interest.

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