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Year : 2020  |  Volume : 1  |  Issue : 1  |  Page : 7-10

Post-COVID-19 sequelae-issue which remain unanswered

Department of Pulmonary Medicine, AIIMS, Patna, Bihar, India

Date of Submission25-Nov-2020
Date of Acceptance07-Dec-2020
Date of Web Publication31-Dec-2020

Correspondence Address:
Dr. Deependra Kumar Rai
Department of Pulmonary Medicine, AIIMS, Patna, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jascp.jascp_8_20

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COVID-19 is known to involve multiple organs and physiological systems in all age group humans. There are a growing number of patients worldwide who have survived COVID-19 but continue to battle the symptoms of the illness, long after they have clinically tested negative for the disease. This narrative review summarizes current clinical evidence regarding post COVID health issue specially post COVID pulmonary fibrosis, post COVID thrombosis, post COVID syndrome, and post COVID ICU syndrome. Many aspects regarding post COVID sequelae remain answered, necessitate hot area for research.

Keywords: Lung fibrosis, post-COVID-19, post-COVID syndrome, thrombosis

How to cite this article:
Rai DK. Post-COVID-19 sequelae-issue which remain unanswered. J Appl Sci Clin Pract 2020;1:7-10

How to cite this URL:
Rai DK. Post-COVID-19 sequelae-issue which remain unanswered. J Appl Sci Clin Pract [serial online] 2020 [cited 2023 Mar 29];1:7-10. Available from: http://www.jascp.org/text.asp?2020/1/1/7/306104

  Introduction Top

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide.[1] As of September 30, 2020, the cases of COVID-19 infection continues to soar worldwide with no peak in sight making total case tally standing at 63, 12, 585 including 9,40,705 active cases, 52,73,202 cured/discharged/migrated and 98,678 deaths, according to the Ministry of Health and Family Welfare. While whole medical fraternity and researchers across the world continue to learn more about the novel contagion and its bizarre array of symptoms, it is becoming clear that the battle with COVID-19 is not an easy one.

After the COVID outbreak, there are a growing number of patients worldwide who have survived COVID-19 but continue to battle the symptoms of the illness, long after they have clinically tested negative for the disease. They are called as long – haulers. As we move forward through this pandemic, the challenging part is how to manage this COVID-19 Sequelae which may vary from mild in terms of fatigue and body aches to severe in form of requiring long term oxygen therapy and lung transplantation due to lung fibrosis, significant cardiac abnormalities and stroke leading to significant impairment in Quality of health. Various studies have reported that around 70-80% of patients who recovered from COVID-19 presents with persistence of at least 1 or more symptoms, even after being declare COVID- free.[2],[3]

Many active clinical trials and studies are underway to know more about the entity post COVID sequelae. The long-term complication of Covid 19 has been summarized in [Figure 1]. This narrative review summarizes current clinical evidence regarding post COVID sequelae, treatment for managing long term complication caused by this novel epidemic coronavirus. We mainly covered post covid Pulmonary fibrosis, post covid thrombosis, post covid syndrome, and post covid ICU syndrome.
Figure 1: Summarizing long term complication of COVID-19

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  Clinical Predictors of Post COVID Pulmonary Fibrosis Top

There are various mechanisms of lung injury in COVID-19 have been described, with both viral and immune-mediated mechanisms being implicated.[4] One of the risk factors for the development of lung fibrosis in COVID-19 is advanced age and this finding is same as in MERS and SARS-CoV.[5],[6],[7]

Second risk factor includes increased disease severity which includes comorbidities such as hypertension, diabetes, and coronary artery disease[8] and Lab findings like lymphopenia, leukocytosis, and elevated lactate dehydrogenase (LDH).[9] Serum LDH level has been used as a marker of disease severity following acute lung injuries. It is an indicator of pulmonary tissue destruction and correlates with the risk of mortality. According to the World Health Organization, 80% of SARS-CoV-2 infections are mild, 14% develop severe symptoms, and 6% will become critically ill.

Third risk factor includes prolonged ICU stay and duration of mechanical ventilation. While disease severity is closely related to the length of ICU stay, mechanical ventilation poses an additional risk of ventilator-induced lung injury (VILI). Abnormalities of pressure or volume settings underlie this injury leading to a release of proinflammatory modulators, worsening acute lung injury, and increased mortality or pulmonary fibrosis in survivors.[10]

Smokers are 1.4 times more likely to have severe symptoms of COVID-19 and 2.4 times more likely to need ICU admission and mechanical ventilation or die compared to nonsmokers.[11],[12]

The World Health Organization (WHO) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) have issued communications warning people to avoid excessive drinking, saying it may increase COVID-19 susceptibility and severity. Alcohol use disorder increases the risk for complications of COVID-19.[13]

Radiological aspects of post-COVID pulmonary fibrosis

In one of the study[14] chest CT scan was performed on the last day before discharge, two weeks and four weeks after discharge. Compared with the last CT scan before discharge, the abnormalities (including focal/multiple GGO, consolidation, interlobular septal thickening, subpleural lines and irregular lines) in lungs were gradually absorbed in the first and second follow-ups after discharge. The lung lesions of 64.7% discharged patients were fully absorbed after 4-week follow-up. It indicated that the damage to lung tissue by COVID-19 could be reversible for the common COVID-19 patients. It also suggested that the prognosis of non-severe patients is favorable, and the clinical intervention should be conducted in time to prevent common COVID-19 patients from worsening to severe patients.

Another study[2] conducted at Italy (between April 2020 to May 2020) assessing persistent symptoms in 143 patients who were discharged from the hospital after recovery from COVID-19.Patients were assessed a mean of 60.3 days after onset of the first COVID-19 symptom; at the time of the evaluation, only 18 (12.6%) were completely free of any COVID-19–related symptom, while 32% had 1 or 2 symptoms and 55% had 3 or more. None of the patients had fever or any signs or symptoms of acute illness. Worsened quality of life was observed among 44.1% of patients. They also found that most common symptom persistent beyond discharge was fatigue (53.1%), dyspnea (43.4%), joint pain, (27.3%) and chest pain (21.7%).

Another follow up study[15] which studied the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery enrolled 55 patients and found different degrees of radiological abnormalities were detected in 39 patients. Blood Urea nitrogen concentration at admission was associated with the presence of CT abnormalities.

Currently, no fully proven options are available for the treatment of post inflammatory COVID 19 pulmonary fibrosis. Various treatment strategies are under evaluation. It has been proposed that prolonged use of anti-viral, anti-inflammatory and anti-fibrotic drugs diminish the probability of development of lung fibrosis. However, it is yet to be ascertained whether early and prolonged use of antiviral agents may prevent remodeling of lung or which of the available antiviral is more effective. Though risk-benefit ratio should be assessed prior to use, prolonged low dose corticosteroid may prevent remodeling of lung in survivors.[16] Anti-fibrotic drugs, such as pirfenidone and nintedanib, have anti-inflammatory effects as well and thus they may be used even in the acute phase of COVID-19 pneumonia.[17] Pirfenidone exerts anti-fibrotic, anti-oxidative and anti-inflammatory properties. Rehabilitation in the acute stage and particularly in the recovery stage is beneficial.[18] It improves respiratory function, exercise endurance, self-care in daily living activities and psychological support. However, scientific research is required for concluding its definite benefits.

Many studies have shown that most common abnormality of lung function in discharged survivors with COVID-19 is impairment of diffusion capacity, followed by restrictive ventilatory defects, which are both associated with the severity of the disease.[19],[20] Both decreased alveolar volume and KCO contribute to the pathogenesis of impaired diffusion capacity.[21] At 3-months after discharge, residual abnormalities of pulmonary function were observed in 25.45% of the cohort which was lower than the abnormal pulmonary function in COVID-19 patients when discharge.[6] Lung function abnormalities were detected in 14 out of 55 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect.[15] There is urgent need to define natural course of post covid lung fibrosis by Serial imaging and lung function. How long patient should be followed is not well defined. Some expert recommend follow-up till 3 years after recovery.[22],[23]

  Post-COVID Thrombosis Top

Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state with a high incidence of thrombotic events during hospitalization; however, data examining rates of thrombosis after discharge are limited. COVID-19 may predispose to both venous and arterial thromboembolism due to inflammation, hypoxia, immobilization and DIC. The incidence of thrombosis in COVID-19 has been reported so far to be as high as 25% to 31%, with VTE making up the largest proportion.[24] Elevated D-dimer, prolonged prothrombin time, and prolonged activated partial thromboplastin time have been identified as independent predictors of death in COVID-19.[25] So, all recommendations are for providing VTE prophylaxis (either pharmacological or mechanical) for all hospitalized patients with confirmed or highly suspected COVID-19, regardless of VTE risk assessment score. But the question is about the duration and dose of thromboprophylaxis in high risk group patients after discharge from hospital. Extended-duration pharmacological thromboprophylaxis is recommended for high-risk surgical patients,[26],[27] but the net clinical benefit in acutely ill medical patients is less clear and is thus not universally recommended.[28] Similarly, we don't have much data on this debate and whatever information we gather are extrapolations from high risk patients without COVID-19 which suggests that extended VTE prophylaxis is not necessary for all patients with COVID-19 who are being discharged from the hospital. But in case a patient has ongoing VTE risk factors, they suggest that a multidisciplinary discussion should occur at or near the time of discharge looking for the benefit from extended post-hospital VTE prophylaxis. In such high-risk cases they recommend use of betrixaban or rivaroxaban or enoxaparin (adjusted as need based on weight, renal/liver function, and drug-drug interactions) and suggest limiting the total duration as used in the clinical trials (i.e., enoxaparin 6-14 days; rivaroxaban 31-39 days; betrixaban 35-42 days).[29] A recent study showed cumulative incidence of overall thrombosis was 2.5% and of bleeding was 3.7% at day 30 after discharge for hospitalization for COVID-19. They concluded to do always risk-benefit assessment for post discharge extended thromboprophylaxis.

  Post-COVID Syndrome Top

It is characterized by prolonged malaise, headaches, generalized fatigue, painful joints, dyspnea, chest pain and cognitive dysfunction.[30] Approximately 10% of patients experience prolonged illness after Covid-19. It may persistent for months after the acute infection and almost half of patients report reduced quality of life. The underlying mechanism is not known and probably occur due to prolonged immune disturbance with elevated pro- and anti-inflammatory cytokines. Treatment could include course of corticosteroids (in elevated CRP), DHA, Atorvastatin 40mg daily and Multivitamin with adequate vitamin D.[31]

  Post-Intensive Care Unit COVID Syndrome Top

The termed PICS, an acronym used for both post-intensive care unit syndrome and for persistent inflammation, immunosuppression, and catabolism syndrome. PICS is an ongoing challenge that may potentially present a public health crisis. PICS is a term used to describe the group of impairments faced by ICU survivors. It can persist for months or years. It encompasses a combination of physical, neurological, social, and psychological decline. Critically ill covid patients are considered the most vulnerable to PICS. Among these, 30% suffer from depression and 70% experience anxiety and PTSD after ICU discharge. Telemedicine follow up for all patients, especially those who were sick, at 3-4 weeks then at 2 months followed by 6 months although patients who had been in ICU requires multi-specialty follow up including pulmonary, nephrology, cardiology, neurology and psychology. Rehabilitation education and nutritional support also plays a major role.[18]

  Conclusion Top

COVID-19 infection is not only associated with acute illness rather also have several long term sequeale. Sequelae that may vary from mild illness of fatigue and body aches to severe in form of lung fibrosis, cardiac abnormalities (Myocarditis) and stroke leading to significant impairment in Quality of health. We don't know course of these post COVID sequalae and it would be prudent to do long-term monitoring of all recovered COVID patient specially moderate to severe disease for early identification of sequelae and management.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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