Autor : Rey Darío Raul
Director of the Bachelor’s Degree in Pulmonology, UBA (Universidad de Buenos Aires), Academic Unit, Hospital Tornú
https://orcid.org/0000-0002-6586-2643
Since the first publications of
patients affected by COVID-19 in December, 2019, neither the World Health
Organization (WHO) nor the government health organizations could have foreseen
the magnitude of the global morbidity and mortality caused by this virus, which
is still present. The disease had mild, moderate, and severe clinical forms;
the latter requiring hospitalization and causing sequelae
worthy of being spread to alert the medical community1, 2.
The first studies already
reported complications: Wang et al published 138 cases treated in January,
2020 and reported that 29% of health professionals had been infected by
hospitalized patients and that, besides the already known signs and symptoms
(fever, dyspnea and nonproductive cough), which were widely propagated later,
new symptoms were added: prolonged prothrombin time
(58%), acute respiratory distress syndrome (61%), arrythmia
(44.4%) and shock (30.6%).
36 patients (26%) were treated at
the ICU (Intensive Care Unit), with more probabilities of having comorbidities
(72.2%), whereas chest tomographies (CT) showed
“ground glass” opacities in all the cases3. Complications have been described,
such as pulmonary thromboembolism, cor pulmonale, cerebrovascular disease of large vessels and, in
relation to the specialty, post-Covid pulmonary
fibrosis. The article from Pérez Conde, which
motivated this editorial, is an example of such complications4-6.
Even though most patients with
mild and moderate forms of COVID-19 will not show long-term pulmonary sequelae, it is assumed that 10% will tend to suffer
post-COVID-19 severe pneumonia, and 5% will develop acute respiratory distress
syndrome (ARDS). Some will get better throughout the course of the disease;
others will experience progression towards pulmonary fibrosis7.
The natural recovery evolution of
COVID-19 is unknown. There is poor knowledge regarding clinical evolution and
health recovery in mild and outpatient forms of the disease. Tenforde et al conducted a telephone survey in adults with
positive results for COVID-19 infection and, two or three weeks after result
confirmation, 35% of the individuals hadn’t returned yet to their previous
health condition. One in five young individuals with no pre-existing diseases
were in that situation, thus, COVID-19 may originate a prolonged disease, even
among adults without underlying chronic conditions8.
One previously described
characteristic, pulmonary fibrosis with detrimental physiological effects, was
present in acute respiratory distress syndrome (ARDS) and Middle East
respiratory syndrome (MERS).
As described in the Pérez Conde article, when he cites Thomas et al, there are four
stages of COVID-19 in the chest CT:
1) Early course: characterized by normal lung or
“ground glass” opacities.
2) Progressive course: increase in opacities and
appearance of crazy paving.
3) Peak course: characterized by progressive
consolidation.
4) Late course: characterized by a gradual
decrease in consolidation and “ground glass” opacities; signs of pulmonary
fibrosis can start manifesting9,
10.
With regard to COVID-19 patients
who attended the ICU with moderate or severe forms of the disease, the Bhatraj group reported the following as the most common
causes of admission: respiratory failure requiring mechanical respiratory
assistance (MRA), severe hypotension requiring vasopressor treatment and
mechanical ventilation, hypotension that motivated vasopressor treatment, or
both. The mortality rate in these critically ill patients was high: 50% of the
patients died from this disease11.
Every viral disease is treated
with antivirals, broad spectrum antibiotics (to cover a possible bacterial superinfection), corticoids as anti-inflammatories and, for
lung fibrosis sequelae, antifibrotic
drugs, mostly when its natural course is unknown.
COVID-19 was also included in
these general guidelines, so such treatment guidelines were extrapolated.
Steroids have been used with good results, as in the cohort of Myall et al, in which 30 patients survived with pulmonary
inflammatory lesions evident in imaging studies and persistent functional
deficit. As observed, long-term follow-up of COVID-19 had the objective of
preventing progression to pulmonary fibrosis with permanent functional deficit.
Early treatment with steroids is well-tolerated and associated with rapid
improvement12.
Umemura et al wanted to investigate the certainty and activity of nintedanib in COVID-19. To that end, 30 patients with
COVID-19 received nintedanib versus a similar control
group who didn’t receive the medication. There weren’t any differences between
the groups in terms of mortality after 30 days, but there was less mechanical
ventilation and a lower lesion regression rate in the CT in the treated cohort,
so the authors believe the administration of nintedanib
may be beneficial to reduce pulmonary lesions in COVID-19.
According to Shen,
there aren’t any studies about the relationship between pirfenidone,
a drug that is widely used for pulmonary fibrosis, and the treatment of
COVID-19. Before it is indicated, it is important to consider the annual cost
of treatment. In 2020, the cost was USD 40,000 (pirfenidone)
and USD 20,000 (nintedanib), respectively13-15.
Tocilizumab is a monoclonal antibody that has shown a good anti-inflammatory
response in rheumatoid arthritis. So, the group of Veiga
et al thought it could be used for severe forms of COVID-19. In a cohort of
129 patients, results were discouraging. The Follow-up Committee recommended
that the study had to be interrupted, given the high mortality rate registered
15 days after administration (17% as opposed to 3% in the control group)16.
Nugroho et al did a meta-analysis of the use of tocilizumab
in post-COVID-19 pneumonia, since there isn’t any certified treatment for that
complication.
They evaluated 26 studies
investigated in PubMed, EMBASE, Medline and Cochrane, published between March
and October, 2019, with 2112 patients enrolled in the COVID-19 cohort versus
6160 in the control group.
Tocilizumab has an effective result against mortality for all the causes. For
optimum results, it should be cautiously administered and adapted to patients
according to selection criteria17.
To conclude, it is necessary to
highlight the importance of strict checkups of large groups of COVID-19
survivors by means of periodic functional and tomographic studies. This will
allow us to eventually determine the course of the viral infection, the natural
history of the disease and also the therapeutic response of these patients.
REFERENCES
1. Zhu N, Zhang D, Wang W y col.
A Novel Coronavirus from Patients with Pneumonia in China, 2019 N Engl J Med 2020; 382: 727-33. https://doi.org/10.1056/NEJMoa2001017
2. Hui D, Azhar E, Madani T y col. The continuing
2019-nCoV epidemic threat of novel coronaviruses to global health: the latest
2019 novel coronavirus outbreak in Wuhan, China Int J
Infect Dis. 2020; 91: 264-6.
https://doi.org/10.1016/j.ijid.2020.01.009
3. Wang D, Hu B, Hu C y col. Clinical
Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-
Infected Pneumonia in Wuhan, China JAMA. 2020; 323: 1061-9.
https://doi.org/10.1001/jama.2020.1585
4. Xie
Y, Wang X, Yang P. COVID-19 Complicated by Acute Pulmonary Embolism Radiology:
Cardiothoracic Imaging 2020; 2: e2000 https://doi.org/10.1148/ryct.2020200067
5. Creel-Bulos
C, Hockstein M, Amin N, Melhem
S, Truong A, Sharifpour M. Acute Cor
Pulmonale in Critically Ill Patients with Covid-19.
New Engl J Med 2020; 382: e70.
https://doi.org/10.1056/NEJMc2010459
6. Oxley T, Mocco
J, Majidi S y col. Large-Vessel Stroke as a Presenting
Feature of Covid-19 in the Young. N Engl
J Med. 2020 May 14;
382(20): e60. https://doi.org/10.1056/NEJMc2009787
7. Udwadia
Z, Koul P, Richeldi L. PostCOVID lung fibrosis: The tsunami that will follow the
earthquake Lung India. 2021;38(Supplement):S41-S47.
8. Tenforde
M, Kim S, Lindsell Ch y
col. Symptom Duration and Risk Factors for Delayed Return to Usual Health
Among Outpatients with COVID-19 in a Multistate Health Care Systems Network -
United States, March-June 2020. MMWR Morb
Mortal Wkly Rep 2020; 69:
993-8.
9. Pérez Conde L. Fibrosis pulmonar pos
neumonía causada por COVID-19. (Reporte de 3 Casos) Rev Am Med Resp 2022; 21: 160-3.
10. Kwee
TC, Kwee RM. Chest CT in COVID-19: What the
Radiologist Needs to Know. Radiographics. 2020; 40(7): 1848-65.
https://doi.org/10.1148/rg.2020200159.
11. Bhatraju
P, Ghassemieh B, Nichols M y col. Covid-19 in
Critically Ill Patients in the Seattle Region - Case Series N Engl J Med 2020;382:2012-22.
https://doi.org/10.1056/NEJMoa2004500
12. Myall
K, Mukherjee B, Castanheira A y col. Persistent
Post-COVID-19 Interstitial Lung Disease An Observational Study of
Corticosteroid Treatment Ann Am Thorac Soc 2021; 18: 799-806. https://doi.org/10.1513/
AnnalsATS.202008-1002OC
13. Umemura Y, Mitsuyama Y, Monami K y col. J infect Dis 2021; 108.454-60.
14. Shen
H, Zhang N, Liu Y y col. The
interaction between pulmonary fibrosis and Covid 19
and the application of related antifibrotic drugs.
Front Pharmacol 2022; 12: 805535.
https://doi.org/10.3389/fphar.2021.805535
15. Corral, M, De Young K, Kong AM. Treatment Patterns, Healthcare Resource Utilization, and
Costs Among Patients with Idiopathic Pulmonary Fibrosis Treated with Antifibrotic Medications in US-Based Commercial and
Medicare Supplemental Claims Databases: a Retrospective Cohort Study. BMC Pulm Med 2020; 20:
188. https://doi.org/10.1186/s12890-020-01224-5
16. Veiga V, Prat J, Farias D y col. Effect of tocilizumab on clinical outcomes at 15 days in patients
with severe or critical coronavirus disease 2019: randomised
controlled trial BMJ 2021; 372: n84 | https://doi.org/10.1136/bmj.n84
17. Nugroho C; Suryantoro S, Yuliasih Y y col. Yuliasih Optimal use of tocilizumab for severe and critical COVID-19: a systematic
review and meta-analysis [version 1; peer review: 1approved, 2 approved with
reservations F1000Research 2021, 10:73 https://doi.org/10.12688/f1000research.45046.1approved,
2 approved with reservations