Título

REVIEW ARTICLE

REVISTA DE LA FACULTAD DE MEDICINA HUMANA 2020 - Universidad Ricardo Palma
DOI 10.25176/RFMH.v20i3.2984

COVID-19: LITERATURE REVIEW AND ITS IMPACT ON THE PERUVIAN HEALTH REALITY

COVID-19 REVISIÓN DE LA LITERATURA Y SU IMPACTO EN LA REALIDAD SANITARIA PERUANA

Alberto Córdova-Aguilar1,a,b, Germán Rossani A.2,a,c

1 Facultad de Medicina, Universidad Nacional de San Marcos. Lima, Perú
2 nstituto de Investigación en Ciencias Biomédicas, Universidad Ricardo Palma. Lima, Perú.
aMedical specialist in plastic surgery.
bMasters in Public Health.

ABSTRACT
Introduction:

The disease called COVID-19 is a pandemic caused by the SARS-CoV-2 virus (severe acute respiratory syndrome 2). In Peru, patient zero or first case with COVID-19 was detected on March 6 and since then the virus has continued to spread. The national government fights against this disease on several fronts, but the health situation differs greatly from developed countries. Objective: To review the current state of the disease and analyze its possible impact on the Peruvian health system. Methods: A bibliographic search of various studies was carried out since the appearance of the disease (December 2019) in different databases (PUBMED, MEDLINE, PLOs, SciELO) and Google Scholar. Results: The virus is transmitted mainly by the respiratory route; the average incubation period is 14 days; most patients have mild disease or are asymptomatic but 5% of these will require hospitalization, some will even require intensive therapy with mechanical ventilation; the current treatment is basically symptomatic, though antibiotics, antivirals and antiparasitics have also been used. Conclusions: The quarantine with strict measures of isolation and social distancing is accurate given the Peruvian health reality and the imminent contagion of the population.

Keywords: SARS-CoV-2; COVID-19; Pandemics; Coronavirus Infections; Health Systems. (Source: MEDLINE MeSH).

RESUMEN

Introducción: La enfermedad denominada COVID-19 es una pandemia causada por el virus SARS-CoV-2 (síndrome agudo respiratorio severo 2). En el Perú, el paciente cero o primer caso con COVID-19 fue detectado el último 6 de marzo y desde entonces el virus continúa su propagación. El gobierno nacional lucha contra esta enfermedad desde varios frentes, pero la situación sanitaria difiere mucho con la de países desarrollados. Objetivo: Revisar el estado actual de la enfermedad y analizar su posible impacto en el sistema de salud peruano. Métodos: Se realizó una búsqueda bibliográfica de diversos estudios desde la aparición de la enfermedad (diciembre 2019) en las diferentes bases de datos (PUBMED, MEDLINE, PLOs, SciELO) y también en Google Académico. Resultados: Se encontró que el virus se trasmite principalmente por vía respiratoria; el periodo de incubación promedio es 14 días; la mayoría de los pacientes tienen una enfermedad leve o son asintomáticos pero un 5% de estos requerirán hospitalización, algunos incluso de terapia intensiva con ventilación mecánica; el tratamiento actual es básicamente sintomático, pero también prescriben antibióticos, antivirales y antiparasitarios. Conclusiones: La cuarentena con medidas estrictas de aislamiento y distanciamiento social es precisa, dada la realidad sanitaria peruana y el inminente contagio de la población.

Palabras clave: SARS-CoV-2; COVID-19; Pandemias; Infecciones por Coronavirus; Sistemas de Salud (Fuente: DeCs BIREME).

INTRODUCTION

On the last day of 2019, China reported 27 cases of pneumonia of unknown cause in the city of Wuhan, which had a close relation to the Huanan market where diverse exotic animals are sold, such as bats, pangolins and snakes (1,2). The characteristic clinical presentation of these patients included fever, dry cough and dyspnea. A week after the report, the Chinese Center of Disease Control and Prevention discovered that the cause of this disease was a new coronavirus (SARS-CoV-2) that the WHO later denominated COVID-19, from the English acronym “Coronavirus Disease 2019” (3). Such was the spread of disease that the confirmed cases and deaths kept increasing in China and rapidly COVID-19 reached other countries from various continents until it was considered a pandemic (4).

In the following weeks it was proven that the majority of patients with COVID-19 resolved spontaneously. Likewise, we saw that the disease affects both genders with a slight predominance towards men. Of those affected patients, some require hospital admission and even mechanical ventilation support (5).These complications are frequent in people with chronic diseases (diabetes mellitus, hypertension, asthma, obesity, etc.) in whom the fatality is greater than the general population (6).The need for hospitalization and use of intensive therapy converted this pandemic in a real threat for the health systems worldwide.

In Peru, around the middle of March 2020 due to the imminent contagion of the population, the government established healthcare policies similar to those of the Chinese government. This way, quarantine and social distancing measures, the acquisition of new beds and intensive care equipment were established, as well as, the hiring and redistribution of trained professionals in intensive care. However, any strategy applied in another country to counteract the pandemic must be adapted to our reality, since it seems that the quarantine alone is not enough to prevent the spread and the socioeconomic impact of the disease is worrisome. This review was carried out with the objective of determining the current state of the disease and its possible impact on the Peruvian health system.

Methods

A literature search was performed in PUBMED, MEDLINE, PLOs, and SciELO databases as well as Google Academic; available papers with complete text in Spanish and English were selected with the keywords SARS-CoV-2, COVID-19, pandemics and health systems. The relevant information was extracted from the first reported cases to the present and compared to the current Peruvian health situation.

Results

Etiology and transmission mechanism

COVID-19 is a disease caused by SARS-CoV-2, a virus belonging to the coronavirus family that originated two prior zoonotic epidemics, SARS-Co-V caused Severe Acute Respiratory Syndrome in 2002 and MERS-CoV that caused the Middle East Respiratory Syndrome in 2012 (7).). While SARS-CoV-2 is a virus found in snakes, bats and pangolins, apparently one of these animals began the transmission chain in being consumed by various people in Wuhan. However, it is difficult to determine an exact origin of the virus; rather, it seems to have a mixed origin among the diverse animal reservoirs including another unknown one (8,9).

Once the SARS-CoV-2 infection is acquired, the disease has an average incubation period of 14 days, although some reports suggest up to 24 days; which is why the quarantine period should be greater than the latter. A person infected with SARS-CoV-2, even if asymptomatic, could infect 2 or 2.5 people. Although the effective transmission is through large drops via inhalation or contact with oral or ocular mucosa, the virus has also been found in feces, blood and even microdroplets released during a normal conversation; for this reason the general public should wear adequate masks when leaving their home. Furthermore, the transmission associated with medical care reaches over 40%, an important data to reinforce the personal protective equipment in different health establishments. Fortunately, there does not seem to be a perinatal transmission (6,10-12).

Physiopathology

After SARS-CoV-2 exposure, the virus travels through the respiratory tract until reaching the alveolar epithelial cells -pneumocytes- type I and II, that is where it joins the Angiotensin-converting enzyme type 2 (ACE2) receptor. In the normal human lung, the ACE2 is mainly expressed in the type 2 pneumocytes, which produce surfactant, a substance that lowers the surface tension within the alveoli to avoid its collapse. The fact that men have a greater ACE2 level in their pneumocytes explains why they have a greater possibility of presenting complications and an increase in lethality(13).The binding of SARS-CoV-2 to the ACE2 receptor is up to 20 times greater than that of SARS-CoV, which explains its greater infectivity. Its binding to ACE2 activates a great expression to said enzyme which leads to the death of the infected alveolar cell and the infection of the contiguous cells. In such way, the virus rapidly injures the lung tissue causing pneumonia. Since it is a virus similar to SARS-CoV and MERS-CoV, the pulmonary histopathology shows similar findings between these pathologies: the hyaline membrane formation in the alveoli and the mononuclear interstitial inflammatory infiltrates with multinucleated giant cells(14).

Clinical presentation and diagnosis

Despite the great transmissibility of SARS‐CoV‐2, the majority of patients have a mild disease or are asymptomatic. 5% of the infected population requires hospital admission and even some require intensive therapy with mechanical ventilation support (15).In addition, those who survive the disease could suffer from pulmonary fibrosis, this would be one of the most feared complications after recovery (16).

Furthermore, in symptomatic patients the clinical presentation is mainly fever in over 80%, dry cough in over 70%, dyspnea in over 50%, and also asthenia and myalgias, although less than 50% of cases. Other less reported symptoms are headache, odynophagia, abdominal pain and diarrhea (17).

Two tests are used for diagnosis. A serologic test, also called rapid test because its results are ready in 15 minutes. This test identifies the IgM and IgG antibodies present in the blood or plasma of sick patients. If the test reveals an elevated number of antibodies, the rapid test will be positive, and it is concluded that the person has or recently had the disease. The rapid test has a high specificity, which is useful but requires complementing with the molecular test. This one, also known as PCR-RT, for its English initials, involves a reverse transcriptase polymerase chain reaction and is the test of choice for SARS-CoV-2 diagnosis. It is based on the viral RNA analysis, ideally found in a sample of the lower respiratory tract, although these tests often come from a nasopharyngeal swab (18,19).

Likewise, the most frequent abnormal laboratory findings are lymphopenia, prolonged prothrombin time and elevated lactate dehydrogenase. The thoracic X-rays are characterized by irregular bilateral infiltrates and almost all thoracic computerized tomographies show some alteration such as consolidation or “ground-glass opacity” infiltrates (15,20).

Prevention and treatment

There still does not exist a vaccine to prevent COVID-19, which is why the current treatment is basically symptomatic. Antibiotics, antivirals and antiparasitics have been used with promising results, but the efficacy of these drugs have yet to be verified through large clinical trials. Since we do not count on an effective treatment at this moment, the best way to fight this pandemic is through control of possible sources of infection including asymptomatic patients, early diagnosis and notification, social distancing and support therapies. Also, protective measures for the general population is based on improving personal hygiene, wearing masks -preferably disposable ones- and keeping spaces well ventilated (20).

Tabla 1.Resumen de algunos artículos relevantes sobre la COVID-19 hasta el 12 de abril de 2020

Article

Results

Conclusions

(6) Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China.

Of a total of 138 patients with COVID-19, 36 patients (26.1%) were in the intensive care unit (ICU): 22 with acute respiratory distress syndrome (61.1%), 16 with arrhythmia (44.4%) and 11 with shock (30.6%). The median time from the first symptom to dyspnea 5 days, to hospital admission 7 days and to ARDS 8 days. Patients treated in the ICU (n = 36), compared to patients not treated in the ICU (n = 102), older adults (mean age, 66 years) and were more likely to have underlying comorbidities.

Of 138 hospitalized patients with pneumonia due to 2019-nCoV: 41% had a possible hospital transmission, 26% were treated in the ICU and mortality was 4.3%.

(7) Paules CI, Marston HD, Fauci AS. Coronavirus Infections—More Than Just the Common Cold.

The coronavirus (nCoV-2019) produces fever, cough, dyspnea, and / or watery diarrhea. Up to 30% of infected patients required mechanical ventilation and 10% died, the highest mortality rates were related to patients with greater comorbidities.

The trajectory of the outbreak and the appearance of the outbreak by nCoV-2019 is unpredictable, therefore, early diagnosis and effective isolation are required.

(8) 2020 Crossspecies transmission of the newly identified COVID-19.

After analyzing 276 coronavirus genomes, the sequence of nCoV-2019 appears to be a recombination between the bat coronavirus and other isolates of unknown origin, located within the spike glycoprotein that the cell surface receptor recognizes. Likewise, the genetic information of nCoV-2019 is similar with the bat coronavirus and especially with snakes in China.

135/5000 The results suggest that homologous recombination may occur that contributes to nCoV-2019 cross-species transmission.

(9) Presumed Asymptomatic Carrier Transmission of COVID-19.

A family group of 5 patients with fever and respiratory symptoms admitted to the Fifth Anyang People's Hospital, China was reported. Asymptomatic patient 1 was isolated and observed, but never presented symptoms. The results of RT-PCR tests, chest tomography images were initially normal, as well as C-reactive protein and lymphocyte count. Patients 2 to 6 developed nCoV-2019, 4 were women between 42 and 57 years old, none had visited Wuhan or had any contact with another individual, except for patient 1. Two patients developed severe pneumonia, with opacities in the tomography of chest and multifocal frosted glass appearance. One patient had subsegmental areas of consolidation and pulmonary fibrosis.

Preventing infection from an asymptomatic nCoV-2019 carrier is challenging. The mechanism by which asymptomatic carriers can acquire and transmit the nCoV-2019 coronavirus requires further study.

(10) Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes.

The presence of nCoV-2019 in anal swabs and blood. Two groups were performed: the first one collected samples from 39 patients and the second one collected samples from 139 patients, with detection of positive viral nucleotides.

The nCoV-2019 can be eliminated through multiple routes, so there could be fecal-oral transmission.

(11) Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records.

9 pregnant women between 26 and 40 years of age, with a history of epidemiological exposure to nCoV-2019, all in their third trimester with a range of weeks of gestation on admission ranging from 36 to 39 weeks plus 4 days and undergoing caesarean section, were studied. None of the patients had underlying chronic diseases. One patient developed an influenza virus infection upon entering the hospital. Seven of the nine patients had fever without chills, but none had body temperature> 39 ° C. None developed severe pneumonia. Almost all patients (8/9) showed typical findings on chest tomography: multiple irregular shadows on ground glass in the lungs.

The clinical characteristics of nCoV-2019 pneumonia in pregnant women were similar to those reported in non-pregnant adult patients. There is currently no evidence of perinatal nCoV-2019 infection in late pregnancy.

(12) Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov.

According to the WHO, nCoV-2019 has caused 76,392 confirmed cases and 2,348 deaths in China as of February 22, 2020. SARS-CoV-2 was reported to share with SARS-CoV the same receptor on the angiotensin-converting enzyme. 2 (ACE2). The expression of this receptor is concentrated in type II alveolar cells (AT2) that also expressed other genes that positively regulate the entry, reproduction and transmission of the virus.

This study provides biological support for the future development of the anti-ACE2 therapeutic strategy.

(13) Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation.

Se probaron varios anticuerpos monoclonales específicos de SARS-CoV y se halló que no tienen una unión apreciable al nCoV-2019. Además, se demostró la evidencia biofísica y estructural de que el nCoV-2019 se une al receptor de la ACE2 con mayor afinidad que el SARS-CoV.

The structure of nCoV-2019 would allow for greater infectivity and spread of the virus.

(14) Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 Cases from the Chinese Center for Disease Control and Prevention.

 

Among a total of 72,314 case records, 44,672 were classified as confirmed cases of COVID-19. Most of the cases were between 30 and 79 years old (87%), 1% were 9 years old or younger, 1% were between 10 and 19 years old and 3% were 80 years old or older. Most of the cases were diagnosed in Hubei province (75%) and the majority of Wuhan-related exposures (86%). Most of the cases were classified as mild (81%), 14% were severe and 5% were critical. The overall case fatality rate was 2.3% (1,023 deaths among 44,672 confirmed cases). There were no deaths in the group aged 9 years or younger and the case fatality rate among critical cases was 49%. Of the 44 672 cases, 1716 were health workers (3.8%), 1080 of whom were in Wuhan (63%). 14.8% of confirmed cases among health workers were classified as serious or critical and 5 deaths were observed.

COVID-19 quickly spread from a single city to all of China in just 30 days. The high speed of geographic expansion and the sudden increase in the number of cases surprised and quickly overwhelmed health and public health services in China, particularly in Wuhan City and Hubei Province.

(15) Viral Infection Increases the Risk of Idiopathic Pulmonary Fibrosis.

Of 1287 participants, the pooled OR of all viruses indicated that viral infection could significantly increase the risk of idiopathic pulmonary fibrosis (OR, 3.48; 95% CI 1.61-7.52; p = .001), but not that of its exacerbation ( OR, 0.99; 95% CI, 0.47-2.12; p = 0.988).

All the viruses analyzed, including Epstein-Barr virus, cytomegalovirus, human herpes virus 7 and human herpes virus 8 were associated with a significant increase in the risk of idiopathic pulmonary fibrosis, except for human herpes virus 6.

126/5000 These findings imply that viral infection could be a potential risk factor for idiopathic pulmonary fibrosis.

(16) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.

As of January 2, 2020, 41 patients were identified as infected with nCoV-2019. Most of those infected were men (73%) and less than half had underlying diseases (32%). The median age was 49 years (RIC 41.0 - 58.0). 66% of patients had been exposed to the Huanan seafood market. Common symptoms at disease onset were fever (98%), cough (76%), and myalgia or fatigue (44%). Dyspnea developed in 55% of cases, and the mean time from disease onset to dyspnea was 8 days. 63% of patients had lymphopenia. All 41 patients presented pneumonia with abnormal findings on chest tomography. Complications included acute respiratory distress syndrome (29%), anemia (15%), acute heart failure (12%), and secondary infection (10%). 32% of the cases were admitted to an ICU and 15% died.

The 2019-nCoV infection caused a severe respiratory illness similar to the coronavirus of severe acute respiratory syndrome. It was associated with increased ICU admission and high mortality.

(17) Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA.

1070 samples were collected from 205 patients with COVID-19 who had a mean age of 44 years (range, 5-67 years) and 68% of men. Most of the patients presented fever, dry cough and fatigue. 19% had serious underlying disease. Bronchoalveolar lavage fluid samples showed the highest positive rates (93%), followed by sputum (72%), nasal swabs (63%), fiberoptic brush biopsy (46%), pharyngeal swabs (32%), feces (29%) and blood (1%). None of the 72 urine samples tested positive.

255/5000 The samples with the highest positive rates for detection of nCoV-2019 were those of the lower respiratory tract (bronchoalveolar lavage), while the samples with the most false negatives were those obtained from pharyngeal swabs, faeces and blood.

(18) Clinical characteristics of 2019 novel coronavirus infection in China.

Data from 1099 patients were extracted, the median age was 47 years, and 41.9% were women. Only 1.18% of patients had direct contact with wildlife, while 31.30% had been in Wuhan and 71.8% had contacted people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, the typical radiological finding on chest tomography (50%) was ground glass opacity. The most severe cases were diagnosed by symptoms plus reverse transcriptase polymerase chain reaction. Lymphopenia was observed in 82.1% of patients. 5% patients entered the intensive care unit and only 1.36% died.

The nCoV-2019 epidemic is rapidly spreading by person-to-person transmission.

(19) The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China.

As of January 10, 2020, 41 patients were diagnosed with 2019-nCoV infection. The onset of the disease in the 41 cases varies from December 8, 2019 to January 2, 2020. Symptoms included fever (more than 90% of cases), malaise, dry cough (80%), difficulty breathing ( 20%) and respiratory distress (15%). Vital signs were stable in most cases, while leukopenia and lymphopenia were common. The 2019-nCoV infection in Wuhan appears clinically milder than SARS or MERS in severity and case fatality.

The Wuhan outbreak is a clear reminder of the continuing threat of zoonotic diseases for global health security. Sharing the experiences of all geographic regions will be the key to counteracting the epidemic.



Discussion

Despite the high transmissibility of SARS-CoV-2, its fatality is apparently low (3%) related to SARS (9.6%) and MERS (34.4%). Likewise, the majority of infected patients are asymptomatic or have few symptoms. The most frequent complication is acute respiratory distress syndrome which requires mechanical ventilation support in 5% of patients (1,6,21). Upon extrapolating these numbers to almost 32 million of inhabitants in Peru (22), as long as the Peruvian population has the same characteristics as the revised series and without applying any preventive measure, we expect to have 1.6 million hospitalized in the country, of which 48 thousand would die; in addition to a possible national health system collapse which could generate over 5% mortality.

It is difficult for any government to make decisions in an unprecedented global crisis. No health system is prepared to handle this pandemic. Furthermore, a bad public health decision can be devastating for the population and lead to the collapse of the health system in any country. For this reason, in view of the imminent COVID-19 contagion of the population, the Peruvian government enacted a health state of emergency with measures of social immobilization and mandatory home isolation from March 16 to April 26 as a disease containment measure. Undoubtedly, these restrictive measures will generate a great socioeconomic impact, but nothing compared to the loss of hundreds or thousands of human lives. In this way, the national government strategy was to minimize the spread of COVID-19 through “flattening of the curve” of those possibly infected and that way reduce the overload on health services. A logical decision, given that other herd immunity strategies opted by some developed countries implicated the contagion and recovery from viral infection of more than 60% of the population, with the consequent risk that this could bring to the health system. Those countries that began with this last strategy, in the following weeks changed to more restrictive measures, since it seems very difficult to fight the virus due to its high infectivity and that the uncalculated collapse of health system.

The main health problem in Peru is the deficient infrastructure, a fact verified by the Public Defender’s Office on April 2018, just as in the last great national census of health infrastructure in 2006 where it was found that 20% of high complexity hospitals (level III) lacked adequate equipment for care. For example, the intensive care units (ICU) of the entire Peruvian health system (MINSA, EsSalud, FFAA, PNP and private clinics) had barely 685 beds, of which only 60 (15%) were available given that the others were already occupied (23). The precarious situation of our health system is clear; if the number of those infected increases, the system will simply collapse. In addition to that, there is also a lack of capacitated human resources: the Colegio Médico del Perú reports a major deficit of 15 thousand medical specialists (24).

In light of this landscape, the Peruvian government’s health strategy includes the purchase of new beds in ICU, the suspension of outpatient visits and elective surgeries, reinforcement of emergencies, notification of suspected patients, as well as, the home monitoring of confirmed cases and the transfer of complicated cases to COVID-19 referred hospitals.

On the other hand, the need for diverse materials and medical supplies in the middle of a crisis provoked by the pandemic also limits the acquisition of these. For example, the acquisition of mechanical ventilators for ICU normally is a process that takes around 2 months, Currently the great demand for these worldwide and considering that many countries already placed their importation orders before Peru; it will most probably take longer. For this reason, the national government has coordinated with Peruvian universities the making of mechanical ventilators and in this way attempt to alleviate the demand (25). All this effort on behalf of the Peruvian government and society does not guarantee success, but not doing so leads to an unnecessary loss of many human lives. Although it might not eliminate COVID-19 in the following months, the rational political response is to fight it now with quarantine.

Conclusions

Quarantine with strict measures of social isolation and distancing is precise given the Peruvian health reality and the imminent contagion of the population. These restrictive measures must be evaluated on an ongoing basis in the country to avoid the collapse of the health system. Finally, it is necessary to promote more research on this topic in our reality to obtain first-hand information and make more adequate decisions.


Author contributions: The authors participated in the creation of the idea, the design, data collection, analysis of the results and the preparation of the manuscript.
Financing: Self-financed.
Conflict of interests: The authors declare that there is no conflict of interests in the publications of this article.
Recibido: April 19, 2020
Aprobado: May 18, 2020


Correspondence: Alberto Córdova Aguilar.
Address: Jr. Paseo del Prado 133 – Urb. Las Lomas, La Molina. Lima, Perú.
Telephone number: (511) 999 779 789
Email: acordovaa@unmsm.edu.pe

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