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. 2021 Jan 20;9(1):e14. doi: 10.22037/aaem.v9i1.1058

Late Complications of COVID-19; a Systematic Review of Current Evidence

SeyedAhmad SeyedAlinaghi 1, Amir Masoud Afsahi 2, Mehrzad MohsseniPour 1, Farzane Behnezhad 3, Mohammad Amin Salehi 1, Alireza Barzegary 4, Pegah Mirzapour 1, Esmaeil Mehraeen 5,*, Omid Dadras 6
PMCID: PMC7927752  PMID: 33681819

Introduction

Introduction:

COVID-19 is a new rapidly spreading epidemic. The symptoms of this disease could be diverse as the virus can affect any organ in the body of an infected person. This study aimed to investigate the available evidence for long-term complications of COVID-19.

Methods:

This study was a systematic review of current evidence conducted in November 2020 to investigate probable late and long-term complications of COVID-19. We performed a systematic search, using the keywords, in online databases including PubMed, Scopus, Science Direct, Up to Date, and Web of Science, to find papers published from December 2019 to October 2020. Peer-reviewed original papers published in English, which met the eligibility criteria were included in the final report. Addressing non-human studies, unavailability of the full-text document, and duplicated results in databases, were characteristics that led to exclusion of the papers from review.

Results:

The full-texts of 65 articles have been reviewed. We identified 10 potential late complications of COVID-19. A review of studies showed that lung injuries (n=31), venous/arterial thrombosis (n=28), heart injuries (n=26), cardiac/brain stroke (n=23), and neurological injuries (n=20) are the most frequent late complications of COVID-19.

Conclusion:

Since we are still at the early stages of the COVID-19 epidemic, it is too soon to predict what long-term complications are likely to appear in the survivors of the disease in years after recovery. Furthermore, the complexity of COVID-19 behaviors and targets in the human body creates uncertainty in anticipating long-term complications.

Introduction

Coronavirus disease 2019 (COVID-19) is an extremely contagious infectious disease caused by SARS-CoV-2 (1). COVID-19 infection was first reported in Wuhan, China, and spread quickly and turned into an unprecedented global pandemic (2-5).

The novel coronavirus affects not only the respiratory tract, but also other organs in the human body. COVID-19 could cause injuries in the lungs, liver, kidney, heart, vessels, and other organs (6). Respiratory failure and acute respiratory distress syndrome (ARDS) are the most common complications of severe COVID-19 infection; the majority of hospitalized COVID-19 patients suffer from severe lung injuries and fatal multi-organ failure as well as hemolytic anemia. However; super infection, acute liver, kidney, and cardiac injuries, shock, and hypoxic encephalopathy are less common symptoms (7-9). Some COVID-19 patients may also present signs of tissue damage including rhabdomyolysis or hemoptysis, which lead to cellular injury, release of heme proteins, and collection of heme in body tissues (10).

SARS-CoV-2 usually affects the respiratory system (11), nervous system involvement has also been reported in some recent studies among patients with COVID-19 (12). Coronaviruses can attack the neural tissue including microglia, astrocytes, and macrophages, and cause nerve injury through direct nerve infection (13). The nervous system injuries could manifest as headache, dizziness, seizure, impaired consciousness, acute cerebrovascular disease, and ataxia. The virus could also affect the peripheral nervous system (PNS) and cause olfactory dysfunction, dysgeusia, vision impairment, and neuropathic pain (12, 13). 

COVID‐19 could also cause cardiac injuries such as cardiomyopathy and conduction system malfunction. Studies suggest the direct involvement of cardiac muscles in some patients (4, 14, 15). Generally, infectious myocarditis is the most common cardiac complication of COVID-19 infection. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptors to infect host cells, through which it can cause pneumonia and myocardial injuries. High expression of ACE2 receptors in the lungs and heart could increase the risk of myocardial injuries in COVID‐19 patients (14). ACE2 is also expressed in the intravascular endothelium, intestinal epithelium, and the kidneys; therefore, these organs could be a target for SARS-CoV-2 infection. Tachyarrhythmia is also a common cardiovascular complication in COVID-19 patients. Electrocardiography and echocardiography could be used in diagnosing and predicting the prognosis in COVID-19 patients (16).

Some COVID-19 patients could suffer from earache that may be a sign of sub-acute thyroiditis. Studies have shown that a few weeks after upper respiratory tract involvement, subacute thyroiditis may occur and it might be a late complication in patients with COVID-19 infection. Therefore, thyroid functions should be checked after discharge in patients with COVID-19 (17, 18). In addition, there is an abnormal rise in various biochemical parameters such as erythrocyte sedimentation rate (ESR), albumin levels, serum ferritin levels, lactate dehydrogenase (LDH) levels, and C-reactive protein (CRP) levels in the infected patients; on the other hand, the hemoglobin levels and lymphocyte count could reduce in these patients. These complications could lead to cytokine storm, causing multiple organ dysfunction (19, 20).

The coronavirus pandemic showed that COVID-19 could affect many organs besides the lungs, like heart and brain, which increases the risk of long-term health problems. There are several ways that the infection can affect someone’s health. Much is still unknown about how COVID-19 will affect people over time. While most patients infected with COVID-19 recover quickly, the potential long-lasting problems caused by COVID-19 make it necessary to look for and study its late complications. This review aims to present a systematic review of late complications of COVID-19 and identify how prevalent these symptoms are and who is most likely to be affected by them.

Methods

Study design and setting

This study was a systematic review of current evidence conducted in October 2020 and subsequently updated on November 4, 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was employed.

Data sources

We performed a systematic search using the keywords in the online databases including PubMed, Scopus, Science Direct, Up to Date, and Web of Science. All the related papers and reports published in English from December 2019 through October 2020 were retrieved and then updated in November 2020. Our search strategy in each of the above-mentioned databases included several combinations of keywords in the following orders:

A. “Coronavirus” OR “COVID-19”OR“SARS-CoV-2” OR “Novel Coronavirus” OR “2019-nCoV" [Title/Abstract]

B. "Clinical characteristics” OR “clinical feature” OR “clinical manifestation" [Title/Abstract]

C. "Consequences” OR “Chronic complications” OR“ Late complications” OR “Long-term effects" [Title/Abstract]

D. [A] AND [B] AND [C]

Study selection

The most relevant studies based on titles and abstracts were retrieved by three independent investigators. The full contents of the retrieved papers were reviewed, and the most relevant papers were selected based on the eligibility criteria. The relevant data were extracted and organized in tables. The peer-reviewed original papers published in English that met the eligibility criteria were included in the final report. The exclusion criteria were as follows:

  • Papers addressing non-human studies including in vitro investigations or publications concentrating on animal experiments, or discussing COVID-19 in general, without reference to the keywords of this study.

  • Unavailability of the full-text document.

  • Duplicated results in databases.

Data extraction

We used the data extraction sheet (Table 2) to summarize the information of the authors, type of article (e.g., case series), country of origin, study population, and clinical symptoms (late complications in this study). Two independent investigators gathered this information and further organized them in the Tables. All the selected articles were cross-checked by other authors to ensure no duplications or overlap exists in the content.

Table 2.

Identified late complications of COVID-19

ID First author Study type Country Study Population Late complications
Neurologic Lung disease Liver diseases Heart damage Thrombosis Kidneydisease Stroke Other
1 Ali Sepehrinezhad (21) Perspective Review Iran Patients with neurological complications √ × × × × × × --
2 Filatov A (22) Case Report USA 74-year-old male √ × × × × × × Encephalopathy
3 Helms J (25) Editorial France COVID19 patients √ × × × × × √ --
4 Heneka MT (2) Review Germany COVID19 patients √ × × × × × × --
5 Kochi AN (26) Review Italy COVID19 patients × √ × √ × × √ --
6 Klok FA (27) Case-control Netherlands COVID19 patients × × × × √ × × --
7 Klok FA (30) Case-Control Netherlands COVID19 patients × × × √ √ × √ Symptomatic acute pulmonary embolism (PE), myocardial infarction or systemic arterial embolism
8 Klok FA(30) Case-Control Netherlands COVID19 patients admitted to the ICU × × × √ √ × √ Pulmonary embolism, DVT, Ischemic, systemic arterial embolism
9 Kunutsor SK(44) Letter to Editor UK COVID 19 patients × × √ × × × × Hypoproteinemia
10 Landi A (28) Letter to Editor Italy COVID-19 patients admitted to ICU × √ × √ √ × √ --
11 Lazar HL (45) Commentary USA COVID19 patients admitted to the ICU × √ × × × × × --
12 Lee M (46) Letter to Editor China COVID 19 patients with a history of cardiovascular diseases × × × √ × × × --
13 Liabeuf S(47) Cohort France hospitalized patients with laboratory-confirmed COVID-19 × √ × × × √ × GI damage, septic shock
14 Liu B (48) Authors Reply China COVID19 Patients × √ × × √ × × --
15 Lorenzo-Villalba N(49) Case Report France a patient hospitalized for COVID-19 × √ × × √ × × Parotiditis, cutaneous complications such as hemorrhagic bullae with intra-bullae blood clots and dissecting hematomas, Isolated herpetiform lesions, petechial rash
16 Loungani RS(50) Review USA COVID 19 Patients × × × √ × × √
17 Lodigiani C(34) Cohort Italy COVID19 patients admitted to hospital × × × √ √ × √ Acute coronary syndrome (ACS)/myocardial infarction (MI),overt disseminated intravascular coagulation (DIC)
18 Long B (51) Cohort USA COVID19 patients × √ × √ √ × × Systematic inflammation, myocardial injury, acute myocardial infarction, dysrhythmias,
19 Lopez M (52) Review USA COVID19 patients √ √ √ √ √ × √ Psychological distress
20 Ma J (53) Letter to Editor China three critically ill patients with coronavirus disease 2019 (COVID-19) √ × × × √ √ √ Multiple organ dysfunction syndrome, dry gangrene, multiple cerebral infarction, refractory disseminated intravascular coagulation (DIC) and pneumothorax
21 Ma L (54) Review China COVID19 patients × √ × √ × × √ Pneumonia, persistent hypotension
22 Mao L(43) Research article China Hospitalized Patients
With Coronavirus Disease 2019		 √ √ × × × × × --
23 Mauro V(55) Point of view Italy COVID19 patients × × √ × × × × --
24 Mendoza-Pinto C(56) Letter to Editor Mexico COVID19 patients × × × √ √ √ × Elevated D-dimer, and coagulation abnormalities, catastrophic antiphospholipid syndrome (CAPS), multiple small vessel occlusions, multiorgan system failure
25 Nobile B (57) Letter to Editor France COVID19 patients using Cloripramine √ √ × × × × √ Psychological distress, ischemic attacks, leading to brain inflammation and lesions
26 Nogueira MS (29) Review Ireland COVID19 patients × √ × × × × × Pneumonia, acute respiratory distress syndrome (ARDS) and lymphadenopathy
27 Orsi FA(33) Review Brazil HospitalizedCOVID-19 patients × √ × × √ × × Septic shock or multiple organ dysfunction, ARDS, Hypercoagulability
28 Oudkerk M(58) Special Report Netherlands COVID-19 patients × √ × √ √ √ × GI damage, vascular endothelial damage
29 Palmer K (59) Review Italy COVID-19 patients with non-communicable disease (NCD) × √ × √ √ × √ Psychological distress,
exacerbated chronic NCD conditions (e.g., asthma, chronic obstructive, congestive cardiac failure)
30 Poggiali E (35) Case Reports  Italy An 82-year-old woman, A 64-year-old man × √ × × √ × × Venous thromboembolism, Deep Pulmonary Embolism
31 Parry AH (60) Letter to Editor India COVID-19 patients with pneumonia × √ × × √ × × Diffuse alveolar damage, acute respiratory distress syndrome, pulmonary vascular damage, PTE
32 Patel VG (61) Letter to Editor-Cohort USA COVID-19 patients with prostate cancer × √ × × × × × --
33 Paul P (62) Letter to Editor India COVID-19 patients × √ × √ × × × ARDS, pneumonia, multiple organ failure, infective myocarditis
34 Paybast S (42) Review Iran COVID-19 patients √ √ × × × √ √ GI disease, Intracranial hemorrhage, hyposmia and hypogeusia, disorientation, third nerve palsy
35 Pryce-Roberts A(38) Review UK COVID-19 patients √ × × × × × √ Dysgeusia, hyposmia, disorientation, encephalitis, meningoencephalitis, and encephalopathy
36 Puntmann VO(37) Clinical trial Germany Patients Recently Recovered From COVID-19 × × × √ × × × --
37 Rey JR (63) Letter to editor Spain patients attended due to COVID-19 × √ × √ √ × √ Acute coronary syndrome
38 Roche JA(64) Hypothesis USA COVID 19 patients with deregulated BK signaling × √ × × × × × --
39 Rosen RJ(65) Letter to editor USA × × × × √ × √ --
40 Saban-Ruiz J (66) Review Spain Cardiometabolic health/medicine × × × √ × × √ --
41 Sheraton M (39) Review USA Patients with neurological complications √ × × × × × × Guillain-Barre syndrome
42 Siguret V (67) Letter to the editor France Thrombotic complications in critically ill COVID-19 × × × × √ × √ --
43 Silingardi R (68) Letter to the editor Italy Acute limb ischemia in COVID-19 patients × × × × √ × × Acute limb ischemia-Pulmonary Embolism-Aortic floating thrombus
44 Silverman – Chen Lin DA (69) Review USA COVID-19 patients × √ × × × × × --
45 Singh Y (23) Letter to the editor India Cellular metabolism mediated complications in COVID-19infection √ √ × √ × √ √ Cell death triggered by ferroptotic stress
46 Stevens DV (70) Case-Study USA Complications of Orbital Emphysema in a COVID-19 Patient × √ × × √ × × --
47 Strafella C (40) Analytic Italy Analysis of ACE2 Genetic Variability Among Populations √ √ × √ × √ × Sepsis
48 Tian D (71) Review China COVID-19 patients × × √ × × × × --
49 Thomas W (72) Letter to the editor United Kingdom Thrombotic complication of a patient with COVID-19 × × × × √ × √ --
50 Terpos E (73) Review Greece Hematologic complications in COVID-19 patients × × × √ √ × × --
51 Varatharaj A (41) Case-control UK COVID-19 patients √ × × × × × √ Thrombotic complication of a patient with COVID-19
52 Varatharajah N (24) Letter to the editor USA Microthrombotic complications of patients with COVID-19 × √ × × √ × × Hematologic complications in COVID-19 patients
53 Wagener F (10) Viewpoint Netherlands Critically ill COVID-19 patients × √ × × × × × Coagulation abnormality
54 Wang X (6) Research article China Chronic diseases among patients with COVID-19 × × √ √ √ √ × --
55 Zhu H (74) Review USA patients with COVID-19 × √ × √ × × × Coagulopathy-DIC
56 Abboud H (75) Review Morocco patients with COVID-19 √ × × × × × × --
57 Khan S (76) Review Malaysia patients with COVID-19 × × × × √ × × --
58 Khandait H (77) Research article India patients with COVID-19 × √ × √ √ × √ Coagulopathy-DIC-Pulmonary Embolism-Deep vein thrombosis
59 Msigwa S S(78) Review China patients with COVID-19 √ × × × × × × --
60 Sheikh A B (79) Case-report USA 56-year-old man with COVID-19 × × × √ √ × × --
61 Siripanthong B (80) Review UK patients with COVID-19 × × × √ × × × Myocarditis
62 Vonck K (81) Review Belgium patients with COVID-19 √ × × × × × × central nervous system (CNS) manifestations [dizziness, headache, impaired, consciousness, acute cerebrovascular disease (CVD), ataxia and seizure], cranial and peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment and neuropathy), and skeletal muscular injury manifestations
63 Wijeratne T (82) Review Australia patients with COVID-19 √ × × × × × √ Acute ischemic stroke
64 Yachou Y (83) Review Russia patients with COVID-19 √ × × × × × × --
65 Zaim S (84) Review UK patients with COVID-19 √ √ √ √ × √ × DIC
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DVT: Deep vein thrombosis; GI: gastrointestinal; PTE: pulmonary thromboembolism; DIC: disseminated intravascular coagulation.

Quality assessment

For bias risk assessment, two independent reviewers rated the quality of included studies by applying the National Institute of Health (NIH) Quality Assessment Tools for Case Series Studies. For this purpose, we have designed a table and evaluated the studies according to NIH questionnaire (Table 1). A third independent investigator was consulted to resolve probable difference of opinions in any case. The full text of select articles was fully read and the key findings were extracted. The final report including the key findings is summarized in Table 2.

Table 1.

Quality ratings of included studies based on NIH quality assessment (QA) tool for case series studies

First Author *Question
 Rating
1 2 3 4 5 6 7 8 9 # 1 # 2
Ali Sepehrinezhad (21) Yes Yes CD CD NA Yes CD NA Yes Fair Fair
Filatov A (22) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Helms J (25) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Heneka MT (2) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Kochi AN (26) Yes Yes CD CD NA Yes CD NA Yes Fair Fair
Klok FA (27) Yes Yes NA CD NA Yes CD NA Yes Fair Fair
Klok FA (30) Yes Yes NR NA NA Yes CD Yes Yes Fair Fair
Klok FA(30) Yes Yes CD CD NA Yes CD NA Yes Fair Fair
Kunutsor SK(44) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Landi A (28) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Lazar HL (45) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Lee M (46) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Liabeuf S(47) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Liu B (48) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Lorenzo-Villalba N(49) Yes Yes NR CD NA Yes CD Yes Yes Fair Fair
Loungani RS(50) Yes Yes NR CD NA Yes CD Yes Yes Fair Fair
Lodigiani C(34) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Long B (51) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Lopez M (52) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Ma J (53) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Ma L (54) Yes Yes CD NA NA Yes CD NA Yes Fair Fair
Mao L(43) Yes Yes CD NA NA Yes CD NA Yes Fair Fair
Mauro V(55) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Mendoza-Pinto C(56) Yes Yes NR CD NA Yes CD Yes Yes Fair Fair
Nobile B (57) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Nogueira MS (29) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Orsi FA(33) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Oudkerk M(58) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Palmer K (59) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Poggiali E (35) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Parry AH (60) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Patel VG (61) Yes Yes NA NA NA Yes CD NA Yes Fair Fair
Paul P (62) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Paybast S (42) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Pryce-Roberts A(38) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Puntmann VO(37) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Rey JR (63) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Roche JA(64) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Rosen RJ(65) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Saban-Ruiz J (66) Yes Yes NR CD NA Yes CD Yes Yes Fair Fair
Sheraton M (39) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Siguret V (67) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Silingardi R (68) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Silverman – Chen Lin DA (69) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Singh Y (23) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Stevens DV (70) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Strafella C (40) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Tian D (71) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Thomas W (72) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Terpos E (73) Yes Yes NR CD NA Yes CD Yes Yes Fair Fair
Varatharaj A (41) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Varatharajah N (24) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Wagener F (10) Yes Yes CD CD NA Yes CD NA Yes Fair Fair
Wang X (6) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Zhu H (74) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Abboud H (75) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Khan S (76) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Khandait H (77) Yes Yes CD CD NA Yes CD Yes Yes Fair Fair
Msigwa S S(78) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Sheikh A B (79) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
Siripanthong B (80) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Vonck K (81) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Wijeratne T (82) Yes Yes NA NA NA Yes CD Yes Yes Fair Fair
Yachou Y (83) Yes Yes CD NA NA Yes CD Yes Yes Fair Fair
Zaim S (84) Yes Yes NA CD NA Yes CD Yes Yes Fair Fair
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NA: not applicable; NIH: National Institutes of Health; NR: not reported; CD: cannot determine

*The NIH Quality Assessment Tool for Case Series Studies contains nine questions: 1 = Was the study question or objective clearly stated?, 2 = Was the study population clearly and fully described, including a case definition?, 3 = Were the cases consecutive?, 4 = Were the subjects comparable?, 5 = Was the intervention clearly described?, 6 = Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?, 7 = Was the length of follow-up adequate?, 8 = Were the statistical methods well-described?, 9 = Were the results well-described?

Results

We retrieved 1325 documents using a systematic search strategy. After an initial review of retrieved articles, 542 duplicates were removed, and the titles and abstracts of the remaining 783 articles were reviewed. Applying the selection criteria, 718 articles were excluded, and only 65 articles met the inclusion criteria and were included in the final review (Figure 1).

Figure 1.

Figure 1

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Flow diagram of the selection process of articles identified.

We identified 10 potential late complications of COVID-19 including neurological injuries, lung, liver, kidney, and heart injuries, thromboembolism, cardiac/brain stroke, encephalopathy, and psychological distress. Furthermore, some studies have pointed out other complications such as hypoproteinemia, septic shock, and multiple organ dysfunction syndromes (Table 1).

Review of studies showed that lung injuries (n=31), venous/arterial thrombosis (n=28), heart injuries (n=26), cardiac/brain stroke (n=23), and neurological injuries (n=20) were the most frequent late complications of COVID-19. Frequencies of identified late complications of COVID-19 are demonstrated in Figure 2.

Figure 2.

Figure 2

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Frequency of identified late complications of COVID-19.

Discussion

One of the most important unknown features of COVID-19 is the duration of symptoms. In the early stages of the disease, the experts believed that the recovery time for mild cases of COVID-19 is 1-2 weeks (21). However, later in many patients, the symptoms lasted for 8 to 10 weeks or even longer, and in some cases, the initial symptoms were replaced by long-term complications such as lung or cardiac injuries (22). Since COVID-19 is a novel virus, there are limited studies about its late complications; it is just a few months since the recovery of the first patients in China. However, the available evidence suggests that the coronavirus can cause long-term complications in an infected person as it may cause major injuries to the heart, kidneys, brain, and even blood vessels (6, 10, 23, 24).

The available evidence indicates the recurrence of symptoms in some patients who presented with severe initial symptoms (2, 25, 26). The key question is “what causes the recurrence of symptoms?”. It may be caused by the recurrence or persistence of the primary COVID-19 infection or super infection with another virus or even bacteria due to the compromised immune system (27). In addition, the systemic and multiorgan involvement in advanced phases of COVID-19 pneumonia can cause renal failure, liver dysfunction, thrombocytopenia, and coagulation disorders (28). Therefore, the survivors may present a variety of long-term complications in different organs, including a post-recovery syndrome that doctors call "post-COVID lung disease" (29). By looking at the organs affected during an infection, one can imagine what organs are likely to be affected by long-term complications of COVID-19 infection (30).

The most common long-term complication of COVID-19 is lung disease (8, 29, 31). Most of the COVID-19 patients could be recovered completely except for some minor complications such as cough and shortness of breath. However, a certain proportion of patients have excessive lung damage, and some of them develop pulmonary fibrosis (32). Autopsy studies demonstrated the predominance of microvascular thrombosis in the lungs, coincident with markers of inflammation, which is a hallmark of prolonged infection and sepsis (33). Severe lung involvement in COVID-19 patients could increase the likelihood of progression to chronic lung disease and lead to long-term complications (8, 33).

COVID-19 patients may experience both venous and arterial thrombosis due to severe inflammation and hypoxia, long immobilization, and diffuse intravascular coagulation (27, 28). Klok et al. reported the incidence rate of thrombotic complications to be 31% among ICU patients with severe COVID-19 infection (27). The results of another study reported the high number of arterial and, in particular, venous thrombo-embolic late complications (34). Poggiali et al. described two patients with COVID-19 pneumonia who developed venous thromboembolism and reported hypoxia and sepsis as the potential risk factors for vein thromboembolism (VTE)(35).

Recent studies reported an increased risk of heart failure in COVID-19 patients (26, 28, 30). Moreover, episodes of clinical myocarditis have been observed (15). Heart injuries related to COVID-19 may occur over the course of the disease(36). Late involvement of cardiac muscle has been documented in a study by Puntmannet al. In this study, the researchers investigated the cardiac complications in 100 recovered patients; 78% of patients had cardiac involvement in cardiac magnetic resonance imaging (MRI), 76% had detectable high-sensitivity troponin, and 60% had abnormal native T1 and T2, which indicates the presence of active myocardial (37). Compared to the control group with similar preexisting conditions, left ventricle ejection fraction was lower and the ventricular size was higher in COVID-19 patients. In addition, 32% of patients had late gadolinium enhancement and 22% of them had pericardial involvement (36, 37).

COVID-19 can cause damage to the central nervous system, with potentially long-term consequences (38-41). Late neurological complications of COVID-19, whether caused by the virus or by the triggered inflammation, include decreased awareness and absorption, disturbed memory, and dysfunction of the peripheral nervous system (42). In one study from China, more than a third of hospitalized patients with confirmed COVID-19 had neurological symptoms, including dizziness, headaches, impaired consciousness, vision, taste/smell impairment, and nerve pain. These symptoms were more common in patients with severe disease, where the incidence increased to almost 47 percent (43). Another study in France found neurologic features in 58 of 64 critically ill COVID-19 patients (25).

Conclusion

Since we are still at the early stages of the COVID-19 epidemic, it is too soon to predict what long-term complications are likely to appear in the survivors of the disease in years after recovery. Furthermore, the complexity of COVID-19 behaviors and variety of its targets in the human body create uncertainty in anticipating long-term complications. However, several ongoing studies are set up to examine the physical, psychological, and socio-economic consequences of the COVID-19.

Acknowledgments

The present study was conducted in collaboration with Khalkhal University of Medical Sciences, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, and Department of Global Health and Socioepidemiology, Kyoto University.

Ethics approval and consent to participate

The present study was extracted from the research project with code IR.KHALUMS.REC.1399.001 entitled "Investigation of effective drugs for people affected by Coronavirus disease 2019 (COVID-19) in selected hospitals in Ardabil" conducted at Khalkhal University of Medical Sciences in 2020.

Funding

This research did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

Consent to publication

Not applicable

Availability of data and material

The authors stated that all information provided in this article are available.

Competing interests

The authors declare that there is no conflict of interest regarding the publication of this manuscript.

References

  • 1.Orlandi M, Lepri G, Bruni C, Wang Y, Bartoloni A, Zammarchi L, et al. The systemic sclerosis patient in the COVID-19 era: the challenging crossroad between immunosuppression, differential diagnosis and long-term psychological distress. Clinical Rheumatology. 2020:1. doi: 10.1007/s10067-020-05193-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimer's research & therapy. 2020;12(1):69. doi: 10.1186/s13195-020-00640-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Mehraeen E, Behnezhad F, Salehi MA, Noori T, Harandi H, SeyedAlinaghi S. Olfactory and gustatory dysfunctions due to the coronavirus disease (COVID-19): a review of current evidence. European Archives of Oto-Rhino-Laryngology. 2020:1–6. doi: 10.1007/s00405-020-06120-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Mehraeen E, Hayati B, Saeidi S, Heydari M, Seyed Alinaghi S. Self-Care Instructions for People Not Requiring Hospitalization for Coronavirus Disease 2019 (COVID-19) Archives of Clinical Infectious Diseases. 2020;15(COVID-19) [Google Scholar]
  • 5.SeyedAlinaghi S, Ghadimi M, Hajiabdolbaghi M, Rasoolinejad M, Abbasian L, Nezhad MH, et al. Prevalence of COVID-19-like symptoms among people living with HIV, and using antiretroviral therapy for prevention and treatment. Current HIV Research. 2020 doi: 10.2174/1570162X18666200712175535. [DOI] [PubMed] [Google Scholar]
  • 6.Wang X, Fang X, Cai Z, Wu X, Gao X, Min J, et al. Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis. Research (Washington, DC). 2020;2020:2402961. doi: 10.34133/2020/2402961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Consoli L, Bendotti V, Cicchinelli S, Gaioni F, Prandolini P, Bettonagli M, et al. 2019 novel coronavirus (COVID-19) pneumonia complications: the importance of lung ultrasound. Journal of ultrasound. 2020:1–4. doi: 10.1007/s40477-020-00494-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Asadollahi-Amin A, Hasibi M, Ghadimi F, Rezaei H, SeyedAlinaghi S. Lung involvement found on chest ct scan in a pre-symptomatic person with SARS-CoV-2 infection: a case report. Tropical medicine and infectious disease. 2020;5(2):56. doi: 10.3390/tropicalmed5020056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Ghiasvand F, Miandoab SZ, Harandi H, Golestan FS, Alinaghi SAS. A patient with COVID-19 disease in a Referral Hospital in Iran: a typical case. Infectious disorders drug targets. 2020 doi: 10.2174/1871526520666200429115535. [DOI] [PubMed] [Google Scholar]
  • 10.Wagener F, Pickkers P, Peterson SJ, Immenschuh S, Abraham NG. Targeting the Heme-Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections. Antioxidants (Basel, Switzerland) 2020;9(6) doi: 10.3390/antiox9060540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Montalvan V, Lee J, Bueso T, De Toledo J, Rivas K. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clinical Neurology and Neurosurgery. 2020;194:105921. doi: 10.1016/j.clineuro.2020.105921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimer's Research & Therapy. 2020;12:1–3. doi: 10.1186/s13195-020-00640-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Beghi E, Feigin V, Caso V, Santalucia P, Logroscino G. COVID-19 Infection and Neurological Complications: Present Findings and Future Predictions. Neuroepidemiology. 2020;4:1–6. doi: 10.1159/000508991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Aghagoli G, Gallo Marin B, Soliman LB, Sellke FW. Cardiac involvement in COVID‐19 patients: Risk factors, predictors, and complications: A review. Journal of Cardiac Surgery. 2020 doi: 10.1111/jocs.14538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19) JAMA cardiology. 2020 doi: 10.1001/jamacardio.2020.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Bandyopadhyay D, Akhtar T, Hajra A, Gupta M, Das A, Chakraborty S, et al. COVID-19 pandemic: Cardiovascular complications and future implications. American Journal of Cardiovascular Drugs. 2020:1–14. doi: 10.1007/s40256-020-00420-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Bellastella G, Maiorino M, Esposito K. Endocrine complications of COVID-19: what happens to the thyroid and adrenal glands? Journal of Endocrinological Investigation. 2020:1. doi: 10.1007/s40618-020-01311-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. medRxiv. 2020 doi: 10.1136/bmj.m1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Singh Y, Gupta G, Kazmi I, Al‐Abbasi FA, Negi P, Chellappan D, et al. SARS CoV‐2 aggravates cellular metabolism mediated complications in COVID‐19 infection. Dermatologic therapy. 2020 doi: 10.1111/dth.13871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine & Growth Factor Reviews. 2020 doi: 10.1016/j.cytogfr.2020.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Sepehrinezhad A, Shahbazi A, Negah SS. COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review. Journal of neurovirology. 2020;26(3):324–9. doi: 10.1007/s13365-020-00851-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Filatov A, Sharma P, Hindi F, Espinosa PS. Neurological complications of coronavirus disease (COVID-19): encephalopathy. Cureus. 2020;12(3) doi: 10.7759/cureus.7352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Singh Y, Gupta G, Kazmi I, Al-Abbasi FA, Negi P, Chellappan DK, et al. SARS CoV-2 aggravates cellular metabolism mediated complications in COVID-19 infection. Dermatologic therapy. :e13871. doi: 10.1111/dth.13871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Varatharajah N, Rajah S. Microthrombotic Complications of COVID-19 Are Likely Due to Embolism of Circulating Endothelial Derived Ultralarge Von Willebrand Factor (eULVWF) Decorated-Platelet Strings. Federal practitioner : for the health care professionals of the VA, DoD, and PHS. 2020;37(6):e1–e2. [PMC free article] [PubMed] [Google Scholar]
  • 25.Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. New England Journal of Medicine. 2020 doi: 10.1056/NEJMc2008597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Kochi AN, Tagliari AP, Forleo GB, Fassini GM, Tondo C. Cardiac and arrhythmic complications in patients with COVID-19. Journal of cardiovascular electrophysiology. 2020;31(5):1003–8. doi: 10.1111/jce.14479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Klok FA, Kruip M, van der Meer NJM, Arbous MS, Gommers D, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis research. 2020;191:145–7. doi: 10.1016/j.thromres.2020.04.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Landi A, De Servi S. The burden of thrombotic complications in critically ill patients with COVID-19: charting the uncharted. Internal and emergency medicine. 2020:1–3. doi: 10.1007/s11739-020-02393-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Nogueira MS. Optical theranostics and treatment dosimetry for COVID-19 lung complications: towards increasing the survival rate of vulnerable populations. Photodiagnosis and photodynamic therapy. 2020;31:101892. doi: 10.1016/j.pdpdt.2020.101892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Klok FA, Kruip M, van der Meer NJM, Arbous MS, Gommers D, Kant KM, et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thrombosis research. 2020;191:148–50. doi: 10.1016/j.thromres.2020.04.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Consoli L, Bendotti V, Cicchinelli S, Gaioni F, Prandolini P, Bettonagli M, et al. 2019 novel coronavirus (COVID-19) pneumonia complications: the importance of lung ultrasound. Journal of ultrasound. 2020:1–4. doi: 10.1007/s40477-020-00494-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Lifelong Lung Damage: The Serious COVID-19 Complication That Can Hit People in Their 20s [Internet] Healthline. 2020. Available from: https://www.healthline.com/health-news/lifelong-lung-damage-the-serious-covid-19-complication-that-can-hit-people-in-their-20s.
  • 33.Orsi FA, De Paula EV, Santos FO, Teruchkin MM, Campêlo DHC, Mello TT, et al. Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy. Hematology, transfusion and cell therapy. 2020 doi: 10.1016/j.htct.2020.06.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thrombosis research. 2020;191:9–14. doi: 10.1016/j.thromres.2020.04.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Poggiali E, Bastoni D, Ioannilli E, Vercelli A, Magnacavallo A. Deep Vein Thrombosis and Pulmonary Embolism: Two Complications of COVID-19 Pneumonia? European journal of case reports in internal medicine. 2020;7(5):001646. doi: 10.12890/2020_001646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Yancy CW, Fonarow GC. Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter? JAMA cardiology. 2020 doi: 10.1001/jamacardio.2020.3575. [DOI] [PubMed] [Google Scholar]
  • 37.Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19) JAMA cardiology. 2020 doi: 10.1001/jamacardio.2020.3557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Pryce-Roberts A, Talaei M, Robertson NP. Neurological complications of COVID-19: a preliminary review. Journal of neurology. 2020;267(6):1870–3. doi: 10.1007/s00415-020-09941-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Sheraton M, Deo N, Kashyap R, Surani S. A Review of Neurological Complications of COVID-19. Cureus. 2020;12(5):e8192. doi: 10.7759/cureus.8192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Strafella C, Caputo V, Termine A, Barati S, Gambardella S, Borgiani P, et al. Analysis of ACE2 Genetic Variability among Populations Highlights a Possible Link with COVID-19-Related Neurological Complications. Genes. 2020;11(7) doi: 10.3390/genes11070741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Varatharaj A, Thomas N, Ellul MA, Davies NWS, Pollak TA, Tenorio EL, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. The lancet Psychiatry. 2020 doi: 10.1016/S2215-0366(20)30287-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Paybast S, Emami A, Koosha M, Baghalha F. Novel Coronavirus Disease (COVID-19) and Central Nervous System Complications: What Neurologist Need to Know. Acta neurologica Taiwanica. 2020;29(1):24–31. [Google Scholar]
  • 43.Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA neurology. 2020;77(6):683–90. doi: 10.1001/jamaneurol.2020.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Kunutsor SK, Laukkanen JA. Hepatic manifestations and complications of COVID-19: A systematic review and meta-analysis. The Journal of infection. 2020 doi: 10.1016/j.jinf.2020.06.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Lazar HL. Commentary: Compliance with the American Association for Thoracic Surgery guidelines will prevent sternal wound infections and minimize postoperative complications in cardiac surgery patients during the COVID-19 pandemic. The Journal of thoracic and cardiovascular surgery. 2020;160(2):e44–8. doi: 10.1016/j.jtcvs.2020.04.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Lee M, Chen CS, Ovbiagele B. Covert COVID-19 complications: Continuing the use of evidence-based drugs to minimize potentially lethal indirect effects of the pandemic in stroke patients. Journal of the neurological sciences. 2020;414:116883. doi: 10.1016/j.jns.2020.116883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Liabeuf S, Moragny J, Bennis Y, Batteux B, Brochot E, Schmit JL, et al. Association between renin-angiotensin system inhibitors and COVID-19 complications. European heart journal Cardiovascular pharmacotherapy. 2020 doi: 10.1093/ehjcvp/pvaa062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Liu B, Qi Z. Authors' Reply to: Tocilizumab, Adipokines and Severe Complications of COVID-19. Clinical drug investigation. 2020:1–3. doi: 10.1007/s40261-020-00948-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Lorenzo-Villalba N, Maouche Y, Syrovatkova A, Pham F, Chahbazian JB, Pertoldi P, et al. Cutaneous Complications Secondary to Haemostasis Abnormalities in COVID-19 Infection. European journal of case reports in internal medicine. 2020;7(7):001769. doi: 10.12890/2020_001769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Loungani RS, Rehorn MR, Newby LK, Katz JN, Klem I, Mentz RJ, et al. A care pathway for the cardiovascular complications of COVID-19: Insights from an institutional response. American heart journal. 2020;225:3–9. doi: 10.1016/j.ahj.2020.04.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Long B, Brady WJ, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. The American journal of emergency medicine. 2020;38(7):1504–7. doi: 10.1016/j.ajem.2020.04.048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Lopez M, Bell K, Annaswamy T, Juengst S, Ifejika N. COVID-19 Guide for the Rehabilitation Clinician: A Review of Nonpulmonary Manifestations and Complications. American journal of physical medicine & rehabilitation. 2020;99(8):669–73. doi: 10.1097/PHM.0000000000001479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Ma J, Xia P, Zhou Y, Liu Z, Zhou X, Wang J, et al. Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19. Clinical Immunology (Orlando, Fla). 2020;214:108408. doi: 10.1016/j.clim.2020.108408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Ma L, Song K, Huang Y. Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications. Journal of cardiothoracic and vascular anesthesia. 2020 doi: 10.1053/j.jvca.2020.04.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Mauro V, Lorenzo M, Paolo C, Sergio H. Treat all COVID 19-positive patients, but do not forget those negative with chronic diseases. Internal and emergency medicine. 2020:1–4. doi: 10.1007/s11739-020-02395-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Mendoza-Pinto C, Escárcega RO, García-Carrasco M, Bailey DJO, Gálvez-Romero JL, Cervera R. Viral infections and their relationship with catastrophic antiphospholipid syndrome: a possible pathogenic mechanism of severe COVID-19 thrombotic complications. Journal of internal medicine. 2020 doi: 10.1111/joim.13123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Nobile B, Durand M, Olié E, Guillaume S, Molès JP, Haffen E, et al. Clomipramine Could Be Useful in Preventing Neurological Complications of SARS-CoV-2 Infection. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2020:1–2. doi: 10.1007/s11481-020-09939-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Oudkerk M, Büller HR, Kuijpers D, van Es N, Oudkerk SF, McLoud TC, et al. Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology. 2020:201629. doi: 10.1148/radiol.2020201629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Palmer K, Monaco A, Kivipelto M, Onder G, Maggi S, Michel JP, et al. The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing. Aging clinical and experimental research. 2020;32(7):1189–94. doi: 10.1007/s40520-020-01601-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Parry AH, Wani AH, Yaseen M, Dar MI. Demystifying pulmonary vascular complications in severe coronavirus disease-19 pneumonia (COVID-19) in the light of clinico-radiologic-pathologic correlation. Thrombosis research. 2020 doi: 10.1016/j.thromres.2020.06.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Patel VG, Zhong X, Liaw B, Tremblay D, Tsao CK, Galsky MD, et al. Does androgen deprivation therapy protect against severe complications from COVID-19? Annals of oncology : official journal of the European Society for Medical Oncology. 2020 doi: 10.1016/j.annonc.2020.06.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Paul P. Cardiac Troponin-I may be a predictor of complications and mortality in COVID-19 patients. Current medicine research and practice. 2020;10(3):130–1. doi: 10.1016/j.cmrp.2020.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Rey JR, Caro-Codón J, Poveda Pineda D, Merino JL, Iniesta Á M, López-Sendón JL. Arterial thrombotic complications in hospitalized patients with COVID-19. Revista espanola de cardiologia (English ed) :2020. doi: 10.1016/j.rec.2020.05.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Roche JA, Roche R. A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020;34(6):7265–9. doi: 10.1096/fj.202000967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Rosen RJ. Thrombotic complications in critically ill patients with COVID 19. Thrombosis research. 2020;191 doi: 10.1016/j.thromres.2020.04.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Saban-Ruiz J, Ly-Pen D. COVID-19: A Personalized Cardiometabolic Approach for Reducing Complications and Costs The Role of Aging Beyond Topics. The Journal of Nutrition, Health & Aging. 2020:1. doi: 10.1007/s12603-020-1385-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Siguret V, Voicu S, Neuwirth M, Delrue M, Gayat E, Stépanian A, et al. Are antiphospholipid antibodies associated with thrombotic complications in critically ill COVID-19 patients? Thrombosis Research. 2020 doi: 10.1016/j.thromres.2020.07.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Silingardi R, Gennai S, Migliari M, Covic T, Leone N. Acute limb ischemia in COVID-19 patients: Could Aortic Floating Thrombus be the source of embolic complications? Journal of vascular surgery. 2020 doi: 10.1016/j.jvs.2020.06.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Silverman DA, Lin C, Tamaki A, Puram SV, Carrau RL, Seim NB, et al. Respiratory and pulmonary complications in head and neck cancer patients: Evidence‐based review for the COVID‐19 era. Head & Neck. 2020;42(6):1218–26. doi: 10.1002/hed.26217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Stevens DV, Tran AQ, Kim E. Complications of Orbital Emphysema in a COVID-19 Patient. Ophthalmology. 2020 doi: 10.1016/j.ophtha.2020.05.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Tian D, Ye Q. Hepatic complications of COVID-19 and its treatment. Journal of medical virology. 2020 doi: 10.1002/jmv.26036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Thomas W, Varley J, Johnston A, Symington E, Robinson M, Sheares K, et al. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thrombosis Research. 2020;191:76–7. doi: 10.1016/j.thromres.2020.04.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Terpos E, Ntanasis‐Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, et al. Hematological findings and complications of COVID‐19. American journal of hematology. 2020 doi: 10.1002/ajh.25829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Zhu H, Rhee J-W, Cheng P, Waliany S, Chang A, Witteles RM, et al. Cardiovascular complications in patients with COVID-19: consequences of viral toxicities and host immune response. Current cardiology reports. 2020;22:1–9. doi: 10.1007/s11886-020-01292-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Abboud H, Abboud FZ, Kharbouch H, Arkha Y, El Abbadi N, El Ouahabi A. COVID-19 and SARS-Cov-2 Infection: Pathophysiology and Clinical Effects on the Nervous System. World Neurosurg. 2020;140:49–53. doi: 10.1016/j.wneu.2020.05.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Ahmed SI, Khan S. Coagulopathy and Plausible Benefits of Anticoagulation Among COVID-19 Patients. Curr Probl Cardiol. 2020;45(9):100648. doi: 10.1016/j.cpcardiol.2020.100648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Khandait H, Gandotra G, Sachdeva S, Kramer CA, Nye D, Golamari R, et al. COVID-19 and Hematology-What Do We Know So Far? SN Compr Clin Med. 2020:1–6. doi: 10.1007/s42399-020-00607-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Msigwa SS, Wang Y, Li Y, Cheng X. The neurological insights of the emerging coronaviruses. J Clin Neurosci. 2020;78:1–7. doi: 10.1016/j.jocn.2020.06.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Sheikh AB, Shekhar R, Javed N, Upadhyay S. Inferior Wall Myocardial Infarction in Severe COVID-19 Infection: A Case Report. Am J Case Rep. 2020;21:e926101. doi: 10.12659/AJCR.926101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Siripanthong B, Nazarian S, Muser D, Deo R, Santangeli P, Khanji MY, et al. Recognizing COVID-19-related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm. 2020;17(9):1463–71. doi: 10.1016/j.hrthm.2020.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Vonck K, Garrez I, De Herdt V, Hemelsoet D, Laureys G, Raedt R, et al. Neurological manifestations and neuro-invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2. Eur J Neurol. 2020;27(8):1578–87. doi: 10.1111/ene.14329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Wijeratne T, Sales C, Karimi L, Crewther SG. Acute Ischemic Stroke in COVID-19: A Case-Based Systematic Review. Front Neurol. 2020;11:1031. doi: 10.3389/fneur.2020.01031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Yachou Y, El Idrissi A, Belapasov V, Ait Benali S. Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: understanding the neurological manifestations in COVID-19 patients. Neurol Sci. 2020;41(10):2657–69. doi: 10.1007/s10072-020-04575-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Zaim S, Chong JH, Sankaranarayanan V, Harky A. COVID-19 and Multiorgan Response. Curr Probl Cardiol. 2020;45(8):100618. doi: 10.1016/j.cpcardiol.2020.100618. [DOI] [PMC free article] [PubMed] [Google Scholar]

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