Table 1.
Commonly reported microbial co-pathogens amid COVID-19, their transmission pattern along with the possible mechanism of co-infections and outcomes.
| Type of co-infection | Co-pathogens | Route of transmission | Person to person transmission | Possible mechanism of co-infection and pathogenesis | Possible outcomes |
|---|---|---|---|---|---|
| Viral | Influenza | Respiratory | Yes | IFN induced overexpression of ACE2 triggered by influenza virus aids SARS-CoV-2 infection [112]. | Influenza co-infection can provoke COVID-19 hyper-inflammatory states. Higher incidence of acute cardiac injury was reported [113] |
| HBV | Body fluid | Yes | Increased liver tissue damage and inflammatory responses due to COVID-19 may aid HBV co-infection by overexpressing host cell receptors [114]. It may also fuel the reactivation of pre-existing chronic HBV [115]. | Elevation of ALT, AST, TBIL, ALP, and γ-GT. [116] Higher risk of liver injury. [117] | |
| Dengue | Mosquito bite | No | NR | Increase the severity of symptoms [118]. Decrease in white blood cell, neutrophils, lymphocytes and platelets count and eventual higher mortality rate [119] | |
| HIV | Body fluid | Yes | Suppression of T lymphocyte mediated immunity (as observed in HIV patients) leads to the prognosis of increased disease severity and higher mortality rate during COVID-19 co-infection [120]. | HIV Patients under ART exhibits mild COVID-19 symptoms. But ART-naïve patients show acute COVID-19 clinical representation [121]. Higher maximum body temperatures, longer duration of fever and longer improvement time of chest CT image was reported due to co-infection [122] | |
| HCV | Body fluid | Yes | Both SARS-CoV-2 E and HCV p7 proteins can form similar ion channels which ensure their success in attacking their host and effective replication during co-infection [123]. | The actual outcome is not reported till date. It has been speculated that some investigational COVID‐19 drugs may adversely affect the HCV‐related decompensated cirrhosis patients [124]. | |
| Rhinovirus | Respiratory | Yes | Major disease-causing rhinovirus serotype HRV-A16 infection upregulates ACE2 and TMPRSS2 expression in epithelial cells by inducing IFNb1. This event facilitates SARS-CoV-2 transmission and further disease severity [125] | One case has been reported in a young patient expressing critical illness as the outcome of co-infection [126] | |
| Adenovirus | Respiratory | Yes | Similar ion channel forming capability of SARS-CovV-2 E and Adenovirus 6K proteins facilitates co-infection [123] | Unfavorable prognostic outcome including ARDS [127] | |
| Bacterial | Streptococcus pneumoniae | Respiratory | Yes | Opportunistic normal flora of human upper respiratory track | Severe respiratory distress followed by pleural effusion and necrotizing pneumonia [128], higher mortality rate [129] |
| Staphylococcus aureus | Respiratory/Digestive/Contact | Yes | Opportunistic normal flora of human upper respiratory track, gut mucosa and skin | Necrotizing pneumonia [130]. Bacteremia and higher mortality [131] |
|
| Pseudomonas aeruginosa | Contact | Yes | Opportunistic pathogen causing HAI mostly related with poor hygiene, mechanical ventilation and urinary catheterization. | NR | |
| Acinetobacter baumannii | Contact | Yes | Mechanical ventilation | NR | |
| Klebsiella pneumoniae | Respiratory/Contact | Yes | Opportunistic normal flora of human mouth, skin, and intestines | Fatal sepsis [132] | |
| Mycoplasma pneumoniae | Respiratory/contact | Yes | NR | Severe pneumonia [133]. Increased morbidity, mortality and disease severity [134] | |
| Clamydia pneumoniae | Respiratory/contact | Yes | NR | Severe pneumonia [133]. | |
| Legionella pneumophila | Digestive/Respiratory | Yes | NR | Elevated aspartate aminotransferase, blood urea nitrogen, creatinine, lactate dehydrogenase and C-reactive protein [135] | |
| Haemophilus influenzae | Respiratory/contact | Yes | Opportunistic normal flora of human upper respiratory track | NR | |
| Neisseria meningitides | Respiratory/contact | Yes | NR | Convulsion [136], elevated C-reactive protein, headache, neck stiffness, rigors, confusion, and a new purpuric rash over hands and feet [137] | |
| Mycobacterium tuberculosis | Respiratory | Yes | Cytokine storm produced by COVID-19 may reactivate latent TB or boost the development of active TB. Lung damages caused by TB may also escalate the disease severity caused by SARS-CoV-2 [138]. | Co-infection is associated with disease severity and disease progression rate [139]. 2.17 times higher risk-of-death and 25% lower risk-of-recovery was reported. Also shorter time-to-death and longer time-to-recovery was found [140]. | |
| Fungal | Aspergillus spp. | Respiratory | No | Pro-inflammatory cytokines (especially IL-6 and IL-10) released during COVID-19 results in tissue necrosis and ARDS, which eventually makes patient more vulnerable to Aspergillosis [141]. | Invasive pulmonary aspergillosis, higher case fatality rate (64.7% reported) [141] |
| Candida spp. | Perinatal/Contact | No | Opportunistic pathogen found in human skin. | Candidemia and increased mortality rate [142]. |
IFN: Interferon; ACE2: Angiotensin-converting enzyme 2; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19: Coronavirus disease 2019; HBV: Hepatitis B Virus; HIV: Human Immunodeficiency Virus; HCV: Hepatitis C Virus; ALT: Alanine transaminase; AST: Aspartate transaminase; TBIL: Total bilirubin; ALP: Alkaline phosphatase; γ-GT: Gamma-glutamyl transferase; ART: Antiretroviral therapy; CT: Computed Tomography; HRV-A16: Human rhinovirus A16; TMPRSS2: Transmembrane protease, serine 2; IFNb1: Interferon Beta 1; ARDS: Acute respiratory distress syndrome; HAI: Hospital Acquired Infections TB: Tuberculosis; IL-6: Interleukin 6; IL-10: Interleukin 10; NR: Not Reported.