Study selection
Our search retrieved 4438 results. After de-duplication and removal of 3141 irrelevant records via first-level screening, eligibility screening was performed on full-text 97 articles. Of these, 90 articles were excluded due to their study design, representative population, or/and outcome. Finally, an additional article was found and cross-referenced in previously included articles -totaling eight articles eligible for analysis. The detailed study selection process is depicted in Figure 1.
We analyzed data from 2418 COVID-19 patients from the eight studies included.31–38 Equal number of studies were found in both prospective (N = 4) and retrospective designs (N = 4). Seven studies had patients belonging to the age group >17 years and one study involved children only [median age = 4.5 years; interquartile range (IQR) = 0.4-7.5].37; one study included on pregnant women31 (see Table 1). Five studies (adult and pediatric) reported comorbidity-related data. Two of the seven studies (on adults) reported malaria or dengue coinfections in healthcare workers (HCWs).32,33 Studies focusing on bacterial (N=4/8) coinfections were higher than those on and viral (N = 3/8), parasitic (N = 3/8), and fungal (N = 2/8) coinfections.
Coinfections
We found the overall prevalence of coinfections ranged from 4% to 46%31–38. Bacterial coinfections showed the highest prevalence (57.3%) followed by parasitic (21.1%), and viral coinfections (14.6%); fungal coinfections were the least (6.9%). Klebsiella Pneumoniae and Staphylococcus Aureus were most the prominent bacterial species (28.57%) (Figure 2). Amongst viruses, dengue virus (26.47%) and human rhinovirus (HRV) (11.76%) (Figure 3) were prevalent; Mucormycosis and Pseudomonas Jirovecii prevailed in fungal coinfections.34,36
Comorbidities
Comorbidity(ies) were noted in COVID-19 patients with and without coinfections. They included DM, hypertension (HTN), congestive heart disease (CHD), chronic kidney disease (CKD), asthma, malignancy, neurological disorder, and other renal and cardiac diseases in both adult and pediatric patients.32,33,35–37 Mahajan et al. studied co-occurrence of pre-eclampsia in a pregnant patient. Patients with a history of chronic liver disease (CLD) and thrombocytopenia were also reported.31
Interestingly, neurological complications were significantly more common among patients with SARS-CoV-2 and Mycoplasma pneumoniae or Chlamydia pneumoniae coinfections than those with only SARS‑CoV‑2 infection (35.7% Vs 3.4%, p<0.001), as reported by Chaudhry et al.35 In addition, adults coinfected with M. pneumoniae or C. pneumoniae were more likely to develop acute respiratory distress syndrome (ARDS) (76.5% vs. 46.9%, p = 0.023) than patients with only SARS‐CoV‐2,35 implying the effect of coinfection on the severity of COVID-19 infection.
Clinical presentation/symptoms
As per our analysis, the commonly manifested symptoms in COVID-19 patients included fever, cough, confusion, myalgia, dyspnea, and headache.31,32,35,36 A higher prevalence of confusion and headache was observed in the M. pneumoniae or C. pneumoniae coinfected group (41.2% and 29.4%, respectively), than those with only SARS-CoV-2 infection (16.4% and 5.6%, respectively).35 Among pediatrics, fever duration was significantly higher in the coinfected group compared to non-coinfected [6 days (3–10) vs. 3.5 days (1–7), p=0.012].37 However, respiratory distress was reported more frequently in children with moderate to severe COVID-19 infection (45.7%, N = 27/59) than those presenting with coinfections (32.5%, N = 14/43).37
Amongst HCWs, except for 3 asymptomatic cases, the remaining reported symptoms of malaria or dengue along with COVID-19 symptoms. The difference in viral clearance was statistically significant (11 days [IQR 8–15] vs. 7 days [IQR 5-11] (p < 0.001).32
Intensive Care Unit Length of Stay
The proportion of COVID-19 patients with coinfections requiring ICU admissions ranged from 60% to >80%32,35–37 and the average length of hospital stay was 13.67+3.51 days. A higher rate of ICU admission was observed in adults with coinfections compared to those without coinfections (77.7% vs. 68.3%, p=0.143), as reported by Sreenath et al.36 Similarly among children, coinfected patients required longer pediatric ICU (PICU) stay than those without coinfections (8 vs 6.5 days, p=0.02).37 Also, coinfected children required mechanical ventilator support in a higher proportion compared to the non-coinfected children (34.8% vs. 15.2%, p=0.03).37
Mortality
The mortality rate in COVID-19 patients with coinfections ranged from 9% to 65%.35–37 According to Sharma et al. coinfected patients had a significantly higher mortality rate than the non‑coinfected patients (53.4% vs. 24%, p<0.00001). A similar finding was reported by Chaudhry et al., 64.7% of patients died in the M. pneumoniae or C. pneumoniae co‐infection group compared to 32.8% in non-coinfected group (p = 0.029). Patients of older age with comorbidities were more likely to die.35
Raychaudhri et al. noticed a higher mortality rate in coinfected children than the non-coinfected group (9.3% vs. 1.7%) however, this was non-significant.37 Amongst the four patients, one with malarial coinfection suffered an intrauterine fetal demise.31
Surprisingly, one study found that adults with malarial coinfection had faster recovery with respect to virus clearance (mean 7.7 days) compared to those without malarial coinfection (mean 11.5 days) (p < .005).32
Quality assessment
We used the “JBI checklist for prevalence studies” to assess the risk of bias among the included studies. The overall assessment showed a low risk of bias. The study design and statistical analysis-based requirements were majorly fulfilled by all studies (Figure 4). However, a few questions such as adequate sample size, standard methods used for identification, and measuring the condition were marked “unclear”.
Our review involved two cases series31,34 which were subjected to “JBI checklist for case series” (Figure 5).